Wt1 dictates the fate of fetal and adult Leydig cells during development in the mouse testis.

PubMed

Wen, Qing; Zheng, Qiao-Song; Li, Xi-Xia; Hu, Zhao-Yuan; Gao, Fei; Cheng, C Yan; Liu, Yi-Xun

2014-12-15

Wilms' tumor 1 (Wt1) is a tumor suppressor gene encoding ∼24 zinc finger transcription factors. In the mammalian testis, Wt1 is expressed mostly by Sertoli cells (SCs) involved in testis development, spermatogenesis, and adult Leydig cell (ALC) steroidogenesis. Global knockout (KO) of Wt1 is lethal in mice due to defects in embryogenesis. Herein, we showed that Wt1 is involved in regulating fetal Leydig cell (FLC) degeneration and ALC differentiation during testicular development. Using Wt1(-/flox);Amh-Cre mice that specifically deleted Wt1 in the SC vs. age-matched wild-type (WT) controls, FLC-like-clusters were found in Wt1-deficient testes that remained mitotically active from postnatal day 1 (P1) to P56, and no ALC was detected at these ages. Leydig cells in mutant adult testes displayed morphological features of FLC. Also, FLC-like cells in adult mutant testes had reduced expression in ALC-associated genes Ptgds, Sult1e1, Vcam1, Hsd11b1, Hsd3b6, and Hsd17b3 but high expression of FLC-associated genes Thbs2 and Hsd3b1. Whereas serum LH and testosterone level in mutant mice were not different from controls, intratesticular testosterone level was significantly reduced. Deletion of Wt1 gene also perturbed the expression of steroidogenic enzymes Star, P450c17, Hsd3b6, Hsd3b1, Hsd17b1, and Hsd17b3. FLCs in adult mutant testes failed to convert androstenedione to testosterone due to a lack of Hsd17b3, and this defect was rescued by coculturing with fetal SCs. In summary, FLC-like cells in mutant testes are putative FLCs that remain mitotically active in adult mice, illustrating that Wt1 dictates the fate of FLC and ALC during postnatal testis development. Copyright © 2014 the American Physiological Society.

Ehd4 is required to attain normal pre-pubertal testis size but dispensable for fertility in male mice

PubMed Central

George, Manju; Rainey, Mark A.; Naramura, Mayumi; Ying, GuoGuang; Harms, Don W.; Vitaterna, Martha H.; Doglio, Lynn; Crawford, Susan E.; Hess, Rex A.; Band, Vimla; Band, Hamid

2010-01-01

The four highly homologous members of the C-terminal EH domain-containing (EHD) protein family (EHD1-4) regulates endocytic recycling. To delineate the role of EHD4 in normal physiology and development, mice with a conditional knockout of the Ehd4 gene were generated. PCR of genomic DNA and Western blotting of organ lysates from Ehd4−/− mice confirmed EHD4 deletion. Ehd4−/− mice were viable and born at expected Mendelian ratios; however, males showed a 50% reduction in testis weight, obvious from postnatal day 31. An early (day 10) increase in germ cell proliferation and apoptosis and a later increase in apoptosis (day 31) were seen in the Ehd4−/− testis. Other defects included a progressive reduction in seminiferous tubule diameter, dysregulation of seminiferous epithelium and head abnormalities in elongated spermatids. As a consequence, lower sperm counts and reduced fertility were observed in Ehd4−/− males. Interestingly, EHD protein expression was seen to be temporally regulated in the testis and levels peaked between days 10 and 15. In the adult testis, EHD4 was highly expressed in primary spermatocytes and EHD4 deletion altered the levels of other EHD proteins in an age-dependent manner. We conclude that high levels of EHD1in the adult Ehd4−/− testis functionally compensate for lack of EHD4 and prevents the development of severe fertility defects. Our results suggest a role for EHD4 in the proper development of post-mitotic and post-meiotic germ cells and implicate EHD protein-mediated endocytic recycling as an important process in germ cell development and testis function. PMID:20213691

Assessment of fetal testis function and postnatal development of the male rat following in utero exposure to diethylhexyl phthalate, dipentyl phthalate, diisobutyl phthalate, diisoheptyl phthalate and diisononyl phthalate

EPA Science Inventory

Phthalate esters are a large class of plasticizer compounds widely used in many consumer product applications. Some phthalates induce male fetal endocrine toxicity and reproductive malformations through disruption of hormone production during sexual differentiation. Regulatory ag...

A novel gene, RSD-3/HSD-3.1, encodes a meiotic-related protein expressed in rat and human testis.

PubMed

Zhang, Xiaodong; Liu, Huixian; Zhang, Yan; Qiao, Yuan; Miao, Shiying; Wang, Linfang; Zhang, Jianchao; Zong, Shudong; Koide, S S

2003-06-01

The expression of stage-specific genes during spermatogenesis was determined by isolating two segments of rat seminiferous tubule at different stages of the germinal epithelium cycle delineated by transillumination-delineated microdissection, combined with differential display polymerase chain reaction to identify the differential transcripts formed. A total of 22 cDNAs were identified and accepted by GenBank as new expressed sequence tags. One of the expressed sequence tags was radiolabeled and used as a probe to screen a rat testis cDNA library. A novel full-length cDNA composed of 2228 bp, designated as RSD-3 (rat sperm DNA no.3, GenBank accession no. AF094609) was isolated and characterized. The reading frame encodes a polypeptide consisting of 526 amino acid residues, containing a number of DNA binding motifs and phosphorylation sites for PKC, CK-II, and p34cdc2. Northern blot of mRNA prepared from various tissues of adult rats showed that RSD-3 is expressed only in the testis. The initial expression of the RSD-3 gene was detected in the testis on the 30th postnatal day and attained adult level on the 60th postnatal day. Immunolocalization of RSD-3 in germ cells of rat testis showed that its expression is restricted to primary spermatocytes, undergoing meiosis division I. A human testis homologue of RSD-3 cDNA, designated as HSD-3.1 (GenBank accession no. AF144487) was isolated by screening the Human Testis Rapid-Screen arrayed cDNA library panels by RT-PCR. The exon-intron boundaries of HSD-3.1 gene were determined by aligning the cDNA sequence with the corresponding genome sequence. The cDNA consisted of 12 exons that span approximately 52.8 kb of the genome sequence and was mapped to chromosome 14q31.3.

Identification and validation of suitable reference genes for RT-qPCR analysis in mouse testis development.

PubMed

Gong, Zu-Kang; Wang, Shuang-Jie; Huang, Yong-Qi; Zhao, Rui-Qiang; Zhu, Qi-Fang; Lin, Wen-Zhen

2014-12-01

RT-qPCR is a commonly used method for evaluating gene expression; however, its accuracy and reliability are dependent upon the choice of appropriate reference gene(s), and there is limited information available on suitable reference gene(s) that can be used in mouse testis at different stages. In this study, using the RT-qPCR method, we investigated the expression variations of six reference genes representing different functional classes (Actb, Gapdh, Ppia, Tbp, Rps29, Hprt1) in mice testis during embryonic and postnatal development. The expression stabilities of putative reference genes were evaluated using five algorithms: geNorm, NormFinder, Bestkeeper, the comparative delta C(t) method and integrated tool RefFinder. Analysis of the results showed that Ppia, Gapdh and Actb were identified as the most stable genes and the geometric mean of Ppia, Gapdh and Actb constitutes an appropriate normalization factor for gene expression studies. The mRNA expression of AT1 as a test gene of interest varied depending upon which of the reference gene(s) was used as an internal control(s). This study suggested that Ppia, Gapdh and Actb are suitable reference genes among the six genes used for RT-qPCR normalization and provide crucial information for transcriptional analyses in future studies of gene expression in the developing mouse testis.

Transforming Growth Factor Beta (TGFβ1, TGFβ2 and TGFβ3) Null-Mutant Phenotypes in Embryonic Gonadal Development

PubMed Central

Memon, Mushtaq A.; Anway, Matthew D.; Covert, Trevor R.; Uzumcu, Mehmet; Skinner, Michael K.

2008-01-01

The role transforming growth factor beta (TGFb) isoforms TGFb1, TGFb2 and TGFb3 have in the regulation of embryonic gonadal development was investigated with the use of null-mutant (i.e. knockout) mice for each of the TGFb isoforms. Late embryonic gonadal development was investigated because homozygote TGFb null-mutant mice generally die around birth, with some embryonic loss as well. In the testis, the TGFb1 null-mutant mice had a decrease in the number of germ cells at birth, postnatal day 0 (P0). In the testis, the TGFb2 null-mutant mice had a decrease in the number of seminiferous cords at embryonic day 15 (E15). In the ovary, the TGFb2 null-mutant mice had an increase in the number of germ cells at P0. TGFb isoforms appear to have a role in gonadal development, but interactions between the isoforms is speculated to compensate in the different TGFb isoform null-mutant mice. PMID:18790002

Selective ablation of Ppp1cc gene in testicular germ cells causes oligo-teratozoospermia and infertility in mice.

PubMed

Sinha, Nilam; Puri, Pawan; Nairn, Angus C; Vijayaraghavan, Srinivasan

2013-11-01

The four isoforms of serine/threonine phosphoprotein phosphatase 1 (PP1), derived from three genes, are among the most conserved proteins known. The Ppp1cc gene encodes two alternatively spliced variants, PP1 gamma1 (PPP1CC1) and PP1 gamma2 (PPP1CC2). Global deletion of the Ppp1cc gene, which causes loss of both isoforms, results in male infertility due to impaired spermatogenesis. This phenotype was assumed to be due to the loss of PPP1CC2, which is abundant in testis. While PPP1CC2 is predominant, other PP1 isoforms are also expressed in testis. Given the significant homology between the four PP1 isoforms, the lack of compensation by the other PP1 isoforms for loss of one, only in testis, is surprising. Here we document, for the first time, expression patterns of the PP1 isoforms in postnatal developing and adult mouse testis. The timing and sites of testis expression of PPP1CC1 and PPP1CC2 in testis are nonoverlapping. PPP1CC2 is the only one of the four PP1 isoforms not detected in sertoli cells and spermatogonia. Conversely, PPP1CC2 may be the only PP1 isoform expressed in postmeiotic germ cells. Deletion of the Ppp1cc gene in germ cells at the differentiated spermatogonia stage of development and beyond in Stra8 promoter-driven Cre transgenic mice results in oligo-terato-asthenozoospermia and male infertility, thus phenocopying global Ppp1cc null (-/-) mice. Taken together, these results confirm that spermatogenic defects observed in the global Ppp1cc knockout mice and in mice expressing low levels of PPP1CC2 in testis are due to compromised functions of PPP1CC2 in meiotic and postmeiotic germ cells.

Identification of Hedgehog signaling outcomes in mouse testis development using a hanging drop-culture system.

PubMed

Szczepny, Anette; Hogarth, Cathryn A; Young, Julia; Loveland, Kate L

2009-02-01

The Hedgehog (Hh) signaling pathway affects fetal testis growth. Recently, we described the dynamic cellular production of Hh signaling pathway components in juvenile and adult rodent testes. The Hh signaling is understood to regulate cord formation in the fetal testis, but minimal knowledge exists regarding how Hh signaling impacts the postnatal testis. To investigate this, we employed hanging drop cultures, which are used routinely in embryoid body formation. This approach has the advantage of using small media volume, and we examined its suitability for short-term culture of both murine embryonic gonads and adult testis tubules. The effects of cyclopamine, a specific Hh signaling inhibitor, were examined following culture of Embryonic Day 11.5 urogenital ridges (as control) and adult seminiferous tubule fragments for 24-48 h using histological, cell proliferation, and gene expression analyses. Cultured embryonic testes displayed generally normal cord structure, anti-Müllerian hormone (Amh) expression, and cell proliferation; known Hh target gene expression (Gli1, osteopontin, official symbol Spp1, and Amh) was altered in response to cyclopamine. Cultured adult tubules exhibited some loss of seminiferous epithelium organization over 48 h. Spermatogonia continued to proliferate, however, and no significant loss of viability was noted overall. Addition of cyclopamine significantly affected levels of Gli1, Igfbp6, Ccnd2 (cyclin D2), Ccnb1 (cyclin B1), Spp1, Kit, and Amh mRNAs; these genes have been shown previously to be expressed in Sertoli and germ cells. These novel results identify Hh target genes in the testis and demonstrate this signaling pathway likely affects cell survival and differentiation in the context of normal adult testis.

Identification of Hedgehog Signaling Outcomes in Mouse Testis Development Using a Hanging Drop-Culture System1

PubMed Central

Szczepny, Anette; Hogarth, Cathryn A.; Young, Julia; Loveland, Kate L.

2008-01-01

The Hedgehog (Hh) signaling pathway affects fetal testis growth. Recently, we described the dynamic cellular production of Hh signaling pathway components in juvenile and adult rodent testes. The Hh signaling is understood to regulate cord formation in the fetal testis, but minimal knowledge exists regarding how Hh signaling impacts the postnatal testis. To investigate this, we employed hanging drop cultures, which are used routinely in embryoid body formation. This approach has the advantage of using small media volume, and we examined its suitability for short-term culture of both murine embryonic gonads and adult testis tubules. The effects of cyclopamine, a specific Hh signaling inhibitor, were examined following culture of Embryonic Day 11.5 urogenital ridges (as control) and adult seminiferous tubule fragments for 24–48 h using histological, cell proliferation, and gene expression analyses. Cultured embryonic testes displayed generally normal cord structure, anti-Müllerian hormone (Amh) expression, and cell proliferation; known Hh target gene expression (Gli1, osteopontin, official symbol Spp1, and Amh) was altered in response to cyclopamine. Cultured adult tubules exhibited some loss of seminiferous epithelium organization over 48 h. Spermatogonia continued to proliferate, however, and no significant loss of viability was noted overall. Addition of cyclopamine significantly affected levels of Gli1, Igfbp6, Ccnd2 (cyclin D2), Ccnb1 (cyclin B1), Spp1, Kit, and Amh mRNAs; these genes have been shown previously to be expressed in Sertoli and germ cells. These novel results identify Hh target genes in the testis and demonstrate this signaling pathway likely affects cell survival and differentiation in the context of normal adult testis. PMID:18843087

Prenatal lipopolysaccharide exposure affects maternal behavior and male offspring sexual behavior in adulthood.

PubMed

Bernardi, Maria M; Kirsten, Thiago B; Matsuoka, Suzana M; Teodorov, Elizabeth; Habr, Soraya F; Penteado, Sandra H W N; Palermo-Neto, João

2010-01-01

This study investigates the effects of prenatal lipopolysaccharide (LPS) exposure on the maternal behavior of pregnant rats and the physical development and sexual behavior of their male offspring in adulthood. For two experiments, pregnant rats were injected with LPS (250 microg/kg, i.p.) on gestation day (GD) 21. In the first experiment, the maternal behavior (postnatal day, PND, 6) and the dam's open-field general activity (PND7) were evaluated. In the second experiment, the maternal pre- and postnatal parameters, the pup's development, the offspring's sexual behavior in adulthood, and the pup's organ weights were assessed. Compared to the control group, the LPS-treated dams presented reduced maternal behavior, decreased general activity, a smaller body weight difference between GD21 and PND1, a greater number of perinatal deaths, and smaller litters. For the male pups, LPS treatment resulted in a decreased body weight on PND2, whereas the anogenital distance and the day of testis descent were not modified. The male sexual behavior was impaired by prenatal LPS. Particularly the number of ejaculating animals was reduced. The testis weight was also lower in the prenatally LPS-treated rats than in the control rats. We propose that prenatal LPS exposure on GD21 acts as an imprinting factor that interferes with the programming of brain sexual determination in offspring. Copyright 2009 S. Karger AG, Basel.

Gene Suppression of Mouse Testis In Vivo Using Small Interfering RNA Derived from Plasmid Vectors

PubMed Central

Takizawa, Takami; Ishikawa, Tomoko; Kosuge, Takuji; Mizuguchi, Yoshiaki; Sato, Yoko; Koji, Takehiko; Araki, Yoshihiko; Takizawa, Toshihiro

2012-01-01

We evaluated whether inhibiting gene expression by small interfering RNA (siRNA) can be used for an in vivo model using a germ cell-specific gene (Tex101) as a model target in mouse testis. We generated plasmid-based expression vectors of siRNA targeting the Tex101 gene and transfected them into postnatal day 10 mouse testes by in vivo electroporation. After optimizing the electroporation conditions using a vector transfected into the mouse testis, a combination of high- and low-voltage pulses showed excellent transfection efficiency for the vectors with minimal tissue damage, but gene suppression was transient. Gene suppression by in vivo electroporation may be helpful as an alternative approach when designing experiments to unravel the basic role of testicular molecules. PMID:22489107

Effects of gestational exposure to di-n-butyl phthalate and mineral oil on testis development of the Mongolian gerbil.

PubMed

Christante, C M; Pinto-Fochi, M E; Negrin, A C; Taboga, S R; Góes, R M

2018-06-14

Phthalate esters are endocrine disrupters that can affect the development of the testis in a species-specific manner. However, their interference in the male gonads of the Mongolian gerbil is unknown. The aim of the present study was to evaluate whether gestational exposure to di-n-butyl phthalate (DBP) interferes with the development of the gerbil testis during the first six weeks of life. Males were evaluated at 1, 7, 14, 28, 35 and 42 days of age in an untreated (control) group or groups exposed from 8 to 23 days gestation to DBP (100mgkg-1day-1 in mineral oil) or vehicle by maternal gavage. DBP exposure impaired cell proliferation within the seminiferous cords at birth, but increased proliferation at the end of the first week, when higher testosterone concentrations were observed. The vehicle (mineral oil) reduced the total number of gonocytes and attenuated the decrease in testosterone concentrations at 7 days. The vehicle also altered gonocyte relocation at 14 days and increased oestrogen concentrations at 28 days by approximately 112%. In summary, both DBP and oil interfered in gonadal development and testosterone plasma concentrations in the first week of postnatal life. However, the changes observed at the beginning of puberty were not seen after exposure to DBP, indicating a more harmful effect of mineral oil in this period.

Anatomy and histology of the scrotal ligament in adults: inconsistency and variability of the gubernaculum testis.

PubMed

Cavalie, G; Bellier, Alexandre; Marnas, G; Boisson, B; Robert, Y; Rabattu, P Y; Chaffanjon, P

2018-04-01

The anatomy of gubernaculum testis (GT) is often discussed; however, the postnatal anatomy of the GT or scrotal ligament (SL) is rarely described. Hence, we performed an anatomical and histological study to analyze histologically the structures between testis and scrotum. We performed anatomical dissections on 25 human fresh cadavers' testes. Each testis was removed with its envelopes and macroscopically analyzed. Then samples were included for histological study. Finally, they were analyzed under microscope, looking for attachments between testis, epididymis and scrotal envelopes. The absence of proximal and distal attachment was found in 56.0% of cases. Looking at the proximal attachment of the SL, the main one found is the epididymal attachment (28.0%), whereas no cases of testis attachment was found. Distally, there are more variations with scrotal attachment (12%) and cremaster attachment (12.0%). We found a significant prevalence of multiple adherences in 16.0% of cases too. Finally, in 15 cases (57.7%) an attachment is present between testis and epididymis, as it is commonly described. In the majority of cases there is no attachment of the lower pole of the testis and epididymis and these structures remain free. So it seems that the SL disappears with aging. Moreover, there is not only one kind of ligamentous attachment, but a high variability of attachments at the lower pole of the testiculo-epididymal structure. When it exists, this structure is never a real ligament and it seems more appropriate to use the term "attachments".

Nestin in the epididymis is expressed in vascular wall cells and is regulated during postnatal development and in case of testosterone deficiency.

PubMed

Reckmann, Ansgar N; Tomczyk, Claudia U M; Davidoff, Michail S; Michurina, Tatyana V; Arnhold, Stefan; Müller, Dieter; Mietens, Andrea; Middendorff, Ralf

2018-01-01

Vascular smooth muscle cells (SMCs), distinguished by the expression of the neuronal stem cell marker nestin, may represent stem cell-like progenitor cells in various organs including the testis. We investigated epididymal tissues of adult nestin-GFP mice, rats after Leydig cell depletion via ethane dimethane sulfonate (EDS), rats and mice during postnatal development and human tissues. By use of Clarity, a histochemical method to illustrate a three-dimensional picture, we could demonstrate nestin-GFP positive cells within the vascular network. We localized nestin in the epididymis in proliferating vascular SMCs by colocalization with both smooth muscle actin and PCNA, and it was distinct from CD31-positive endothelial cells. The same nestin localization was found in the human epididymis. However, nestin was not found in SMCs of the epididymal duct. Nestin expression is high during postnatal development of mouse and rat and down-regulated towards adulthood when testosterone levels increase. Nestin increases dramatically in rats after Leydig cell ablation with EDS and subsequently low testosterone levels. Interestingly, during this period, the expression of androgen receptor in the epididymis is low and increases until nestin reaches normal levels of adulthood. Here we show that nestin, a common marker for neuronal stem cells, is also expressed in the vasculature of the epididymis. Our results give new insights into the yet underestimated role of proliferating nestin-expressing vascular SMCs during postnatal development and repair of the epididymis.

Xenotransplantation as a model for human testicular development.

PubMed

Hutka, Marsida; Smith, Lee B; Mitchell, Rod T

The developing male reproductive system may be sensitive to disruption by a wide range of exogenous 'endocrine disruptors'. In-utero exposure to environmental chemicals and pharmaceuticals have been hypothesized to have an impact in the increasing incidence of male reproductive disorders. The vulnerability to adverse effects as a consequence of such exposures is elevated during a specific 'window of susceptibility' in fetal life referred to as the masculinisation programing window (MPW). Exposures that occur during prepuberty, such as chemotherapy treatment for cancer during childhood, may also affect future fertility. Much of our current knowledge about fetal and early postnatal human testicular development derives from studies conducted in animal models predictive for humans. Therefore, over recent years, testicular transplantation has been employed as a 'direct' approach to understand the development of human fetal and prepubertal testis in health and disease. In this review we describe the potential use of human testis xenotransplantation to study testicular development and its application for (i) assessing the effects of environmental exposures in humans, and (ii) establishing fertility preservation options for prepubertal boys with cancer. Copyright © 2017 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

Genomic organization, expression, and chromosome localization of a third aurora-related kinase gene, Aie1.

PubMed

Hu, H M; Chuang, C K; Lee, M J; Tseng, T C; Tang, T K

2000-11-01

We previously reported two novel testis-specific serine/threonine kinases, Aie1 (mouse) and AIE2 (human), that share high amino acid identities with the kinase domains of fly aurora and yeast Ipl1. Here, we report the entire intron-exon organization of the Aie1 gene and analyze the expression patterns of Aie1 mRNA during testis development. The mouse Aie1 gene spans approximately 14 kb and contains seven exons. The sequences of the exon-intron boundaries of the Aie1 gene conform to the consensus sequences (GT/AG) of the splicing donor and acceptor sites of most eukaryotic genes. Comparative genomic sequencing revealed that the gene structure is highly conserved between mouse Aie1 and human AIE2. However, much less homology was found in the sequence outside the kinase-coding domains. The Aie1 locus was mapped to mouse chromosome 7A2-A3 by fluorescent in situ hybridization. Northern blot analysis indicates that Aie1 mRNA likely is expressed at a low level on day 14 and reaches its plateau on day 21 in the developing postnatal testis. RNA in situ hybridization indicated that the expression of the Aie1 transcript was restricted to meiotically active germ cells, with the highest levels detected in spermatocytes at the late pachytene stage. These findings suggest that Aie1 plays a role in spermatogenesis.

In utero betamethasone affects 3β-hydroxysteroid dehydrogenase and inhibin-α immunoexpression during testis development.

PubMed

Pedrana, G; Viotti, H; Lombide, P; Sanguinetti, G; Pino, C; Cavestany, D; Sloboda, D M; Martin, G B

2016-08-01

Prenatal glucocorticoids, commonly used in women at risk of preterm delivery, can predispose the newborn to disease in later life. Since male reproductive function is likely to reflect testis development during fetal life, we studied the effects of prenatal glucocorticoids on two key intra-testicular factors that play roles in cellular proliferation and differentiation, 3β-hydroxysteroid dehydrogenase (3β-HSD) and inhibin-α. Pregnant sheep (n=42) were treated with betamethasone (0.5 mg/kg) or saline (control) at 104, 111 and 118 days of gestation (DG). Testicular tissue was sampled from fetuses at 121 and 132DG, and from lambs at 45 and 90 postnatal days (PD). Within the betamethasone treated group, 3β-HSD immunostaining area was greater at 121DG than at 90PD (P=0.04), but the intensity of immunostaining was higher at 90PD than at 121DG (P=0.04), 132DG (P=0.04) and 45PD (P=0.03). Control animals showed no changes in 3β-HSD area or intensity of immunostaining. No significant differences were observed between treated and control animals in immunostaining area, but immunostaining was more intense in the treated group than in the control group at 90PD (P=0.03). For inhibin-α, the proportion of immunostaining area declined in treated offspring from 121DG to 45PD, in contrast to control values, but recovered fully by 90PD, concomitantly with the onset of spermatogenesis. In conclusion, prenatal betamethasone increased the postnatal testicular expression of inhibin-α but reduced the expression of 3β-HSD. These effects could compromise androgen-mediated testicular development and therefore adult capacity for spermatogenesis.

Characterization of rtSH3p13 gene encoding a development protein involved in vesicular traffic in spermiogenesis.

PubMed

Qiao, Yuan; Yang, Ju Xiang; Zhang, Xiao Dong L; Liu, Yu; Zhang, Jian Chao; Zong, Shu Dong; Miao, Shi Ying; Wang, Lin Fang; Koide, Samuel S

2004-06-01

A cDNA, designated as rtSH3p13, was isolated from a rat testis cDNA library. It consists of 1463 bp nuclear acids, which encodes a protein of 312 amino acids and was assigned the GenBank accession number AF227439. The deduced rtSH3p13 protein is a truncated isoform of SH3p13 as a result of mRNA alternative splicing. It is mainly expressed in the rat testis, detected in spermatids at the steps 8-19 of spermiogenesis, and found around the acrosome. During postnatal development, rtSH3p13 appears on day 18 and reaches maximum on day 60. Further experimental results suggested that rtSH3p13 forms a complex with activated epidermal growth factor receptor (EGFR) and interacts with synaptojanin I. Surprisingly, similar to SH3 domain, the V region of rtSH3p13 also inhibits endocytosis in CHO cells. Our results reveal a link between an rtSH3p13-synaptojanin-clathrin complex-mediated formation of pits and the process of spermiogenesis.

Effects of prenatal exposure to a 900 MHz electromagnetic field on 60-day-old rat testis and epididymal sperm quality.

PubMed

Odacı, E; Hancı, H; Yuluğ, E; Türedi, S; Aliyazıcıoğlu, Y; Kaya, H; Çolakoğlu, S

2016-01-01

We investigated the effects of exposure in utero to a 900 megahertz (MHz) electromagnetic field (EMF) on 60-day-old rat testis and epididymis. Pregnant rats were divided into control (CG; no treatment) and EMF (EMFG) groups. The EMFG was exposed to 900 MHz EMF for 1 h each day during days 13 - 21 of pregnancy. Newborn rats were either newborn CG (NCG) or newborn EMF groups (NEMFG). On postnatal day 60, a testis and epididymis were removed from each animal. Epididymal semen quality, and lipid and DNA oxidation levels, apoptotic index and histopathological damage to the testis were compared. We found a higher apoptotic index, greater DNA oxidation levels and lower sperm motility and vitality in the NEMFG compared to controls. Immature germ cells in the seminiferous tubule lumen, and altered seminiferous tubule epithelium and seminiferous tubule structure also were observed in hematoxylin and eosin stained sections of NEMFG testis. Nuclear changes that indicated apoptosis were identified in TUNEL stained sections and large numbers of apoptotic cells were observed in most of the seminiferous tubule epithelium in the NEMFG. Sixty-day-old rat testes exposed to 900 MHz EMF exhibited altered sperm quality and biochemical characteristics.

Interaction between basigin and monocarboxylate transporter 2 in the mouse testes and spermatozoa

PubMed Central

Chen, Cheng; Maekawa, Mamiko; Yamatoya, Kenji; Nozaki, Masami; Ito, Chizuru; Iwanaga, Toshihiko; Toshimori, Kiyotaka

2016-01-01

Basigin is a member of the immunoglobulin superfamily and plays various important roles in biological events including spermatogenesis. To examine the basigin molecular variants during spermatogenesis and sperm maturation in the mouse, immunoprecipitated basigin samples from testis and epididymal spermatozoa were analyzed by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). The results demonstrated that basigin molecules from the testis and spermatozoa were separable into two major bands and that the differences in the molecular sizes were possibly because of an endoproteolytic cleavage. Since basigin is known to be a chaperone for the monocarboxylate transporter 1 (MCT1), the localization of basigin, MCT1 and MCT2 was examined during postnatal testicular development. Immunohistochemical studies showed different expression patterns of MCT1 and MCT2. MCT1 was localized on the surface of spermatogonia, spermatocytes, and spermatids. In contrast, MCT2 appeared on the principal piece of spermatozoa in the testis, where basigin was also observed. In mature epididymal spermatozoa, MCT2 was located on the midpiece, where basigin co-localized with MCT2 but not with MCT1. Furthermore, MCT2 was immunoprecipitated with basigin in mouse testes and sperm. These results suggest that basigin has a functional role as a binding partner with MCT2 in testicular and epididymal spermatozoa. PMID:26208397

Transgenerational effect of the endocrine disruptor vinclozolin on male spermatogenesis.

PubMed

Anway, Matthew D; Memon, Mushtaq A; Uzumcu, Mehmet; Skinner, Michael K

2006-01-01

The current study was designed to examine the actions of a model endocrine disruptor on embryonic testis development and male fertility. Pregnant rats (F0) that received a transient embryonic exposure to an environmental endocrine disruptor, vinclozolin, had male offspring (F1) with reduced spermatogenic capacity. The reduced spermatogenetic capacity observed in the F1 male offspring was transmitted to the subsequent generations (F2-F4). The administration of vinclozolin, an androgen receptor antagonist, at 100 mg/kg/day from embryonic day 8-14 (E8-E14) of pregnancy to only the F0 dam resulted in a transgenerational phenotype in the subsequent male offspring in the F1-F4 generations. The litter size and male/female sex ratios were similar in controls and the vinclozolin generations. The average testes/body weight index of the postnatal day 60 (P60) males was not significantly different in the vinclozolin-treated generations compared to the controls. However, the testicular spermatid number, as well as the epididymal sperm number and motility, were significantly reduced in the vinclozolin generations compared to the control animals. Postnatal day 20 (P20) testis from the vinclozolin F2 generation had no morphological abnormalities, but did have an increase in spermatogenic cell apoptosis. Although the P60 testis morphology was predominantly normal, the germ cell apoptosis was significantly increased in the testes cross sections of animals from the vinclozolin generations. The increase in apoptosis was stage-specific in the testis, with tubules at stages IX-XIV having the highest increase in apoptotic germ cells. The tubules at stages I-V also had an increase in apoptotic germ cells compared to the control samples, but tubules at stages VI-VIII had no increase in apoptotic germ cells. An outcross of a vinclozolin generation male with a wild-type female demonstrated that the reduced spermatogenic cell phenotype was transmitted through the male germ line. An outcross with a vinclozolin generation female with a wild-type male had no phenotype. A similar phenotype was observed in outbred Sprague Dawley and inbred Fisher rat strains. Observations demonstrate that a transient exposure at the time of male sex determination to the antiandrogenic endocrine disruptor vinclozolin can induce an apparent epigenetic transgenerational phenotype with reduced spermatogenic capacity.

piRNA biogenesis during adult spermatogenesis in mice is independent of the ping-pong mechanism.

PubMed

Beyret, Ergin; Liu, Na; Lin, Haifan

2012-10-01

piRNAs, a class of small non-coding RNAs associated with PIWI proteins, have broad functions in germline development, transposon silencing, and epigenetic regulation. In diverse organisms, a subset of piRNAs derived from repeat sequences are produced via the interplay between two PIWI proteins. This mechanism, termed "ping-pong" cycle, operates among the PIWI proteins of the primordial mouse testis; however, its involvement in postnatal testes remains elusive. Here we show that adult testicular piRNAs are produced independent of the ping-pong mechanism. We identified and characterized large populations of piRNAs in the adult and postnatal developing testes associated with MILI and MIWI, the only PIWI proteins detectable in these testes. No interaction between MILI and MIWI or sequence feature for the ping-pong mechanism among their piRNAs was detected in the adult testis. The majority of MILI- and MIWI-associated piRNAs originate from the same DNA strands within the same loci. Both populations of piRNAs are biased for 5' Uracil but not for Adenine on the 10th nucleotide position, and display no complementarity. Furthermore, in Miwi mutants, MILI-associated piRNAs are not downregulated, but instead upregulated. These results indicate that the adult testicular piRNAs are predominantly, if not exclusively, produced by a primary processing mechanism instead of the ping-pong mechanism. In this primary pathway, biogenesis of MILI- and MIWI-associated piRNAs may compete for the same precursors; the types of piRNAs produced tend to be non-selectively dictated by the available precursors in the cell; and precursors with introns tend to be spliced before processed into piRNAs.

Pattern and density of vascularization in mammalian testes, ovaries, and ovotestes.

PubMed

Lupiáñez, Darío G; Real, Francisca M; Dadhich, Rajesh K; Carmona, Francisco D; Burgos, Miguel; Barrionuevo, Francisco J; Jiménez, Rafael

2012-05-01

According to the classical paradigm, the vasculature of the embryonic testis is more dense and complex than that of the ovary, but recent studies based on whole-mount detection of Caveolin-1 (CAV1) as an endothelial cell marker, have suggested that the level of ovarian vascularization is higher than previously assumed. However, this new hypothesis has been neither tested using alternative methodology nor investigated in other mammalian species. In this paper, we have studied the vascularization process in the gonads of males and females of two mammalian species, the mouse (Mus musculus) and the Iberian mole (Talpa occidentalis). Our results show that the pattern of testis vascularization is very well conserved among mammals, including both pre- and postnatal stages of development and, at least in the mole, it is conserved irrespectively of whether the testicular tissue is XY or XX. We have shown that CAV1 is present not only in endothelial cells but also in prefollicular oocytes and in an ovarian population of somatic cortical cells. These data clearly establish that: (1) according to the classical hypothesis, the degree of vascularization of the developing ovary is lower than that of the testis, (2) ovarian vascularization is also evolutionarily conserved as it occurs similarly both in moles and in mice, and (3) that the degree of vascular development of the mammalian ovary is age-dependent increasing significatively at puberty. The expression of CAV1 in the ovary of most animal taxa, from nematodes to mammals, strongly suggests a role for this gene in the female meiosis. © 2012 WILEY PERIODICALS, INC.

Male Hypogonadism and Germ Cell Loss Caused by a Mutation in Polo-Like Kinase 4

PubMed Central

Harris, Rebecca M.; Weiss, Jeffrey

2011-01-01

The genetic etiologies of male infertility remain largely unknown. To identify genes potentially involved in spermatogenesis and male infertility, we performed genome-wide mutagenesis in mice with N-ethyl-N-nitrosourea and identified a line with dominant hypogonadism and patchy germ cell loss. Genomic mapping and DNA sequence analysis identified a novel heterozygous missense mutation in the kinase domain of Polo-like kinase 4 (Plk4), altering an isoleucine to asparagine at residue 242 (I242N). Genetic complementation studies using a gene trap line with disruption in the Plk4 locus confirmed that the putative Plk4 missense mutation was causative. Plk4 is known to be involved in centriole formation and cell cycle progression. However, a specific role in mammalian spermatogenesis has not been examined. PLK4 was highly expressed in the testes both pre- and postnatally. In the adult, PLK4 expression was first detected in stage VIII pachytene spermatocytes and was present through step 16 elongated spermatids. Because the homozygous Plk4I242N/I242N mutation was embryonic lethal, all analyses were performed using the heterozygous Plk4+/I242N mice. Testis size was reduced by 17%, and histology revealed discrete regions of germ cell loss, leaving only Sertoli cells in these defective tubules. Testis cord formation (embryonic day 13.5) was normal. Testis histology was also normal at postnatal day (P)1, but germ cell loss was detected at P10 and subsequent ages. We conclude that the I242N heterozygous mutation in PLK4 is causative for patchy germ cell loss beginning at P10, suggesting a role for PLK4 during the initiation of spermatogenesis. PMID:21791561

Mal-Development of the Penis and Loss of Fertility in Male Rats Treated Neonatally with Female Contraceptive 17α-Ethinyl Estradiol: A Dose-Response Study and a Comparative Study with a Known Estrogenic Teratogen Diethylstilbestrol

PubMed Central

Mathews, Ensa; Braden, Tim D.; Williams, Carol S.; Williams, John W.; Bolden-Tiller, Olga; Goyal, Hari O.

2009-01-01

The objectives of this study were to find a minimal dose of 17α-ethinyl estradiol (EE) that is detrimental to the developing penis and fertility and to compare estrogenic effects between EE and diethylstilbestrol (DES). Neonatal rats received EE at 10 ng (1 μg/kg), 100 ng, 1 μg, or 10 μg per pup on alternate days from postnatal days 1 to 11 (dose-response study) or received EE or DES at 100 ng per pup daily from postnatal days 1 to 6 (comparative study). Effects of EE were dose dependent, with ≥ 100-ng dose inducing significant (p < 0.05) reductions in penile length, weight, and diameter. Additionally, the penis was malformed, characterized by underdeveloped os penis and accumulation of fat cells. Fertility was 0% in the ≥ 1-μg groups, in contrast to 60% in the 100-ng group and 100% in the 10-ng and control groups. Animals treated with ≥ 10 ng had significant reductions in the weight of bulbospongious muscle, testis, seminal vesicle, epididymal fat pad, and in epididymal sperm numbers. A comparison of EE and DES effects showed similar reductions in penile weight and length and the weight of bulbospongiosus muscle, testis, seminal vesicle, epididymis, and epididymal fat pad in both adolescent and adult rats. While 5/6 control males sired, only 1/6 in the EE group and 0/6 in the DES group sired. Hence, neonatal exposure to EE at 10 ng (environmentally relevant dose) adversely affects male reproductive organs. A dose ten times higher than this leads to permanently mal-developed penis and infertility. Furthermore, EE and DES exposures show similar level of toxicity to male reproductive organs. PMID:19729556

Germline stem cells and neo-oogenesis in the adult human ovary.

PubMed

Liu, Yifei; Wu, Chao; Lyu, Qifeng; Yang, Dongzi; Albertini, David F; Keefe, David L; Liu, Lin

2007-06-01

It remains unclear whether neo-oogenesis occurs in postnatal ovaries of mammals, based on studies in mice. We thought to test whether adult human ovaries contain germline stem cells (GSCs) and undergo neo-oogenesis. Rather than using genetic manipulation which is unethical in humans, we took the approach of analyzing the expression of meiotic marker genes and genes for germ cell proliferation, which are required for neo-oogenesis, in adult human ovaries covering an age range from 28 to 53 years old, compared to testis and fetal ovaries served as positive controls. We show that active meiosis, neo-oogenesis and GSCs are unlikely to exist in normal, adult, human ovaries. No early meiotic-specific or oogenesis-associated mRNAs for SPO11, PRDM9, SCP1, TERT and NOBOX were detectable in adult human ovaries using RT-PCR, compared to fetal ovary and adult testis controls. These findings are further corroborated by the absence of early meiocytes and proliferating germ cells in adult human ovarian cortex probed with markers for meiosis (SCP3), oogonium (OCT3/4, c-KIT), and cell cycle progression (Ki-67, PCNA), in contrast to fetal ovary controls. If postnatal oogenesis is confirmed in mice, then this species would represent an exception to the rule that neo-oogenesis does not occur in adults.

Phthalate-induced testicular dysgenesis syndrome: Leydig cell influence.

PubMed

Hu, Guo-Xin; Lian, Qing-Quan; Ge, Ren-Shan; Hardy, Dianne O; Li, Xiao-Kun

2009-04-01

Phthalates, the most abundantly produced plasticizers, leach out from polyvinyl chloride plastics and disrupt androgen action. Male rats that are exposed to phthalates in utero develop symptoms characteristic of the human condition referred to as testicular dysgenesis syndrome (TDS). Environmental influences have been suspected to contribute to the increasing incidence of TDS in humans (i.e. cryptorchidism and hypospadias in newborn boys and testicular cancer and reduced sperm quality in adult males). In this review, we discuss the recent findings that prenatal exposure to phthalates affects Leydig cell function in the postnatal testis. This review also focuses on the recent progress in our understanding of how Leydig cell factors contribute to phthalate-mediated TDS.

Studies of the hormonal control of postnatal testicular descent in the rat.

PubMed

Spencer, J R; Vaughan, E D; Imperato-McGinley, J

1993-03-01

Dihydrotestosterone is believed to control the transinguinal phase of testicular descent based on hormonal manipulation studies performed in postnatal rats. In the present study, these hormonal manipulation experiments were repeated, and the results were compared with those obtained using the antiandrogens flutamide and cyproterone acetate. 17 beta-estradiol completely blocked testicular descent, but testosterone and dihydrotestosterone were equally effective in reversing this inhibition. Neither flutamide nor cyproterone acetate prevented testicular descent in postnatal rats despite marked peripheral antiandrogenic action. Further analysis of the data revealed a correlation between testicular size and descent. Androgen receptor blockade did not produce a marked reduction in testicular size and consequently did not prevent testicular descent, whereas estradiol alone caused marked testicular atrophy and testicular maldescent. Reduction of the estradiol dosage or concomitant administration of androgens or human chorionic gonadotropin resulted in both increased testicular size and degree of descent. These data suggest that growth of the neonatal rat testis may contribute to its passage into the scrotum.

FOXL2 impairment in human disease.

PubMed

Verdin, Hannah; De Baere, Elfride

2012-01-01

FOXL2 encodes a forkhead transcription factor that plays important roles in the ovary during development and in post-natal, adult life. Here, we focus on the clinical consequences of FOXL2 impairment in human disease. In line with other forkhead transcription factors, its constitutional genetic defects and a somatic mutation lead to developmental disease and cancer, respectively. More than 100 unique constitutional mutations and regulatory defects have been found in blepharophimosis syndrome (BPES), a complex eyelid malformation associated (type I) or not (type II) with premature ovarian failure (POF). In agreement with the BPES phenotype, FOXL2 is expressed in the developing eyelids and in fetal and adult ovaries. Two knock-out mice and at least one natural animal model, the Polled Intersex Syndrome goat, are known. They recapitulate the BPES phenotype and have provided many insights into the ovarian pathology. Only a few constitutional mutations have been described in nonsyndromic POF. Moreover, a recurrent somatic mutation p.C134W was found to be specific for adult ovarian granulo-sa cell tumors. Functional studies investigating the consequences of FOXL2 mutations or regulatory defects have shed light on the molecular pathogenesis of the aforementioned conditions, and contributed considerably to genotype-phenotype correlations. Recently, a conditional knock-out of Foxl2 in the mouse induced somatic transdifferentiation of ovary into testis in adult mice, suggesting that Foxl2 has an anti-testis function in the adult ovary. This changed our view on the ovary and testis as terminally differentiated organs in adult mammals. Finally, this might have potential implications for the understanding and treatment of frequent conditions such as POF and polycystic ovary syndrome. Copyright © 2012 S. Karger AG, Basel.

Androgen action in the masculinization programming window and development of male reproductive organs.

PubMed

Macleod, D J; Sharpe, R M; Welsh, M; Fisken, M; Scott, H M; Hutchison, G R; Drake, A J; van den Driesche, S

2010-04-01

We have shown previously that deficient androgen action within a masculinization programming window (MPW; e15.5-e18.5 in rats) is important in the origin of male reproductive disorders and in programming male reproductive organ size, but that androgen action postnatally may be important to achieve this size. To further investigate importance of the MPW, we used two rat models, in which foetal androgen production or action was impaired during the MPW by exposing in utero to either di(n-butyl) phthalate (DBP) or to flutamide. Reduced anogenital distance (AGD) was used as a monitor of androgen production/action during the MPW. Offspring were evaluated in early puberty (Pnd25) to establish if reproductive organ size was altered. The testes, penis, ventral prostate (VP) and seminal vesicles (SV) were weighed and penis length measured. Both DBP and flutamide exposure in the MPW significantly reduced penis, VP and SV size along with AGD at Pnd25; AGD and organ size were highly correlated. In DBP-, but not flutamide-, exposed animals, testis weight was also reduced and correlated with AGD. Intratesticular testosterone was also measured in control and DBP-exposed males during (e17.5) or after (e21.5) the MPW and related to AGD at e21.5. To evaluate the importance of postnatal androgen action in reproductive organ growth, the effect of combinations of prenatal and postnatal maternal treatments on AGD and penis size at Pnd25 was evaluated. In prenatally DBP-exposed animals, further postnatal exposure to either DBP or flutamide significantly reduced AGD and penis size in comparison with prenatal DBP exposure alone. In comparison, rats exposed postnatally to testosterone propionate after prenatal vehicle-exposure showed considerable increase in these parameters vs. controls. In conclusion, we show that the size of all male reproductive organs is programmed by androgen exposure in the MPW, but that growth towards this size is dependent on androgen action postnatally.

The Fate of Spermatogonial Stem Cells in the Cryptorchid Testes of RXFP2 Deficient Mice

PubMed Central

Ferguson, Lydia; How, Javier J.; Agoulnik, Alexander I.

2013-01-01

The environmental niche of the spermatogonial stem cell pool is critical to ensure the continued generation of the germ cell population. To study the consequences of an aberrant testicular environment in cryptorchidism we used a mouse model with a deletion of Rxfp2 gene resulting in a high intra-abdominal testicular position. Mutant males were infertile with the gross morphology of the cryptorchid testis progressively deteriorating with age. Few spermatogonia were identifiable in 12 month old cryptorchid testes. Gene expression analysis showed no difference between mutant and control testes at postnatal day 10. In three month old males a decrease in expression of spermatogonial stem cell (SSC) markers Id4, Nanos2, and Ret was shown. The direct counting of ID4+ cells supported a significant decrease of SSCs. In contrast, the expression of Plzf, a marker for undifferentiated and differentiating spermatogonia was not reduced, and the number of PLZF+ cells in the cryptorchid testis was higher in three month old testes, but equal to control in six month old mutants. The PLZF+ cells did not show a higher rate of apoptosis in cryptorchid testis. The expression of the Sertoli cell FGF2 gene required for SSC maintenance was significantly reduced in mutant testis. Based on these findings we propose that the deregulation of somatic and germ cell genes in the cryptorchid testis, directs the SSCs towards the differentiation pathway. This leads to a depletion of the SSC pool and an increase in the number of PLZF+ spermatogonial cells, which too, eventually decreases with the exhaustion of the stem cell pool. Such a dynamic suggests that an early correction of cryptorchidism is critical for the retention of the SSC pool. PMID:24098584

The fragmented testis method: development and its advantages of a new quantitative evaluation technique for detection of testis-ova in male fish.

PubMed

Lin, Bin-Le; Hagino, Satoshi; Kagoshima, Michio; Iwamatsu, Takashi

2009-02-01

A new quantitative evaluation technique, termed the fragmented testis method, has been developed for the detection of testis-ova in genotypic male fish using the medaka (Oryzias latipes). The routine traditional histological method for detection of testis-ova in male fish exposed to estrogens or suspected endocrine-disrupting chemicals has several disadvantages, including possible oversight of testis-ova due to limited sampling of selected tissue sections. The method we have developed here allows for the accurate determination of the developmental stages and the number and the size of testis-ova in a whole testis. Each testis was removed from the fish specimen, fixed with 10% buffered formalin solution, and then divided into small fragments on a glass slide with a dissecting needle or scalpel and aciform forceps in glycerin solution containing a small amount of methylene blue or toluidine blue. If present, all developing testis-ova of various sizes in fragmented testicular tissues were clearly stained and were observable under a dissecting microscope. Testis-ova occurred in controls were ascertained, while spermatozoa were also distinguishable using this method. This proved to be a convenient and cost-effective method for quantitatively evaluating testis-ova appearance in fish, and it may help to clarify the mechanism of testis-ova formation and the biological significance of testis-ova in future studies of endocrine disruption.

Effects of postnatal administration of diethylstilbestrol on puberty and thyroid function in male rats.

PubMed

Shin, Jae-Ho; Kim, Tae Sung; Kang, Il Hyun; Kang, Tae Seok; Moon, Hyun Ju; Han, Soon-Young

2009-10-01

To examine the effects of diethylstilbestrol (DES) on male pubertal development and thyroid function, juvenile male Sprague-Dawley rats were given DES daily by oral intubation at doses of 10, 20 and 40 microg/kg/day from postnatal day 33 for 20 days. Prepuce separation was significantly delayed at the dose of 20 microg/kg/day and above in the DES-treated rats. DES treatment induced a significant reduction in the weights of testes, epididymides, the ventral prostate, seminal vesicles plus coagulating glands and fluid, levator ani bulbocavernosus muscles, Cowper's glands and the glans penis. The weights of the liver and adrenals increased in the DES-treated animals. DES caused a dose-dependent reduction in germ cells; in particular the spermatids were mainly affected. The serum levels of testosterone and luteinizing hormone were significantly reduced in the DES-treated groups, but that of estradiol decreased. No differences were observed in the serum thyroxine levels of the control and DES-treated groups. In microscopic observation of the DES-treated animals, degeneration of germ cells and tubular atrophy in the testis were noted, but there were no microscopic changes in the thyroid. These results indicate that DES affected the pubertal development of juvenile male rats and that its mode of action may be related to alterations in hormone levels.

Timing of entry of meiosis depends on a mark generated by DNA methyltransferase 3a in testis.

PubMed

Yaman, Ruken; Grandjean, Valérie

2006-03-01

Reprogramming of DNA methylation is an essential part of gametogenesis, and a role of two members of the DNA methyltransferase (Dnmt) family, Dnmt3a and Dnmt3L, has been recognized. In an attempt to elucidate the role of Dnmt3a, we analyzed the progression of spermatogenesis in Dnmt3a (-/-) homozygotes during the first 3 weeks of post-natal development. The emerging picture was markedly different from that recently reported for the Dnmt3L protein. In the Dnmt3a (-/-) testis, at the expected time of entry into meiosis (11-13 dpp), the number of spermatocytes was greatly reduced. They progressively accumulated during the following days, but at a slower rate than in the wild type. Once started, however, the pachytene stage was apparently completed with normal chromosome pairing and formation of the sex vesicle, and spermatogenesis further progressed with the appearance and the expression of round spermatid specific markers. Interestingly and unlike Dnmt3L (-/-) spermatocytes, Dnmt3a (-/-) germ cells showed only a minor reduction in the methylation of interspersed repetitive elements and retroposons. The Dnmt3a might thus generate a mark important for the initiation of male meiosis that is distinct from that created by Dnmt3L. (c) 2005 Wiley-Liss, Inc.

Accumulation of the mitochondrial form of the sulphydryl oxidase Erv1p/Alrp during the early stages of spermatogenesis.

PubMed

Klissenbauer, Monika; Winters, Silke; Heinlein, Uwe A O; Lisowsky, Thomas

2002-07-01

In this study, we investigated the expression of the mammalian FAD-dependent sulphydryl oxidase Erv1p/Alrp in the rat and mouse and during mouse spermatogenesis. Up to three forms of Alrp were identified in protein extracts from different tissues and organs, but very little enzyme was present in blood samples. The three forms of Alrp represent the full-length protein of 23 kDa and fragments of 21 kDa and 15 kDa. All forms of Alrp were assembled into dimers in vivo. In contrast to samples from other organs, the protein analysis of mouse testis identified predominantly full-length 23 kDa Alrp. This finding prompted us to investigate in more detail the expression of Alrp during spermatogenesis. Testis samples of individual mice from postnatal days 13-29 were probed with an antibody specific for mammalian Alrp. In addition, cells from whole testis preparations were fractionated on a bovine serum albumin column gradient. Protein expression of mouse Alrp was compared with those of testis-specific cyritestin, the cytoskeleton marker actin and mitochondrial subunit Vb of cytochrome oxidase and cytochrome c. These studies demonstrated a specific accumulation of full-length mouse Alrp during the early stages of spermatogenesis. The highest levels of Alrp were found in spermatogonia and primary spermatocytes. Levels of expression of Alrp did not correlate with the synthesis of components of the respiratory chain, indicating that full-length Alrp in the mitochondria of spermatogonia and spermatocytes has another function in addition to its role in oxidative phosphorylation.

Developmental expression of the glutathione S-transferase Yo subunit in the rat testis and epididymis using light microscope immunocytochemistry.

PubMed

Papp, S; Robaire, B; Hermo, L

1994-11-01

Glutathione S-transferases (GSTs) are a family of isozymes that catalyze the conjugation of glutathione with various toxic electrophilic compounds. GSTs are composed of several classes based on the degree of sequence homology of their subunits. The Yo subunit, a member of the mu class, is expressed at high levels in the testis and epididymis. The purpose of this study was to immunolocalize the GST-Yo in these tissues during development. The testes and epididymides of rats aged 7, 15, 21, 28, 39, 42, 45, 49, and 56 days were fixed in Bouin's fixative, and immunostained for light microscopic analysis. In the testis the cytoplasm of all germ cells was unreactive until day 39. At that time, step 18 spermatids appeared moderately reactive, while the few observed step 19 spermatids were intensely reactive as were their residual bodies. The presence of residual bodies indicates that spermiation takes place as early as day 39; however, the number of step 19 spermatids is low at this age. A progressive increase in the size of the tubule and number of elongating spermatids was seen between days 42 and 49. In addition, by day 49, a weak staining was observed in steps 12-15, moderate in steps 16-17, and intense in steps 18-19 spermatids. In terms of the intensity of staining, cell types stained, size of the tubules, and number of elongating spermatids, no difference was noted between day 49, 56, and adult animals. Thus Yo protein expression in germ cells reached maturity by day 49. The epithelial cells of the rete testis were intensely reactive at day 7 and remained so throughout development. In contrast, while the epithelial cells of the efferent ducts at day 7 were intensely reactive, they were weakly reactive by day 39 and remained so at later ages. Along the entire epididymis, the columnar epithelial cells showed a moderate apical/supranuclear reaction from day 7 to 28. By day 39 principal cells of the initial segment became weakly reactive, while those in the caput and corpus were moderately stained, a situation seen at later ages including adults. Only by day 49 did principal cells of the proximal cauda become moderately stained as seen in adult animals. Thus the expression of the Yo protein in the principal cells of the proximal cauda may be regulated by different factors than those of the caput and corpus epididymidis. Alternatively, the expression of the Yo subunit in principal cells of the proximal cauda may develop later since this region would be the last to receive luminally derived testicular products. In the initial segment, the decrease in staining of principal cells at day 39 may be due to an inhibiting factor emanating from the testis. Spermatozoa appeared in the lumen of each epididymal region well after the expression of Yo had reached its adult staining pattern indicating that they are not a factor. Overall these results suggest that the expression of GST-Yo in the various cells of the testis and epididymis are controlled by different factors during postnatal development.

Sex-biased miRNAs in gonad and their potential roles for testis development in yellow catfish.

PubMed

Jing, Jing; Wu, Junjie; Liu, Wei; Xiong, Shuting; Ma, Wenge; Zhang, Jin; Wang, Weimin; Gui, Jian-Fang; Mei, Jie

2014-01-01

Recently, YY super-male yellow catfish had been created by hormonal-induced sex reversal and sex-linked markers, which provides a promising research model for fish sex differentiation and gonad development, especially for testis development. MicroRNAs (miRNAs) have been revealed to play crucial roles in the gene regulation and gonad development in vertebrates. In this study, three small RNA libraries constructed from gonad tissues of XX female, XY male and YY super-male yellow catfish were sequenced. The sequencing data generated a total of 384 conserved miRNAs and 113 potential novel miRNAs, among which 23, 30 and 14 miRNAs were specifically detected in XX ovary, XY testis, and YY testis, respectively. We observed relative lower expression of several miR-200 family members, including miR-141 and miR-429 in YY testis compared with XY testis. Histological analysis indicated a higher degree of testis maturity in YY super-males compared with XY males, as shown by larger spermatogenic cyst, more spermatids and fewer spermatocytes in the spermatogenic cyst. Moreover, five miR-200 family members were significantly up-regulated in testis when treated by 17α-ethinylestradiol (EE2), high dose of which will impair testis development and cell proliferation. The down-regulation of miR-141 and 429 coincides with the progression of testis development in both yellow catfish and human. At last, the expression pattern of nine arbitrarily selected miRNAs detected by quantitative RT-PCR was consistent with the Solexa sequencing results. Our study provides a comprehensive miRNA transcriptome analysis for gonad of yellow catfish with different sex genotypes, and identifies a number of sex-biased miRNAs, some of that are potentially involved in testis development and spermatogenesis.

Effects of pre- and postnatal exposure to the UV-filter Octyl Methoxycinnamate (OMC) on the reproductive, auditory and neurological development of rat offspring

DOE Office of Scientific and Technical Information (OSTI.GOV)

Axelstad, Marta, E-mail: maap@food.dtu.dk; Boberg, Julie; Hougaard, Karin Sorig

Octyl Methoxycinnamate (OMC) is a frequently used UV-filter in sunscreens and other cosmetics. The aim of the present study was to address the potential endocrine disrupting properties of OMC, and to investigate how OMC induced changes in thyroid hormone levels would be related to the neurological development of treated offspring. Groups of 14-18 pregnant Wistar rats were dosed with 0, 500, 750 or 1000 mg OMC/kg bw/day during gestation and lactation. Serum thyroxine (T{sub 4}), testosterone, estradiol and progesterone levels were measured in dams and offspring. Anogenital distance, nipple retention, postnatal growth and timing of sexual maturation were assessed. Onmore » postnatal day 16, gene expression in prostate and testes, and weight and histopathology of the thyroid gland, liver, adrenals, prostate, testes, epididymis and ovaries were measured. After weaning, offspring were evaluated in a battery of behavioral and neurophysiological tests, including tests of activity, startle response, cognitive and auditory function. In adult animals, reproductive organ weights and semen quality were investigated. Thyroxine (T{sub 4}) levels showed a very marked decrease during the dosing period in all dosed dams, but were less severely affected in the offspring. On postnatal day 16, high dose male offspring showed reduced relative prostate and testis weights, and a dose-dependent decrease in testosterone levels. In OMC exposed female offspring, motor activity levels were decreased, while low and high dose males showed improved spatial learning abilities. The observed behavioral changes were probably not mediated solely by early T{sub 4} deficiencies, as the observed effects differed from those seen in other studies of developmental hypothyroxinemia. At eight months of age, sperm counts were reduced in all three OMC-dosed groups, and prostate weights were reduced in the highest dose group. Taken together, these results indicate that perinatal OMC-exposure can affect both the reproductive and neurological development of rat offspring, which may be a cause of concern, as humans are systematically exposed to the compound through usage of sunscreens and other cosmetics.« less

Testis tumor associated to microlithiasis.

PubMed

Jesus, Lisieux Eyer de; Maciel, Felipe; Monnerat, Andrea Lima C; Fernandes, Marcia Antunes; Dekermache, Samuel

2013-12-01

To discuss the relationship between testicular microlithiasis and testis tumors in children and to consider the chances of testis preserving surgery in specific cases. Pre-adolescent presenting testicular microlithiasis and a larger left testis, corresponding to a cystic testicular tumor. The tumor was excised, with ipsilateral testis preservation. Histology diagnosed a testis dermoid tumor. The relationship between testis tumors and testicular microlithiasis is ill defined in children. Pediatric urologists need to develop specific follow-up protocols for pre-pubertal children.

Testis tumor associated to microlithiasis

PubMed Central

de Jesus, Lisieux Eyer; Maciel, Felipe; Monnerat, Andrea Lima C.; Fernandes, Marcia Antunes; Dekermache, Samuel

2013-01-01

OBJECTIVE: To discuss the relationship between testicular microlithiasis and testis tumors in children and to consider the chances of testis preserving surgery in specific cases. CASE DESCRIPTION: Pre-adolescent presenting testicular microlithiasis and a larger left testis, corresponding to a cystic testicular tumor. The tumor was excised, with ipsilateral testis preservation. Histology diagnosed a testis dermoid tumor. COMMENTS: The relationship between testis tumors and testicular microlithiasis is ill defined in children. Pediatric urologists need to develop specific follow-up protocols for pre-pubertal children. PMID:24473964

Early prenatal androgen exposure reduces testes size and sperm concentration in sheep without altering neuroendocrine differentiation and masculine sexual behavior.

PubMed

Scully, C M; Estill, C T; Amodei, R; McKune, A; Gribbin, K P; Meaker, M; Stormshak, F; Roselli, C E

2018-01-01

Prenatal androgens are largely responsible for growth and differentiation of the genital tract and testis and for organization of the control mechanisms regulating male reproductive physiology and behavior. The aim of the present study was to evaluate the impact of inappropriate exposure to excess testosterone (T) during the first trimester of fetal development on the reproductive function, sexual behavior, and fertility potential of rams. We found that biweekly maternal T propionate (100 mg) treatment administered from Day 30-58 of gestation significantly decreased (P < 0.05) postpubertal scrotal circumference and sperm concentration. Prenatal T exposure did not alter ejaculate volume, sperm motility and morphology or testis morphology. There was, however, a trend for more T-exposed rams than controls to be classified as unsatisfactory potential breeders during breeding soundness examinations. Postnatal serum T concentrations were not affected by prenatal T exposure, nor was the expression of key testicular genes essential for spermatogenesis and steroidogenesis. Basal serum LH did not differ between treatment groups, nor did pituitary responsiveness to GnRH. T-exposed rams, like control males, exhibited vigorous libido and were sexually attracted to estrous females. In summary, these results suggest that exposure to exogenous T during the first trimester of gestation can negatively impact spermatogenesis and compromise the reproductive fitness of rams. Copyright © 2017 Elsevier Inc. All rights reserved.

Molecular cloning and subcellular localization of Tektin2-binding protein 1 (Ccdc 172) in rat spermatozoa.

PubMed

Yamaguchi, Airi; Kaneko, Takane; Inai, Tetsuichiro; Iida, Hiroshi

2014-04-01

Tektins (TEKTs) are composed of a family of filament-forming proteins localized in cilia and flagella. Five types of mammalian TEKTs have been reported, all of which have been verified to be present in sperm flagella. TEKT2, which is indispensable for sperm structure, mobility, and fertilization, was present at the periphery of the outer dense fiber (ODF) in the sperm flagella. By yeast two-hybrid screening, we intended to isolate flagellar proteins that could interact with TEKT2, which resulted in the isolation of novel two genes from the mouse testis library, referred as a TEKT2-binding protein 1 (TEKT2BP1) and -protein 2 (TEKT2BP2). In this study, we characterized TEKT2BP1, which is registered as a coiled-coil domain-containing protein 172 (Ccdc172) in the latest database. RT-PCR analysis indicated that TEKT2BP1 was predominantly expressed in rat testis and that its expression was increased after 3 weeks of postnatal development. Immunocytochemical studies discovered that TEKT2BP1 localized in the middle piece of rat spermatozoa, predominantly concentrated at the mitochondria sheath of the flagella. We hypothesize that the TEKT2-TEKT2BP1 complex might be involved in the structural linkage between the ODF and mitochondria in the middle piece of the sperm flagella.

A maternal low protein diet during pregnancy and lactation in the rat impairs male reproductive development

PubMed Central

Zambrano, E; Rodríguez-González, GL; Guzmán, C; García-Becerra, R; Boeck, L; Díaz, L; Menjivar, M; Larrea, F; Nathanielsz, PW

2005-01-01

Nutrient restriction during pregnancy and lactation impairs growth and development. Recent studies demonstrate long-term programming of function of specific organ systems resulting from suboptimal environments during fetal life and development up to weaning. We determined effects of maternal protein restriction (50% control protein intake) during fetal development and/or lactation in rats on the reproductive system of male progeny. Rats were fed either a control 20% casein diet (C) or a restricted diet (R) of 10% casein during pregnancy. After delivery mothers received either C or R diet until weaning to provide four groups: CC, RR, CR and RC. We report findings in male offspring only. Maternal protein restriction increased maternal serum corticosterone, oestradiol and testosterone (T) concentrations at 19 days gestation. Pup birth weight was unchanged but ano-genital distance was increased by maternal protein restriction (P < 0.05). Testicular descent was delayed 4.4 days in RR, 2.1 days in CR and 2.2 days in RC and was not related to body weight. Body weight and testis weight were reduced in RR and CR groups at all ages with the exception of CR testis weight at 270 days postnatal age (PN). At 70 days PN luteinizing hormone and T concentrations were reduced in RR, CR and RC. mRNA for P450 side chain cleavage (P450scc) was reduced in RR and CR at 21 days PN but was unchanged at 70 days PN. Fertility rate was reduced at 270 days PN in RC and sperm count in RR and RC. We conclude that maternal protein delays sexual maturation in male rats and that some effects only emerge in later life. PMID:15611025

Sertoli Cell Wt1 Regulates Peritubular Myoid Cell and Fetal Leydig Cell Differentiation during Fetal Testis Development.

PubMed

Wen, Qing; Wang, Yuqian; Tang, Jixin; Cheng, C Yan; Liu, Yi-Xun

2016-01-01

Sertoli cells play a significant role in regulating fetal testis compartmentalization to generate testis cords and interstitium during development. The Sertoli cell Wilms' tumor 1 (Wt1) gene, which encodes ~24 zinc finger-containing transcription factors, is known to play a crucial role in fetal testis cord assembly and maintenance. However, whether Wt1 regulates fetal testis compartmentalization by modulating the development of peritubular myoid cells (PMCs) and/or fetal Leydig cells (FLCs) remains unknown. Using a Wt1-/flox; Amh-Cre mouse model by deleting Wt1 in Sertoli cells (Wt1SC-cKO) at embryonic day 14.5 (E14.5), Wt1 was found to regulate PMC and FLC development. Wt1 deletion in fetal testis Sertoli cells caused aberrant differentiation and proliferation of PMCs, FLCs and interstitial progenitor cells from embryo to newborn, leading to abnormal fetal testis interstitial development. Specifically, the expression of PMC marker genes α-Sma, Myh11 and Des, and interstitial progenitor cell marker gene Vcam1 were down-regulated, whereas FLC marker genes StAR, Cyp11a1, Cyp17a1 and Hsd3b1 were up-regulated, in neonatal Wt1SC-cKO testes. The ratio of PMC:FLC were also reduced in Wt1SC-cKO testes, concomitant with a down-regulation of Notch signaling molecules Jag 1, Notch 2, Notch 3, and Hes1 in neonatal Wt1SC-cKO testes, illustrating changes in the differentiation status of FLC from their interstitial progenitor cells during fetal testis development. In summary, Wt1 regulates the development of FLC and interstitial progenitor cell lineages through Notch signaling, and it also plays a role in PMC development. Collectively, these effects confer fetal testis compartmentalization.

Estrogen Sensitivity of Target Genes and Expression of Nuclear Receptor Co-Regulators in Rat Prostate after Pre- and Postnatal Exposure to the Ultraviolet Filter 4-Methylbenzylidene Camphor

PubMed Central

Durrer, Stefan; Ehnes, Colin; Fuetsch, Michaela; Maerkel, Kirsten; Schlumpf, Margret; Lichtensteiger, Walter

2007-01-01

Background and objectives In previous studies, we found that the ultraviolet filter 4-methyl-benzylidene camphor (4-MBC) exhibits estrogenic activity, is a preferential estrogen receptor (ER)-β ligand, and interferes with development of female reproductive organs and brain of both sexes in rats. Here, we report effects on male development. Methods 4-MBC (0.7, 7, 24, 47 mg/kg/day) was administered in chow to the parent generation before mating, during gestation and lactation, and to offspring until adulthood. mRNA was determined in prostate lobes by real-time reverse transcription–polymerase chain reaction and protein was determined by Western blot analysis. Results 4-MBC delayed male puberty, decreased adult prostate weight, and slightly increased testis weight. Androgen receptor (AR), insulin-like growth factor-1 (IGF-1), ER-α, and ER-β expression in prostate were altered at mRNA and protein levels, with stronger effects in dorsolateral than ventral prostate. To assess sensitivity of target genes to estrogens, offspring were castrated on postnatal day 70, injected with 17β-estradiol (E2; 10 or 50 μg/kg, sc) or vehicle on postnatal day 84, and sacrificed 6 hr later. Acute repression of AR and IGF-1 mRNAs by E2, studied in ventral prostate, was reduced by 4-MBC exposure. This was accompanied by reduced co-repressor N-CoR (nuclear receptor co-repressor) protein in ventral and dorsolateral prostate, whereas steroid receptor coactivator-1 (SRC-1) protein levels were unaffected. Conclusions Our data indicate that 4-MBC affects development of male reproductive functions and organs, with a lowest observed adverse effect level of 0.7 mg/kg. Nuclear receptor coregulators were revealed as targets for endocrine disruptors, as shown for N-CoR in prostate and SRC-1 in uterus. This may have widespread effects on gene regulation. PMID:18174949

FGF9, activin and TGFβ promote testicular characteristics in an XX gonad organ culture model.

PubMed

Gustin, Sonja E; Stringer, Jessica M; Hogg, Kirsten; Sinclair, Andrew H; Western, Patrick S

2016-11-01

Testis development is dependent on the key sex-determining factors SRY and SOX9, which activate the essential ligand FGF9. Although FGF9 plays a central role in testis development, it is unable to induce testis formation on its own. However, other growth factors, including activins and TGFβs, also present testis during testis formation. In this study, we investigated the potential of FGF9 combined with activin and TGFβ to induce testis development in cultured XX gonads. Our data demonstrated differing individual and combined abilities of FGF9, activin and TGFβ to promote supporting cell proliferation, Sertoli cell development and male germ line differentiation in cultured XX gonads. FGF9 promoted proliferation of supporting cells in XX foetal gonads at rates similar to those observed in vivo during testis cord formation in XY gonads but was insufficient to initiate testis development. However, when FGF9, activin and TGFβ were combined, aspects of testicular development were induced, including the expression of Sox9, morphological reorganisation of the gonad and deposition of laminin around germ cells. Enhancing β-catenin activity diminished the testis-promoting activities of the combined growth factors. The male promoting activity of FGF9 and the combined growth factors directly or indirectly extended to the germ line, in which a mixed phenotype was observed. FGF9 and the combined growth factors promoted male germ line development, including mitotic arrest, but expression of pluripotency genes was maintained, rather than being repressed. Together, our data provide evidence that combined signalling by FGF9, activin and TGFβ can induce testicular characteristics in XX gonads. © 2016 Society for Reproduction and Fertility.

Testicular steroidogenesis is not altered by 137 cesium Chernobyl fallout, following in utero or post-natal chronic exposure.

PubMed

Grignard, Elise; Guéguen, Yann; Grison, Stéphane; Dublineau, Isabelle; Gourmelon, Patrick; Souidi, Maâmar

2010-05-01

The testis is especially sensitive to pollutants, including radionuclides. Following the Chernobyl nuclear power plant accident, several of these radionuclides were emitted and spread in the environment. Subsequently, children presented some disruptions of the endocrine system. To determine whether these disruptions were due to 137 cesium ((137)Cs) exposure, the effects of chronic contamination with low doses of (137)Cs in utero or from birth on testicular steroidogenesis in rats were studied. Contamination was continued for 9 months. No modification was observed in circulating level of hormones (17beta-estradiol, testosterone, follicle-stimulating hormone, luteinizing hormone) following in utero or post-natal contamination. Expression of several genes involved in testicular steroidogenesis was affected (cyp19a1, fxr, sf-1), without modification of protein expression or activity. Our results suggest that growing organisms may be affected at the molecular level by (137)Cs contamination at this post-accidental dose. Copyright 2010 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Effects of prenatal irradiation with accelerated heavy-ion beams on postnatal development in rats: III. Testicular development and breeding activity

NASA Astrophysics Data System (ADS)

Wang, B.; Murakami, M.; Eguchi-Kasai, K.; Nojima, K.; Shang, Y.; Tanaka, K.; Watanabe, K.; Fujita, K.; Moreno, S. G.; Coffigny, H.; Hayata, I.

With a significant increase in human activities dealing with space missions, potential teratogenic effects on the mammalian reproductive system from prenatal exposure to space radiation have become a hot topic that needs to be addressed. However, even for the ground experiments, such effects from exposure to high LET ionizing radiation are not as well studied as those for low LET ionizing radiations such as X-rays. Using the Heavy-Ion Medical Accelerator in Chiba (HIMAC) and Wistar rats, effects on gonads in prenatal male fetuses, on postnatal testicular development and on breeding activity of male offspring were studied following exposure of the pregnant animals to either accelerated carbon-ion beams with a LET value of about 13 keV/μm or neon-ion beams with a LET value of about 30 keV/μm at a dose range from 0.1 to 2.0 Gy on gestation day 15. The effects of X-rays at 200 kVp estimated for the same biological end points were studied for comparison. A significantly dose-dependent increase of apoptosis in gonocytes appeared 6 h after irradiations with a dose of 0.5 Gy or more. Measured delayed testis descent and malformed testicular seminiferous tubules were observed to be significantly different from the control animals at a dose of 0.5 Gy. These effects are observed to be dose- and LET-dependent. Markedly reduced testicular weight and testicular weight to body weight ratio were scored at postnatal day 30 even in the offspring that were prenatally irradiated with neon-ions at a dose of 0.1 Gy. A dose of 0.5 Gy from neon-ion beams induced a marked decrease in breeding activity in the prenatally irradiated male rats, while for the carbon-ion beams or X-rays, the significantly reduced breeding activity was observed only when the prenatal dose was at 1.0 Gy or more. These findings indicated that prenatal irradiations with heavy-ion beams on gestation day 15 generally induced markedly detrimental effects on prenatal gonads, postnatal testicular development and male breeding activity in rats, which seemed to be a dose and LET-related event.

Male sex determination: insights into molecular mechanisms

PubMed Central

McClelland, Kathryn; Bowles, Josephine; Koopman, Peter

2012-01-01

Disorders of sex development often arise from anomalies in the molecular or cellular networks that guide the differentiation of the embryonic gonad into either a testis or an ovary, two functionally distinct organs. The activation of the Y-linked gene Sry (sex-determining region Y) and its downstream target Sox9 (Sry box-containing gene 9) triggers testis differentiation by stimulating the differentiation of Sertoli cells, which then direct testis morphogenesis. Once engaged, a genetic pathway promotes the testis development while actively suppressing genes involved in ovarian development. This review focuses on the events of testis determination and the struggle to maintain male fate in the face of antagonistic pressure from the underlying female programme. PMID:22179516

High levels of the extracellular matrix proteoglycan decorin are associated with inhibition of testicular function

PubMed Central

Adam, Marion; Urbanski, Henryk F.; Garyfallou, Vasilios T.; Welsch, Ulrich; Köhn, Frank M.; Schwarzer, J. Ullrich; Strauss, Leena; Poutanen, Matti; Mayerhofer, Artur

2011-01-01

Decorin (DCN), a component of the extracellular matrix of the peritubular wall and the interstitial areas of the human testis, can interact with growth factor (GF) signaling, thereby blocking downstream actions of GFs. In the present study the expression and regulation of DCN using both human testes and two experimental animal models, namely the rhesus monkey and mouse, were examined. DCN protein was present in peritubular and interstitial areas of adult human and monkey testes, while it was almost undetectable in adult wild-type mice. Interestingly, the levels and sites of testicular DCN expression in the monkeys were inversely correlated with testicular maturation markers. A strong DCN expression associated with the abundant connective tissue of the interstitial areas in the postnatal through prepubertal phases was observed. In adult and old monkeys the DCN pattern was similar to the one in normal human testes, presenting strong expression at the peritubular region. In the testes of both infertile men and in a mouse model of inflammation associated infertility (aromatase-overexpressing transgenic mice), the fibrotic changes and increased numbers of Tumor necrosis factor (TNF)-α-producing immune cells were shown to be associated with increased production of DCN. Furthermore, studies with human testicular peritubular cells isolated from fibrotic testis indicated that TNF-α significantly increased DCN production. The data, thus, show that an increased DCN level is associated with impaired testicular function, supporting our hypothesis that DCN interferes with paracrine signaling of the testis in health and disease. PMID:22413766

Genetic regulation of mammalian gonad development.

PubMed

Eggers, Stefanie; Ohnesorg, Thomas; Sinclair, Andrew

2014-11-01

Sex-specific gonadal development starts with formation of the bipotential gonad, which then differentiates into either a mature testis or an ovary. This process is dependent on activation of either the testis-specific or the ovary-specific pathway while the opposite pathway is continuously repressed. A network of transcription factors tightly regulates initiation and maintenance of these distinct pathways; disruption of these networks can lead to disorders of sex development in humans and male-to-female or female-to-male sex reversal in mice. Sry is the Y-linked master switch that is both required and sufficient to drive the testis-determining pathway. Another key component of the testis pathway is Sox9, which acts immediately downstream of Sry. In contrast to the testis pathway, no single sex-determining factor has been identified in the ovary pathway; however, multiple genes, such as Foxl2, Rspo1, Ctnnb1, and Wnt4, seem to work synergistically and in parallel to ensure proper ovary development. Our understanding of the regulatory networks that underpin testis and ovary development has grown substantially over the past two decades.

Thyroid Hormone Role and Economy in the Developing Testis.

PubMed

Hernandez, Arturo

2018-01-01

Thyroid hormones (TH) exhibit pleiotropic regulatory effects on growth, development, and metabolism, and it is becoming increasingly apparent that the developing testis is an important target for them. Testicular development is highly dependent on TH status. Both hypo- and hyperthyroidism affect testis size and the proliferation and differentiation of Sertoli, Leydig, and germ cells, with consequences for steroidogenesis, spermatogenesis, and male fertility. These observations suggest that an appropriate content of TH and by implication TH action in the testis, whether the result of systemic hormonal levels or regulatory mechanisms at the local level, is critical for normal testicular and reproductive function. The available evidence indicates the presence in the developing testis of a number of transporters, deiodinases and receptors that could play a role in the timely delivery of TH action on testicular cells. These include the thyroid hormone receptor alpha (THRA), the MCT8 transporter, the TH-activating deiodinase DIO2, and the TH-inactivating deiodinase DIO3, all of which appear to modulate testicular TH economy and testis outcomes. © 2018 Elsevier Inc. All rights reserved.

ACTIONS OF THE ENDOCRINE DISRUPTOR METHOXYCHLOR AND ITS ESTROGENIC METABOLITE ON IN VITRO EMBRYONIC RAT SEMINIFEROUS CORD FORMATION AND PERINATAL TESTIS GROWTH. (R827405)

EPA Science Inventory

Abstract

The current study examines the actions of methoxychlor and its estrogenic metabolite, 2, 2-bis-(p-hydroxyphenyl)-1, 1, 1-trichloroethane (HPTE), on seminiferous cord formation and growth of the developing rat testis. The developing testis in the embryonic and ...

Signaling through the TGF Beta-Activin Receptors ALK4/5/7 Regulates Testis Formation and Male Germ Cell Development

PubMed Central

Stringer, Jessica M.; van den Bergen, Jocelyn A.; Wilhelm, Dagmar; Sinclair, Andrew H.; Western, Patrick S.

2013-01-01

The developing testis provides an environment that nurtures germ cell development, ultimately ensuring spermatogenesis and fertility. Impacts on this environment are considered to underlie aberrant germ cell development and formation of germ cell tumour precursors. The signaling events involved in testis formation and male fetal germ cell development remain largely unknown. Analysis of knockout mice lacking single Tgfβ family members has indicated that Tgfβ's are not required for sex determination. However, due to functional redundancy, it is possible that additional functions for these ligands in gonad development remain to be discovered. Using FACS purified gonadal cells, in this study we show that the genes encoding Activin's, TGFβ's, Nodal and their respective receptors, are expressed in sex and cell type specific patterns suggesting particular roles in testis and germ cell development. Inhibition of signaling through the receptors ALK4, ALK5 and ALK7, and ALK5 alone, demonstrated that TGFβ signaling is required for testis cord formation during the critical testis-determining period. We also show that signaling through the Activin/NODAL receptors, ALK4 and ALK7 is required for promoting differentiation of male germ cells and their entry into mitotic arrest. Finally, our data demonstrate that Nodal is specifically expressed in male germ cells and expression of the key pluripotency gene, Nanog was significantly reduced when signaling through ALK4/5/7 was blocked. Our strategy of inhibiting multiple Activin/NODAL/TGFβ receptors reduces the functional redundancy between these signaling pathways, thereby revealing new and essential roles for TGFβ and Activin signaling during testis formation and male germ cell development. PMID:23342175

A Novel Testis-Specific Gene, Ccdc136, Is Required for Acrosome Formation and Fertilization in Mice.

PubMed

Geng, Qiang; Ni, Liwei; Ouyang, Bin; Hu, Yanhua; Zhao, Yu; Guo, Jun

2016-10-01

Testis-specific genes are essential for the spermatogenesis in mammalian male reproduction. In this study, we have identified a novel testis-specific gene, Ccdc136 (coiled-coil domain containing 136), from the results of high-throughput gene expression profiling in the developmental stage of mouse testes. Ccdc136 was conserved across species in evolution. Quantitative real-time polymerase chain reaction and Western blot analyses showed that Ccdc136 messenger RNA and protein were extraordinarily expressed in mouse testes, which was first presented at postnatal 3 week and increased in an age-dependent manner before adulthood. Immunofluorescence staining revealed that CCDC136 protein was most abundantly located in the acrosome of round spermatids and elongating spermatids within seminiferous tubules of the adult mouse testes. To investigate the function of Ccdc136 in mouse testes, we generated the Ccdc136-knockout mice using Cas9/RNA-mediated gene targeting technology. Interestingly, we found Ccdc136(-/-) males were infertile, due to severe defect of disrupting acrosome formation. The expression levels of proteins (SPACA1 and PICK1) involved in acrosome formation were significantly downregulated in the testes of Ccdc136(-/-) mice than wide-type mice. Moreover, in vitro fertilization assay revealed that anti-CCDC136 antibody could remarkably inhibit fertilization, suggesting CCDC136 also plays an important role in fertilization. All of these demonstrated the essential role of CCDC136-mediated acrosome formation in spermatogenesis and fertilization, which might also provide new insight into the genetic causes of human infertility. © The Author(s) 2016.

Expression of peroxisome proliferator-activated receptor alpha messenger ribonucleic acid and protein in human and rat testis.

PubMed

Schultz, R; Yan, W; Toppari, J; Völkl, A; Gustafsson, J A; Pelto-Huikko, M

1999-07-01

Peroxisome proliferator-activated receptor a (PPARalpha), a member of the steroid hormone receptor superfamily, has been linked to lipid homeostasis and tumorigenesis in tissues with high expression of receptor protein. On the other hand, the role of PPARalpha in tissues with a lower expression is not well known. Here we demonstrate the localization of PPARalpha messenger RNA (mRNA) and protein in developing and adult rat testis. Additionally, we demonstrate the expression of PPARalpha protein in adult human testis. Our experiments with Northern analysis, in situ hybridization and immunocytochemistry reveal a complex distribution of PPARalpha in tubular and interstitial cells of both adult and developing rat testis. The overall expression is rather low but may be modified by exogenous or endogenous stimuli. An up-regulation of PPARalpha mRNA could be observed after stimulation with FSH. In the developing rat testis, a clear expression of PPARalpha mRNA was present from the first days after birth. Additionally, PPARalpha mRNA and protein increased toward adulthood. In adult human testis PPARalpha immunoreactivity (IR) was present in interstitial Leydig cells and tubular cells. In the seminiferous epithelium of adult human testis the expression of PPARalpha-IR could be seen in meiotic spermatocytes, spermatids and myoid peritubular cells. The findings of our study suggest that PPARalpha may be involved in the regulation of growth and differentiation of tubular and interstitial cells in rat and human testis.

THE GERMLINE STEM CELL NICHE UNIT IN MAMMALIAN TESTES

PubMed Central

Oatley, Jon M.; Brinster, Ralph L.

2014-01-01

This review addresses current understanding of the germline stem cell niche unit in mammalian testes. Spermatogenesis is a classic model of tissue-specific stem cell function relying on self-renewal and differentiation of spermatogonial stem cells (SSCs). These fate decisions are influenced by a niche microenvironment composed of a growth factor milieu that is provided by several testis somatic support cell populations. Investigations over the last two decades have identified key determinants of the SSC niche including cytokines that regulate SSC functions and support cells providing these factors, adhesion molecules that influence SSC homing, and developmental heterogeneity of the niche during postnatal aging. Emerging evidence suggests that Sertoli cells are a key support cell population influencing the formation and function of niches by secreting soluble factors and possibly orchestrating contributions of other support cells. Investigations with mice have shown that niche influence on SSC proliferation differs during early postnatal development and adulthood. Moreover, there is mounting evidence of an age-related decline in niche function, which is likely influenced by systemic factors. Defining the attributes of stem cell niches is key to developing methods to utilize these cells for regenerative medicine. The SSC population and associated niche comprise a valuable model system for study that provides fundamental knowledge about the biology of tissue-specific stem cells and their capacity to sustain homeostasis of regenerating tissue lineages. While the stem cell is essential for maintenance of all self-renewing tissues and has received considerable attention, the role of niche cells is at least as important and may prove to be more receptive to modification in regenerative medicine. PMID:22535892

Gene expression profiles in the testis associated with testis-ova in adult Japanese medaka (Oryziaslatipes) exposed to 17α-ethinylestradiol.

PubMed

Hirakawa, Ikumi; Miyagawa, Shinichi; Katsu, Yoshinao; Kagami, Yoshihiro; Tatarazako, Norihisa; Kobayashi, Tohru; Kusano, Teruhiko; Mizutani, Takeshi; Ogino, Yukiko; Takeuchi, Takashi; Ohta, Yasuhiko; Iguchi, Taisen

2012-05-01

The occurrence of oocytes in the testis (testis-ova) of several fish species is often associated with exposure of estrogenic chemicals. However, induction mechanisms of the testis-ova remain to be elucidated. To develop marker genes for detecting testis-ova in the testis, adult male medaka were exposed to nominal concentration of 100 ng L(-1) of 17α-ethinylestradiol (EE2) for 3-5 weeks, and 800 ng estradiol benzoate (EB) for 3 weeks (experiment I), and a measured concentration of 20 ng L(-1) EE2 for 1-6 weeks (experiment II). Histological analysis was performed for the testis, and microarray analyses were performed for the testis, liver and brain. Microarray analysis in the estrogen-exposed medaka liver showed vitellogenin and choriogenin as estrogen responsive genes. Testis-ova were induced in the testis after 4 weeks of exposure to 100 ng L(-1) EE2, 3 weeks of exposure to 800 ng EB, and 6 weeks of exposure to 20 ng L(-1) EE2. Microarray analysis of estrogen-exposed testes revealed up-regulation of genes related to zona pellucida (ZP) and the oocytes marker gene, 42Sp50. Using quantitative RT-PCR we confirmed that Zpc5 gene can be used as a marker for the detection of testis-ova in male medaka. Copyright © 2011 Elsevier Ltd. All rights reserved.

Disruption of Testis Cords by Cyclopamine or Forskolin Reveals Independent Cellular Pathways in Testis Organogenesis

PubMed Central

Yao, Humphrey Hung-Chang; Capel, Blanche

2014-01-01

Most studies to date indicate that the formation of testis cords is critical for proper Sertoli cell differentiation, inhibition of germ cell meiosis, and regulation of Leydig cell differentiation. However, the connections between these events are poorly understood. The objective of this study was to dissect the molecular and cellular relationships between these events in testis formation. We took advantage of the different effects of two hedgehog signaling inhibitors, cyclopamine and forskolin, on gonad explant cultures. Both hedgehog inhibitors phenocopied the disruptive effect of Dhh−/− on formation of testis cords without influencing Sertoli cell differentiation. However, they exhibited different effects on other cellular events during testis development. Treatment with cyclopamine did not affect inhibition of germ cell meiosis and mesonephric cell migration but caused defects in Leydig cell differentiation. In contrast, forskolin treatment induced germ cell meiosis, inhibited mesonephric cell migration, and had no effect on Leydig cell differentiation. By carefully contrasting the different effects of these two hedgehog inhibitors, we demonstrate that although formation of testis cords and development of other cell types normally take place in a tightly regulated sequence, each of these events can occur independent of the others. PMID:12051821

Testis development, fertility, and survival in Ethanolamine kinase 2-deficient mice.

PubMed

Gustin, Sonja E; Western, Patrick S; McClive, Peter J; Harley, Vincent R; Koopman, Peter A; Sinclair, Andrew H

2008-12-01

Ethanolamine kinase 2 (Eki2) was previously isolated from a differential expression screen designed to identify candidate genes involved in testis development and differentiation. In mouse, Eki2 is specifically up-regulated in Sertoli cells of the developing testis at the time of sex determination. Based on this expression profile, Eki2 was considered a good candidate testis-determining gene. To investigate a possible role of Eki2 in testis development, we have generated a mouse with targeted disruption of the Eki2 gene by using an EGFP replacement strategy. No abnormalities were detected in the Eki2-deficient mice with regard to embryonic and adult testis morphology, differentiation, function, or fertility. Furthermore, no significant differences were observed in litter sizes, pup mortality rates, or distribution of the sexes among the offspring. Ethanolamine kinases are involved in the biosynthesis of phosphatidylethanolamine, a major membrane phospholipid. Expression analysis indicates that the absence of an apparent phenotype in the Eki2-deficient mice may be due to compensation by Eki2-family members or the activation of an alternative pathway to generate phosphatidylethanolamine. Expression of EGFP in this mouse model enabled the isolation of gonad cell populations, providing a useful resource from which to obtain relatively pure early steroidogenic cells for further studies.

Dynamics of testis-ova in a wild population of Japanese pond frogs, Rana nigromaculata.

PubMed

Kobayashi, Tohru; Kumakura, Masahiko; Yoshie, Sumio; Sugishima, Tomomi; Horie, Yoshifumi

2015-02-01

Although many studies have reported the occurrence of testis-ova in wild frog populations, the origin and trigger of testis-ova differentiation/development remain unclear. A high frequency of testis-ova has been previously reported for wild populations of the Japanese pond frog, Rana nigromaculata (cf. Iwasawa and Asai, '59). In the present study, we aimed to clarify the dynamics of testis-ova in this frog species, including the origin and artificial induction of testis-ova. Testis-ova were observed in both mature frogs and puberty-stage frogs (i.e., 0- and 1-year-old frogs). However, the early stages of testis-ova (~pachytene stage) were mostly observed in puberty-stage male frogs at the onset of spermatogenesis. The early stages of testis-ova were observed in the cysts of early secondary spermatogonia and the single cysts of the primary spermatogonium. This finding indicates that testis-ova differentiation occurs during spermatogonial proliferation and that it is correlated with the initiation of spermatogenesis. We also examined whether estrogen exposure induced testis-ova differentiation and how it is correlated with the progression of spermatogenesis. When 1-year-old frogs were exposed to estradiol-17β during spring (i.e., when spermatogenesis was initiated), testis-ova differentiation was induced in a dose-dependent manner. However, this phenomenon did not occur in 1-year-old frogs during summer, (i.e., when the transition from spermatogonia to spermatocytes mainly occurs). These results present the first evidence that testis-ova of the Japanese pond frog are derived from primary and early secondary spermatogonia, and that estrogen exposure induces testis-ova differentiation accompanied by the initiation of spermatogenesis. © 2015 Wiley Periodicals, Inc.

The histone demethylase KDM1A is essential for the maintenance and differentiation of spermatogonial stem cells and progenitors.

PubMed

Lambrot, Romain; Lafleur, Christine; Kimmins, Sarah

2015-11-01

Little is known of the fundamental processes governed by epigenetic mechanisms in the supplier cells of spermatogenesis, the spermatogonial stem cells (SSCs). The histone H3 lysine demethylase KDM1A is expressed in spermatogonia. We hypothesized that KDM1A serves in transcriptional regulation of SSCs and fertility. Using a conditional deletion of Kdm1a [conditional knockout (cKO)] in mouse spermatogonia, we determined that Kdm1a is essential for spermatogenesis as adult cKO males completely lack germ cells. Analysis of postnatal testis development revealed that undifferentiated and differentiating spermatogonial populations form in Kdm1a-cKO animals, yet the majority fail to enter meiosis. Loss of germ cells in the cKO was rapid with none remaining by postnatal day (PND) 21. To gain insight into the mechanistic implications of Kdm1a ablation, we isolated PND 6 spermatogonia enriched for SSCs and analyzed their transcriptome by RNA sequencing. Loss of Kdm1a was associated with altered transcription of 1206 genes. Importantly, differentially expressed genes between control and Kdm1a-cKO animals included those that are essential for SSC and progenitor maintenance and spermatogonial differentiation. The complete loss of fertility and failure to establish spermatogenesis indicate that Kdm1a is a master controller of gene transcription in spermatogonia and is required for SSC and progenitor maintenance and differentiation. © FASEB.

Diethylstilbestrol affects the expression of GPER in the gubernaculum testis.

PubMed

Zhang, Xuan; Ke, Song; Chen, Kai-Hong; Li, Jian-Hong; Ma, Lian; Jiang, Xue-Wu

2015-01-01

Recent evidence suggested a positive correlation between environmental estrogens (EEs) and high incidence of abnormalities in male urogenital system. EEs are known to cause the abnormalities of testes development and testicular descent. Diethylstilbestrol (DES) is a nonsteroidal synthetic estrogen that disrupts the morphology and proliferation of gubernacular cells, and its nongenomic effects on gubernaculum testis cells may be mediated by G protein-coupled estrogen receptor (GPER). In this study, we detected the expression of GPER in mouse gubernacular testis and investigated the effects of DES on the expression of GPER in gubernaculum testis cells. RT-PCR analysis revealed that GPER mRNA was expressed in the gubernaculum. GPER protein was detected in the parenchymal cells of the gubernaculum early in development. Furthermore, we demonstrate that GPER inhibitor G15 relieved DES-induced inhibition of GPER expression in gubernaculum testis cell, but ER inhibitor ICI 182780 had the converse effects on DES-induced inhibition of GPER expression in these cells. These data suggest that the effects of DES on mouse gubernaculum testis cells are mediated at least partially by the regulation of GPER expression.

Cell junction dynamics in the testis: Sertoli-germ cell interactions and male contraceptive development.

PubMed

Cheng, C Yan; Mruk, Dolores D

2002-10-01

Spermatogenesis is an intriguing but complicated biological process. However, many studies since the 1960s have focused either on the hormonal events of the hypothalamus-pituitary-testicular axis or morphological events that take place in the seminiferous epithelium. Recent advances in biochemistry, cell biology, and molecular biology have shifted attention to understanding some of the key events that regulate spermatogenesis, such as germ cell apoptosis, cell cycle regulation, Sertoli-germ cell communication, and junction dynamics. In this review, we discuss the physiology and biology of junction dynamics in the testis, in particular how these events affect interactions of Sertoli and germ cells in the seminiferous epithelium behind the blood-testis barrier. We also discuss how these events regulate the opening and closing of the blood-testis barrier to permit the timely passage of preleptotene and leptotene spermatocytes across the blood-testis barrier. This is physiologically important since developing germ cells must translocate across the blood-testis barrier as well as traverse the seminiferous epithelium during their development. We also discuss several available in vitro and in vivo models that can be used to study Sertoli-germ cell anchoring junctions and Sertoli-Sertoli tight junctions. An in-depth survey in this subject has also identified several potential targets to be tackled to perturb spermatogenesis, which will likely lead to the development of novel male contraceptives.

Loss of Smad4 in Sertoli and Leydig Cells Leads to Testicular Dysgenesis and Hemorrhagic Tumor Formation in Mice1

PubMed Central

Archambeault, Denise R.; Yao, Humphrey Hung-Chang

2014-01-01

ABSTRACT As the central component of canonical TGFbeta superfamily signaling, SMAD4 is a critical regulator of organ development, patterning, tumorigenesis, and many other biological processes. Because numerous TGFbeta superfamily ligands are expressed in developing testes, there may exist specific requirements for SMAD4 in individual testicular cell types. Previously, we reported that expansion of the fetal testis cords requires expression of SMAD4 by the Sertoli cell lineage. To further uncover the role of Smad4 in murine testes, we produced conditional knockout mice lacking Smad4 in either Leydig cells or in both Sertoli and Leydig cells simultaneously. Loss of Smad4 concomitantly in Sertoli and Leydig cells led to underdevelopment of the testis cords during fetal life and mild testicular dysgenesis in young adulthood (decreased testis size, partially dysgenic seminiferous tubules, and low sperm production). When the Sertoli/Leydig cell Smad4 conditional knockout mice aged (56- to 62-wk old), the testis phenotypes became exacerbated with the appearance of hemorrhagic tumors, Leydig cell adenomas, and a complete loss of spermatogenesis. In contrast, loss of Smad4 in Leydig cells alone did not appreciably alter fetal and adult testis development. Our findings support a cell type-specific requirement of Smad4 in testis development and suppression of testicular tumors. PMID:24501173

A survey of etiologic hypotheses among testicular cancer researchers.

PubMed

Stang, A; Trabert, B; Rusner, C; Poole, C; Almstrup, K; Rajpert-De Meyts, E; McGlynn, K A

2015-01-01

Basic research results can provide new ideas and hypotheses to be examined in epidemiological studies. We conducted a survey among testicular cancer researchers on hypotheses concerning the etiology of this malignancy. All researchers on the mailing list of Copenhagen Testis Cancer Workshops and corresponding authors of PubMed-indexed articles identified by the search term 'testicular cancer' and published within 10 years (in total 2750 recipients) were invited to respond to an e-mail-based survey. Participants of the 8th Copenhagen Testis Cancer Workshop in May 2014 were subsequently asked to rate the plausibility of the suggested etiologic hypotheses on a scale of 1 (very implausible) to 10 (very plausible). This report describes the methodology of the survey, the score distributions by individual hypotheses, hypothesis group, and the participants' major research fields, and discuss the hypotheses that scored as most plausible. We also present plans for improving the survey that may be repeated at a next international meeting of experts in testicular cancer. Overall 52 of 99 (53%) registered participants of the 8th Copenhagen Testis Cancer Workshop submitted the plausibility rating form. Fourteen of 27 hypotheses were related to exposures during pregnancy. Hypotheses with the highest mean plausibility ratings were either related to pre-natal exposures or exposures that might have an effect during pregnancy and in post-natal life. The results of the survey may be helpful for triggering more specific etiologic hypotheses that include factors related to endocrine disruption, DNA damage, inflammation, and nutrition during pregnancy. The survey results may stimulate a multidisciplinary discussion about new etiologic hypotheses of testicular cancer. Published 2014. This article is a U. S. Government work and is in the public domain in the USA.

Effects of acute postnatal exposure to 3,3',4,4'-tetrachlorobiphenyl on sperm function and hormone levels in adult rats.

PubMed

Hsu, Ping-Chi; Guo, Yueliang Leon; Li, Mei-Hui

2004-02-01

Polychlorinated biphenyls (PCBs) are considered potential endocrine disruptors due to their ability to act as estrogens, antiestrogens and goitrogens. The aim of this study is to ascertain whether acute postnatal treatment with 3,3',4,4'-tetrachlorobiphenyl (CB 77) affects sperm function and hormone levels in adult rats. Male Sprague-Dawley rats received CB 77 by ip injection of 2 or 20 mg/kg at day 21 and sacrificed at day 112. At day 112, right and left testis weights were significantly increased, whereas sperm count, motility, total motile sperm count, curvilinear velocity, average path velocity, straight-line velocity, and beat-cross frequency for motile sperm were significantly decreased in rats treated with 20 mg/kg CB 77. Sperm-oocyte penetration rate was significantly reduced in rats treated with either 2 or 20 mg/kg CB 77. There was high sperm acrosome reaction rate (ARR) in the 20 mg/kg CB 77-treated rats. There was a significant increase in thyroid-stimulating hormone level in the 20 mg/kg CB 77 group. However, no changes were seen in serum testosterone, thyroid hormones, or prolactin concentrations at day 112. In summary, this study showed that postnatal exposure to CB 77 might affect spermatogenesis, motility, ARR, and ability of fertilizing oocytes in mature rats. These results suggest that the sperm functions may be more susceptible or adapt less readily than the thyroid functions to endocrine disruption caused by dioxin-like PCB congeners.

Drug transporters, the blood–testis barrier, and spermatogenesis

PubMed Central

Su, Linlin; Mruk, Dolores D; Cheng, C Yan

2015-01-01

The blood–testis barrier (BTB), which is created by adjacent Sertoli cells near the basement membrane, serves as a ‘gatekeeper’ to prohibit harmful substances from reaching developing germ cells, most notably postmeiotic spermatids. The BTB also divides the seminiferous epithelium into the basal and adluminal (apical) compartment so that postmeiotic spermatid development, namely spermiogenesis, can take place in a specialized microenvironment in the apical compartment behind the BTB. The BTB also contributes, at least in part, to the immune privilege status of the testis, so that anti-sperm antibodies are not developed against antigens that are expressed transiently during spermatogenesis. Recent studies have shown that numerous drug transporters are expressed by Sertoli cells. However, many of these same drug transporters are also expressed by spermatogonia, spermatocytes, round spermatids, elongating spermatids, and elongated spermatids, suggesting that the developing germ cells are also able to selectively pump drugs ‘in’ and/or ‘out’ via influx or efflux pumps. We review herein the latest developments regarding the role of drug transporters in spermatogenesis. We also propose a model utilized by the testis to protect germ cell development from ‘harmful’ environmental toxicants and xenobiotics and/or from ‘therapeutic’ substances (e.g. anticancer drugs). We also discuss how drug transporters that are supposed to protect spermatogenesis can work against the testis in some instances. For example, when drugs (e.g. male contraceptives) that can perturb germ cell adhesion and/or maturation are actively pumped out of the testis or are prevented from entering the apical compartment, such as by efflux pumps. PMID:21134990

Effects of maternal dietary selenium (Se-enriched yeast) on testis development, testosterone level and testicular steroidogenesis-related gene expression of their male kids in Taihang Black Goats.

PubMed

Shi, Lei; Song, Ruigao; Yao, Xiaolei; Duan, Yunli; Ren, Youshe; Zhang, Chunxiang; Yue, Wenbin; Lei, Fulin

2018-07-01

To investigate the effects of maternal dietary selenium (Se-enriched yeast) on testis development, testosterone level and steroidogenesis-related gene expression in testis of their male kids, selected pregnant Taihang Black Goats were randomly allotted to four treatment groups. They were fed the basal gestation and lactation diets supplemented with 0 (control), 0.5, 2.0 and 4.0 mg of Se/kg DM. Thirty days after weaning, testes were collected from the kids. After the morphological development status of testis was examined, tissue samples were collected for analyzing testosterone concentration and histological parameters. Testosterone synthesis-related genes were detected using real-time PCR. Localization and quantification of androgen receptor (AR) in testis of goats were determined by immunohistochemical and western blot analysis. The results show that Se supplementation in the diet of dams led to higher (p < 0.05) testicular weight, volume, length, width, transverse and vertical grith of their male kids. Excessive Se (4.0 mg/kg) can inhibit the development of testis by decreasing testicular weight and volume. The density of spermatogenic cells and Leydig cells in the Se treatment groups was significantly (p < 0.05) higher than that in the control. Maternal dietary Se did not affect the thickness of testes, thickness of germinal epithelium and diameter of seminiferous tubule. Se supplemented in the diet of dams improved the testosterone level in testis tissue and serum, and promote the expression of testosterone-related genes. The mRNA expression of StAR, 3β-HSD and CYP11A1 was decreased with the increasing dietary Se levels of dams. Maternal dietary Se can improve the AR protein abundance in testis of their offspring. AR immunopositive product was detected in Leydig cells, peritubular myoid cells, perivascular smooth muscle cells, primary spermatocytes and spermatids. The expression of AR in spermatogenetic cells is stage specific. This study suggests that maternal dietary Se can influence the testis development and spermatogenesis of their male kids by modulating testosterone synthesis in goats. More attention should be given to the potential role of maternal nutrition in improving reproductive performance of their offspring. Copyright © 2018 Elsevier Inc. All rights reserved.

Effective Condition for Whole Testis Cryopreservation of Endangered Miho Spine Loach (Cobitis choii) Through the Optimization of Mud Loach (Misgurnus mizolepis) Whole Testis Cryopreservation Condition.

PubMed

Kim, J J; Nam, Y K; Bang, I C; Gong, S P

　　BACKGROUND: Miho spine loach (Cobitis choii) is an endangered Korean endemic fish. Whole testis cryopreservation is a good way for species preservation, but needs to the sacrifice of a large number of fish to optimize the freezing condition. Considering this limitation, a surrogate fish species was used for the protocol development. This study was to establish the effective condition for Miho spine loach whole testis cryopreservation by optimizing the conditions for whole testis cryopreservation in an allied species, mud loach (Misgurnus mizolepis). The condition for whole testis cryopreservation was optimized in mud loach first, and then the optimal condition was applied to Miho spine loach testes. The optimal condition for mud loach testis cryopreservation consists of the freezing medium containing 1.3 M dimethyl sulfoxide, 6% fetal bovine serum and 0.3 M trehalose, -1 C/min cooling rate and 26 degree C thawing temperature, which also permits effective cryopreservation of Miho spine loach testes. An effective cryopreservation condition for whole testis of the endangered Miho spine loach has been established by using mud loach as a surrogate fish.

Mutation of Gonadal soma-derived factor induces medaka XY gonads to undergo ovarian development.

PubMed

Imai, Takuto; Saino, Kentaro; Matsuda, Masaru

2015-11-06

Gonochoristic species have a bipotential gonad that develops into a testis or an ovary. In species whose sex is determined by a genetic factor, the expression of a sex-determining gene is the first cue that directs the development of a bipotential gonad. Subsequent expression of downstream genes induces the gonad to develop into a testis or an ovary. The TGF-ß family member Gonadal soma-derived factor (Gsdf) is thought to be an important gene for gonadal development in teleost fish, and it is expressed at higher levels in the testis than in the ovary from early to mature stages. However, there is little functional information about the gene. In this study, we targeted the Gsdf coding region in the medaka fish Oryzias latipes using transcription activator-like effector nucleases (TALENs) and studied the phenotypes of the Gsdf mutant medaka. Although normal and heterozygous XY gonads developed into a testis, all XY gonads with a homozygous mutation in Gsdf developed into an ovary at early developmental stages. However, two-thirds of Gsdf mutant XY gonads developed into testes in the adult stages. These results demonstrate that although a gonad can develop into a complete testis in the absence of Gsdf, Gsdf function is critical for directing the bipotential gonad at early developmental stages. Therefore, Gsdf is an endogenous inducer of testicular development similar to a master sex-determining gene. Copyright © 2015 Elsevier Inc. All rights reserved.

Stochastic anomaly of methylome but persistent SRY hypermethylation in disorder of sex development in canine somatic cell nuclear transfer

PubMed Central

Jeong, Young-Hee; Lu, Hanlin; Park, Chi-Hun; Li, Meiyan; Luo, Huijuan; Kim, Joung Joo; Liu, Siyang; Ko, Kyeong Hee; Huang, Shujia; Hwang, In Sung; Kang, Mi Na; Gong, Desheng; Park, Kang Bae; Choi, Eun Ji; Park, Jung Hyun; Jeong, Yeon Woo; Moon, Changjong; Hyun, Sang-Hwan; Kim, Nam Hyung; Jeung, Eui-Bae; Yang, Huanming; Hwang, Woo Suk; Gao, Fei

2016-01-01

Somatic cell nuclear transfer (SCNT) provides an excellent model for studying epigenomic reprogramming during mammalian development. We mapped the whole genome and whole methylome for potential anomalies of mutations or epimutations in SCNT-generated dogs with XY chromosomal sex but complete gonadal dysgenesis, which is classified as 78, XY disorder of sex development (DSD). Whole genome sequencing revealed no potential genomic variations that could explain the pathogenesis of DSD. However, extensive but stochastic anomalies of genome-wide DNA methylation were discovered in these SCNT DSD dogs. Persistent abnormal hypermethylation of the SRY gene was observed together with its down-regulated mRNA and protein expression. Failure of SRY expression due to hypermethylation was further correlated with silencing of a serial of testis determining genes, including SOX9, SF1, SOX8, AMH and DMRT1 in an early embryonic development stage at E34 in the XYDSD gonad, and high activation of the female specific genes, including FOXL2, RSPO1, CYP19A1, WNT4, ERα and ERβ, after one postnatal year in the ovotestis. Our results demonstrate that incomplete demethylation on the SRY gene is the driving cause of XYDSD in these XY DSD dogs, indicating a central role of epigenetic regulation in sex determination. PMID:27501986

Multiple Renal Cyst Development but Not Situs Abnormalities in Transgenic RNAi Mice against Inv::GFP Rescue Gene

PubMed Central

Kamijho, Yuki; Shiozaki, Yayoi; Sakurai, Eiki; Hanaoka, Kazunori; Watanabe, Daisuke

2014-01-01

In this study we generated RNA interference (RNAi)-mediated gene knockdown transgenic mice (transgenic RNAi mice) against the functional Inv gene. Inv mutant mice show consistently reversed internal organs (situs inversus), multiple renal cysts and neonatal lethality. The Inv::GFP-rescue mice, which introduced the Inv::GFP fusion gene, can rescue inv mutant mice phenotypes. This indicates that the Inv::GFP gene is functional in vivo. To analyze the physiological functions of the Inv gene, and to demonstrate the availability of transgenic RNAi mice, we introduced a short hairpin RNA expression vector against GFP mRNA into Inv::GFP-rescue mice and analyzed the gene silencing effects and Inv functions by examining phenotypes. Transgenic RNAi mice with the Inv::GFP-rescue gene (Inv-KD mice) down-regulated Inv::GFP fusion protein and showed hypomorphic phenotypes of inv mutant mice, such as renal cyst development, but not situs abnormalities or postnatal lethality. This indicates that shRNAi-mediated gene silencing systems that target the tag sequence of the fusion gene work properly in vivo, and suggests that a relatively high level of Inv protein is required for kidney development in contrast to left/right axis determination. Inv::GFP protein was significantly down-regulated in the germ cells of Inv-KD mice testis compared with somatic cells, suggesting the existence of a testicular germ cell-specific enhanced RNAi system that regulates germ cell development. The Inv-KD mouse is useful for studying Inv gene functions in adult tissue that are unable to be analyzed in inv mutant mice showing postnatal lethality. In addition, the shRNA-based gene silencing system against the tag sequence of the fusion gene can be utilized as a new technique to regulate gene expression in either in vitro or in vivo experiments. PMID:24586938

[Molecular mechanisms in sex determination: from gene regulation to pathology].

PubMed

Ravel, C; Chantot-Bastaraud, S; Siffroi, J-P

2004-01-01

Testis determination is the complex process by which the bipotential gonad becomes a normal testis during embryo development. As a consequence, this process leads to sexual differentiation corresponding to the masculinization of both genital track and external genitalia. The whole phenomenon is under genetic control and is particularly driven by the presence of the Y chromosome and by the SRY gene, which acts as the key initiator of the early steps of testis determination. However, many other autosomal genes, present in both males and females, are expressed during testis formation in a gene activation pathway, which is far to be totally elucidated. All these genes act in a dosage-sensitive manner by which quantitative gene abnormalities, due to chromosomal deletions, duplications or mosaicism, may lead to testis determination failure and sex reversal.

De novo transcriptome analysis and differentially expressed genes in the ovary and testis of the Japanese mantis shrimp Oratosquilla oratoria by RNA-Seq.

PubMed

Yan, Hongwei; Cui, Xin; Shen, Xufang; Wang, Lianshun; Jiang, Linan; Liu, Haiying; Liu, Ying; Liu, Qi; Jiang, Chen

2018-06-01

The mantis shrimp Oratosquilla oratoria is a widely distributed, commercially important crustacean species. Although its conservation and the development of successful artificial breeding technologies have recently received considerable attention, there are currently no available data regarding the molecular mechanisms in controlling reproduction. In this study, we performed transcriptome sequencing of the testis, ovary, female and male eyestalks and the androgenic gland of O. oratoria, and compared the expression pattern of transcripts from the testis and ovary libraries to identify genes involved in gonadal development. A total of 147,130,937 clean reads were retrieved after removing the adapters in reads and filtering out low-quality data. All the reads were assembled into 94,990 unigenes (23,133 in testis and ovary) with an average length of 783 base pairs (bp) and N50 of 1502 bp. A search of all-unigenes against COG, GO, KEGG, KOG, Pfam, Swiss-Prot and Nr databases resulted in a total of 19,404 annotated unigenes. Comparison of the sequences in the ovary and testis libraries revealed that 1188 unigenes were up-regulated in the ovary and 2732 were up-regulated in the testis. Twenty ovary-up-regulated and 21 testis-up-regulated unigenes were confirmed by quantitative real-time PCR. Additionally, 13,437 simple sequence repeats (SSRs) and 275,799 putative single nucleotide polymorphisms (SNPs) were identified. The important functional genes and pathways identified here provide a valuable dataset for understanding the molecular mechanisms controlling gonad development in O. oratoria, and the numerous (13,437 SSRs and 275,799 SNPs) molecular markers obtained here will provide fundamental basis for functional genomic and population genetic studies of O. oratoria. Copyright © 2018 Elsevier Inc. All rights reserved.

Perinatal exposure to 2,2',4'4' -Tetrabromodiphenyl ether induces testicular toxicity in adult rats.

PubMed

Khalil, Ahmed; Parker, Mikhail; Brown, Sarah E; Cevik, Sebnem E; Guo, Lian W; Jensen, Jake; Olmsted, Alexandra; Portman, Daneal; Wu, Haotian; Suvorov, Alexander

2017-08-15

Since 1965, polybrominated diphenyl ethers (PBDEs) have been used internationally as flame-retardant additives. PBDEs were recently withdrawn from commerce in North America and Europe due to their environmental persistence, bioaccumulative properties and endocrine-disrupting effects. Generations exposed perinatally to the highest environmental doses of PBDE account for one-fifth of the total United States population. While, toxicity of PBDE for the male reproductive system has been demonstrated in several human and animal studies, the long-lasting effects of perinatal exposures on male reproduction are still poorly understood. In this study, pregnant Wistar rats were exposed to 0.2mg/kg 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) from gestation day 8 until postnatal day 21. Male reproductive outcomes were analyzed on postnatal day 120 in offspring. Exposed animals had significantly smaller testes, displayed decreased sperm production per testis weight, had significantly increased percentage of morphologically abnormal spermatozoa, and showed an increase in spermatozoa head size. Perinatal BDE-47 exposure led to significant changes in testes transcriptome, including suppression of genes essential for spermatogenesis and activation of immune response genes. In particular, we observed a 4-fold average decrease in expression of protamine and transition protein genes in testes, suggesting that histone-protamine exchange may be dysregulated during spermatogenesis, resulting in an aberrant sperm epigenome. The possibility of long-lasting effects of developmental PBDE exposures calls for additional studies to build a foundation for the development of preventive and protective interventions against the environmentally-induced decline in fertility. Copyright © 2017 Elsevier B.V. All rights reserved.

Retinoic Acid Is Present in the Postnatal Rat Olfactory Organ and Persists in Vitamin A–Depleted Neural Tissue1–3

PubMed Central

Asson-Batres, Mary Ann; Smith, W. Bradford; Clark, Gale

2009-01-01

Vitamin A (VA), all-trans-retinol (at-ROL), and its derivative, all-trans-retinoic acid (at-RA), are required for neuron development. The effects of these retinoids are dependent upon the nutritional status of the rat and tissue-specific dynamics of retinoid access and utilization. The purpose of this study was to determine the status of at-ROL and at-RA in the peripheral olfactory organ of postnatal rats fed a normal diet and rats fed a VA-deficient (VAD) diet. Extracted retinoids were analyzed by HPLC. Resolved sample peaks were identified by comparing their elution times and spectra with those of authentic standards. Mean at-RA and at-ROL concentrations of 23 pmol/g olfactory tissue and 0.13 nmol/g, respectively, were recovered from olfactory tissue. The ratio of at-RA:at-ROL in olfactory was ∼2 times that in testis and 200 times that in liver. at-ROL was depleted from the liver and olfactory organ of rats fed a VAD diet from birth to 70 d of age. Surprisingly, at-RA was still present in olfactory tissue from these rats. At 90 d of age, the VAD rats were frankly deficient and at-RA was no longer detectable in olfactory tissue. The comparatively high ratio of at-RA:at-ROL in the peripheral olfactory organ and the persistence of at-RA in at-ROL-depleted tissues strongly suggests that maintenance of local stores of at-RA is functionally relevant in this tissue. PMID:19403718

Morphological and histomorphological structures of testes and ovaries in early developmental stages of the silkworm, Bombyx mori.

PubMed

Sakai, Hiroki; Kirino, Yohei; Katsuma, Susumu; Aoki, Fugaku; Suzuki, Masataka G

2016-01-01

The gonad develops as a testis in male or an ovary in female. In the silkworm, B. mori , little is known about testis and ovary in the embryonic stages and early larval stages. In this study, we performed morphological and histomorphological observations of ovaries and testes from the late embryonic stage to the 1st instar larval stage. Results obtained with lack of accurate information on sex of examined individuals may be misleading, thus we performed phenotypic observations of gonads by utilizing sex-limited strain that enables us to easily discriminate female embryos from male ones based on those egg colors. In testis, four testicular follicles were clearly observed in the testis at the first instar larval stage, and boundary layers were formed between the testicular follicles. At the late embryonic stage, the testis consisted of four testicular follicles, while the boundary layers were still obscure. In ovary, four ovarioles were easily recognizable in the ovary at the first instar larval stage, and boundary layers were formed between the ovarioles. However, in the late embryonic stage, it was quite difficult to identify four ovarioles. Morphological characteristics were almost similar between testis and ovary in early developmental stages. Our present study demonstrates that the most reliable difference between testis and ovary in early developmental stages is the attaching point of the duct. Formation and development of the duct may be sensitive to the sex-determining signal and display sexual dimorphism in early embryonic stages.

Expression analysis of sox3 during testicular development, recrudescence, and after hCG induction in catfish, Clarias batrachus.

PubMed

Rajakumar, Anbazhagan; Senthilkumaran, Balasubramanian

2014-01-01

In teleosts, the expression of steroidogenic enzymes and related transcription factor genes occurs in a stage- and tissue-specific manner causing sexual development. The role of sox3, an evolutionary ancestor of SRY, has not been studied in detail. Therefore, the full-length cDNA of sox3 (1,197 kb) was cloned from catfish testis, and mRNA expression was analyzed during gonadal development, during the seasonal reproductive cycle, and after human chorionic gonadotropin (hCG) induction. Tissue distribution analysis showed that sox3 expression was higher in testis, ovary, and brain compared to other tissues analyzed. Developing and mature testis showed higher sox3 expression than ovary of corresponding stages, and more sox3 transcripts were found during the spawning phase of the seasonal reproductive cycle. Expression of sox3 was upregulated by hCG after in vivo and in vitro induction, suggesting that gonadotropins might stimulate it. In situ hybridization and immunohistochemistry showed the presence of sox3 mRNA and protein in somatic and interstitial cell layers of the testis. Sox3 could also be found in the zona radiata of developing and mature oocytes. Exposure of methyltestosterone (1 µg/l) and ethinylestradiol (1 µg/l) for 21 days during testicular development showed lower sox3 expression levels in the testis and brain, indicating a certain feedback intervention. These results suggest a possible role for Sox3 in the regulation of testicular development and function. © 2014 S. Karger AG, Basel.

Assessing the impact of in-utero exposures: potential effects of paracetamol on male reproductive development.

PubMed

Kilcoyne, Karen R; Mitchell, Rod T

2017-12-01

Human male reproductive disorders (cryptorchidism, hypospadias, testicular cancer and low sperm counts) are common and some may be increasing in incidence worldwide. These associated disorders can arise from subnormal testosterone production during fetal life. This has resulted in a focus on in-utero environmental influences that may result in reproductive effects on the offspring in later life. Over recent years, there has been a dramatic increase in the scientific literature describing associations between in-utero environmental exposures (eg, industrial chemicals and pharmaceuticals) and subsequent reproductive outcomes in male offspring. This includes studies investigating a potential role for in-utero analgesic exposure(s) on the fetal testis; however, providing definitive evidence of such effects presents numerous challenges. In this review, we describe an approach to assessing the potential clinical relevance of in-utero (and postnatal) environmental exposures on subsequent male reproductive function using exposure to the analgesic paracetamol as an example. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Chronic exposure of adult, postnatal and in utero rat models to low-dose 137Cesium: impact on circulating biomarkers

PubMed Central

Manens, Line; Grison, Stéphane; Bertho, Jean-Marc; Lestaevel, Philippe; Guéguen, Yann; Benderitter, Marc; Aigueperse, Jocelyne; Souidi, Maâmar

2016-01-01

The presence of 137Cesium (137Cs) in the environment after nuclear accidents at Chernobyl and more recently Fukushima Daiichi raises many health issues for the surrounding populations chronically exposed through the food chain. To mimic different exposure situations, we set up a male rat model of exposure by chronic ingestion of a 137Cs concentration likely to be ingested daily by residents of contaminated areas (6500 Bq.l−1) and tested contaminations lasting 9 months for adult, neonatal and fetal rats. We tested plasma and serum biochemistry to identify disturbances in general indicators (lipids, proteins, carbohydrates and electrolytes) and in biomarkers of thyroid, heart, brain, bone, kidney, liver and testis functions. Analysis of the general indicators showed increased levels of cholesterol (+26%), HDL cholesterol (+31%), phospholipids B (+15%) and phosphorus (+100%) in the postnatal group only. Thyroid, heart, brain, bone and kidney functions showed no blood changes in any model. The liver function evaluation showed changes in total bilirubin (+67%) and alkaline phosphatase (–11%) levels, but only for the rats exposed to 137Cs intake in adulthood. Large changes in 17β-estradiol (–69%) and corticosterone (+36%) levels affected steroidogenesis, but only in the adult model. This study showed that response profiles differed according to age at exposure: lipid metabolism was most radiosensitive in the postnatal model, and steroid hormone metabolism was most radiosensitive in rats exposed in adulthood. There was no evidence of deleterious effects suggesting a potential impact on fertility or procreation. PMID:27466399

Positional cloning of the PIS mutation in goats and its impact on understanding mammalian sex-differentiation

PubMed Central

2005-01-01

In goats, the PIS (polled intersex syndrome) mutation is responsible for both the absence of horns in males and females and sex-reversal affecting exclusively XX individuals. The mode of inheritance is dominant for the polled trait and recessive for sex-reversal. In XX PIS-/- mutants, the expression of testis-specific genes is observed very precociously during gonad development. Nevertheless, a delay of 4–5 days is observed in comparison with normal testis differentiation in XY males. By positional cloning, we demonstrate that the PIS mutation is an 11.7-kb regulatory-deletion affecting the expression of two genes, PISRT1 and FOXL2 which could act synergistically to promote ovarian differentiation. The transcriptional extinction of these two genes leads, very early, to testis-formation in XX homozygous PIS-/- mutants. According to their expression profiles and bibliographic data, we propose that FOXL2 may be an ovary-differentiating gene, and the non-coding RNA PISRT1, an anti-testis factor repressing SOX9, a key regulator of testis differentiation. Under this hypothesis, SRY, the testis-determining factor would inhibit these two genes in the gonads of XY males, to ensure testis differentiation. PMID:15601595

Positional cloning of the PIS mutation in goats and its impact on understanding mammalian sex-differentiation.

PubMed

Pailhoux, Eric; Vigier, Bernard; Schibler, Laurent; Cribiu, Edmond P; Cotinot, Corinne; Vaiman, Daniel

2005-01-01

In goats, the PIS (polled intersex syndrome) mutation is responsible for both the absence of horns in males and females and sex-reversal affecting exclusively XX individuals. The mode of inheritance is dominant for the polled trait and recessive for sex-reversal. In XX PIS-/- mutants, the expression of testis-specific genes is observed very precociously during gonad development. Nevertheless, a delay of 4-5 days is observed in comparison with normal testis differentiation in XY males. By positional cloning, we demonstrate that the PIS mutation is an 11.7-kb regulatory-deletion affecting the expression of two genes, PISRT1 and FOXL2 which could act synergistically to promote ovarian differentiation. The transcriptional extinction of these two genes leads, very early, to testis-formation in XX homozygous PIS-/- mutants. According to their expression profiles and bibliographic data, we propose that FOXL2 may be an ovary-differentiating gene, and the non-coding RNA PISRT1, an anti-testis factor repressing SOX9, a key regulator of testis differentiation. Under this hypothesis, SRY, the testis-determining factor would inhibit these two genes in the gonads of XY males, to ensure testis differentiation.

Differential display cloning of a novel rat cDNA (RNB6) that shows high expression in the neonatal brain revealed a member of Ena/VASP family.

PubMed

Ohta, S; Mineta, T; Kimoto, M; Tabuchi, K

1997-08-18

We have used the differential display method to identify genes that control the neural cell development in CNS. Screening of the differential display bands that showed higher expression at neonate than at adult age enabled us to identify a novel rat cDNA (RNB6) coding for a protein of 393 amino acid residues. Database search revealed this gene as a rat homologue of the murine EVL, a member of Ena/VASP protein family that is implicated to be involved in the control of cell motility through actin filament assembly by their GP5 motifs. Although the precise characterization of EVL was not reported, our Northern blot and immunoblot analyses demonstrated that RNB6 expression in the brain gradually increases during embryonic development, reaches maximum at postnatal day 1 and decreases thereafter. Studies of tissue distribution revealed the expression of RNB6 not only in the brain but also in the spleen, thymus and testis. Histochemical analyses showed that RNB6 protein is mainly expressed in neurons and may be expressed in neural fibers. Our analyses suggest that RNB6 is critically involved in the development of CNS probably through the control of neural cell motility and/or including neuronal fiber extension.

Characterizing Transcriptional Networks in Male Rainbow Darter (Etheostoma caeruleum) that Regulate Testis Development over a Complete Reproductive Cycle

PubMed Central

McMaster, Mark E.; Servos, Mark R.; Martyniuk, Christopher J.; Munkittrick, Kelly R.

2016-01-01

Intersex is a condition that has been associated with exposure to sewage effluents in male rainbow darter (Etheostoma caeruleum). To better understand changes in the transcriptome that are associated with intersex, we characterized annual changes in the testis transcriptome in wild, unexposed fish. Rainbow darter males were collected from the Grand River (Ontario, Canada) in May (spawning), August (post-spawning), October (recrudescence), January (developing) and March (pre-spawning). Histology was used to determine the proportion of spermatogenic cell types that were present during each period of testicular maturation. Regression analysis determined that the proportion of spermatozoa versus spermatocytes in all stages of development (R2 ≥ 0.58) were inversely related; however this was not the case when males were in the post-spawning period. Gene networks that were specific to the transition from developing to pre-spawning stages included nitric oxide biosynthesis, response to wounding, sperm cell function, and stem cell maintenance. The pre-spawning to spawning transition included gene networks related to amino acid import, glycogenesis, Sertoli cell proliferation, sperm capacitation, and sperm motility. The spawning to post-spawning transition included unique gene networks associated with chromosome condensation, ribosome biogenesis and assembly, and mitotic spindle assembly. Lastly, the transition from post-spawning to recrudescence included gene networks associated with egg activation, epithelial to mesenchymal transition, membrane fluidity, and sperm cell adhesion. Noteworthy was that there were a significant number of gene networks related to immune system function that were differentially expressed throughout reproduction, suggesting that immune network signalling has a prominent role in the male testis. Transcripts in the testis of post-spawning individuals showed patterns of expression that were most different for the majority of transcripts investigated when compared to the other stages. Interestingly, many transcripts associated with female sex differentiation (i.e. esr1, sox9, cdca8 and survivin) were significantly higher in the testis during the post-spawning season compared to other testis stages. At post-spawning, there were higher levels of estrogen and androgen receptors (esr1, esr2, ar) in the testis, while there was a decrease in the levels of sperm associated antigen 1 (spag1) and spermatogenesis associated 4 (spata4) mRNA. Cyp17a was more abundant in the testis of fish in the pre-spawning, spawning, and post-spawning seasons compared to those individuals that were recrudescent while aromatase (cyp19a) did not vary in expression over the year. This study identifies cell process related to testis development in a seasonally spawning species and improves our understanding regarding the molecular signaling events that underlie testicular growth. This is significant because, while there are a number of studies characterizing molecular pathways in the ovary, there are comparatively less describing transcriptomic patterns in the testis in wild fish. PMID:27861489

DEVELOPMENT OF A 950-GENE DNA ARRAY FOR EXAMINING GENE EXPRESSION PATTERNS IN MOUSE TESTIS

EPA Science Inventory

Development of a 950-gene DNA array for examining gene expression patterns in mouse testis.

Rockett JC, Christopher Luft J, Brian Garges J, Krawetz SA, Hughes MR, Hee Kirn K, Oudes AJ, Dix DJ.

Reproductive Toxicology Division, National Health and Environmental Effec...

Effective Delivery of Male Contraceptives Behind the Blood-Testis Barrier (BTB) – Lesson from Adjudin

PubMed Central

Chen, Haiqi; Mruk, Dolores D.; Xia, Weiliang; Bonanomi, Michele; Silvestrini, Bruno; Cheng, Chuen-Yan

2016-01-01

The blood-testis barrier (BTB) is one of the tightest blood-tissue barriers in the mammalian body. It divides the seminiferous epithelium of the seminiferous tubule, the functional unit of the testis, where spermatogenesis takes place, into the basal and the adluminal (apical) compartments. Functionally, the BTB provides a unique microenvironment for meiosis I/II and post-meiotic spermatid development which take place exclusively in the apical compartment, away from the host immune system, and it contributes to the immune privilege status of testis. However, the BTB also poses major obstacles in developing male contraceptives (e.g., adjudin) that exert their effects on germ cells in the apical compartment, such as by disrupting spermatid adhesion to the Sertoli cell, causing germ cell exfoliation from the testis. Besides the tight junction (TJ) between adjacent Sertoli cells at the BTB that restricts the entry of contraceptives from the microvessels in the interstitium to the adluminal compartment, drug transporters, such as P-glycoprotein and multidrug resistance-associated protein 1 (MRP1), are also present that actively pump drugs out of the testis, limiting drug bioavailability. Recent advances in drug formulations, such as drug particle micronization (<50 μm) and co-grinding of drug particles with ß-cyclodextrin have improved bioavailability of contraceptives via considerable increase in solubility. Herein, we discuss development in drug formulations using adjudin as an example. We also put emphasis on the possible use of nanotechnology to deliver adjudin to the apical compartment with multidrug magnetic mesoporous silica nanoparticles. These advances in technology will significantly enhance our ability to develop effective non-hormonal male contraceptives for men. PMID:26758796

Effective Delivery of Male Contraceptives Behind the Blood-Testis Barrier (BTB) - Lesson from Adjudin.

PubMed

Chen, Haiqi; Mruk, Dolores D; Xia, Weiliang; Bonanomi, Michele; Silvestrini, Bruno; Cheng, Chuen-Yan

2016-01-01

The blood-testis barrier (BTB) is one of the tightest blood-tissue barriers in the mammalian body. It divides the seminiferous epithelium of the seminiferous tubule, the functional unit of the testis, where spermatogenesis takes place, into the basal and the adluminal (apical) compartments. Functionally, the BTB provides a unique microenvironment for meiosis I/II and post-meiotic spermatid development which take place exclusively in the apical compartment, away from the host immune system, and it contributes to the immune privilege status of testis. However, the BTB also poses major obstacles in developing male contraceptives (e.g., adjudin) that exert their effects on germ cells in the apical compartment, such as by disrupting spermatid adhesion to the Sertoli cell, causing germ cell exfoliation from the testis. Besides the tight junction (TJ) between adjacent Sertoli cells at the BTB that restricts the entry of contraceptives from the microvessels in the interstitium to the adluminal compartment, drug transporters, such as P-glycoprotein and multidrug resistance-associated protein 1 (MRP1), are also present that actively pump drugs out of the testis, limiting drug bioavailability. Recent advances in drug formulations, such as drug particle micronization (<50 μm) and co-grinding of drug particles with ß-cyclodextrin have improved bioavailability of contraceptives via considerable increase in solubility. Herein, we discuss development in drug formulations using adjudin as an example. We also put emphasis on the possible use of nanotechnology to deliver adjudin to the apical compartment with multidrug magnetic mesoporous silica nanoparticles. These advances in technology will significantly enhance our ability to develop effective non-hormonal male contraceptives for men.

The Drosophila ovarian and testis stem cell niches: similar somatic stem cells and signals.

PubMed

Decotto, Eva; Spradling, Allan C

2005-10-01

The stem cell niches at the apex of Drosophila ovaries and testes have been viewed as distinct in two major respects. While both contain germline stem cells, the testis niche also contains "cyst progenitor" stem cells, which divide to produce somatic cells that encase developing germ cells. Moreover, while both niches utilize BMP signaling, the testis niche requires a key JAK/STAT signal. We now show, by lineage marking, that the ovarian niche also contains a second type of stem cell. These "escort stem cells" morphologically resemble testis cyst progenitor cells and their daughters encase developing cysts before undergoing apoptosis at the time of follicle formation. In addition, we show that JAK/STAT signaling also plays a critical role in ovarian niche function, and acts within escort cells. These observations reveal striking similarities in the stem cell niches of male and female gonads, and suggest that they are largely governed by common mechanisms.

SRY protein is expressed in ovotestis and streak gonads from human sex-reversal.

PubMed

Salas-Cortés, L; Jaubert, F; Nihoul-Feketé, C; Brauner, R; Rosemblatt, M; Fellous, M

2000-01-01

In mammals, a master gene located on the Y chromosome, the testis-determining gene SRY, controls sex determination. SRY protein is expressed in the genital ridge before testis determination, and in the testis it is expressed in Sertoli and germ cells. Completely sex-reversed patients are classified as either 46,XX males or 46,XY females. SRY mutations have been described in only 15% of patients with 46,XY complete or partial gonadal dysgenesis. However, although incomplete or partial sex-reversal affects 46,XX true hermaphrodites, 46,XY gonadal dysgenesis, and 46,XX/46,XY mosaicism, only 15% of the 46,XX true hermaphrodites analyzed have the SRY gene. Here, we demonstrate that the SRY protein is expressed in the tubules of streak gonads and rete testis, indicating that the SRY protein is normally expressed early during testis determination. Based on these results, we propose that some factors downstream from SRY may be mutated in these 46,XY sex-reversal patients. We have also analyzed SRY protein expression in the ovotestis from 46,XX true hermaphrodites and 46,XX/46,XY mosaicism, demonstrating SRY protein expression in both testicular and ovarian portions in these patients. This suggests that the SRY protein does not inhibit ovary development. These results confirm that other factors are needed for complete testis development, in particular, those downstream of the SRY protein. Copyright 2001 S. Karger AG, Basel

Crlz-1 Is Prominently Expressed in Spermatogonia and Sertoli Cells during Early Testis Development and in Spermatids during Late Spermatogenesis

PubMed Central

Lim, Jung-Hyun; Choi, Seong-Young; Yoo, Han-Woong; Cho, Sun-Jung; Son, Youngsook

2013-01-01

The expression of the Crlz-1 gene in mouse testis, where it was found to be expressed most highly among the tested mouse organs, was analyzed spatiotemporally by employing RT-PCR and in situ hybridization techniques with the aid of immunohistochemistry and/or immunofluorescence methods. In 1-week-old neonatal testis, Crlz-1 was strongly expressed in the spermatogonia and Sertoli cells in its seminiferous cord. In 2- to 3-week-old prepubertal testis, where Sertoli cells cease to proliferate, Crlz-1 expression dropped and remained weakly at the rim layer of seminiferous cords and/or tubules, where spermatogonia are present. In the adult testis at 12 weeks after birth, Crlz-1 was expressed mainly in the spermatids near the lumen of seminiferous tubules. In a further in situ hybridization of Crlz-1 in the 12-week-old adult testis with hematoxylin nuclear counterstaining, Crlz-1 was mainly expressed at step 16 of spermatids between stages VII and VIII of seminiferous tubules as well as in their residual bodies at stage IX of seminiferous tubules. PMID:23525569

[Morphological verification problems of Chernobyl factor influence on the testis of coal miners of Donbas-liquidators of Chernobyl accident].

PubMed

Danylov, Iu V; Motkov, K V; Shevchenko, T I

2013-01-01

Problem of a diagnostic of Chernobyl factor influences on different organs and systems of Chernobyl accident liquidators are remain actually until now. Though morbidly background which development at unfavorable work conditions in underground coalminers prevents from objective identification features of Chernobyl factor influences. The qualitative and quantitative histological and immunohistochemical law of morphogenesis changes in testis of Donbas's coalminer - non-liquidators Chernobyl accident in comparison with the group of Donbas's coalminers-liquidators Chernobyl accident, which we were stationed non determined problem. This reason stipulates to development and practical use of mathematical model of morphogenesis of a testis changes.

GESTATIONAL EXPOSURE TO ETHANE DIMETHANESULFONATE (EDS) ALTERS DEVELOPMENT OF THE MOUSE TESTIS

EPA Science Inventory

GESTATIONAL EXPOSURE TO ETHANE DIMETHANESULFONATE (EDS) ALTERS DEVELOPMENT OF THE MOUSE TESTIS. D.K. Tarka*1,2, J.D. Suarez*2, N.L. Roberts*2, J.M. Rogers*1,2, M.P. Hardy3, and G.R. Klinefelter1,2. 1University of North Carolina, Curriculum in Toxicology, Chapel Hill, NC; 2USEPA,...

The testis-specific VAD1.3/AEP1 interacts with β-actin and syntaxin 1 and directs peri-nuclear/Golgi expression with bipartite nucleus localization (BNL) sequence.

PubMed

Zuo, Yan; Gao, Jing; Yeung, William S B; Lee, Kai-Fai

2010-10-15

VAD1.3 (AEP1), a novel testis-specific gene, was first isolated from the testis of a retinol-treated vitamin-A-deficient (VAD) rat model. It is expressed at the acrosomal region of spermatids from postnatal day 25. VAD1.3 immunoreactivity is present in rat, human, monkey and porcine spermatids and spermatozoa, suggesting that VAD1.3 may play a role in acrosome formation. However, direct evidence on the detailed sub-cellular localization of the VAD1.3 protein in the acrosome and how VAD1.3 is involved in acrosome formation remains largely unknown. Here, we isolated and identified VAD1.3 interacting proteins by immunoprecipitation followed by mass spectrometry, and determined the functional motifs of VAD1.3 that were important for its specific sub-cellular location in vitro. We found that VAD1.3 bound to syntaxin 1 and β-actin proteins in vitro. Immunogold electron microscopic study localized VAD1.3 immunoreactivity to the acrosome membranes and matrix, and colocalized it with the β-actin protein. The full-length GFP-VAD (1-3601) and GFP-VAD (1-730) fusion proteins that contain the bipartite nucleus localization (BNL) signal were located in the peri-nucleus/Golgi of the transfected cells. In addition, the GFP signal colocalized with the endoplasmic reticulum marker and the syntaxin 1 protein in the transfected HeLa and GC-2spd cells. The C-terminal GFP-VAD (1770-3601) was expressed in the nucleus. Taken together, VAD1.3 interacts with β-actin and syntaxin 1 in vitro. The BNL signal may mediate the peri-nuclei localization of the protein that may interact with syntaxin 1 and β-actin for acrosome formation in spermatogenesis. Crown Copyright © 2010. Published by Elsevier Inc. All rights reserved.

α-lipoic acid inhibits oxidative stress in testis and attenuates testicular toxicity in rats exposed to carbimazole during embryonic period.

PubMed

Prathima, P; Venkaiah, K; Pavani, R; Daveedu, T; Munikumar, M; Gobinath, M; Valli, M; Sainath, S B

2017-01-01

The aim of this study was to evaluate the probable protective effect of α-lipoic acid against testicular toxicity in rats exposed to carbimazole during the embryonic period. Time-mated pregnant rats were exposed to carbimazole from the embryonic days 9-21. After completion of the gestation period, all the rats were allowed to deliver pups and weaned. At postnatal day 100, F1 male pups were assessed for the selected reproductive endpoints. Gestational exposure to carbimazole decreased the reproductive organ indices, testicular daily sperm count, epididymal sperm variables viz ., sperm count, viable sperm, motile sperm and HOS-tail coiled sperms. Significant decrease in the activity levels of 3β- and 17β-hydroxysteroid dehydrogenases and expression of StAR mRNA levels with a significant increase in the total cholesterol levels were observed in the testis of experimental rats over the controls. These events were also accompanied by a significant reduction in the serum testosterone levels in CBZ exposed rats, indicating reduced steroidogenesis. In addition, the deterioration of the testicular architecture and reduced fertility ability were noticed in the carbimazole exposed rats. Significant reduction in the activity levels of superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase and reduced glutathione content with a significant increase in the levels of lipid peroxidation were observed in the testis of carbimazole exposed rats over the controls. Conversely, supplementation of α-lipoic acid (70 mg/Kg bodyweight) ameliorated the male reproductive health in rats exposed to carbimazole during the embryonic period as evidenced by enhanced reproductive organ weights, selected sperm variables, testicular steroidogenesis, and testicular enzymatic and non-enzymatic antioxidants. To conclude, diminished testicular antioxidant balance associated with reduced spermatogenesis and steroidogenesis might be responsible for the suppressed reproduction in rats exposed to the carbimazole transplacentally. On the other hand, α-lipoic acid through its antioxidant and steroidogenic properties mitigated testicular toxicity which eventually restored the male reproductive health of carbimazole-exposed rats.

Isolation and characterization of string-forming female germline stem cells from ovaries of neonatal mice.

PubMed

Liu, Jing; Shang, Dantong; Xiao, Yao; Zhong, Pei; Cheng, Hanhua; Zhou, Rongjia

2017-09-29

Germline stem cells are essential in the generation of both male and female gametes. In mammals, the male testis produces sperm throughout the entire lifetime, facilitated by testicular germline stem cells. Oocyte renewal ceases in postnatal or adult life in mammalian females, suggesting that germline stem cells are absent from the mammalian ovary. However, studies in mice, rats, and humans have recently provided evidence for ovarian female germline stem cells (FGSCs). A better understanding of the role of FGSCs in ovaries could help improve fertility treatments. Here, we developed a rapid and efficient method for isolating FGSCs from ovaries of neonatal mice. Notably, our FGSC isolation method could efficiently isolate on average 15 cell "strings" per ovary from mice at 1-3 days postpartum. FGSCs isolated from neonatal mice displayed the string-forming cell configuration at mitosis ( i.e. a "stringing" FGSC (sFGSC) phenotype) and a disperse phenotype in postnatal mice. We also found that sFGSCs undergo vigorous mitosis especially at 1-3 days postpartum. After cell division, the sFGSC membranes tended to be connected to form sFGSCs. Moreover, F-actin filaments exhibited a cell-cortex distribution in sFGSCs, and E-cadherin converged in cell-cell connection regions, resulting in the string-forming morphology. Our new method provides a platform for isolating FGSCs from the neonatal ovary, and our findings indicate that FGCSs exhibit string-forming features in neonatal mice. The sFGSCs represent a valuable resource for analysis of ovary function and an in vitro model for future clinical use to address ovarian dysfunction. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Prenatal exposure to aflatoxin B1: developmental, behavioral, and reproductive alterations in male rats

NASA Astrophysics Data System (ADS)

Supriya, Ch.; Reddy, P. Sreenivasula

2015-06-01

Previous studies have shown that aflatoxin B1 (AfB1) inhibits androgen biosynthesis as a result of its ability to form a high-affinity complex with the steroidogenic acute regulatory protein. The results of the present study demonstrate the postnatal effects of in utero exposure to AfB1 in the rat. Pregnant Wistar rats were given 10, 20, or 50 μg AfB1/kg body weight daily from gestation day (GD) 12 to GD 19. At parturition, newborns were observed for clinical signs and survival. All animals were born alive and initially appeared to be active. Male pups from control and AfB1-exposed animals were weaned and maintained up to postnatal day (PD) 100. Litter size, birth weight, sex ratio, survival rate, and crown-rump length of the pups were significantly decreased in AfB1-exposed rats when compared to controls. Elapsed time (days) for testes to descend into the scrotal sac was significantly delayed in experimental pups when compared to control pups. Behavioral observations such as cliff avoidance, negative geotaxis, surface rightening activity, ascending wire mesh, open field behavior, and exploratory and locomotory activities were significantly impaired in experimental pups. Body weights and the indices of testis, cauda epididymis, prostate, seminal vesicles, and liver were significantly reduced on PD 100 in male rats exposed to AfB1 during embryonic development when compared with controls. Significant reduction in the testicular daily sperm production, epididymal sperm count, and number of viable, motile, and hypo-osmotic tail coiled sperm was observed in experimental rats. The levels of serum testosterone and activity levels of testicular hydroxysteroid dehydrogenases were significantly decreased in a dose-dependent manner with a significant increase in the serum follicle-stimulating hormone and luteinizing hormone in experimental rats. Deterioration in the testicular and cauda epididymal architecture was observed in experimental rats. The results of fertility studies revealed a significant decrease in the mating index in experimental rats with an increase in the pre- and post-implantation losses in rats mated with prenatal AfB1-exposed males, indicating poor male reproductive performance. These results indicate that in utero exposure to AfB1 severely compromised postnatal development of neonatal rats, and caused a delay in testes descent and reduction in steroidogenesis and spermatogenesis that were accomplished by suppressed reproduction at adulthood.

MALFORMATIONS IN GUBERNACULAR LIGAMENT DEVELOPMENT INDUCED BY DEHP, DBP, AND BBP ARE ASSOCIATED WITH DECREASES IN INSL3 GENE EXPRESSION IN THE FETAL RAT TESTIS

EPA Science Inventory

Malformations in gubernacular ligament development induced by DEHP, DBP, and BBP are associated with decreases in insl3 gene expression in the fetal rat testis.
Vickie S.Wilson, Christy Lambright, Johnathan Furr, Carmen Wood, Gary Held, L. Earl Gray Jr. U.S. EPA, ORD, NHEER...

Chronic exposure of adult, postnatal and in utero rat models to low-dose 137Cesium: impact on circulating biomarkers.

PubMed

Manens, Line; Grison, Stéphane; Bertho, Jean-Marc; Lestaevel, Philippe; Guéguen, Yann; Benderitter, Marc; Aigueperse, Jocelyne; Souidi, Maâmar

2016-11-01

The presence of 137 Cesium ( 137 Cs) in the environment after nuclear accidents at Chernobyl and more recently Fukushima Daiichi raises many health issues for the surrounding populations chronically exposed through the food chain. To mimic different exposure situations, we set up a male rat model of exposure by chronic ingestion of a 137 Cs concentration likely to be ingested daily by residents of contaminated areas (6500 Bq.l -1 ) and tested contaminations lasting 9 months for adult, neonatal and fetal rats. We tested plasma and serum biochemistry to identify disturbances in general indicators (lipids, proteins, carbohydrates and electrolytes) and in biomarkers of thyroid, heart, brain, bone, kidney, liver and testis functions. Analysis of the general indicators showed increased levels of cholesterol (+26%), HDL cholesterol (+31%), phospholipids B (+15%) and phosphorus (+100%) in the postnatal group only. Thyroid, heart, brain, bone and kidney functions showed no blood changes in any model. The liver function evaluation showed changes in total bilirubin (+67%) and alkaline phosphatase (-11%) levels, but only for the rats exposed to 137 Cs intake in adulthood. Large changes in 17β-estradiol (-69%) and corticosterone (+36%) levels affected steroidogenesis, but only in the adult model. This study showed that response profiles differed according to age at exposure: lipid metabolism was most radiosensitive in the postnatal model, and steroid hormone metabolism was most radiosensitive in rats exposed in adulthood. There was no evidence of deleterious effects suggesting a potential impact on fertility or procreation. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Identification and characterization of Rhox13, a novel X-linked mouse homeobox gene

PubMed Central

Geyer, Christopher B.; Eddy, Edward M.

2008-01-01

Homeobox genes encode transcription factors whose expression organizes programs of development. A number of homeobox genes expressed in reproductive tissues have been identified recently, including a colinear cluster on the X chromosome in mice. This has led to an increased interest in understanding the role(s) of homeobox genes in regulating development of reproductive tissues including the testis, ovary, and placenta. Here we report the identification and characterization of a novel homeobox gene of the paired-like class on the X chromosome distal to the reproductive homeobox (Rhox) cluster in mice. Transcripts are found in the testis and ovary as early as 13.5 days post-coitum (dpc). Transcription ceases in the ovary by 3 days post-partum (dpp), but continues in the testis through adulthood. The Rhox13 gene encodes a 25.3 kDa protein expressed in the adult testis in germ cells at the basal aspect of the seminiferous epithelium. PMID:18675325

Trace elemental analysis in cancer-afflicted tissues of penis and testis by PIXE technique

NASA Astrophysics Data System (ADS)

Naga Raju, G. J.; John Charles, M.; Bhuloka Reddy, S.; Sarita, P.; Seetharami Reddy, B.; Rama Lakshmi, P. V. B.; Vijayan, V.

2005-04-01

PIXE technique was employed to estimate the trace elemental concentrations in the biological samples of cancerous penis and testis. A 3 MeV proton beam was employed to excite the samples. From the present results it can be seen that the concentrations of Cl, Fe and Co are lower in the cancerous tissue of the penis when compared with those in normal tissue while the concentrations of Cu, Zn and As are relatively higher. The concentrations of K, Ca, Ti, Cr, Mn, Br, Sr and Pb are in agreement within standard deviations in both cancerous and normal tissues. In the cancerous tissue of testis, the concentrations of K, Cr and Cu are higher while the concentrations of Fe, Co and Zn are lower when compared to those in normal tissue of testis. The concentrations of Cl, Ca, Ti and Mn are in agreement in both cancerous and normal tissues of testis. The higher levels of Cu lead to the development of tumor. Our results also support the underlying hypothesis of an anticopper, antiangiogenic approach to cancer therapy. The Cu/Zn ratios of both penis and testis were higher in cancer tissues compared to that of normal.

[Studies on the endocrine and spermatogenetic testicular function 6. In-vitro biosynthesis of testosterone in fractions of the smooth endoplasmic reticulum from the rat's testis in relationship to age and quality of dietary proteins].

PubMed

Tönhardt, H; Wehrberger, K; Schülke, B

1976-01-01

The metabolic activity of testosterone biosynthesis in fractions of the unstriated endoplasmatic reticulum of testicular tissue in animals in puberty living on corn gluten was about 20 per cent below that in animals that were fed corn gluten plus supplemented amino acids. Such lowered metabolic activity was recordable even from adult animals for another 30 days despite change of feed to high-quality proteins. The conversion rate of progesterone in testostrone still was lowered by some ten per cent. If change of enzyme activity in testosterone biosynthesis was caused by feeding different protein qualities, such variation could not be normalised within short time. Testosterone biosynthesis during postnatal development of rat was of two-phase nature even in the presence of temporary deficit due to low-quality feed protein. A regulation mechanism is assumed to exist and to enable completion of sexual maturity even on the basis of low-quality feed proteins. The metabolic activity at the time of qualitative transformation of the A/T ratio was significantly reduced, and this resulted in delayed occurrence of spermatogenesis as well as in retardation of body and testicular weight development.

Induction of apoptosis by accelerated heavy-ion beams in cultured fetal rat testes and its modification

NASA Astrophysics Data System (ADS)

Wang, Bing; Tanaka, Kaoru; Shang, Yi; Fujita, Kazuko; Ninomiya, Yasuharu; Moreno, Stephanie G.; Coffigny, Herve; Hayata, Isamu; Murakami, Masahiro; Eguchi-Kasai, Kiyomi; Nenoi, Mitsuru

The increasing human activities in space missions make the study on effects from high-LET ionizing radiation an important issue to be addressed. We reported previously that prenatal irradiations with heavy-ion beams on gestation day 15 generally induced markedly detrimental effects on prenatal gonads, postnatal testicular development and male breeding activity in rats. To explore the mechanisms involved in radiation-induced gonocyte apoptosis in fetal gonads, which played a critical role in the fate of postnatal testis development, accelerated heavy-ion irradiations and organotypic culture of Wistar fetal rat testes were applied to investigations focused on cellular and molecular events after irradiations with or without chemical addition. Results showed that, in addition to the clustered distribution, both the time course and the percentage of apoptosis in gonocytes on gestation day 15 equivalent in vitro appeared similar to that in utero after exposure to either carbon-ion beams with a LET value of about 13 keV/µm or neon-ion beams with a LET value of about 30 keV/µm. Irradiations induced increased p53 expression in a dose dependent manner and decreased expressions of p21 and Bcl- 2 by Western Blot examination. Administration of pan-caspase inhibitor prior to irradiations effectively inhibited apoptosis occurrence and reduced the extent of clustered apoptosis, while such effects were not observed with the presence of p53 inhibitor, gap junction inhibitor, or nitric oxide specific scavenger. These findings indicated that irradiations of cultured fetal rat testes manifested pathologically similar apoptosis induction in gonocytes to that in utero. P53 expression was possibly responsible for the response to radiation damage rather than induction of apoptosis. The syncytial organization of gonocytes played a key role in formation of the clustered apoptosis, an event that both gap junction inhibitor and nitric oxide specific scavenger were incapable of preventing.

Duplication of SOX9 is not a common cause of 46,XX testicular or 46,XX ovotesticular DSD.

PubMed

Seeherunvong, Tossaporn; Ukarapong, Supamit; McElreavey, Kenneth; Berkovitz, Gary D; Perera, Erasmo M

2012-01-01

Translocation of the SRY gene to the paternal X chromosome is the explanation for testis development in the majority of subjects with 46,XX testicular disorder of sexual development (DSD). However, nearly all subjects with 46,XX ovotesticular DSD and up to one third of subjects with 46,XX testicular DSD lack SRY. SRY-independent expression of SOX9 has been implicated in the etiology of testis development in some individuals. We amplified microsatellite markers in the region of SOX9 from a cohort of 30 subjects with either 46,XX testicular or 46,XX ovotesticular DSD to detect SOX9 duplications. Duplication of the SOX9 region in 17q was not detected in any subject. Duplication in the region of 17q that contains SOX9 is not a common cause of testis development in subjects with SRY-negative 46,XX testicular or ovotesticular DSD.

Alterations in the developing testis transcriptome following embryonic vinclozolin exposure.

PubMed

Clement, Tracy M; Savenkova, Marina I; Settles, Matthew; Anway, Matthew D; Skinner, Michael K

2010-11-01

The current study investigates the direct effects of in utero vinclozolin exposure on the developing F1 generation rat testis transcriptome. Previous studies have demonstrated that exposure to vinclozolin during embryonic gonadal sex determination induces epigenetic modifications of the germ line and transgenerational adult onset disease states. Microarray analyses were performed to compare control and vinclozolin treated testis transcriptomes at embryonic days 13, 14 and 16. A total of 576 differentially expressed genes were identified and the major cellular functions and pathways associated with these altered transcripts were examined. The sets of regulated genes at the different development periods were found to be transiently altered and distinct. Categorization by major known functions of altered genes was performed. Specific cellular process and pathway analyses suggest the involvement of Wnt and calcium signaling, vascular development and epigenetic mechanisms as potential mediators of the direct F1 generation actions of vinclozolin. Copyright © 2010 Elsevier Inc. All rights reserved.

ALTERATIONS IN THE DEVELOPING TESTIS TRANSCRIPTOME FOLLOWING EMBRYONIC VINCLOZOLIN EXPOSURE

PubMed Central

Clement, Tracy M.; Savenkova, Marina I.; Settles, Matthew; Anway, Matthew D.; Skinner, Michael K.

2010-01-01

The current study investigates the direct effects of in utero vinclozolin exposure on the developing F1 generation rat testis transcriptome. Previous studies have demonstrated that exposure to vinclozolin during embryonic gonadal sex determination induces epigenetic modifications of the germ line and transgenerational adult onset disease states. Microarray analyses were performed to compare control and vinclozolin treated testis transcriptomes at embryonic day 13, 14 and 16. A total of 576 differentially expressed genes were identified and the major cellular functions and pathways associated with these altered transcripts were examined. The sets of regulated genes at the different development periods were found to be transiently altered and distinct. Categorization by major known functions of altered genes was performed. Specific cellular process and pathway analyses suggest the involvement of Wnt and calcium signaling, vascular development and epigenetic mechanisms as potential mediators of the direct F1 generation actions of vinclozolin. PMID:20566332

Identification and Characterization of MicroRNAs in Ovary and Testis of Nile Tilapia (Oreochromis niloticus) by Using Solexa Sequencing Technology

PubMed Central

Zhou, Yi; Yu, Fan; Gao, Yun; Luo, Yongju; Tang, Zhanyang; Guo, Zhongbao; Guo, Enyan; Gan, Xi; Zhang, Ming; Zhang, Yaping

2014-01-01

MicroRNAs (miRNAs) are endogenous non-coding small RNAs which play important roles in the regulation of gene expression by cleaving or inhibiting the translation of target gene transcripts. Thereinto, some specific miRNAs show regulatory activities in gonad development via translational control. In order to further understand the role of miRNA-mediated posttranscriptional regulation in Nile tilapia (Oreochromis niloticus) ovary and testis, two small RNA libraries of Nile tilapia were sequenced by Solexa small RNA deep sequencing methods. A total of 9,731,431 and 8,880,497 raw reads, representing 5,407,800 and 4,396,281 unique sequences were obtained from the sexually mature ovaries and testes, respectively. After comparing the small RNA sequences with the Rfam database, 1,432,210 reads in ovaries and 984,146 reads in testes were matched to the genome sequence of Nile tilapia. Bioinformatic analysis identified 764 mature miRNA, 209 miRNA-5p and 202 miRNA-3p were found in the two libraries, of which 525 known miRNAs are both expressed in the ovary and testis of Nile tilapia. Comparison of expression profiles of the testis, miR-727, miR-129 and miR-29 families were highly expressed in tilapia ovary. Additionally, miR-132, miR-212, miR-33a and miR-135b families, showed significant higher expression in testis compared with that in ovary. Furthermore, the expression patterns of the miRNAs were analyzed in different developmental stages of gonad. The result showed different expression patterns were observed during development of testis and ovary. In addition, the identification and characterization of differentially expressed miRNAs in the ovaries and testis of Nile tilapia provides important information on the role of miRNA in the regulation of the ovarian and testicular development and function. This data will be helpful to facilitate studies on the regulation of miRNAs during teleosts reproduction. PMID:24466258

Activation of GPER-1 estradiol receptor downregulates production of testosterone in isolated rat Leydig cells and adult human testis.

PubMed

Vaucher, Laurent; Funaro, Michael G; Mehta, Akanksha; Mielnik, Anna; Bolyakov, Alexander; Prossnitz, Eric R; Schlegel, Peter N; Paduch, Darius A

2014-01-01

Estradiol (E2) modulates testicular functions including steroidogenesis, but the mechanisms of E2 signaling in human testis are poorly understood. GPER-1 (GPR30), a G protein-coupled membrane receptor, mediates rapid genomic and non-genomic response to estrogens. The aim of this study was to evaluate GPER-1 expression in the testis, and its role in estradiol dependent regulation of steroidogenesis in isolated rat Leydig cells and human testis. Isolated Leydig cells (LC) from adult rats and human testicular tissue were used in this study. Expression and localization studies of GPER-1 were performed with qRT-PCR, immunofluorescence, immunohistochemistry and Western Blot. Luteinizing Hormone (LH) -stimulated, isolated LC were incubated with estradiol, G-1 (GPER-1-selective agonist), and estrogen receptor antagonist ICI 182,780. Testosterone production was measured with radioimmunoassay. LC viability after incubation with G-1 was measured using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. GPER-1 mRNA is abundantly expressed in rat LC and human testis. Co-localization experiments showed high expression levels of GPER-1 protein in LC. E2-dependent activation of GPER-1 lowers testosterone production in isolated rats LCs and in human testis, with statistically and clinically significant drops in testosterone production by 20-30% as compared to estradiol-naïve LC. The exposure to G-1 does not affect viability of isolated LCs. Our results indicate that activation of GPER-1 lowers testosterone levels in the rat and human testis. The expression of GPER-1 in human testis, which lack ERα, makes it an exciting target for developing new agents affecting testosterone production in men.

Ultrasonographic Assessment of Testicular Viability Using Heterogeneity Levels in Torsed Testicles.

PubMed

Samson, Patrick; Hartman, Christopher; Palmerola, Ricardo; Rahman, Zara; Siev, Michael; Palmer, Lane S; Ghorayeb, Sleiman R

2017-03-01

Gross testicular heterogeneity on ultrasound has been associated with testis loss following testicular torsion in children. We aimed to quantify the extent of temporal heterogeneity associated with testis loss in testicular torsion cases using a noninvasive technique to determine a HI (heterogeneity index) on ultrasound images. We retrospectively studied the records of patients who presented with acute scrotal pain to the Pediatric Emergency Department over a 6-year period. Ultrasound images of the affected testis and the unaffected contralateral testis were examined using a proprietary program to determine the extent of heterogeneity of each image. The difference between the HI of the torsed testis and that of the contralateral normal testis was termed ΔHI. Receiver operating characteristics curve analysis was performed to determine the ΔHI threshold for nonviability. Among 529 patients who presented with acute scrotal pain 147 had testicular torsion based on surgical findings. Of these 147 patients 110 (74.8%) were found to have a viable testis while 37 (25.2%) had a nonviable testis. Using the ΔHI cutoff of 0.394 or greater for nonviability, sensitivity and specificity were 100% and 94.5%, respectively. Positive and negative predictive values were 86% and 100%, respectively. Our results demonstrate that a quantifiable temporal gradation of heterogeneity exists and the heterogeneity index can be used as an objective parameter to determine the viability of a torsed testicle. By developing the technology to measure the heterogeneity index in real time, we could potentially identify which patients with testicular torsion have a nonviable testicle and, thus, would not require immediate surgical exploration. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Sry and SoxE genes: How they participate in mammalian sex determination and gonadal development?

PubMed

She, Zhen-Yu; Yang, Wan-Xi

2017-03-01

In mammals, sex determination defines the differentiation of the bipotential genital ridge into either testes or ovaries. Sry, the mammalian Y-chromosomal testis-determining gene, is a master regulator of male sex determination. It acts to switch the undifferentiated genital ridge towards testis development, triggering the adoption of a male fate. Sry initiates a cascade of gene networks through the direct regulation of Sox9 expression and promotes supporting cell differentiation, Leydig cell specification, vasculature formation and testis cord development. In the absence of Sry, alternative genetic cascades, including female sex-determining genes RSPO1, Wnt4/β-catenin and Foxl2, are involved in the formation of female genitalia and the maintenance of female ovarian development. The mutual antagonisms between male and female sex-determining pathways are crucial in not just the initiation but also the maintenance of the somatic sex of the gonad throughout the organism's lifetime. Any imbalances in above sex-determining genes can cause disorders of sex development in humans and mice. In this review, we provide a detailed summary of the expression profiles, biochemical properties and developmental functions of Sry and SoxE genes in embryonic testis development and adult gonadal development. We also briefly summarize the dedicate balances between male and female sex-determining genes in mammalian sex development, with particular highlights on the molecular actions of Sry and Sox9 transcription factors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Heterogeneity in sexual bipotentiality and plasticity of granulosa cells in developing mouse ovaries.

PubMed

Harikae, Kyoko; Miura, Kento; Shinomura, Mai; Matoba, Shogo; Hiramatsu, Ryuji; Tsunekawa, Naoki; Kanai-Azuma, Masami; Kurohmaru, Masamichi; Morohashi, Ken-Ichirou; Kanai, Yoshiakira

2013-07-01

In mammalian sex determination, SRY directly upregulates the expression of SOX9, the master regulatory transcription factor in Sertoli cell differentiation, leading to testis formation. Without SRY action, the bipotential gonadal cells become pre-granulosa cells, which results in ovarian follicle development. When, where and how pre-granulosa cells are determined to differentiate into developing ovaries, however, remains unclear. By monitoring SRY-dependent SOX9 inducibility (SDSI) in an Sry-inducible mouse system, we were able to identify spatiotemporal changes in the sexual bipotentiality/plasticity of ovarian somatic cells throughout life. The early pre-granulosa cells maintain the SDSI until 11.5 d.p.c., after which most pre-granulosa cells rapidly lose this ability by 12.0 d.p.c. Unexpectedly, we found a subpopulation of the pre-granulosa cells near the mesonephric tissue that continuously retains SDSI throughout fetal and early postnatal stages. After birth, these SDSI-positive pre-granulosa cells contribute to the initial round of folliculogenesis by the secondary follicle stage. In experimental sex reversal of 13.5-d.p.c. ovaries grafted into adult male nude mice, the differentiated granulosa cells re-acquire the SDSI before other signs of masculinization. Our data provide direct evidence of an unexpectedly high sexual heterogeneity of granulosa cells in developing mouse ovaries in a stage- and region-specific manner. Discovery of such sexually bipotential granulosa cells provides a novel entry point to the understanding of masculinization in various cases of XX disorders of sexual development in mammalian ovaries.

In utero protein restriction causes growth delay and alters sperm parameters in adult male rats

PubMed Central

2011-01-01

Background Recent studies have supported the concept of "fetal programming" which suggests that during the intrauterine development the fetus may be programmed to develop diseases in adulthood. The possible effects of in utero protein restriction on sexual development of rat male offspring were evaluated in the present study. Methods Pregnant Wistar rats were divided into two experimental groups: one group treated with standard chow (SC, n = 8, 17% protein) and the other group treated with hypoproteic chow (HC, n = 10, 6% protein) throughout gestation. After gestation the two experimental groups received standard chow. To evaluate the possible late reproductive effects of in utero protein restriction, the male offspring of both groups were assessed at different phases of sexual development: prepubertal (30 days old); peripubertal (60 days old); adult (90 days old). Student's t-test and Mann-Whitney test were utilized. Differences were considered significant when p < 0.05. Results We found that in utero protein restriction reduced the body weight of male pups on the first postnatal day and during the different sexual development phases (prepubertal, peripubertal and adult). During adulthood, Sertoli cell number, sperm motility and sperm counts in the testis and epididymal cauda were also reduced in HC. Furthermore, the numbers of sperm presenting morphological abnormalities and cytoplasmic drop retention were higher in HC. Conclusions In conclusion, in utero protein restriction, under these experimental conditions, causes growth delay and alters male reproductive-system programming in rats, suggesting impairment of sperm quality in adulthood. PMID:21702915

In utero protein restriction causes growth delay and alters sperm parameters in adult male rats.

PubMed

Toledo, Fabíola C; Perobelli, Juliana E; Pedrosa, Flávia P C; Anselmo-Franci, Janete A; Kempinas, Wilma D G

2011-06-24

Recent studies have supported the concept of "fetal programming" which suggests that during the intrauterine development the fetus may be programmed to develop diseases in adulthood. The possible effects of in utero protein restriction on sexual development of rat male offspring were evaluated in the present study. Pregnant Wistar rats were divided into two experimental groups: one group treated with standard chow (SC, n = 8, 17% protein) and the other group treated with hypoproteic chow (HC, n = 10, 6% protein) throughout gestation. After gestation the two experimental groups received standard chow. To evaluate the possible late reproductive effects of in utero protein restriction, the male offspring of both groups were assessed at different phases of sexual development: prepubertal (30 days old); peripubertal (60 days old); adult (90 days old). Student's t-test and Mann-Whitney test were utilized. Differences were considered significant when p < 0.05. We found that in utero protein restriction reduced the body weight of male pups on the first postnatal day and during the different sexual development phases (prepubertal, peripubertal and adult). During adulthood, Sertoli cell number, sperm motility and sperm counts in the testis and epididymal cauda were also reduced in HC. Furthermore, the numbers of sperm presenting morphological abnormalities and cytoplasmic drop retention were higher in HC. In conclusion, in utero protein restriction, under these experimental conditions, causes growth delay and alters male reproductive-system programming in rats, suggesting impairment of sperm quality in adulthood.

Organogenesis of the Ovary

PubMed Central

Ditewig, Amy C

2005-01-01

The general perspective of ovary organogenesis is that the ovary is the default organ which develops in the absence of testis-promoting factors. Testis formation, on the other hand, is a male-specific event promoted by active components that override the default ovarian process. However, when comparing the sex determination mechanism among different vertebrate species, it is apparent that this default view of ovary formation can only be applied to mammals. In species such as reptiles and birds, ovary formation is an active process stimulated by estrogen. Remnants of this estrogen-dominant pathway are still present in marsupials, a close relative of eutherian mammals, like humans and mice. Although initial formation of the mammalian ovary has become strictly regulated by genetic components and is therefore independent of estrogen, the feminizing effect of estrogen regains its command in adult ovaries. When estrogen production, or its signaling, is inhibited, transdifferentiation of ovarian tissues to testis structures occur in adult females. Taken together, these observations prompt us to reconsider the process of ovary organogenesis as the default organ and question if testis development is actually the default pathway. PMID:19521565

Germ cell differentiation and proliferation in the developing testis of the South American plains viscacha, Lagostomus maximus (Mammalia, Rodentia).

PubMed

Gonzalez, C R; Muscarsel Isla, M L; Fraunhoffer, N A; Leopardo, N P; Vitullo, A D

2012-08-01

Cell proliferation and cell death are essential processes in the physiology of the developing testis that strongly influence the normal adult spermatogenesis. We analysed in this study the morphometry, the expression of the proliferation cell nuclear antigen (PCNA), cell pluripotency marker OCT-4, germ cell marker VASA and apoptosis in the developing testes of Lagostomus maximus, a rodent in which female germ line develops through abolished apoptosis and unrestricted proliferation. Morphometry revealed an increment in the size of the seminiferous cords with increasing developmental age, arising from a significant increase of PCNA-positive germ cells and a stable proportion of PCNA-positive Sertoli cells. VASA showed a widespread cytoplasmic distribution in a great proportion of proliferating gonocytes that increased significantly at late development. In the somatic compartment, Leydig cells increased at mid-development, whereas peritubular cells showed a stable rate of proliferation. In contrast to other mammals, OCT-4 positive gonocytes increased throughout development reaching 90% of germ cells in late-developing testis, associated with a conspicuous increase in circulating FSH from mid- to late-gestation. TUNEL analysis was remarkable negative, and only a few positive cells were detected in the somatic compartment. These results show that the South American plains viscacha displays a distinctive pattern of testis development characterized by a sustained proliferation of germ cells throughout development, with no signs of apoptosis cell demise, in a peculiar endocrine in utero ambiance that seems to promote the increase of spermatogonial number as a primary direct effect of FSH.

Developmentally regulated expression of APG-1, a member of heat shock protein 110 family in murine male germ cells.

PubMed

Kaneko, Y; Kimura, T; Nishiyama, H; Noda, Y; Fujita, J

1997-04-07

Apg-1 encodes a heat shock protein belonging to the heat shock protein 110 family, and is inducible by a 32 degrees C to 39 degrees C heat shock. Northern blot analysis of the testis from immature and adult mice, and of the purified germ cells revealed the quantitative change of the apg-1 transcripts during germ cell development. By in situ hybridization histochemistry the expressions of the apg-1 transcripts were detected in germ cells at specific stages of development including spermatocytes and spermatids. Although heat-induction of the apg-1 transcripts was observed in W/Wv mutant testis lacking germ cells, it was not detected in wild-type testis nor in the purified germ cells. Thus, the apg-1 expression is not heat-regulated but developmentally regulated in germ cells, suggesting that APG-1 plays a role in normal development of germ cells.

Gonadal Identity in the Absence of Pro-Testis Factor SOX9 and Pro-Ovary Factor Beta-Catenin in Mice1

PubMed Central

Nicol, Barbara; Yao, Humphrey H.-C.

2015-01-01

Sex-reversal cases in humans and genetic models in mice have revealed that the fate of the bipotential gonad hinges upon the balance between pro-testis SOX9 and pro-ovary beta-catenin pathways. Our central query was: if SOX9 and beta-catenin define the gonad's identity, then what do the gonads become when both factors are absent? To answer this question, we developed mouse models that lack either Sox9, beta-catenin, or both in the somatic cells of the fetal gonads and examined the morphological outcomes and transcriptome profiles. In the absence of Sox9 and beta-catenin, both XX and XY gonads progressively lean toward the testis fate, indicating that expression of certain pro-testis genes requires the repression of the beta-catenin pathway, rather than a direct activation by SOX9. We also observed that XY double knockout gonads were more masculinized than their XX counterpart. To identify the genes responsible for the initial events of masculinization and to determine how the genetic context (XX vs. XY) affects this process, we compared the transcriptomes of Sox9/beta-catenin mutant gonads and found that early molecular changes underlying the XY-specific masculinization involve the expression of Sry and 21 SRY direct target genes, such as Sox8 and Cyp26b1. These results imply that when both Sox9 and beta-catenin are absent, Sry is capable of activating other pro-testis genes and drive testis differentiation. Our findings not only provide insight into the mechanism of sex determination, but also identify candidate genes that are potentially involved in disorders of sex development. PMID:26108792

Stage-dependency of apoptosis and the blood-testis barrier in the dogfish shark (Squalus acanthias): cadmium-induced changes as assessed by vital fluorescence techniques.

PubMed

McClusky, Leon M

2006-09-01

Naturally occurring heavy metals and synthetic compounds are potentially harmful for testicular function but evidence linking heavy metal exposure to reduced semen parameters is inconclusive. Elucidation of the exact stage at which the toxicant interferes with spermatogenesis is difficult because the various germ cell stages may have different sensitivities to any given toxicant, germ cell development is influenced by supporting testicular somatic cells and the presence of inter-Sertoli cell tight junctions create a blood-testis barrier, sequestering meiotic and postmeiotic germ cells in a special microenvironment. Sharks such as Squalus acanthias provide a suitable model for studying aspects of vertebrate spermatogenosis because of their unique features: spermatogenesis takes place within spermatocysts and relies mainly on Sertoli cells for somatic cell support; spermatocysts are linearly arranged in a maturational order across the diameter of the elongated testis; spermatocysts containing germ cells at different stages of development are topographically separated, resulting in visible zonation in testicular cross sections. We have used the vital dye acridine orange and a novel fluorescence staining technique to study this model to determine (1) the efficacy of these methods in assays of apoptosis and blood-testis barrier function, (2) the sensitivity of the various spermatogonial generations in Squalus to cadmium (as an illustrative spermatotoxicant) and (3) the way that cadmium might affect more mature spermatogenic stages and other physiological processes in the testis. Our results show that cadmium targets early spermatogenic stages, where it specifically activates a cell death program in susceptible (mature) spermatogonial clones, and negatively affects blood-testis barrier function. Since other parameters are relatively unaffected by cadmium, the effects of this toxicant on apoptosis are presumably process-specific and not attributable to general toxicity.

Conditions in utero and cancer risk.

PubMed

Grotmol, Tom; Weiderpass, Elisabete; Tretli, Steinar

2006-01-01

There is increasing recognition that conditions in utero are of importance for later cancer risk in several organs, particularly the testis and breast. A review of the most recent literature on this topic is therefore warranted. The PubMed database was searched for relevant recent literature on intrauterine conditions associated with cancer risk later in life, with particular emphasis on the testis, breast, but also studies pertaining to other organs were included. Epidemiological and experimental data support the hypothesis that factors acting in utero play a role in the development of cancer in the testis and breast. For other organs, such as the prostate, urinary system and colorectum, the results are inconclusive. While conditions during foetal life are associated with later cancer risk in the testis and breast, the biological mechanisms are for the most part elusive. They are, however, likely to involve hormonal disturbances, number of cells at risk, and genetic or epigenetic events.

Human Fetal Testis Xenografts Are Resistant to Phthalate-Induced Endocrine Disruption

PubMed Central

Heger, Nicholas E; Hall, Susan J; Sandrof, Moses A; McDonnell, Elizabeth V; Hensley, Janan B; McDowell, Erin N; Martin, Kayla A; Gaido, Kevin W; Johnson, Kamin J

2012-01-01

Background: In utero exposure to endocrine-disrupting chemicals may contribute to testicular dysgenesis syndrome (TDS), a proposed constellation of increasingly common male reproductive tract abnormalities (including hypospadias, cryptorchidism, hypospermatogenesis, and testicular cancer). Male rats exposed in utero to certain phthalate plasticizers exhibit multinucleated germ cell (MNG) induction and suppressed steroidogenic gene expression and testosterone production in the fetal testis, causing TDS-consistent effects of hypospadias and cryptorchidism. Mice exposed to phthalates in utero exhibit MNG induction only. This disparity in response demonstrates a species-specific sensitivity to phthalate-induced suppression of fetal Leydig cell steroidogenesis. Importantly, ex vivo phthalate exposure of the fetal testis does not recapitulate the species-specific endocrine disruption, demonstrating the need for a new bioassay to assess the human response to phthalates. Objectives: In this study, we aimed to develop and validate a rat and mouse testis xenograft bioassay of phthalate exposure and examine the human fetal testis response. Methods: Fetal rat, mouse, and human testes were xenografted into immunodeficient rodent hosts, and hosts were gavaged with a range of phthalate doses over multiple days. Xenografts were harvested and assessed for histopathology and steroidogenic end points. Results: Consistent with the in utero response, phthalate exposure induced MNG formation in rat and mouse xenografts, but only rats exhibited suppressed steroidogenesis. Across a range of doses, human fetal testis xenografts exhibited MNG induction but were resistant to suppression of steroidogenic gene expression. Conclusions: Phthalate exposure of grafted human fetal testis altered fetal germ cells but did not reduce expression of genes that regulate fetal testosterone biosynthesis. PMID:22511013

CHANGES IN FETAL TESTIS GENE EXPRESSION AND STEROID HORMONE SYNTHESIS INDUCED IN MALE OFFSPRING AFTER MATERNAL TREATMENT WITH PHTHALATE ESTERS

EPA Science Inventory

Targeted inactivation of the insulin-like hormone 3 (insl3) gene in male mice results in altered gubernacular development, disrupted testis decent, and cryptorchidism. Cryptorchidism is a fairly common human malformation, being displayed in 1-3% of males at birth. Since only a s...

Sex cord-gonadal stromal tumor of the rete testis.

PubMed

Sajadi, Kamran P; Dalton, Rory R; Brown, James A

2009-01-01

A 34-year-old tetraplegic patient with suppurative epididymitis was found on follow-up examination and ultrasonography to have a testicular mass. The radical orchiectomy specimen contained an undifferentiated spindled sex cord-stromal tumor arising in the rete testis. Testicular sex cord-stromal tumors are far less common than germ cell neoplasms and are usually benign. The close relationship between sex cords and ductules of the rete testis during development provides the opportunity for these uncommon tumors to arise anatomically within the rete tesis. This undifferentiated sex cord-stromal tumor, occurring in a previously unreported location, is an example of an unusual lesion mimicking an intratesticular malignant neoplasm.

In Utero Exposure to Di-(2-Ethylhexyl) Phthalate Induces Testicular Effects in Neonatal Rats That Are Antagonized by Genistein Cotreatment1

PubMed Central

Jones, Steven; Boisvert, Annie; Francois, Sade; Zhang, Liandong; Culty, Martine

2015-01-01

Fetal exposure to endocrine disruptors (EDs) is believed to predispose males to reproductive abnormalities. Although males are exposed to combinations of chemicals, few studies have evaluated the effects of ED mixtures at environmentally relevant doses. Our previous work showed that fetal exposure to a mixture of the phytoestrogen genistein (GEN) and the plasticizer di-(2-ethylhexyl) phthalate (DEHP) induced unique alterations in adult testis. In this follow-up study, we examined Postnatal Day 3 (PND3) and PND6 male offspring exposed from Gestational Day 14 to parturition to corn oil, 10mg/kg GEN, DEHP, or their combination, to gain insight into the early molecular events driving long-term alterations. DEHP stimulated the mRNA and protein expression of the steroidogenic enzyme HSD3B, uniquely at PND3. DEHP also increased the mRNA expression of Nestin, a Leydig progenitor/Sertoli cell marker, and markers of Sertoli cell (Wt1), gonocyte (Plzf, Foxo1), and proliferation (Pcna) at PND3, while these genes were unchanged by the mixture. Redox (Nqo1, Sod2, Sod3, Trx, Gst, Cat) and xenobiotic transporter (Abcb1b, Abcg2) gene expression was also increased by DEHP at PND3, while attenuated when combined with GEN, suggesting the involvement of cellular stress in short-term DEHP effects and a protective effect of GEN. The direct effects of GEN and mono-(2-ethylhexyl) phthalate, the principal bioactive metabolite of DEHP, on testis were investigated in PND3 organ cultures, showing a stimulatory effect of 10 μM mono-(2-ethylhexyl) phthalate on basal testosterone production that was normalized by GEN. These effects contrasted with previous reports of androgen suppression and decreased gene expression in perinatal rat testis by high DEHP doses, implying that neonatal effects are not predictive of adult effects. We propose that GEN, through an antioxidant action, normalizes reactive oxygen species-induced neonatal effects of DEHP. The notion that these EDs do not follow classical dose-response effects and involve different mechanisms of toxicity from perinatal ages to adulthood highlights the importance of assessing impacts across a range of doses and ages. PMID:26316063

Dramatic changes in 67 miRNAs during initiation of first wave of spermatogenesis in Mus musculus testis: global regulatory insights generated by miRNA-mRNA network analysis.

PubMed

Sree, Sreesha; Radhakrishnan, Karthika; Indu, Sivankutty; Kumar, Pradeep G

2014-09-01

We mapped global changes in miRNA and mRNA profiles spanning the first wave of spermatogenesis using prepubertal (Postnatal Day 8 [P8]), pubertal (P16), and adolescent (P24) Mus musculus testes and identified the differential expression of 67 miRNAs and 8226 mRNAs. These two data sets were integrated into miRNA-dependent regulatory networks based on miRWalk predictions. In a network representing the P8 to P16 transition, downregulation of four miRNAs and upregulation of 19 miRNAs were linked with 81 upregulated target mRNAs and 228 downregulated target mRNAs, respectively. Furthermore, during the P16 to P24 transition, two miRNAs were downregulated, and eight miRNAs were upregulated, which linked with 64 upregulated mRNAs and 389 downregulated mRNAs, respectively. Only three of the miRNAs present in the network (miR-34b-5p, miR-34c, and miR-449a) showed a progressive increase from P8 through P16 to P24, while the remaining miRNAs in the network showed statistically significant changes in their levels either during the P8 to P16 transition or during the P16 to P24 transition. Analysis of the chromosomal location of these differentially expressed miRNAs showed that 14 out of 25 miRNAs upregulated from P8 to P16, and 18 out of 40 miRNAs upregulated from P8 to P24 were X-linked. This is suggestive of their escape from meiotic sex chromosome inactivation and postmeiotic sex chromatin. This integrated network of miRNA-level and mRNA-level changes in mouse testis during the first wave of spermatogenesis is expected to build a base for evaluating the role of miRNA-mediated gene expression regulation in maturing mammalian testis. © 2014 by the Society for the Study of Reproduction, Inc.

Promyelocytic leukaemia zinc finger maintains self-renewal of male germline stem cells (mGSCs) and its expression pattern in dairy goat testis.

PubMed

Song, W; Zhu, H; Li, M; Li, N; Wu, J; Mu, H; Yao, X; Han, W; Liu, W; Hua, J

2013-08-01

Previous studies have shown that promyelocytic leukaemia zinc finger (PLZF) is a spermatogonia-specific transcription factor in the testis, required to regulate self-renewal and maintenance of the spermatogonia stem cell. Up to now, expression and function of PLZF in the goat testis has not been known. The objectives of this study were to investigate PLZF expression pattern in the dairy goat and its effect on male goat germline stem cell (mGSC) self-renewal and differentiation. Testis development and expression patterns of PLZF in the dairy goat were analysed by haematoxylin and eosin staining, immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). Furthermore, effects of PLZF overexpression on mGSC self-renewal and differentiation were evaluated by quantitative RT-PCR (QRT-PCR), immunofluorescence and BrdU incorporation assay. Promyelocytic leukaemia zinc finger was essential for dairy goat testis development and expression of several proliferation and pluripotency-associated proteins including OCT4, C-MYC were upregulated by PLZF overexpression. The study demonstrated that PLZF played a key role in maintaining self-renewal of mGSCs and its overexpression enhanced expression of proliferation-associated genes. Promyelocytic leukaemia zinc finger could function in the dairy goat as well as in other species in maintaining self-renewal of germline stem cells and this study provides a model to study the mechanism on self-renewal and differentiation of mGSCs in livestock. © 2013 John Wiley & Sons Ltd.

Cloning and characterization of full length of a novel zebrafish gene Zsrg abundantly expressed in the germline stem cells.

PubMed

Lv, Daoyuan; Song, Ping; Chen, Yungui; Gong, Wuming; Mo, Saijun

2005-04-08

Using the digital differential display program of the National Center for Biotechnology Information, we identified a contig of expression sequence tags (ESTs) (Accession No. BM316936), which came from zebrafish ovary and testis libraries. The full-length cDNA of this transcript was cloned and further confirmed by polymerase chain reaction and sequencing. The full-length cDNA of the novel gene is 807bp and encodes a novel protein of 187 amino acids, which shares no significant homology with any other known proteins. Characterization of genomic sequences of the gene revealed that it spans 6kb on the linkage group 3 and is composed of five exons and four introns. RT-PCR analysis showed that it was expressed in mature oocytes and one-cell stage, and persisted until 24h of development. RT-PCR also revealed that it is expressed in gonad and kidney, with the highest level of expression in the testis. The expression sites of the novel gene in adult gonad were further localized by in situ hybridization to oogonia and growing oocytes in ovary and to spermatogonia, spermatocytes but not to spermatids in testis. Based on its abundance in testis and the germline stem cell-spermatogonia and oogonia, we hypothesize that it may function as a testicular development and gametogenesis related gene that plays important roles in spermatogenesis, and named it Zsrg (zebrafish testis spermatogenesis related gene, Zsrg).

Does the cranial suspensory ligament have a role in cryptorchidism?

PubMed

Kassim, Normadiah M; Russell, D A; Payne, A P

2010-01-01

The cranial suspensory ligament (CSL) is a fibromuscular structure anchoring the embryonic gonad to the posterior abdominal wall in male and female mammals. Its persistence in females is believed to be responsible for retaining the ovaries within the abdomen, while its regression in males permits testis descent. Embryonic loss of the CSL in males is believed to be an androgen-dependent event, and failure of this process has been proposed as a cause of cryptorchidism. The present study demonstrates that the nuclei of mesenchymal cells in the caudal part of the CSL are immunoreactively positive for androgen receptor. We examined the effects of exposure of the non-steroidal antiandrogen flutamide during the period from gestational day 10 to birth on the development of the CSL and on testis descent. Exposure of male Albino Swiss rats to the antiandrogen flutamide during this period resulted in feminization of the external genitalia and the suppression of growth of the testes and male reproductive tracts. In adulthood, testes were found to be located in diverse positions including normal scrotal (50%), intra-abdominal (10%) and ectopic suprainguinal (40%). The CSL of the testis persisted into adulthood in all flutamide-treated males, regardless of testis location. In all cases, the ligament consisted of bundles of smooth muscle fibres in the retroperitoneal fat of the posterior abdominal wall. These findings suggest that androgen blockade during embryonic development interferes with testicular descent, but that maldescent cannot be correlated with either the persistence of the CSL of the testis or its structure.

Expression pattern of phb2 and its potential function in spermatogenesis of scallop ( Chlamys farreri)

NASA Astrophysics Data System (ADS)

Han, Tiantian; Ma, Xiaoshi; Liang, Shaoshuai; Gao, Beibei; Zhang, Zhifeng

2015-12-01

Prohibitin (PHB) participates in several biological processes including apoptosis, transcription regulation and suppression of cell proliferation in mammals. In this study, we cloned the full-length cDNA of prohibitin 2 ( Cf-phb2) from the testis of scallop ( Chlamys farreri). The deduced amino acid sequence presented a characteristic of PHB family with the PHB domain, and clustered with PHB2 of other species. Temporal and spatial expression of Cf-phb2 in testis during the reproductive cycle was detected by quantitative real-time PCR (qRT-PCR) and in situ hybridization. The expression of Cf-phb2 in the testis increased when testis developed from the resting stage to mature stage. The mRNA abundance of Cf-phb2 was the highest at mature stage, which was about 15-fold higher than that at proliferative stage. The expression of Cf-phb2 could be detected by in situ hybridization in all types of germ cells in testis, including spermatogonia, spermatocytes, spermatids and spermatozoa. The intensity of the signal increased with the spermatogenesis and was the highest in spermatids, which suggested that CF-PHB2 might affect the spermatogenesis of C. farreri.

Thyroid Hormone and Leptin in the Testis

PubMed Central

Ramos, Cristiane Fonte; Zamoner, Ariane

2014-01-01

Leptin is primarily expressed in white adipose tissue; however, it is expressed in the hypothalamus and reproductive tissues as well. Leptin acts by activating the leptin receptors (Ob-Rs). Additionally, the regulation of several neuroendocrine and reproductive functions, including the inhibition of glucocorticoids and enhancement of thyroxine and sex hormone concentrations in human beings and mice are leptin functions. It has been suggested that thyroid hormones (TH) could directly regulate leptin expression. Additionally, hypothyroidism compromises the intracellular integration of leptin signaling specifically in the arcuate nucleus. Two TH receptor isoforms are expressed in the testis, TRa and TRb, with TRa being the predominant one that is present in all stages of development. The effects of TH involve the proliferation and differentiation of Sertoli and Leydig cells during development, spermatogenesis, and steroidogenesis. In this context, TH disorders are associated with sexual dysfunction. An endocrine and/or direct paracrine effect of leptin on the gonads inhibits testosterone production in Leydig cells. Further studies are necessary to clarify the effects of both hormones in the testis during hypothyroidism. The goal of this review is to highlight the current knowledge regarding leptin and TH in the testis. PMID:25505448

The Petit Rat (pet/pet), a New Semilethal Mutant Dwarf Rat with Thymic and Testicular Anomalies

PubMed Central

Chiba, Junko; Suzuki, Katsushi; Suzuki, Hiroetsu

2008-01-01

The petit rat (pet/pet) is a recently discovered semilethal mutant dwarf. The neonatal pet/pet rats had a low body weight and small thymus and testis. During the first 3 d after birth, 50% of the male and 80% of the female pet/pet pups were lost or found dead. Surviving pet/pet rats showed marked retardation of postnatal growth, and their body weights were 41% (female rats) and 32% (male rats) of those of normal rats at the adult stage. The pet/pet rats exhibited proportional dwarfism, and their longitudinal bones were shorter than those of controls without skeletal malformations. Most organs of male pet/pet rats, especially the thymus, testis, adipose tissue surrounding the kidney, and accessory sex organs, weighed markedly less at 140 d of age than did those of their normal counterparts. The thymus of pet/pet rats was small with abnormal thymic follicles. Testes from pet/pet rats exhibited 2 patterns of abnormal histology. Spermatogenesis was present in testes that were only slightly anomalous, but the seminiferous tubules were reduced in diameter. In severely affected testes, most of the seminiferous tubules showed degeneration, and interstitial tissue was increased. Plasma growth hormone concentrations did not differ between pet/pet and normal male rats. The dwarf phenotype of pet/pet rats was inherited as an autosomal recessive trait. These results indicate that the pet/pet rat has a semilethal growth-hormone-independent dwarf phenotype that is accompanied by thymic and testicular anomalies and low birth weight. PMID:19149412

The petit rat (pet/pet), a new semilethal mutant dwarf rat with thymic and testicular anomalies.

PubMed

Chiba, Junko; Suzuki, Katsushi; Suzuki, Hiroetsu

2008-12-01

The petit rat (pet/pet) is a recently discovered semilethal mutant dwarf. The neonatal pet/pet rats had a low body weight and small thymus and testis. During the first 3 d after birth, 50% of the male and 80% of the female pet/pet pups were lost or found dead. Surviving pet/pet rats showed marked retardation of postnatal growth, and their body weights were 41% (female rats) and 32% (male rats) of those of normal rats at the adult stage. The pet/pet rats exhibited proportional dwarfism, and their longitudinal bones were shorter than those of controls without skeletal malformations. Most organs of male pet/pet rats, especially the thymus, testis, adipose tissue surrounding the kidney, and accessory sex organs, weighed markedly less at 140 d of age than did those of their normal counterparts. The thymus of pet/pet rats was small with abnormal thymic follicles. Testes from pet/pet rats exhibited 2 patterns of abnormal histology. Spermatogenesis was present in testes that were only slightly anomalous, but the seminiferous tubules were reduced in diameter. In severely affected testes, most of the seminiferous tubules showed degeneration, and interstitial tissue was increased. Plasma growth hormone concentrations did not differ between pet/pet and normal male rats. The dwarf phenotype of pet/pet rats was inherited as an autosomal recessive trait. These results indicate that the pet/pet rat has a semilethal growth-hormone-independent dwarf phenotype that is accompanied by thymic and testicular anomalies and low birth weight.

Follitropin receptors in rat testis. Characterization with enzymatically 125I-labeled human follitropin.

PubMed

Ketelslegers, J M; Catt, K J

1978-07-03

The interaction between enzymatically radioiodinated human follitropin and the follitropin receptors in testis homogenate was investigated in immature and adult rats. The 125I-labeled human follitropin exhibited high binding activity with specific binding of up to 17% in the presence of an excess of testis homogenate. Approx. 50% of the bound hormone could be eluted at pH 5, and the receptor purified tracer exhibited a 3.6-fold increase in binding activity when compared with the original tracer preparation. Quantitative analysis of equilibrium binding data was performed with corrections for the measured specific activity and maximum binding activity of the tracer hormone. The equilibrium association constants (Ka) determined 24 degrees C were not significantly different in immature and adult rat testis, and the mean value for Ka was 3.9 . 10(9) M-1. At 37 degrees C, the Ka value obtained using immature rat testis was 1.3 . 10(10) M-1. The association of 125I-labeled human follitropin with immature rat testis homogenate was time and temperature dependent. In the presence of an excess of unlabeled hormone, 30--60% of the preformed hormone . receptor complex was dissociated after 24 h incubation. A specific and sensitive radioligand-receptor assay for follitropin was developed using immature rat testis homogenate. The minimum detectable dose of purified human follitropin was 0.6 ng, and human urinary and pituitary follitropin, ovine follitropin and pregnant mare serum gonadotropin reacted in the assay with equivalent slopes. The potencies of highly purified pregnent mare serum gonadotropin and highly purified human follitropin were similar in the radioligand-receptor assay, consistent with the follitropin bioactivity of the equine gonadotropin.

Probable gamma-aminobutyric acid involvement in bisphenol A effect at the hypothalamic level in adult male rats.

PubMed

Cardoso, Nancy; Pandolfi, Matías; Lavalle, Justina; Carbone, Silvia; Ponzo, Osvaldo; Scacchi, Pablo; Reynoso, Roxana

2011-12-01

The aim of the present study was to investigate the effects of bisphenol A (BPA) on the neuroendocrine mechanism of control of the reproductive axis in adult male rats exposed to it during pre- and early postnatal periods. Wistar mated rats were treated with either 0.1% ethanol or BPA in their drinking water until their offspring were weaned at the age of 21 days. The estimated average dose of exposure to dams was approximately 2.5 mg/kg body weight per day of BPA. After 21 days, the pups were separated from the mother and sacrificed on 70 day of life. Gn-RH and gamma-aminobutyric acid (GABA) release from hypothalamic fragments was measured. LH, FSH, and testosterone concentrations were determined, and histological and morphometrical studies of testis were performed. Gn-RH release decreased significantly, while GABA serum levels were markedly increased by treatment. LH serum levels showed no changes, and FSH and testosterone levels decreased significantly. Histological studies showed abnormalities in the tubular organization of the germinal epithelium. The cytoarchitecture of germinal cells was apparently normal, and a reduction of the nuclear area of Leydig cells but not their number was observed. Taken all together, these results provide evidence of the effect caused by BPA on the adult male reproductive axis when exposed during pre- and postnatal period. Moreover, our findings suggest a probable GABA involvement in its effect at the hypothalamic level.

Effects of environmental Bisphenol A exposures on germ cell development and Leydig cell function in the human fetal testis

PubMed Central

Guerquin, Marie-Justine; Matilionyte, Gabriele; Kilcoyne, Karen; N’Tumba-Byn, Thierry; Messiaen, Sébastien; Deceuninck, Yoann; Pozzi-Gaudin, Stéphanie; Benachi, Alexandra; Livera, Gabriel; Antignac, Jean-Philippe; Mitchell, Rod; Rouiller-Fabre, Virginie

2018-01-01

Background Using an organotypic culture system termed human Fetal Testis Assay (hFeTA) we previously showed that 0.01 μM BPA decreases basal, but not LH-stimulated, testosterone secreted by the first trimester human fetal testis. The present study was conducted to determine the potential for a long-term antiandrogenic effect of BPA using a xenograft model, and also to study the effect of BPA on germ cell development using both the hFETA and xenograft models. Methods Using the hFeTA system, first trimester testes were cultured for 3 days with 0.01 to 10 μM BPA. For xenografts, adult castrate male nude mice were injected with hCG and grafted with first trimester testes. Host mice received 10 μM BPA (~ 500 μg/kg/day) in their drinking water for 5 weeks. Plasma levels of total and unconjugated BPA were 0.10 μM and 0.038 μM respectively. Mice grafted with second trimester testes received 0.5 and 50 μg/kg/day BPA by oral gavage for 5 weeks. Results With first trimester human testes, using the hFeTA model, 10 μM BPA increased germ cell apoptosis. In xenografts, germ cell density was also reduced by BPA exposure. Importantly, BPA exposure significantly decreased the percentage of germ cells expressing the pluripotency marker AP-2γ, whilst the percentage of those expressing the pre-spermatogonial marker MAGE-A4 significantly increased. BPA exposure did not affect hCG-stimulated androgen production in first and second trimester xenografts as evaluated by both plasma testosterone level and seminal vesicle weight in host mice. Conclusions Exposure to BPA at environmentally relevant concentrations impairs germ cell development in first trimester human fetal testis, whilst gonadotrophin-stimulated testosterone production was unaffected in both first and second trimester testis. Studies using first trimester human fetal testis demonstrate the complementarity of the FeTA and xenograft models for determining the respective short-term and long term effects of environmental exposures. PMID:29385186

Bioluminescent Imaging of Trypanosoma brucei Shows Preferential Testis Dissemination Which May Hamper Drug Efficacy in Sleeping Sickness

PubMed Central

Claes, Filip; Vodnala, Suman K.; van Reet, Nick; Boucher, Nathalie; Lunden-Miguel, Hilda; Baltz, Theo; Goddeeris, Bruno Maria; Büscher, Philippe; Rottenberg, Martin E.

2009-01-01

Monitoring Trypanosoma spread using real-time imaging in vivo provides a fast method to evaluate parasite distribution especially in immunoprivileged locations. Here, we generated monomorphic and pleomorphic recombinant Trypanosoma brucei expressing the Renilla luciferase. In vitro luciferase activity measurements confirmed the uptake of the coelenterazine substrate by live parasites and light emission. We further validated the use of Renilla luciferase-tagged trypanosomes for real-time bioluminescent in vivo analysis. Interestingly, a preferential testis tropism was observed with both the monomorphic and pleomorphic recombinants. This is of importance when considering trypanocidal drug development, since parasites might be protected from many drugs by the blood-testis barrier. This hypothesis was supported by our final study of the efficacy of treatment with trypanocidal drugs in T. brucei-infected mice. We showed that parasites located in the testis, as compared to those located in the abdominal cavity, were not readily cleared by the drugs. PMID:19621071

Hyperthyroidism in the developing rat testis is associated with oxidative stress and hyperphosphorylated vimentin accumulation.

PubMed

Zamoner, Ariane; Barreto, Kátia Padilha; Filho, Danilo Wilhelm; Sell, Fabíola; Woehl, Viviane Mara; Guma, Fátima Costa Rodrigues; Silva, Fátima Regina Mena Barreto; Pessoa-Pureur, Regina

2007-03-15

Hyperthyroidism was induced in rats and somatic indices and metabolic parameters were analyzed in testis. In addition, the morphological analysis evidenced testes maturation and intense protein synthesis and processing, supporting the enhancement in vimentin synthesis in hyperthyroid testis. Furthermore, vimentin phosphorylation was increased, indicating an accumulation of phosphorylated vimentin associated to the cytoskeleton, which could be a consequence of the extracellular-regulated kinase (ERK) activation regulating the cytoskeleton. Biomarkers of oxidative stress demonstrated an increased basal metabolic rate measured by tissue oxygen consumption, as well as, increased TBARS levels. In addition, the enzymatic and non-enzymatic antioxidant defences appeared to respond according to the augmented oxygen consumption. We observed decreased total glutathione levels, with enhancement of reduced glutathione, whereas most of the antioxidant enzyme activities were induced. Otherwise, superoxide dismutase activity was inhibited. These results support the idea that an increase in mitochondrial ROS generation, underlying cellular oxidative damage, is a side effect of hyperthyroid-induced biochemical changes by which rat testis increase their metabolic capacity.

Spermatogonial stem cells and progenitors are refractory to reprogramming to pluripotency by the transcription factors Oct3/4, c-Myc, Sox2 and Klf4

PubMed Central

Corbineau, Sébastien; Lassalle, Bruno; Givelet, Maelle; Souissi-Sarahoui, Inès; Firlej, Virginie; Romeo, Paul Henri; Allemand, Isabelle; Riou, Lydia; Fouchet, Pierre

2017-01-01

The male germinal lineage, which is defined as unipotent, produces sperm through spermatogenesis. However, embryonic primordial germ cells and postnatal spermatogonial stem cells (SSCs) can change their fate and convert to pluripotency in culture when they are not controlled by the testicular microenvironment. The mechanisms underlying these reprogramming processes are poorly understood. Testicular germ cell tumors, including teratoma, share some molecular characteristics with pluripotent cells, suggesting that cancer could result from an abnormal differentiation of primordial germ cells or from an abnormal conversion of SCCs to pluripotency in the testis. Here, we investigated whether the somatic reprogramming factors Oct3/4, Sox2, Klf4 and c-Myc (OSKM) could play a role in SSCs reprogramming and induce pluripotency using a doxycycline-inducible transgenic Col1a1-4F2A-OSKM mouse model. We showed that, in contrast to somatic cells, SSCs from adult mice are resistant to this reprogramming strategy, even in combination with small molecules, hypoxia, or p53 deficiency, which were previously described to favour the conversion of somatic cells to pluripotency. This finding suggests that adult SSCs have developed specific mechanisms to repress reprogramming by OSKM factors, contributing to circumvent testicular cancer initiation events. PMID:28052023

Identification of multiple dmrt1s in catfish: localization, dimorphic expression pattern, changes during testicular cycle and after methyltestosterone treatment.

PubMed

Raghuveer, K; Senthilkumaran, B

2009-05-01

The double sex and mab-3 related (DM) transcription factor 1 (dmrt1) plays an important role in testicular differentiation. Here, we report cloning of multiple dmrt1s, a full-length and two alternative spliced forms from adult catfish (Clarias gariepinus) testis, which encode predicted proteins of 287 (dmrt1a), 253 (dmrt1b) and 233 (dmrt1c) amino acid residues respectively. Interestingly, dmrt1c lacks the majority of the DM domain. Multiple dmrt1s (dmrt1a and dmrt1c) were obtained from Clarias batrachus as well. Tissue distribution (transcript and protein) of catfish dmrt1 revealed exclusive expression in testis. Semi-quantitative RT-PCR revealed the presence of multiple dmrt1s with high levels of dmrt1a in adult testis but not in ovary. Real-time RT-PCR analysis during testicular cycle showed higher levels of dmrt1 transcripts in preparatory and pre-spawning when compared with spawning and post-spawning phases. Immunocytochemical and immunofluorescence localization revealed the presence of catfish Dmrt1 protein in spermatogonia and spermatocytes, which indicates plausible role in spermatogenesis. Histological analysis indicated initiation of gonadal sex differentiation in catfish around 40-50 days after hatching. The potential role for dmrt1 in testicular differentiation is evident from its stage-dependent elevated expression in developing testis. Furthermore, dimorphic expressions of dmrt1s were evident at different stages of gonadal development or recrudescence in catfish. Treatment of methyl testosterone (MT) during early stages of gonadal sex differentiation resulted in adult males. Interestingly, we also obtained MT-treated fishes having ova-testis gonads. Analysis of dmrt1, sox9a, foxl2 and cyp19a1 expression patterns in MT-treated gonads revealed tissue-specific pattern. These results together suggest that multiple dmrt1s are testis-specific markers in catfish.

Identification of Developmentally Regulated PCP-Responsive Non-Coding RNA, prt6, in the Rat Thalamus

PubMed Central

Umino, Asami; Nishikawa, Toru

2014-01-01

Schizophrenia and similar psychoses induced by NMDA-type glutamate receptor antagonists, such as phencyclidine (PCP) and ketamine, usually develop after adolescence. Moreover, adult-type behavioral disturbance following NMDA receptor antagonist application in rodents is observed after a critical period at around 3 postnatal weeks. These observations suggest that the schizophrenic symptoms caused by and psychotomimetic effects of NMDA antagonists require the maturation of certain brain neuron circuits and molecular networks, which differentially respond to NMDA receptor antagonists across adolescence and the critical period. From this viewpoint, we have identified a novel developmentally regulated phencyclidine-responsive transcript from the rat thalamus, designated as prt6, as a candidate molecule involved in the above schizophrenia-related systems using a DNA microarray technique. The transcript is a non-coding RNA that includes sequences of at least two microRNAs, miR132 and miR212, and is expressed strongly in the brain and testis, with trace or non-detectable levels in the spleen, heart, liver, kidney, lung and skeletal muscle, as revealed by Northern blot analysis. The systemic administration of PCP (7.5 mg/kg, subcutaneously (s.c.)) significantly elevated the expression of prt6 mRNA in the thalamus at postnatal days (PD) 32 and 50, but not at PD 8, 13, 20, or 24 as compared to saline-treated controls. At PD 50, another NMDA receptor antagonist, dizocilpine (0.5 mg/kg, s.c.), and a schizophrenomimetic dopamine agonist, methamphetamine (4.8 mg/kg, s.c.), mimicked a significant increase in the levels of thalamic prt6 mRNAs, while a D2 dopmamine receptor antagonist, haloperidol, partly inhibited the increasing influence of PCP on thalamic prt6 expression without its own effects. These data indicate that prt6 may be involved in the pathophysiology of the onset of drug-induced schizophrenia-like symptoms and schizophrenia through the possible dysregulation of target genes of the long non-coding RNA or microRNAs in the transcript. PMID:24886782

[Thick and thin zones of the neurocranium, impressiones gyrorum and foramina parietalia in children and adults (author's transl)].

PubMed

Lang, J; Brückner, B

1981-01-01

At 102 skulls from adults and 67 skulls from children we have investigated 1) The postnatal changes of the thickness from basal parts of the Fossae craniales ant., med. et post. 2) The postnatal thickening and lateral shifting of the Processus clinoideus anterior. 3) The postnatal development at the superior side of the Canalis opticus. 4) Between the Os sphenoidale Clivus angle from newborn age to 17 years of life at 67 skulls. 5) The postnatal changes of the lateral angle at the Pars petrosa and its right-left-differences. 6) The postnatal thickening of the Calvaria (Squama frontalis - Tuber frontale, Os parietale - Tuber parietale). 7) The development, size and position of the Foramina parietalia. 8) The postnatal development of the Protuberantiae gyrorum and Sulci meningei.

Spermatogonial stem cells: Current biotechnological advances in reproduction and regenerative medicine.

PubMed

Aponte, Pedro Manuel

2015-05-26

Spermatogonial stem cells (SSCs) are the germ stem cells of the seminiferous epithelium in the testis. Through the process of spermatogenesis, they produce sperm while concomitantly keeping their cellular pool constant through self-renewal. SSC biology offers important applications for animal reproduction and overcoming human disease through regenerative therapies. To this end, several techniques involving SSCs have been developed and will be covered in this article. SSCs convey genetic information to the next generation, a property that can be exploited for gene targeting. Additionally, SSCs can be induced to become embryonic stem cell-like pluripotent cells in vitro. Updates on SSC transplantation techniques with related applications, such as fertility restoration and preservation of endangered species, are also covered on this article. SSC suspensions can be transplanted to the testis of an animal and this has given the basis for SSC functional assays. This procedure has proven technically demanding in large animals and men. In parallel, testis tissue xenografting, another transplantation technique, was developed and resulted in sperm production in testis explants grafted into ectopical locations in foreign species. Since SSC culture holds a pivotal role in SSC biotechnologies, current advances are overviewed. Finally, spermatogenesis in vitro, already demonstrated in mice, offers great promises to cope with reproductive issues in the farm animal industry and human clinical applications.

Expression profiles of relaxin family peptides and their receptors indicate their influence on spermatogenesis in the domestic cat (Felis catus).

PubMed

Braun, B C; Müller, K; Jewgenow, K

2015-07-01

Disturbed spermatogenesis is a common problem in felines. Studying spermatogenesis in the domestic cat can improve the understanding of the biological background and help to counteract fertility problems in other feline species. Here, we analyzed 3 relaxin family peptides (relaxin, relaxin-3, and INSL3) and their receptors (RXFP1, RXFP2, and RXFP3) as potential spermatogenic factors involving their expression in the testis at different stages of its development. It may be concluded from its stage-dependent expression that relaxin, together with RXFP1, appears to be involved in the first stage of spermatogenesis, whereas relaxin-3 via binding to RXFP3 influences spermiogenesis. Furthermore, correlations were observed between relaxin, relaxin-3, RXFP1, RXFP2 and RXFP3 messenger RNA expression, and the relative numbers of haploid cells in testes. The peptide INSL3 was highly expressed at all testis development stages. Because of the low and stage-independent expression of its receptor RXFP2, an auto- and/or paracrine function of INSL3 in spermatogenesis seems unlikely. In the adult testis, messenger RNA expression of relaxin, RXFP1, and RXFP3 predominantly occurs in the tubular testis compartment, whereas INLS3 is mainly expressed in the interstitium. Copyright © 2015 Elsevier Inc. All rights reserved.

Gene expression profile during testicular development in patients with SRY-negative 46,XX testicular disorder of sex development.

PubMed

Mizuno, Kentaro; Kojima, Yoshiyuki; Kamisawa, Hideyuki; Moritoki, Yoshinobu; Nishio, Hidenori; Kohri, Kenjiro; Hayashi, Yutaro

2013-12-01

To elucidate alternative pathways in testicular development, we attempted to clarify the genetic characteristics of SRY-negative XX testes. We previously reported 5 cases of SRY-negative 46,XX testicular disorders of sex development and demonstrated that coordinated expression of genes such as SOX9, SOX3, and DAX1 was associated with testicular development. We performed a case-control study between the aforementioned boy with 46,XX testicular disorders of sex development and an age-matched patient with hydrocele testis (46,XY). During their consecutive surgeries, testicular biopsy specimens were obtained. Genes with differential expression compared with XY testis were identified using polymerase chain reaction (PCR)-based subtractive hybridization and sequencing. For validation of differential gene expression, real-time RT-PCR was performed using gene-specific primers. The distribution of candidate proteins in the testicular tissue was clarified by immunohistochemistry in human and rodent specimens. Moreover, in vitro inhibitory assays were performed. We identified 13 upregulated and 7 downregulated genes in XX testis. Among the candidate genes, we focused on ROCK1 (Rho-associated, coiled-coil protein kinase 1) in the upregulated gene group, because high expression in XX testis was validated by real-time RT-PCR. ROCK1 protein was detected in germ cells, Leydig cells, and Sertoli cells by immunohistochemistry. Moreover, the addition of specific ROCK1 inhibitor to Sertoli cells decreased SOX9 gene expression. On the basis of in vitro inhibitory assay, it is suggested that ROCK1 phosphorylates and activates SOX9 in Sertoli cells. Testes formation might be initiated by an alternative signaling pathway attributed to ROCK1, not SRY, activation in XX testes. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of prenatal and postnatal maternal emotional stress on toddlers' cognitive and temperamental development.

PubMed

Lin, Yanfen; Xu, Jian; Huang, Jun; Jia, Yinan; Zhang, Jinsong; Yan, Chonghuai; Zhang, Jun

2017-01-01

Maternal stress is associated with impairments in the neurodevelopment of offspring; however, the effects of the timing of exposure to maternal stress on a child's neurodevelopment are unclear. In 2010, we studied 225 mother-child pairs in Shanghai, recruiting mothers in mid-to-late pregnancy and monitoring offspring from birth until 30 months of age. Maternal stress was assessed prenatally (at 28-36 weeks of gestation) and postnatally (at 24-30 months postpartum) using the Symptom-Checklist-90-Revised Scale (SCL-90-R) and Life-Event-Stress Scale to evaluate mothers' emotional stress and life event stress levels, respectively. Children's cognition and temperament were assessed at 24-30 months of age using the Gesell Development Scale and Toddler Temperament Scale, respectively. Multi-variable linear regression models were used to associate prenatal and postnatal stress with child cognitive and temperamental development. Maternal prenatal and postnatal Global Severity Index (GSI) of SCL-90-R were moderately correlated (ICC r=0.30, P<0.001). After adjusting for relevant covariates, the increase in prenatal GSI was associated with decreases in toddlers' gross motor, fine motor, adaptive and social behavior development independently of postnatal GSI, while the increase in postnatal GSI was associated with changes in multiple temperament dimensions independently of prenatal GSI. The effects of prenatal and postnatal depression scores of SCL-90-R were similar to those of GSI. Relatively small sample size. Compared with postnatal exposure, children's cognitive development may be more susceptible to prenatal exposure to maternal emotional stress, whereas temperamental development may be more affected by postnatal exposure to maternal emotional stress compared with prenatal exposure. Copyright © 2016 Elsevier B.V. All rights reserved.

Postnatal exposure to methyl mercury from fish consumption: a review and new data from the Seychelles Child Development Study.

PubMed

Myers, Gary J; Thurston, Sally W; Pearson, Alexander T; Davidson, Philip W; Cox, Christopher; Shamlaye, Conrad F; Cernichiari, Elsa; Clarkson, Thomas W

2009-05-01

Fish is an important source of nutrition worldwide. Fish contain both the neurotoxin methyl mercury (MeHg) and nutrients important for brain development. The developing brain appears to be most sensitive to MeHg toxicity and mothers who consume fish during pregnancy expose their fetus prenatally. Although brain development is most dramatic during fetal life, it continues for years postnatally and additional exposure can occur when a mother breast feeds or the child consumes fish. This raises the possibility that MeHg might influence brain development after birth and thus adversely affect children's developmental outcomes. We reviewed postnatal MeHg exposure and the associations that have been published to determine the issues associated with it and then carried out a series of analyses involving alternative metrics of postnatal MeHg exposure in the Seychelles Child Development Study (SCDS) Main Cohort. The SCDS is a prospective longitudinal evaluation of prenatal MeHg exposure from fish consumption. The Main Cohort includes 779 subjects on whom recent postnatal exposure data were collected at the 6-, 19-, 29-, 66-, and 107-month evaluations. We examined the association of recent postnatal MeHg exposure with multiple 66- and 107-month outcomes and then used three types of alternative postnatal exposure metrics to examine their association with the children's intelligence quotient (IQ) at 107 months of age. Recent postnatal exposure at 107 months of age was adversely associated with four endpoints, three in females only. One alternative postnatal metric was beneficially associated with 9-year IQ in males only. We found several associations between postnatal MeHg biomarkers and children's developmental endpoints. However, as has been the case with prenatal MeHg exposure in the SCDS Main Cohort study, no consistent pattern of associations emerged to support a causal relationship.

Occurrence and degree of intersex (testis-ova) in darters (Etheostoma SPP.) across an urban gradient in the Grand River, Ontario, Canada.

PubMed

Tanna, Rajiv N; Tetreault, Gerald R; Bennett, Charles J; Smith, Brendan M; Bragg, Leslie M; Oakes, Ken D; McMaster, Mark E; Servos, Mark R

2013-09-01

The variability and extent of the intersex condition (oocytes in testes, or testis-ova) was documented in fish along an urban gradient in the Grand River, Ontario, Canada, that included major wastewater treatment plant outfalls. A method for rapid enumeration of testis-ova was developed and applied that increased the capacity to quantify intersex prevalence and severity. Male rainbow darters (Etheostoma caeruleum) sampled downstream of the first major wastewater outfall (Waterloo) had a significant increase, relative to 4 upstream reference sites, in the mean proportion of fish with at least 1 testis-oocyte per lobe of testes (9-20% proportion with ≤ 1 testis-oocyte/lobe vs 32-53% and >1.4 testis-oocyte/lobe). A much higher mean incidence of intersex proportion and degree was observed immediately downstream of the second wastewater outfall (Kitchener; 73-100% and 8-70 testis-oocyte/lobe); but only 6.3 km downstream of the Kitchener outfall, the occurrence of intersex dropped to those of the reference sites. In contrast, downstream of a tertiary treated wastewater outfall on a small tributary, intersex was similar to reference sites. Estrogenicity, measured using a yeast estrogen screen, followed a similar pattern, increasing from 0.81 ± 0.02 ng/L 17b-estradiol equivalents (EEq) (Guelph), to 4.32 ± 0.07 ng/L (Waterloo), and 16.99 ± 0.40 ng/L (Kitchener). Female rainbow darter downstream of the Kitchener outfall showed significant decreases in gonadosomatic index and liver somatic index, and increases in condition factor (k) relative to corresponding reference sites. The prevalence of intersex and alterations in somatic indices suggest that exposure to municipal wastewater effluent discharges can impact endocrine function, energy use, and energy storage in wild fish. Copyright © 2013 SETAC.

TCF21 is related to testis growth and development in broiler chickens.

PubMed

Zhang, Hui; Na, Wei; Zhang, Hong-Li; Wang, Ning; Du, Zhi-Qiang; Wang, Shou-Zhi; Wang, Zhi-Peng; Zhang, Zhiwu; Li, Hui

2017-02-24

Large amounts of fat deposition often lead to loss of reproductive efficiency in humans and animals. We used broiler chickens as a model species to conduct a two-directional selection for and against abdominal fat over 19 generations, which resulted in a lean and a fat line. Direct selection for abdominal fat content also indirectly resulted in significant differences (P < 0.05) in testis weight (TeW) and in TeW as a percentage of total body weight (TeP) between the lean and fat lines. A total of 475 individuals from the generation 11 (G 11 ) were genotyped. Genome-wide association studies revealed two regions on chicken chromosomes 3 and 10 that were associated with TeW and TeP. Forty G 16 individuals (20 from each line), were further profiled by focusing on these two chromosomal regions, to identify candidate genes with functions that may be potentially related to testis growth and development. Of the nine candidate genes identified with database mining, a significant association was confirmed for one gene, TCF21, based on mRNA expression analysis. Gene expression analysis of the TCF21 gene was conducted again across 30 G 19 individuals (15 individuals from each line) and the results confirmed the findings on the G 16 animals. This study revealed that the TCF21 gene is related to testis growth and development in male broilers. This finding will be useful to guide future studies to understand the genetic mechanisms that underlie reproductive efficiency.

Building the mammalian testis: origins, differentiation, and assembly of the component cell populations

PubMed Central

Svingen, Terje; Koopman, Peter

2013-01-01

Development of testes in the mammalian embryo requires the formation and assembly of several cell types that allow these organs to achieve their roles in male reproduction and endocrine regulation. Testis development is unusual in that several cell types such as Sertoli, Leydig, and spermatogonial cells arise from bipotential precursors present in the precursor tissue, the genital ridge. These cell types do not differentiate independently but depend on signals from Sertoli cells that differentiate under the influence of transcription factors SRY and SOX9. While these steps are becoming better understood, the origins and roles of many testicular cell types and structures—including peritubular myoid cells, the tunica albuginea, the arterial and venous blood vasculature, lymphatic vessels, macrophages, and nerve cells—have remained unclear. This review synthesizes current knowledge of how the architecture of the testis unfolds and highlights the questions that remain to be explored, thus providing a roadmap for future studies that may help illuminate the causes of XY disorders of sex development, infertility, and testicular cancers. PMID:24240231

Application of testis germ cell transplantation in breeding systems of food producing species: a review.

PubMed

Herrid, Muren; McFarlane, James R

2013-01-01

A major benefit of advanced reproduction technologies (ART) in animal breeding is the ability to produce more progeny per individual parent. This is particularly useful with animals of high genetic merit. Testis germ cell transplantation (TGCT) is emerging as a novel reproductive technology with application in animal breeding systems, including the potential for use as an alternative to artificial insemination (AI), an alternative to transgenesis, part of an approach to reducing generation intervals, or an approach toward development of interspecies hybrids. There is one major difference in TGCT between rodents and some other species associated with immunotolerance in heterologous transplantation. In particular, livestock and aquatic species do not require an immunesuppression procedure to allow donor cell survival in recipient testis. Testicular stem cells from a genetically elite individual transplanted into others can develop and produce a surrogate male-an animal that produces the functional sperm of the original individual. Spermatozoa produced from testis stem cells are the only cells in the body of males that can transmit genetic information to the offspring. The isolation and genetic manipulation of testis stem cells prior to transplantation has been shown to create transgenic animals. However, the current success rate of the transplantation procedure in livestock and aquatic species is low, with a corresponding small proportion of donor spermatozoa in the recipient's semen. The propagation of donor cells in culture and preparation of recipient animals are the two main factors that limit the commercial application of this technique. The current paper reviews and compares recent progress and examines the difficulties of TGCT in both livestock and aquatic species, thereby providing new insights into the application of TGCT in food producing animals.

[Sclerotherapy with 3% polidocanol for hydrocele testis].

PubMed

Mizoguchi, H; Imagawa, M; Fukunaga, Y; Nomura, Y; Kubota, M; Okita, J

1995-12-01

We studied the clinical efficacy of sclerotherapy with injection of 3% polidocanol for hydrocele testis. From July, 1992 to March, 1995 sclerotherapy with single injection of polidocanol was performed for 11 patients with 12 hydrocele testis on an outpatient basis. We instilled 3 or 5ml of 3% polidocanol after complete removal of fluid in the hydrocele testis. Complete disappearance on ultrasonography was observed in 75% of the hydrocele testis 6 months after this sclerotherapy. There was neither pain during instillation of 3% polidocanol nor any other complication. Two patients with fluid reaccumulation underwent hydrocelectomy 16 and 6 months after sclerotherapy, respectively. This procedure seems to be a safe and useful technique as primary treatment for hydrocele testis.

A Critical Point of Male Gonad Development: Neuroendocrine Correlates of Accelerated Testicular Growth in Rats during Early Life

PubMed Central

Dygalo, Nikolay N.; Shemenkova, Tatjana V.; Kalinina, Tatjana S.; Shishkina, Galina T.

2014-01-01

Testis growth during early life is important for future male fertility and shows acceleration during the first months of life in humans. This acceleration coincides with the peak in gonadotropic hormones in the blood, while the role of hypothalamic factors remains vague. Using neonatal rats to assess this issue, we found that day 9 of life is likely critical for testis development in rats. Before this day, testicular growth was proportional to body weight gain, but after that the testes showed accelerated growth. Hypothalamic kisspeptin and its receptor mRNA levels begin to elevate 2 days later, at day 11. A significant increase in the mRNA levels for gonadotropin-releasing hormone (GnRH) receptors in the hypothalamus between days 5 and 7 was followed by a 3-fold decrease in GnRH mRNA levels in this brain region during the next 2 days. Starting from day 9, hypothalamic GnRH mRNA levels increased significantly and positively correlated with accelerated testicular growth. Triptorelin, an agonist of GnRH, at a dose that had no effect on testicular growth during “proportional” period, increased testis weights during the period of accelerated growth. The insensitivity of testicular growth to GnRH during “proportional” period was supported by inability of a 2.5-fold siRNA knockdown of GnRH expression in the hypothalamus of the 7-day-old animals to produce any effect on their testis weights. GnRH receptor blockade with cetrorelix was also without effect on testis weights during “proportional” period but the same doses of this GnRH antagonist significantly inhibited “accelerated” testicular growth. GnRH receptor mRNA levels in the pituitary as well as plasma LH concentrations were higher during “accelerated” period of testicular growth than during “proportional” period. In general, our data defined two distinct periods in rat testicular development that are primarily characterized by different responses to GnRH signaling. PMID:24695464

Evaluation of in vitro spermatogenesis system effectiveness to study genes behavior: monitoring the expression of the testis specific 10 (Tsga10) gene as a model.

PubMed

Miryounesi, Mohammad; Nayernia, Karim; Mobasheri, Maryam Beigom; Dianatpour, Mahdi; Oko, Richard; Savad, Shahram; Modarressi, Mohammad Hossein

2014-10-01

In vitro generation of germ cells introduces a novel approach to male infertility and provides an effective system in gene tracking studies, however many aspects of this process have remained unclear. We aimed to promote mouse embryonic stem cells (mESC) differentiation into germ cells and evaluate its effectiveness with tracking the expression of the Tsga10 during this process. mESCs were differentiated into germ cells in the presence of Retinoic Acid. Based on developmental schedule of the postnatal testis, samples were taken on the 7th, 12th, and 25th days of the culture and were subjected to expression analysis of a panel of germ cell specific genes. Expression of Tsga10 in RNA and protein levels was then analyzed. Transition from mitosis to meiosis occurred between 7th and 12th days of mESC culture and post-meiotic gene expression did not occur until the 25th day of the culture. Results showed low level of Tsga10expression in undifferentiated stem cells. During transition from meiotic to post-meiotic phase, Tsga10 expression increased in 6.6 folds. This finding is in concordance with in vivo changes during transition from pre-pubertal to pubertal stage. Localization of processed and unprocessed forms of the related protein was similar to those in vivo as well. Expression pattern of Tsga10, as a gene with critical function in spermatogenesis, is similar during in vitro and in vivo germ cell generation. The results suggest that in vitro derived germ cells could be a trusted model to study genes behavior during spermatogenesis.

Disruption of a Spermatogenic Cell-Specific Mouse Enolase 4 (Eno4) Gene Causes Sperm Structural Defects and Male Infertility1

PubMed Central

Nakamura, Noriko; Dai, Qunsheng; Williams, Jason; Goulding, Eugenia H.; Willis, William D.; Brown, Paula R.; Eddy, Edward M.

2013-01-01

ABSTRACT Sperm utilize glycolysis to generate ATP required for motility, and several spermatogenic cell-specific glycolytic isozymes are associated with the fibrous sheath (FS) in the principal piece of the sperm flagellum. We used proteomics and molecular biology approaches to confirm earlier reports that a novel enolase is present in mouse sperm. We then found that a pan-enolase antibody, but not antibodies to ENO2 and ENO3, recognized a protein in the principal piece of the mouse sperm flagellum. Database analyses identified two previously uncharacterized enolase family-like candidate genes, 64306537H0Rik and Gm5506. Northern analysis indicated that 64306537H0Rik (renamed Eno4) was transcribed in testes of mice by Postnatal Day 12. To determine the role of ENO4, we generated mice using embryonic stem cells in which an Eno4 allele was disrupted by a gene trap containing a beta galactosidase (beta-gal) reporter (Eno4+/Gt). Expression of beta-gal occurred in the testis, and male mice homozygous for the gene trap allele (Eno4Gt/Gt) were infertile. Epididymal sperm numbers were 2-fold lower and sperm motility was reduced substantially in Eno4Gt/Gt mice compared to wild-type mice. Sperm from Eno4Gt/Gt mice had a coiled flagellum and a disorganized FS. The Gm5506 gene encodes a protein identical to ENO1 and also is transcribed at a low level in testis. We conclude that ENO4 is required for normal assembly of the FS and provides most of the enolase activity in sperm and that Eno1 and/or Gm5506 may encode a minor portion of the enolase activity in sperm. PMID:23446454

Detection of quantitative trait loci causing abnormal spermatogenesis and reduced testis weight in the small testis (Smt) mutant mouse.

PubMed

Bolor, Hasbaira; Wakasugi, Noboru; Zhao, Wei Dong; Ishikawa, Akira

2006-04-01

The small testis (Smt) mutant mouse is characterized by a small testis of one third to one half the size of a normal testis, and its spermatogenesis is mostly arrested at early stages of meiosis, although a small number of spermatocytes at the late prophase of meiosis and a few spermatids can sometimes be seen. We performed quantitative trait locus (QTL) analysis of these spermatogenic traits and testis weight using 221 F2 males obtained from a cross between Smt and MOM (Mus musculus molossinus) mice. At the genome-wide 5% level, we detected two QTLs affecting meiosis on chromosomes 4 and 13, and two QTLs for paired testis weight as a percentage of body weight on chromosomes 4 and X. In addition, we found several QTLs for degenerated germ cells and multinuclear giant cells on chromosomes 4, 7 and 13. Interestingly, for cell degeneration, the QTL on chromosome 13 interacted epistatically with the QTL on chromosome 4. These results reveal polygenic participation in the abnormal spermatogenesis and small testis size in the Smt mutant.

The relationship between the testis and tunica vaginalis changes with age.

PubMed

Lopez-Marambio, Francisco A; Hutson, John M

2015-12-01

Anatomy of the testis and tunica vaginalis (TV) is taught to pediatric surgeons from adult postmortem material. Textbooks describe the testis as 'behind' the TV, but at pediatric orchidopexy it appears to be inside the TV. We aimed to study whether testis and TV anatomy changes with age. After ethical approval, postmortem photographs and measurements of testis length, width, and mesenteric attachment length (mm) in 37 adults (22-92years), one infant (4/12), and one fetus (19/52) were compared with intraoperative orchidopexies (x6) after opening TV (n=4; 7/12-14years). Testis length, area and perimeter and ratios for mesentery attachment were plotted against age. The fetal and pediatric testes were intraperitoneal with a mesentery (mesorchium), but after 50years secondary adhesions between TV and testis obliterated the mesorchium, so in advanced age the testis appeared to be behind the TV. These results show that in childhood testes were 'intraperitoneal', but after 50years of age the TV progressively shrinks and adheres to the testis, making it appear to be behind the TV. This difference between anatomical texts and childhood anatomy suggests that pediatric surgery may need anatomy texts that specifically highlight age differences. Copyright © 2015 Elsevier Inc. All rights reserved.

A time-course study of long term over-expression of ARR19 in mice

PubMed Central

Qamar, Imteyaz; Ahmad, Mohammad Faiz; Narayanasamy, Arul

2015-01-01

A leucine-rich protein, ARR19 (androgen receptor corepressor-19 kDa), is highly expressed in male reproductive organs and moderately in others. Previously, we have reported that ARR19 is differentially expressed in adult Leydig cells during the testis development and inhibits steroidogenesis by reducing the expression of steroidogenic enzymes. Whereas in prostate, ARR19 represses the transcriptional activity of AR (androgen receptor), it is important for male sexual differentiation and maturation in prostate and epididymis, through the recruitment of HDAC4. In this study we show that long term adenovirus mediated overexpression of ARR19 in mice testis has the potential of inhibiting the differentiation of testicular and prostatic cells by reducing the size of testis and prostate but has no effect on the growth of seminal vesicles. Further, it reduces the level of progesterone and testosterone by reducing the steroidogenic enzymes such as 3HSD, P450c17 and StAR. This is the first study reporting a time-course analysis of the implications of long term overexpression of ARR19 in mice testis and its effect on other organs such as prostate and seminal vesicles. Taken together, these results suggest that ARR19 may play an important role in the differentiation of male reproductive organs such as testis and prostate. PMID:26260329

Histological observation of germ cell development and discovery of spermatophores in ovoviviparous black rockfish ( Sebastes schlegeli Hilgendorf) in reproductive season

NASA Astrophysics Data System (ADS)

Feng, Junrong; Liu, Liming; Jiang, Haibin; Wang, Maojian; Du, Rongbin

2014-10-01

Black rockfish ( Sebastes schlegeli) is an important species for culture; however, its reproductive characteristics have not been fully documented. In this study, we investigated the morphology and developmental process of germ cells in this ovoviviparous rockfish in reproductive season (October 2011-November 2012) with histological methods. We found that the gonad of mature fish showed notable seasonal changes in developmental characteristics and morphological structure. The sperm cells matured during a period lasting from October to December, significantly earlier than the oocytes did. A large number of spermatozoa and other cells occurred in testis at different developmental stages. Vitellogenesis in oocytes began in October, and gestation appeared in April next year. Spermatophores were discovered for the first time in Sebastes, which assembled in testis, main sperm duct, oviduct and genital tract, as well as ovarian cavity in October and April. These organs may serve either as production or hiding places for spermatophores and spermatozoa which were stored and transported in form of spermatophores. Testicular degeneration started from the distal part of testis in April, with spermatophores assembled in degenerating testis and waiting for transportation. The copulation probably lasted for a long period, during which the spermatozoa were discharged in batches as spermatophores. These spermatophores were coated with sticky materials secreted from the interstitial areas of testis and the main sperm duct, then transported into ovary.

Neonatal hypothyroidism affects testicular glucose homeostasis through increased oxidative stress in prepubertal mice: effects on GLUT3, GLUT8 and Cx43.

PubMed

Sarkar, D; Singh, S K

2017-07-01

Thyroid hormones (THs) play an important role in maintaining the link between metabolism and reproduction and the altered THs status is associated with induction of oxidative stress in various organs like brain, heart, liver and testis. Further, reactive oxygen species play a pivotal role in regulation of glucose homeostasis in several organs, and glucose utilization by Leydig cells is essential for testosterone biosynthesis and thus is largely dependent on glucose transporter 8 (GLUT8). Glucose uptake by Sertoli cells is mediated through glucose transporter 3 (GLUT3) under the influence of THs to meet energy requirement of developing germ cells. THs also modulate level of gap junctional protein such as connexin 43 (Cx43), a potential regulator of cell proliferation and apoptosis in the seminiferous epithelium. Although the role of transient neonatal hypothyroidism in adult testis in terms of testosterone production is well documented, the effect of THs deficiency in early developmental period and its role in testicular glucose homeostasis and oxidative stress with reference to Cx43 in immature mice remain unknown. Therefore, the present study was conducted to evaluate the effect of neonatal hypothyroidism on testicular glucose homeostasis and oxidative stress at postnatal days (PND) 21 and 28 in relation to GLUT3, GLUT8 and Cx43. Hypothyroidism induced by 6-propyl-2-thiouracil (PTU) markedly decreased testicular glucose level with considerable reduction in expression level of GLUT3 and GLUT8. Likewise, lactate dehydrogenase (LDH) activity and intratesticular concentration of lactate were also decreased in hypothyroid mice. There was also a rise in germ cell apoptosis with increased expression of caspase-3 in PTU-treated mice. Further, neonatal hypothyroidism affected germ cell proliferation with decreased expression of proliferating cell nuclear antigen (PCNA) and Cx43. In conclusion, our results suggest that neonatal hypothyroidism alters testicular glucose homeostasis via increased oxidative stress in prepubertal mice, thereby affecting germ cell survival and proliferation. © 2017 American Society of Andrology and European Academy of Andrology.

Sex Reversal in C57BL/6J XY Mice Caused by Increased Expression of Ovarian Genes and Insufficient Activation of the Testis Determining Pathway

PubMed Central

Correa, Stephanie M.; Washburn, Linda L.; Kahlon, Ravi S.; Musson, Michelle C.; Bouma, Gerrit J.; Eicher, Eva M.; Albrecht, Kenneth H.

2012-01-01

Sex reversal can occur in XY humans with only a single functional WT1 or SF1 allele or a duplication of the chromosome region containing WNT4. In contrast, XY mice with only a single functional Wt1, Sf1, or Wnt4 allele, or mice that over-express Wnt4 from a transgene, reportedly are not sex-reversed. Because genetic background plays a critical role in testis differentiation, particularly in C57BL/6J (B6) mice, we tested the hypothesis that Wt1, Sf1, and Wnt4 are dosage sensitive in B6 XY mice. We found that reduced Wt1 or Sf1 dosage in B6 XYB6 mice impaired testis differentiation, but no ovarian tissue developed. If, however, a YAKR chromosome replaced the YB6 chromosome, these otherwise genetically identical B6 XY mice developed ovarian tissue. In contrast, reduced Wnt4 dosage increased the amount of testicular tissue present in Sf1+/− B6 XYAKR, Wt1+/− B6 XYAKR, B6 XYPOS, and B6 XYAKR fetuses. We propose that Wt1B6 and Sf1B6 are hypomorphic alleles of testis-determining pathway genes and that Wnt4B6 is a hypermorphic allele of an ovary-determining pathway gene. The latter hypothesis is supported by the finding that expression of Wnt4 and four other genes in the ovary-determining pathway are elevated in normal B6 XX E12.5 ovaries. We propose that B6 mice are sensitive to XY sex reversal, at least in part, because they carry Wt1B6 and/or Sf1B6 alleles that compromise testis differentiation and a Wnt4B6 allele that promotes ovary differentiation and thereby antagonizes testis differentiation. Addition of a “weak” Sry allele, such as the one on the YPOS chromosome, to the sensitized B6 background results in inappropriate development of ovarian tissue. We conclude that Wt1, Sf1, and Wnt4 are dosage-sensitive in mice, this dosage-sensitivity is genetic background-dependant, and the mouse strains described here are good models for the investigation of human dosage-sensitive XY sex reversal. PMID:22496664

Effect of Letrozole, a selective aromatase inhibitor, on testicular activities in adult mice: Both in vivo and in vitro study.

PubMed

Verma, Rachna; Krishna, Amitabh

2017-01-15

The aim of present study was to evaluate the significance of estradiol (E2) in testicular activities and to find out the mechanism by which E2 regulates spermatogenesis in mice. To achieve this, both in vivo and in vitro effect of Letrozole on testis of adult mice was investigated. Letrozole-induced changes in testicular histology, cell proliferation (proliferating cell nuclear antigen; PCNA), cell survival (B cell lymphoma factor-2; Bcl2), apoptotic (cysteine-aspartic proteases; caspase-3), steroidogenic (side chain cleavage; SCC, 3β-hydroxy steroid dehydrogenase enzyme; 3β HSD, steroidogenic acute regulatory protein; StAR, aromatase and luteinizing hormone receptor; LH-R) markers, glucose level, and rate of expression of glucose transporter (GLUT) 8 and insulin receptor (IR) proteins in the testis along with changes in serum E2 and testosterone (T) levels were evaluated. Letrozole acts on testis and caused significant decrease in E2 synthesis, but increase in testosterone level and showed regressive changes in the spermatogenesis. Letrozole-induced changes in various testicular markers were compared with the changes in serum E2 level. The correlation study showed that decreased circulating E2 level may be responsible for decreased insulin receptor (IR) level in the testis. The decreased effects of insulin inhibited the glucose transport in the testis by suppressing GLUT8. The decreased level of testicular glucose may produce less lactate as energy support to developing germ cells consequently resulting in decreased cell proliferation and cell survival, but increased apoptosis. Thus, Letrozole suppresses spermatogenesis by reducing insulin sensitivity and glucose transport in the testis, but significantly increased testosterone level by promoting gonadotrophin release by decreased E2. Copyright © 2016 Elsevier Inc. All rights reserved.

Juvenile granulosa cell tumor of the testis: a bilateral and synchronous case. Should testis-sparing surgery be mandatory?

PubMed

Cosentino, Marco; Algaba, Ferran; Saldaña, Lily; Bujons, Ana; Caffaratti, Jorge; Garat, Jose M; Villavicencio, Humberto

2014-09-01

Granulosa cell tumor of the testis is an infrequent stromal cell tumor that can be distinguished into adult and juvenile, the latter being more common. Juvenile granulosa cell tumor of the testis is a rare pathologic finding, accounting for 1.2%-3.9% of prepubertal testicular tumors. It is considered as a benign stromal sex cord tumor and is usually unilateral. Although radical surgery was previously considered the treatment of choice, testis-sparing surgery is now recommended in all cases where applicable. We report a bilateral synchronous juvenile granulosa cell tumor in a 6-month-old child treated with testis-sparing surgery and provide a review of the literature. Copyright © 2014 Elsevier Inc. All rights reserved.

Regulatory complexity revealed by integrated cytological and RNA-seq analyses of meiotic substages in mouse spermatocytes.

PubMed

Ball, Robyn L; Fujiwara, Yasuhiro; Sun, Fengyun; Hu, Jianjun; Hibbs, Matthew A; Handel, Mary Ann; Carter, Gregory W

2016-08-12

The continuous and non-synchronous nature of postnatal male germ-cell development has impeded stage-specific resolution of molecular events of mammalian meiotic prophase in the testis. Here the juvenile onset of spermatogenesis in mice is analyzed by combining cytological and transcriptomic data in a novel computational analysis that allows decomposition of the transcriptional programs of spermatogonia and meiotic prophase substages. Germ cells from testes of individual mice were obtained at two-day intervals from 8 to 18 days post-partum (dpp), prepared as surface-spread chromatin and immunolabeled for meiotic stage-specific protein markers (STRA8, SYCP3, phosphorylated H2AFX, and HISTH1T). Eight stages were discriminated cytologically by combinatorial antibody labeling, and RNA-seq was performed on the same samples. Independent principal component analyses of cytological and transcriptomic data yielded similar patterns for both data types, providing strong evidence for substage-specific gene expression signatures. A novel permutation-based maximum covariance analysis (PMCA) was developed to map co-expressed transcripts to one or more of the eight meiotic prophase substages, thereby linking distinct molecular programs to cytologically defined cell states. Expression of meiosis-specific genes is not substage-limited, suggesting regulation of substage transitions at other levels. This integrated analysis provides a general method for resolving complex cell populations. Here it revealed not only features of meiotic substage-specific gene expression, but also a network of substage-specific transcription factors and relationships to potential target genes.

Adjudin disrupts spermatogenesis by targeting drug transporters

PubMed Central

Qian, Xiaojing; Cheng, Yan-ho; Jenardhanan, Pranitha; Mruk, Dolores D.; Mathur, Premendu P.; Xia, Weiliang; Silvestrini, Bruno; Cheng, C. Yan

2013-01-01

For non-hormonal male contraceptives that exert their effects in the testis locally instead of via the hypothalamic-pituitary-testicular axis, such as adjudin that disrupts germ cell adhesion, a major hurdle in their development is to improve their bioavailability so that they can be efficiently delivered to the seminiferous epithelium by transporting across the blood-testis barrier (BTB). If this can be done, it would widen the gap between their efficacy and general toxicity. However, Sertoli cells that constitute the BTB, peritubular myoid cells in the tunica propria, germ cells at different stages of their development, as well as endothelial cells that constitute the microvessels in the interstitium are all equipped with multiple drug transporters, most notably efflux drug transporters, such as P-glycoprotein, multidrug resistance-related protein 1 (MRP1) and breast cancer resistance protein (BCRP) that can actively prevent drugs (e.g., adjudin) from entering the seminiferous epithelium to exert their effects. Recent studies have shown that BCRP is highly expressed by endothelial cells of the microvessels in the interstitium in the testis and also peritubular myoid cells in tunica propria even though it is absent from Sertoli cells at the site of the BTB. Furthermore, BCRP is also expressed spatiotemporally by Sertoli cells and step 19 spermatids in the rat testis and stage-specifically, limiting to stage VII‒VIII of the epithelial cycle, and restricted to the apical ectoplasmic specialization [apical ES, a testis-specific F-actin-rich adherens junction (AJ)]. Interestingly, adjudin was recently shown to be capable of downregulating BCRP expression at the apical ES. In this Opinion article, we critically discuss the latest findings on BCRP; in particular, we provide some findings utilizing molecular modeling to define the interacting domains of BCRP with adjudin. Based on this information, it is hoped that the next generation of adjudin analogs to be synthesized can improve their efficacy in downregulating BCRP and perhaps other drug efflux transporters in the testis to improve their efficacy to traverse the BTB by modifying their interacting domains. PMID:23885306

Bilateral cryptorchidism in a dog with persistent cranial testis suspensory ligaments and inverted gubernacula: report of a case with implications for understanding normal and aberrant testis descent.

PubMed Central

Kersten, W; Molenaar, G J; Emmen, J M; van der Schoot, P

1996-01-01

The genital system of a dog with bilateral intra-abdominal testes is described. External virilisation was normal except for an empty scrotum. Internally there was a prostate of normal macroscopic and histological appearances and, bilaterally, a fully developed male genital tract. Testicular vasculature was normal. Cranial to each testis, there was a strong ligament lying at the free edge of the gonadal/genital mesentery and running between the cranial tip of the testis/epididymis and the area craniolateral of the ipsilateral kidney. It was impossible to push the testes into the inguinal canal because of this strong ligament. Caudal to each testis, there was an elongated whitish structure between the caudal pole of the epididymis and the area of the internal inguinal ring. On closer inspection this structure appeared to be the inverted and elongated processus vaginalis sac. There was a minor ligament at the free border of the inguinal fold of the genital mesentery between the tip of this inverted processus vaginalis and the adjacent junction of the cauda epididymidis and vas deferens. The findings suggest that persistence of the fetal cranial gonadal suspensory ligaments could have been the major aetiological factor in this case of cryptorchidism. Their persistence could have prevented caudal outgrowth of the processus vaginalis with its consequent development into an intra-abdominal papilla-like structure. Inappropriate persistence of the cranial suspensory ligaments in male rodents, pig, and cattle has been associated with insufficient exposure of their primordia to androgen during fetal life. It is uncertain whether a similar deficiency could underlie persistence of these structures in the present specimen. The findings add further weight to the hypothesis that regression of the cranial gonadal suspensory ligament in males is a key event in the process of testis descent. The human homologue of this ligament deserves more attention in the analysis and treatment of human cryptorchidism. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 PMID:8771408

The oligosaccharidic content of the glycoconjugates of the prepubertal descended and undescended testis: lectin histochemical study.

PubMed

Gheri, Gherardo; Sgambati, Eleonora; Thyrion, Giorgia D Zappoli; Vichi, Debora; Orlandini, Giovanni E

2004-01-01

The saccharidic content of the glycoconjugates has been studied in the descended the undescended testes of a 8 years old boy. For this purpose, a battery of seven HRP-conjugated lectins (SBA, DBA,PNA,WGA,UEAI, LTA and ConA) was used. D-galactose-N-acetyl-D-galactosamine and alpha-L-fucose sugar residues, which were present in the cytoplasm of the Sertoli cells of the normally positioned prepubertal testis, were not detected in the same cells of the undescended testis. The Leydig's cells of the descended testis appeared characterized by N-acetyl-D-glucosamine which was absent in the rare and atrophic Leydig's cells of the cryptorchid testis. Differences in sugar residues distribution between the descended and the undescended testis were also detected in the lamina propria of the seminiferous tubules. Peritubular myoid cells in the undescended testis only reacted with PNA, after neuraminidase digestion, thus revealing the presence of D-galactose (beta1-->3)-N-acetyl-D-galactosamine and sialic acid. In this study a complete distributional map of the sugar residues of the glycoconjugates in the descended and undescended prepubertal testis is reported.

Cold exposure inhibits hypothalamic Kiss-1 gene expression, serum leptin concentration, and delays reproductive development in male Brandt's vole ( Lasiopodomys brandtii)

NASA Astrophysics Data System (ADS)

Zhang, Qiang; Lin, Yi; Zhang, Xue-Ying; Wang, De-Hua

2015-06-01

Cold commonly affects growth and reproductive development in small mammals. Here, we test the hypothesis that low ambient temperature will affect growth and puberty onset, associated with altered hypothalamic Kiss-1 gene expression and serum leptin concentration in wild rodents. Male Brandt's voles ( Lasiopodomys brandtii) were exposed to cold (4 ± 1 °C) and warm (23 ± 1 °C) conditions from the birth and sacrificed on different developmental stages (day 26, day 40, day 60, and day 90, respectively). Brandt's voles increased the thermogenic capacity of brown adipose tissue, mobilized body fat, decreased serum leptin levels, and delayed the reproductive development especially on day 40 in the cold condition. They increased food intake to compensate for the high energy demands in the cold. The hypothalamic Kiss-1 gene expression on day 26 was decreased, associated with lower wet testis mass and testis testosterone concentration on day 40, in the cold-exposed voles compared to that in the warm. Serum leptin was positively correlated with body fat, testis mass, and testosterone concentration. These data suggested that cold exposure inhibited hypothalamic Kiss-1 gene expression during the early stage of development, decreased serum leptin concentration, and delayed reproductive development in male Brandt's voles.

Perinatal methadone exposure produces physical dependence and altered behavioral development in the rat.

PubMed

Kunko, P M; Smith, J A; Wallace, M J; Maher, J R; Saady, J J; Robinson, S E

1996-06-01

Pregnant rats were implanted with osmotic minipumps containing either methadone hydrochloride (9 mg/kg/day) or sterile water. Their offspring were cross-fostered so that the following prenatal/postnatal exposure groups were obtained: water/water, methadone/water, water/methadone and methadone/methadone. Methadone slightly reduced litter size, particularly the number of male offspring, and reduced litter birth weight. The induction or maintenance of physical dependence in the postnatal methadone exposure groups was confirmed by an experiment in which PD19 pups were challenged with naloxone (1 mg/kg, s.c.). Methadone concentrations were assayed in pup brain on postnatal days 4, 10 and 22. Postnatal exposure to methadone via maternal milk produced measurable levels of methadone which decreased with age. Neuromuscular and physical development were assessed. Exposure to methadone accelerated acquisition of the righting reflex, but tended to delay the acquisition of the negative geotaxic response. Postnatal exposure to methadone was associated with decreased somatic growth as measured through postnatal day 21. The older pups (postnatal day 21) exposed to methadone exhibited variations in activity levels: pups exposed to methadone both prenatally and postnatally exhibited the least amount of spontaneous locomotor activity and pups exposed only postnatally exhibited the most activity. Therefore, it is possible to induce and/or maintain physical dependence via lactation in rat pups fostered to methadone-treated dams. Perinatal exposure to methadone by this route produces several subtle disruptions of pup development in the absence of gross maternal or fetal toxicity.

Synapsin-dependent development of glutamatergic synaptic vesicles and presynaptic plasticity in postnatal mouse brain.

PubMed

Bogen, I L; Jensen, V; Hvalby, O; Walaas, S I

2009-01-12

Inactivation of the genes encoding the neuronal, synaptic vesicle-associated proteins synapsin I and II leads to severe reductions in the number of synaptic vesicles in the CNS. We here define the postnatal developmental period during which the synapsin I and/or II proteins modulate synaptic vesicle number and function in excitatory glutamatergic synapses in mouse brain. In wild-type mice, brain levels of both synapsin I and synapsin IIb showed developmental increases during synaptogenesis from postnatal days 5-20, while synapsin IIa showed a protracted increase during postnatal days 20-30. The vesicular glutamate transporters (VGLUT) 1 and VGLUT2 showed synapsin-independent development during postnatal days 5-10, following which significant reductions were seen when synapsin-deficient brains were compared with wild-type brains following postnatal day 20. A similar, synapsin-dependent developmental profile of vesicular glutamate uptake occurred during the same age periods. Physiological analysis of the development of excitatory glutamatergic synapses, performed in the CA1 stratum radiatum of the hippocampus from the two genotypes, showed that both the synapsin-dependent part of the frequency facilitation and the synapsin-dependent delayed response enhancement were restricted to the period after postnatal day 10. Our data demonstrate that while both synaptic vesicle number and presynaptic short-term plasticity are essentially independent of synapsin I and II prior to postnatal day 10, maturation and function of excitatory synapses appear to be strongly dependent on synapsin I and II from postnatal day 20.

Painful ovulation in a 46,XX SRY −ve adult male with SOX9 duplication

PubMed Central

Kean, Anne-Maree; Ewans, Lisa; Ohnesorg, Thomas; Ayers, Katie L; Watson, Geoff; Vasilaras, Arthur; Sinclair, Andrew H; Twigg, Stephen M; Handelsman, David J

2017-01-01

46,XX disorders of sexual development (DSDs) occur rarely and result from disruptions of the genetic pathways underlying gonadal development and differentiation. We present a case of a young phenotypic male with 46,XX SRY-negative ovotesticular DSD resulting from a duplication upstream of SOX9 presenting with a painful testicular mass resulting from ovulation into an ovotestis. We present a literature review of ovulation in phenotypic men and discuss the role of SRY and SOX9 in testicular development, including the role of SOX9 upstream enhancer region duplication in female-to-male sex reversal. Learning points: In mammals, the early gonad is bipotent and can differentiate into either a testis or an ovary. SRY is the master switch in testis determination, responsible for differentiation of the bipotent gonad into testis. SRY activates SOX9 gene, SOX9 as a transcription factor is the second major gene involved in male sex determination. SOX9 drives the proliferation of Sertoli cells and activates AMH/MIS repressing the ovary. SOX9 is sufficient to induce testis formation and can substitute for SRY function. Assessing karyotype and then determination of the presence or absence of Mullerian structures are necessary serial investigations in any case of DSD, except for mixed gonadal dysgenesis identified by karyotype alone. Treatment is ideal in a multidisciplinary setting with considerations to genetic (implications to family and reproductive recurrence risk), psychological aspects (sensitive individualized counseling including patient gender identity and preference), endocrinological (hormone replacement), surgical (cosmetic, prophylactic gonadectomy) fertility preservation and reproductive opportunities and metabolic health (cardiovascular and bones). PMID:28620497

Painful ovulation in a 46,XX SRY -ve adult male with SOX9 duplication.

PubMed

Shankara Narayana, Nandini; Kean, Anne-Maree; Ewans, Lisa; Ohnesorg, Thomas; Ayers, Katie L; Watson, Geoff; Vasilaras, Arthur; Sinclair, Andrew H; Twigg, Stephen M; Handelsman, David J

2017-01-01

46,XX disorders of sexual development (DSDs) occur rarely and result from disruptions of the genetic pathways underlying gonadal development and differentiation. We present a case of a young phenotypic male with 46,XX SRY-negative ovotesticular DSD resulting from a duplication upstream of SOX9 presenting with a painful testicular mass resulting from ovulation into an ovotestis. We present a literature review of ovulation in phenotypic men and discuss the role of SRY and SOX9 in testicular development, including the role of SOX9 upstream enhancer region duplication in female-to-male sex reversal. In mammals, the early gonad is bipotent and can differentiate into either a testis or an ovary. SRY is the master switch in testis determination, responsible for differentiation of the bipotent gonad into testis.SRY activates SOX9 gene, SOX9 as a transcription factor is the second major gene involved in male sex determination. SOX9 drives the proliferation of Sertoli cells and activates AMH/MIS repressing the ovary. SOX9 is sufficient to induce testis formation and can substitute for SRY function.Assessing karyotype and then determination of the presence or absence of Mullerian structures are necessary serial investigations in any case of DSD, except for mixed gonadal dysgenesis identified by karyotype alone.Treatment is ideal in a multidisciplinary setting with considerations to genetic (implications to family and reproductive recurrence risk), psychological aspects (sensitive individualized counseling including patient gender identity and preference), endocrinological (hormone replacement), surgical (cosmetic, prophylactic gonadectomy) fertility preservation and reproductive opportunities and metabolic health (cardiovascular and bones).

A Novel igf3 Gene in Common Carp (Cyprinus carpio): Evidence for Its Role in Regulating Gonadal Development.

PubMed

Song, Feibiao; Wang, Lanmei; Zhu, Wenbin; Fu, Jianjun; Dong, Juanjuan; Dong, Zaijie

2016-01-01

Since the insulin-like growth factor 3 (igf3) gene was recently discovered in fish ovary, its function in the gonads has received much attention. In this study, we isolated two igf3 subtypes from common carp (Cyprinus carpio), which comprised full-length cDNA of 707 and 1153 nucleotides encoding 205 and 198 amino acids (aa), respectively. The Igf3 aa sequence had the highest gene homology of 72% with the corresponding sequence in zebrafish (Danio rerio). Phylogenetic tree construction revealed that the C. carpio igf3 gene was first clustered with D. rerio and then with other teleost species. Igf3 mRNA was widely expressed, with expression being highest in the gonads and blood. In the gonad development stage, igf3a mRNA expression was highest in the maturity and recession stage of the ovary, and decline phase of the testis, while igf3b was highest in the recession and fully mature periods of the ovaries and testes, respectively. Western blotting of testis protein samples showed two bands of approximately 21 kDa and 34 kDa corresponding to the calculated molecular mass of the two Igf3 subtypes; no signal was detected in the ovary. The Igf3 protein was localized in the ovary granulosa cells and testis spermatogonium and spermatids. 17β-Ethinylestradiol treatment increased both ovary and testis igf3 mRNA expression. These findings suggest that Igf3 may play an important role in C. carpio gonadal development.

A Novel igf3 Gene in Common Carp (Cyprinus carpio): Evidence for Its Role in Regulating Gonadal Development

PubMed Central

Zhu, Wenbin; Fu, Jianjun; Dong, Juanjuan; Dong, Zaijie

2016-01-01

Since the insulin-like growth factor 3 (igf3) gene was recently discovered in fish ovary, its function in the gonads has received much attention. In this study, we isolated two igf3 subtypes from common carp (Cyprinus carpio), which comprised full-length cDNA of 707 and 1153 nucleotides encoding 205 and 198 amino acids (aa), respectively. The Igf3 aa sequence had the highest gene homology of 72% with the corresponding sequence in zebrafish (Danio rerio). Phylogenetic tree construction revealed that the C. carpio igf3 gene was first clustered with D. rerio and then with other teleost species. Igf3 mRNA was widely expressed, with expression being highest in the gonads and blood. In the gonad development stage, igf3a mRNA expression was highest in the maturity and recession stage of the ovary, and decline phase of the testis, while igf3b was highest in the recession and fully mature periods of the ovaries and testes, respectively. Western blotting of testis protein samples showed two bands of approximately 21 kDa and 34 kDa corresponding to the calculated molecular mass of the two Igf3 subtypes; no signal was detected in the ovary. The Igf3 protein was localized in the ovary granulosa cells and testis spermatogonium and spermatids. 17β-Ethinylestradiol treatment increased both ovary and testis igf3 mRNA expression. These findings suggest that Igf3 may play an important role in C. carpio gonadal development. PMID:28002497

Dimorphic expression of sex-related genes in different gonadal development stages of sterlet, Acipenser ruthenus, a primitive fish species.

PubMed

Wang, Wei; Zhu, Hua; Dong, Ying; Tian, ZhaoHui; Dong, Tian; Hu, HongXia; Niu, CuiJuan

2017-12-01

Molecular mechanism of sex determination and differentiation of sturgeon, a primitive fish species, is extraordinarily important due to the valuable caviar; however, it is still poorly known. The present work aimed to identify the major genes involved in regulating gonadal development of sterlet, a small species of sturgeon, from 13 candidate genes which have been shown to relate to gonadal differentiation and development in other teleost fish. The sex and gonadal development of sterlets were determined by histological observation and levels of sex steroids testosterone (T), 11-ketotestosterone (11-KT), and 17β-estradiol (E2) in serum. Sexually dimorphic gene expressions were investigated. The results revealed that gonadal development were asynchronous in 2-year-old male and female sterlets with the testes in early or mid-spermatogenesis and the ovaries in chromatin nucleolus stage or perinucleolus stage, respectively. The levels of T and E2 were not significantly different between sexes or different gonadal development stages while 11-KT had the higher level in mid-spermatogenesis testis stage. In all the investigated gonadal development stages, gene dmrt1 and hsd11b2 were expressed higher in male whereas foxl2 and cyp19a1 were expressed higher in female. Thus, these genes provided the promising markers for sex identification of sterlet. It was unexpected that dkk1 and dax1 had significantly higher expression in ovarian perinucleolus stage than in ovarian chromatin nucleolus stage and in the testis, suggesting that these two genes had more correlation with ovarian development than with the testis, contrary to the previous reports in other vertebrates. Testicular development-related genes (gsdf and amh) and estrogen receptor genes (era and erb) differentially expressed at different testis or ovary development stages, but their expressions were not absolutely significantly different in male and female, depending on the gonadal development stage. Expression of androgen receptor gene ar or rspo, which was supposed to be related to ovarian development, presented no difference between gonadal development stages investigated in this study whenever in male or female.

Postnatal penile growth concurrent with mini-puberty predicts later sex-typed play behavior: Evidence for neurobehavioral effects of the postnatal androgen surge in typically developing boys.

PubMed

Pasterski, Vickie; Acerini, Carlo L; Dunger, David B; Ong, Ken K; Hughes, Ieuan A; Thankamony, Ajay; Hines, Melissa

2015-03-01

The masculinizing effects of prenatal androgens on human neurobehavioral development are well established. Also, the early postnatal surge of androgens in male infants, or mini-puberty, has been well documented and is known to influence physiological development, including penile growth. However, neurobehavioral effects of androgen exposure during mini-puberty are largely unknown. The main aim of the current study was to evaluate possible neurobehavioral consequences of mini-puberty by relating penile growth in the early postnatal period to subsequent behavior. Using multiple linear regression, we demonstrated that penile growth between birth and three months postnatal, concurrent with mini-puberty, significantly predicted increased masculine/decreased feminine behavior assessed using the Pre-school Activities Inventory (PSAI) in 81 healthy boys at 3 to 4years of age. When we controlled for other potential influences on masculine/feminine behavior and/or penile growth, including variance in androgen exposure prenatally and body growth postnally, the predictive value of penile growth in the early postnatal period persisted. More specifically, prenatal androgen exposure, reflected in the measurement of anogenital distance (AGD), and early postnatal androgen exposure, reflected in penile growth from birth to 3months, were significant predictors of increased masculine/decreased feminine behavior, with each accounting for unique variance. Our findings suggest that independent associations of PSAI with AGD at birth and with penile growth during mini-puberty reflect prenatal and early postnatal androgen exposures respectively. Thus, we provide a novel and readily available approach for assessing effects of early androgen exposures, as well as novel evidence that early postnatal aes human neurobehavioral development. Copyright © 2015. Published by Elsevier Inc.

Global transcriptome analysis of the C57BL/6J mouse testis by SAGE: evidence for nonrandom gene order.

PubMed

Divina, Petr; Vlcek, Cestmír; Strnad, Petr; Paces, Václav; Forejt, Jirí

2005-03-05

We generated the gene expression profile of the total testis from the adult C57BL/6J male mice using serial analysis of gene expression (SAGE). Two high-quality SAGE libraries containing a total of 76 854 tags were constructed. An extensive bioinformatic analysis and comparison of SAGE transcriptomes of the total testis, testicular somatic cells and other mouse tissues was performed and the theory of male-biased gene accumulation on the X chromosome was tested. We sorted out 829 genes predominantly expressed from the germinal part and 944 genes from the somatic part of the testis. The genes preferentially and specifically expressed in total testis and testicular somatic cells were identified by comparing the testis SAGE transcriptomes to the available transcriptomes of seven non-testis tissues. We uncovered chromosomal clusters of adjacent genes with preferential expression in total testis and testicular somatic cells by a genome-wide search and found that the clusters encompassed a significantly higher number of genes than expected by chance. We observed a significant 3.2-fold enrichment of the proportion of X-linked genes specific for testicular somatic cells, while the proportions of X-linked genes specific for total testis and for other tissues were comparable. In contrast to the tissue-specific genes, an under-representation of X-linked genes in the total testis transcriptome but not in the transcriptomes of testicular somatic cells and other tissues was detected. Our results provide new evidence in favor of the theory of male-biased genes accumulation on the X chromosome in testicular somatic cells and indicate the opposite action of the meiotic X-inactivation in testicular germ cells.

Global transcriptome analysis of the C57BL/6J mouse testis by SAGE: evidence for nonrandom gene order

PubMed Central

Divina, Petr; Vlček, Čestmír; Strnad, Petr; Pačes, Václav; Forejt, Jiří

2005-01-01

Background We generated the gene expression profile of the total testis from the adult C57BL/6J male mice using serial analysis of gene expression (SAGE). Two high-quality SAGE libraries containing a total of 76 854 tags were constructed. An extensive bioinformatic analysis and comparison of SAGE transcriptomes of the total testis, testicular somatic cells and other mouse tissues was performed and the theory of male-biased gene accumulation on the X chromosome was tested. Results We sorted out 829 genes predominantly expressed from the germinal part and 944 genes from the somatic part of the testis. The genes preferentially and specifically expressed in total testis and testicular somatic cells were identified by comparing the testis SAGE transcriptomes to the available transcriptomes of seven non-testis tissues. We uncovered chromosomal clusters of adjacent genes with preferential expression in total testis and testicular somatic cells by a genome-wide search and found that the clusters encompassed a significantly higher number of genes than expected by chance. We observed a significant 3.2-fold enrichment of the proportion of X-linked genes specific for testicular somatic cells, while the proportions of X-linked genes specific for total testis and for other tissues were comparable. In contrast to the tissue-specific genes, an under-representation of X-linked genes in the total testis transcriptome but not in the transcriptomes of testicular somatic cells and other tissues was detected. Conclusion Our results provide new evidence in favor of the theory of male-biased genes accumulation on the X chromosome in testicular somatic cells and indicate the opposite action of the meiotic X-inactivation in testicular germ cells. PMID:15748293

Identification of Genes Uniquely Expressed in the Germ-Line Tissues of the Jewel Wasp Nasonia vitripennis

PubMed Central

Ferree, Patrick M.; Fang, Christopher; Mastrodimos, Mariah; Hay, Bruce A.; Amrhein, Henry; Akbari, Omar S.

2015-01-01

The jewel wasp Nasonia vitripennis is a rising model organism for the study of haplo-diploid reproduction characteristic of hymenopteran insects, which include all wasps, bees, and ants. We performed transcriptional profiling of the ovary, the female soma, and the male soma of N. vitripennis to complement a previously existing transcriptome of the wasp testis. These data were deposited into an open-access genome browser for visualization of transcripts relative to their gene models. We used these data to identify the assemblies of genes uniquely expressed in the germ-line tissues. We found that 156 protein-coding genes are expressed exclusively in the wasp testis compared with only 22 in the ovary. Of the testis-specific genes, eight are candidates for male-specific DNA packaging proteins known as protamines. We found very similar expression patterns of centrosome associated genes in the testis and ovary, arguing that de novo centrosome formation, a key process for development of unfertilized eggs into males, likely does not rely on large-scale transcriptional differences between these tissues. In contrast, a number of meiosis-related genes show a bias toward testis-specific expression, despite the lack of true meiosis in N. vitripennis males. These patterns may reflect an unexpected complexity of male gamete production in the haploid males of this organism. Broadly, these data add to the growing number of genomic and genetic tools available in N. vitripennis for addressing important biological questions in this rising insect model organism. PMID:26464360

Do retractile testes have anatomical anomalies?

PubMed Central

Anderson, Kleber M.; Costa, Suelen F.; Sampaio, Francisco J.B.; Favorito, Luciano A.

2016-01-01

ABSTRACT Objectives: To assess the incidence of anatomical anomalies in patients with retractile testis. Materials and Methods: We studied prospectively 20 patients (28 testes) with truly retractile testis and compared them with 25 human fetuses (50 testes) with testis in scrotal position. We analyzed the relations among the testis, epididymis and patency of the processus vaginalis (PV). To analyze the relations between the testis and epididymis, we used a previous classification according to epididymis attachment to the testis and the presence of epididymis atresia. To analyze the structure of the PV, we considered two situations: obliteration of the PV and patency of the PV. We used the Chi-square test for contingency analysis of the populations under study (p <0.05). Results: The fetuses ranged in age from 26 to 35 weeks post-conception (WPC) and the 20 patients with retractile testis ranged in ages from 1 to 12 years (average of 5.8). Of the 50 fetal testes, we observed complete patency of the PV in 2 cases (4%) and epididymal anomalies (EAs) in 1 testis (2%). Of the 28 retractile testes, we observed patency of the PV in 6 cases (21.4%) and EA in 4 (14.28%). When we compared the incidence of EAs and PV patency we observed a significantly higher prevalence of these anomalies in retractile testes (p=0.0116). Conclusions: Retractile testis is not a normal variant with a significant risk of patent processus vaginalis and epididymal anomalies. PMID:27564294

Integrative testis transcriptome analysis reveals differentially expressed miRNAs and their mRNA targets during early puberty in Atlantic salmon.

PubMed

Skaftnesmo, K O; Edvardsen, R B; Furmanek, T; Crespo, D; Andersson, E; Kleppe, L; Taranger, G L; Bogerd, J; Schulz, R W; Wargelius, A

2017-10-18

Our understanding of the molecular mechanisms implementing pubertal maturation of the testis in vertebrates is incomplete. This topic is relevant in Atlantic salmon aquaculture, since precocious male puberty negatively impacts animal welfare and growth. We hypothesize that certain miRNAs modulate mRNAs relevant for the initiation of puberty. To explore which miRNAs regulate mRNAs during initiation of puberty in salmon, we performed an integrated transcriptome analysis (miRNA and mRNA-seq) of salmon testis at three stages of development: an immature, long-term quiescent stage, a prepubertal stage just before, and a pubertal stage just after the onset of single cell proliferation activity in the testis. Differentially expressed miRNAs clustered into 5 distinct expression profiles related to the immature, prepubertal and pubertal salmon testis. Potential mRNA targets of these miRNAs were predicted with miRmap and filtered for mRNAs displaying negatively correlated expression patterns. In summary, this analysis revealed miRNAs previously known to be regulated in immature vertebrate testis (miR-101, miR-137, miR-92b, miR-18a, miR-20a), but also miRNAs first reported here as regulated in the testis (miR-new289, miR-30c, miR-724, miR-26b, miR-new271, miR-217, miR-216a, miR-135a, miR-new194 and the novel predicted n268). By KEGG enrichment analysis, progesterone signaling and cell cycle pathway genes were found regulated by these differentially expressed miRNAs. During the transition into puberty we found differential expression of miRNAs previously associated (let7a/b/c), or newly associated (miR-15c, miR-2184, miR-145 and the novel predicted n7a and b) with this stage. KEGG enrichment analysis revealed that mRNAs of the Wnt, Hedgehog and Apelin signaling pathways were potential regulated targets during the transition into puberty. Likewise, several regulated miRNAs in the pubertal stage had earlier been associated (miR-20a, miR-25, miR-181a, miR-202, let7c/d/a, miR-125b, miR-222a/b, miR-190a) or have now been found connected (miR-2188, miR-144, miR-731, miR-8157 and the novel n2) to the initiation of puberty. This study has - for the first time - linked testis maturation to specific miRNAs and their inversely correlated expressed targets in Atlantic salmon. The study indicates a broad functional conservation of already known miRNAs and associated pathways involved in the transition into puberty in vertebrates. The analysis also reveals miRNAs not previously associated with testis tissue or its maturation, which calls for further functional studies in the testis.

Expression analysis of cyp11a1 during gonadal development, recrudescence and after hCG induction and sex steroid analog treatment in the catfish, Clarias batrachus.

PubMed

Rajakumar, Anbazhagan; Senthilkumaran, Balasubramanian

2014-10-01

In teleosts, the levels of steroids are critical for sexual development and hence, expression of steroidogenic enzyme genes and specific substrate availability are indispensable for gonadal steroidogenesis. Early stages of steroidogenesis specifically cholesterol to pregnenolone conversion by Cyp11a1 is crucial for estradiol and testosterone biosynthesis. Based on this, in this study, full length cDNA of cyp11a1 (2581bp) was cloned from catfish testis to investigate the importance of Cyp11a1 by analyzing the expression of cyp11a1 during gonadal development, seasonal reproductive cycle, after human chorionic gonadotropin (hCG) induction and sex steroid analog treatment. Phylogenetic analysis revealed that the Cyp11a1 is more conserved across teleosts. Tissue distribution analysis showed that the cyp11a1 expression was higher in the testis followed by the brain, head kidney, muscle and ovary compared to other tissues analyzed. High expression of cyp11a1 in the head kidney and muscle revealed that Cyp11a1 could potentially regulate the extra-gonadal and/or circulating steroid levels in teleosts. Developing and mature testes showed higher expression of cyp11a1 than the ovary of corresponding age group. Further, cyp11a1 expression was found to be higher during pre-spawning and spawning phases of testicular cycle and was upregulated by hCG, in vivo and in vitro, which indicates the possible regulation by gonadotropin. Exposure of methyltestosterone (1μg/L) and ethinylestradiol (1μg/L) for 21days during catfish testicular development showed lower cyp11a1 expression levels in the testis and brain indicating a certain feedback intervention. These results suggest possible role for Cyp11a1 in the testis development and recrudescence. Copyright © 2014 Elsevier Inc. All rights reserved.

Giant malignant fibrous histiocytoma of the testis/spermatic cord: psychologic and possible etiologic complications of unethical Nazi medical experimentation.

PubMed

Staiman, V R; O'Toole, K M; Rubin, M A; Lowe, F C

1996-12-01

This case of malignant fibrous histiocytoma of the testis/spermatic cord was found in a Holocaust survivor who was injected with an unknown substance in the left testicle while in Auschwitz concentration camp in 1943. Because malignant fibrous histiocytoma is a neoplasm rarely found in this location, with only 26 previously reported cases, a review of this entity was performed. A review of Nazi medical practices in the literature and through the Holocaust Museum research department was undertaken in an attempt to ascertain identification of the unknown substance injected into this patient; however, exact identification of the Auschwitz experiment or experimenter could not be determined. A left radical orchiectomy was performed, and subsequent histolopathologic review revealed a well-encapsulated 27 x 22 x 17-cm malignant fibrous histiocytoma. The left testis was not clearly identified due to necrosis of the tumor. This is the largest malignant fibrous histiocytoma of the spermatic cord/testis recorded in the literature to date. Based on the unusual location and size, the intratesticular injection probably contributed to the tumor development and certainly caused the patient's delay in seeking medical treatment.

PNMA family: Protein interaction network and cell signalling pathways implicated in cancer and apoptosis.

PubMed

Pang, Siew Wai; Lahiri, Chandrajit; Poh, Chit Laa; Tan, Kuan Onn

2018-05-01

Paraneoplastic Ma Family (PNMA) comprises a growing number of family members which share relatively conserved protein sequences encoded by the human genome and is localized to several human chromosomes, including the X-chromosome. Based on sequence analysis, PNMA family members share sequence homology to the Gag protein of LTR retrotransposon, and several family members with aberrant protein expressions have been reported to be closely associated with the human Paraneoplastic Disorder (PND). In addition, gene mutations of specific members of PNMA family are known to be associated with human mental retardation or 3-M syndrome consisting of restrictive post-natal growth or dwarfism, and development of skeletal abnormalities. Other than sequence homology, the physiological function of many members in this family remains unclear. However, several members of this family have been characterized, including cell signalling events mediated by these proteins that are associated with apoptosis, and cancer in different cell types. Furthermore, while certain PNMA family members show restricted gene expression in the human brain and testis, other PNMA family members exhibit broader gene expression or preferential and selective protein interaction profiles, suggesting functional divergence within the family. Functional analysis of some members of this family have identified protein domains that are required for subcellular localization, protein-protein interactions, and cell signalling events which are the focus of this review paper. Copyright © 2018 Elsevier Inc. All rights reserved.

Cadmium inhibits lysine acetylation and succinylation inducing testicular injury of mouse during development.

PubMed

Yang, Qiangzhen; Li, Peifei; Wen, Yi; Li, Sisi; Chen, Jun; Liu, Xurui; Wang, Lirui; Li, Xinhong

2018-07-01

The toxic effects of cadmium (Cd) in the reproductive system have been confirmed, and lysine acetylation and succinylation play important roles in spermatogenesis. However, little attention determined whether Cd could affect lysine acylation and how it might have an impact on the reproductive system. Therefore, with the goal of contributing to this subject, we have examined the effects of Cd on lysine acetylation and succinylation of proteins in the germ cells of male mice testes during different developmental stages. We adopted intraperitoneal injection of cadmium chloride (1.2 mg/kg body weight) in mice once every 5 days from postnatal day 5-60. The results showed that Cd could restrict GAPDH activity, ATP and cAMP levels of germ cells to inhibit lysine acetylation and succinylation in the testes, inducing reproductive injuries. Cd also restricts acetylation of histone H4K5 and H4K12, which could result in failure of spermiogenesis. Remarkably, polarized acetylation occurs in meiosis, and high-level acetylation occurs earlier than high-level succinylation during spermatogenesis. Moreover, Cd has a limited effect on body weight but reduces the weight of the testis and litter size. Our research may provide a new way to reveal the mechanisms of Cd reproductive toxicity related to lysine acetylation and succinylation. Copyright © 2018. Published by Elsevier B.V.

Wi-Fi (2.45 GHz)- and mobile phone (900 and 1800 MHz)-induced risks on oxidative stress and elements in kidney and testis of rats during pregnancy and the development of offspring.

PubMed

Özorak, Alper; Nazıroğlu, Mustafa; Çelik, Ömer; Yüksel, Murat; Özçelik, Derviş; Özkaya, Mehmet Okan; Çetin, Hasan; Kahya, Mehmet Cemal; Kose, Seyit Ali

2013-12-01

The present study was designed to determine the effects of both Wi-Fi (2.45 GHz)- and mobile phone (900 and 1800 MHz)-induced electromagnetic radiation (EMR) on oxidative stress and trace element levels in the kidney and testis of growing rats from pregnancy to 6 weeks of age. Thirty-two rats and their 96 newborn offspring were equally divided into four different groups, namely, control, 2.45 GHz, 900 MHz, and 1800 MHz groups. The 2.45 GHz, 900 MHz, and 1,800 MHz groups were exposed to EMR for 60 min/day during pregnancy and growth. During the fourth, fifth, and sixth weeks of the experiment, kidney and testis samples were taken from decapitated rats. Results from the fourth week showed that the level of lipid peroxidation in the kidney and testis and the copper, zinc, reduced glutathione (GSH), glutathione peroxidase (GSH-Px), and total antioxidant status (TAS) values in the kidney decreased in the EMR groups, while iron concentrations in the kidney as well as vitamin A and vitamin E concentrations in the testis increased in the EMR groups. Results for fifth-week samples showed that iron, vitamin A, and β-carotene concentrations in the kidney increased in the EMR groups, while the GSH and TAS levels decreased. The sixth week results showed that iron concentrations in the kidney and the extent of lipid peroxidation in the kidney and testis increased in the EMR groups, while copper, TAS, and GSH concentrations decreased. There were no statistically significant differences in kidney chromium, magnesium, and manganese concentrations among the four groups. In conclusion, Wi-Fi- and mobile phone-induced EMR caused oxidative damage by increasing the extent of lipid peroxidation and the iron level, while decreasing total antioxidant status, copper, and GSH values. Wi-Fi- and mobile phone-induced EMR may cause precocious puberty and oxidative kidney and testis injury in growing rats.

[Epidermoid cyst of the testis difficult to make a preoperative diagnosis on the echoic examination: a case report].

PubMed

Yamamoto, Keisuke; Takada, Tsuyoshi; Momohara, Chikahiro; Komori, Kazuhiko; Honda, Masahito; Fujioka, Hideki

2003-04-01

A case of epidermoid cyst of the testis is presented. The patient was a 64-year-old man who complained of a painless mass in the left scrotum. Physical examination revealed a hen-egg sized enlargement of the left scrotal contents. The ultrasonographic appearance did not show a hyperechoic partition, which is called echogenic rim, a characteristic of this tumor on the echoic examination, and was homogeneous, almost similar to that of a normal testis. Because malignant testicular tumors could not be excluded preoperatively, excisional biopsy of the left testis was performed first. Histological diagnosis was an epidermoid cyst of the testis. As the left testis was almost completely occupied by the tumor and no normal testicular tissue was recognized, we performed orchiectomy additionally. Epidermoid cyst of the testis is a rare benign tumor that accounts for about 1 percent of all testicular tumors. It clinically resembles malignant testicular tumors, and orchiectomy is often performed for treatment. About 154 cases of testicular epidermoid cyst have been reported in the Japanese literature and are reviewed briefly here.

Genetic control of postnatal human brain growth

PubMed Central

van Dyck, Laura I.; Morrow, Eric M.

2017-01-01

Purpose of review Studies investigating postnatal brain growth disorders inform the biology underlying the development of human brain circuitry. This research is becoming increasingly important for the diagnosis and treatment of childhood neurodevelopmental disorders, including autism and related disorders. Here we review recent research on typical and abnormal postnatal brain growth and examine potential biological mechanisms. Recent findings Clinically, brain growth disorders are heralded by diverging head size for a given age and sex, but are more precisely characterized by brain imaging, postmortem analysis, and animal model studies. Recent neuroimaging and molecular biological studies on postnatal brain growth disorders have broadened our view of both typical and pathological postnatal neurodevelopment. Correlating gene and protein function with brain growth trajectories uncovers postnatal biological mechanisms, including neuronal arborization, synaptogenesis and pruning, and gliogenesis and myelination. Recent investigations of childhood neurodevelopmental and neurodegenerative disorders highlight the underlying genetic programming and experience-dependent remodeling of neural circuitry. Summary In order to understand typical and abnormal postnatal brain development, clinicians and researchers should characterize brain growth trajectories in the context of neurogenetic syndromes. Understanding mechanisms and trajectories of postnatal brain growth will aid in differentiating, diagnosing, and potentially treating neurodevelopmental disorders. PMID:27898583

Early detection and treatment of postnatal depression in primary care.

PubMed

Davies, Bronwen R; Howells, Sarah; Jenkins, Meryl

2003-11-01

Postnatal depression has a relatively high incidence and gives rise to considerable morbidity. There is sound evidence supporting the use of the Edinburgh Postnatal Depression Scale as a screening tool for possible postnatal depression. This paper reports on a project developed by two health visitors and a community mental health nurse working in the United Kingdom. The aim of the project was to improve the early detection and treatment of postnatal depression in the population of the general practice to which they were attached. The health visitors screened for postnatal depression in the course of routine visits on four occasions during the first postpartum year. Women identified as likely to be suffering from postnatal depression were offered 'listening visits' as a first-line intervention, with referral on to the general practitioner and/or community mental health nurse if indicated. Data collected over 3 years showed that the project succeeded in its aim of enhancing early detection and treatment of postnatal depression. These findings replicate those of other studies. The data also showed that a substantial number of women were identified for the first time as likely to be suffering from postnatal depression at 12 months postpartum. Women screened for the first time at 12 months were at greater risk than those who had been screened earlier than this. Health visitors should screen for postnatal depression throughout the period of their contact with mothers, not solely in the immediate postnatal period. It is particularly important to screen women who, for whatever reason, were not screened when their child was younger. The knowledge and skills needed to use the Edinburgh Postnatal Depression Scale and provide first-line intervention and onward referral can be developed at practitioner level through close collaborative working.

Development of new stem cell-based technologies for carnivore reproduction research.

PubMed

Travis, A J; Kim, Y; Meyers-Wallen, V

2009-07-01

New reproductive technologies based on stem cells offer several potential benefits to carnivore species. For example, development of lines of embryonic stem cells in cats and dogs would allow for the generation of transgenic animal models, which could be used to advance both veterinary and human health. Techniques such as spermatogonial stem cell transplantation (SSCT) and testis xenografting offer new approaches to propagate genetically valuable individual males, even if they should die before producing sperm. These techniques might therefore have application to the conservation of endangered species of carnivores, as well as to biomedical research. Recently, our laboratory has successfully performed SSCT in the dog, with a recipient dog producing sperm of donor genetic origin. Testis xenografting has been used to produce sperm from pre-pubertal testis tissue from both cats and ferrets. These early steps reinforce the need not only for research on stem cell technologies, but also for additional research into complementary technologies of assisted reproduction in carnivores, so that the widest array of research and clinical benefits can be realized.

Testicular cell junction: a novel target for male contraception.

PubMed

Lee, Nikki P Y; Wong, Elissa W P; Mruk, Dolores D; Cheng, C Yan

2009-01-01

Even though various contraceptive methods are widely available, the number of unwanted pregnancies is still on the rise in developing countries, pressurizing the already resource limited nations. One of the major underlying reasons is the lack of effective, low cost, and safe contraceptives for couples. During the past decade, some studies were performed using animal models to decipher if the Sertoli-germ cell junction in the testis is a target for male fertility regulation. Some of these study models were based on the use of hormones and/or chemicals to disrupt the hypothalamic-pituitary-testicular axis (e.g., androgen-based implants or pills) and others utilized a panel of chemical entities or synthetic peptides to perturb spermatogenesis either reversibly or non-reversibly. Among them, adjudin, a potential male contraceptive, is one of the compounds exerting its action on the unique adherens junctions, known as ectoplasmic specializations, in the testis. Since the testis is equipped with inter-connected cell junctions, an initial targeting of one junction type may affect the others and these accumulative effects could lead to spermatogenic arrest. This review attempts to cover an innovative theme on how male infertility can be achieved by inducing junction instability and defects in the testis, opening a new window of research for male contraceptive development. While it will still take much time and effort of intensive investigation before a product can reach the consumable market, these findings have provided hope for better family planning involving men.

Rare presentation of a testicular angiofibroma treated with testis sparing surgery.

PubMed

Leone, Luca; Fulvi, Paola; Sbrollini, Giulia; Filosa, Alessandra; Caraceni, Enrico; Marronaro, Angelo; Galosi, Andrea B

2016-12-30

Testicular benign tumors are very rare (< 5%). Testicular Angiofibroma (AF) is one of those, however the gold standard of treatment and follow-up is still unclear. A 47 years-old man with only one functioning testis was referred to our clinic for a palpable right testicular mass and atrophic contralateral testis. Patient underwent testis-sparing surgery with inguinal approach and intraoperative frozen sections examination with diagnosis of AF. Final histology confirmed AF. Post-operative follow-up was uneventful. Clinical and ultrasonographic follow-up was negative after 8 months. We report a conservative surgery in a patient with AF of the solitary testis. AF is a benign para-testicular fibrous neoplasm that could be misinterpreted as malignant tumor and treated with orchiectomy. Testis-sparing surgery is recommended in this case with intraoperative pathological examination. The excision of the mass is enough but in front of a possible recurrence a long follow-up is advisable.

An oncological view on the blood-testis barrier.

PubMed

Bart, Joost; Groen, Harry J M; van der Graaf, Winette T A; Hollema, Harry; Hendrikse, N Harry; Vaalburg, Willem; Sleijfer, Dirk T; de Vries, Elisabeth G E

2002-06-01

The function of the blood-testis barrier is to protect germ cells from harmful influences; thus, it also impedes the delivery of chemotherapeutic drugs to the testis. The barrier has three components: first, a physicochemical barrier consisting of continuous capillaries, Sertoli cells in the tubular wall, connected together with narrow tight junctions, and a myoid-cell layer around the seminiferous tubule. Second, an efflux-pump barrier that contains P-glycoprotein in the luminal capillary endothelium and on the myoid-cell layer; and multidrug-resistance associated protein 1 located basolaterally on Sertoli cells. Third, an immunological barrier, consisting of Fas ligand on Sertoli cells. Inhibition of P-glycoprotein function offers the opportunity to increase the delivery of cytotoxic drugs to the testis. In the future, visualisation of function in the blood-testis barrier may also be helpful to identify groups of patients in whom testis conservation is safe or to select drugs that are less harmful to fertility.

Altered Expression of ZO-1 and ZO-2 in Sertoli Cells and Loss of Blood-Testis Barrier Integrity in Testicular Carcinoma In Situ1

PubMed Central

Fink, Cornelia; Weigel, Roswitha; Hembes, Tanja; Lauke-Wettwer, Heidrun; Kliesch, Sabine; Bergmann, Martin; Brehm, Ralph H

2006-01-01

Abstract Carcinoma in situ (CIS) is the noninvasive precursor of most human testicular germ cell tumors. In normal seminiferous epithelium, specialized tight junctions between Sertoli cells constitute the major component of the blood-testis barrier. Sertoli cells associated with CIS exhibit impaired maturation status, but their functional significance remains unknown. The aim was to determine whether the blood-testis barrier is morphologically and/or functionally altered. We investigated the expression and distribution pattern of the tight junction proteins zonula occludens (ZO) 1 and 2 in normal seminiferous tubules compared to tubules showing CIS. In normal tubules, ZO-1 and ZO-2 immunostaining was observed at the blood-testis barrier region of adjacent Sertoli cells. Within CIS tubules, ZO-1 and ZO-2 immunoreactivity was reduced at the blood-testis barrier region, but spread to stain the Sertoli cell cytoplasm. Western blot analysis confirmed ZO-1 and ZO-2, and their respective mRNA were shown by RT-PCR. Additionally, we assessed the functional integrity of the blood-testis barrier by lanthanum tracer study. Lanthanum permeated tight junctions in CIS tubules, indicating disruption of the blood-testis barrier. In conclusion, Sertoli cells associated with CIS show an altered distribution of ZO-1 and ZO-2 and lose their blood-testis barrier function. PMID:17217619

Estrogen alters gonadal soma-derived factor (Gsdf)/Foxl2 expression levels in the testes associated with testis-ova differentiation in adult medaka, Oryzias latipes.

PubMed

Kobayashi, Tohru; Chiba, Ayaka; Sato, Tadashi; Myosho, Taijun; Yamamoto, Jun; Okamura, Tetsuro; Onishi, Yuta; Sakaizumi, Mitsuru; Hamaguchi, Satoshi; Iguchi, Taisen; Horie, Yoshifumi

2017-10-01

Testis-ova differentiation in sexually mature male medaka (Oryzias latipes) is easily induced by estrogenic chemicals, indicating that spermatogonia persist in sexual bipotentiality, even in mature testes in medaka. By contrast, the effects of estrogen on testicular somatic cells associated with testis-ova differentiation in medaka remain unclear. In this study, we focused on the dynamics of sex-related genes (Gsdf, Dmrt1, and Foxl2) expressed in Sertoli cells in the mature testes of adult medaka during estrogen-induced testis-ova differentiation. When mature male medaka were exposed to estradiol benzoate (EB; 800ng/L), testis-ova first appeared after EB treatment for 14days (observed as the first oocytes of the leptotene-zygotene stage). However, the testis remained structurally unchanged, even after EB treatment for 28days. Although Foxl2 is a female-specific sex gene, EB treatment for 7days induced Foxl2/FOXL2 expression in all Sertoli cell-enclosed spermatogonia before testis-ova first appeared; however, Foxl2 was not detected in somatic cells in control testes. Conversely, Sertoli-cell-specific Gsdf mRNA expression levels significantly decreased after EB treatment for 14days, and no changes were observed in DMRT1 localization following EB treatment, whereas Dmrt1 mRNA levels increased significantly. Furthermore, after EB exposure, FOXl2 and DMRT1 were co-localized in Sertoli cells during testis-ova differentiation, although FOXL2 localization was undetectable in Sertoli-cell-enclosed apoptotic testis-ova, whereas DMRT1 remained localized in Sertoli cells. These results indicated for the first time that based on the expression of female-specific sex genes, feminization of Sertoli cells precedes testis-ova differentiation induced by estrogen in mature testes in medaka; however, complete feminization of Sertoli cells was not induced in this study. Additionally, it is suggested strongly that Foxl2 and Gsdf expression constitute potential molecular markers for evaluating the effects of estrogenic chemicals on testicular somatic cells associated with estrogen-induced testis-ova differentiation in mature male medaka. Copyright © 2017 Elsevier B.V. All rights reserved.

Sexually Dimorphic Expression of Foxl2 and Ftz-F1 in Chinese Giant Salamander Andrias Davidianus.

PubMed

Hu, Qiaomu; Meng, Yan; Tian, Haifeng; Zhang, Y U; Xiao, Hanbing

2016-09-01

Foxl2 and FTZ-F1 play a crucial role in the regulation of gonad development in fish and mammals, but studies of their function in amphibians are scarce. We isolated the full length of Foxl2 (adFoxl2) and Ftz-F1 (adFtz-f1) cDNA from the Chinese giant salamander Andrias davidianus and quantified its expression in various tissues and developing gonads. The adFoxl2 gene encodes 301aa including a conserved forkhead box, and the adFtz-f1 gene encodes 467aa containing an Ftz-F1 box. The amino acid sequences showed high homology with other amphibians. adFoxl2 expression was high in ovary, whereas adFtz-f1 was higher in testis, moderate in pituitary, ovary, and kidney; and low in the remaining tested tissues. Expression of adFoxl2 gradually increased from 1Y to 5Y in ovary, whereas adFtz-f1 expression gradually decreased in testis. In addition, adFoxl2 and adFtz-f1 were detected in granulosa cell in ovary and in spermatocytes in testis. The adFoxl2 transcription was inhibited in brain and ovary after treatment with methyltestosterone and with letrozole, whereas adFtz-f1 expression was upregulated. High-temperature suppressed the expression of adFxl2 in ovary and enhanced the transcription of adFtz-f1. These results suggest that adFoxl2 functioned in ovary differentiation, whereas adFtz-f1 played a role in testis development, which lays a foundation for study of the sex differentiation mechanism in A. davidianus. © 2016 Wiley Periodicals, Inc.

[Subcutaneous transplants of juvenile rat testicular tissues continue to develop and secret androgen in adult rats].

PubMed

Yu, Zhou; Wang, Tong; Cui, Jiangbo; Song, Yajuan; Ma, Xianjie; Su, Yingjun; Peng, Pai

2017-12-01

Objective To explore the effects of subcutaneous microenvironment of adult rats on survival, development and androgen secretion of Leydig cells of transplanted juvenile rat testis. Methods Healthy adult SD rats were randomly divided into control group, sham group, castrated group and non-castrated group. Rats in the control group were kept intact, no testis was transplanted subcutaneously after adult recipients were castrated in the sham group; 5-7-day juvenile rat testes were transplanted subcutaneously in the castrated group, with one testis per side; Testes resected from juvenile rats were directly transplanted subcutaneously on both sides of the recipients in the non-castrated group. The grafts were obtained and weighed 4 weeks later. Then the histological features of the grafts were examined by HE staining; the expression and distribution of hydroxysteroid 17-beta dehydrogenase 1 (HSD-17β1) were investigated by immunohistochemistry; and the serum androgen level was determined by ELISA. Results The average mass of grafts obtained from the castrated group was significantly higher than that of the non-castrated group. Immunohistochemistry indicated that Leydig cells were visible in the tissues from both the castrated and non-castrated groups, but the number of HSD-17β1-posotive cells in the castrated group was larger than that in the non-castrated group. ELISA results showed that the serum androgen level was higher in the control group and non-castrated group than in the sham group and castrated group, and compared with the sham group, the serum androgen level in the castrated group was significantly higher. Conclusion The juvenile rat testis subcutaneously transplanted could further develop under the adult recipient rat skin, and the Leydig cells of grafts harbored the ability to produce and secret androgen.

Analgesic use in pregnancy and male reproductive development

PubMed Central

Hurtado-Gonzalez, Pablo; Mitchell, Rod T.

2017-01-01

Purpose of review Male reproductive disorders are common and increasing in incidence in many countries. Environmental factors (including pharmaceuticals) have been implicated in the development of these disorders. This review aims to summarise the emerging epidemiological and experimental evidence for a potential role of in-utero exposure to analgesics in the development of male reproductive disorders. Recent findings A number of epidemiological studies have demonstrated an association between in-utero exposure to analgesics and the development of cryptorchidism, although these findings are not consistent across all studies. Where present, these associations primarily relate to exposure during the second trimester of pregnancy. In-vivo and in-vitro experimental studies have demonstrated variable effects of exposure to analgesics on Leydig cell function in the fetal testis of rodents, particularly in terms of testosterone production. These effects frequently involve exposures that are in excess of those to which humans are exposed. Investigation of the effects of analgesics on human fetal testis have also demonstrated effects on Leydig cell function. Variation in species, model system, dosage and timing of exposure is likely to contribute to differences in the findings between studies. Summary There is increasing evidence for analgesic effects on the developing testis that have the potential to impair reproductive function. However, the importance of these findings in relation to human-relevant exposures and the risk of male reproductive disorders remains unclear. PMID:28277341

Conflicting cultural perspectives: meanings and experiences of postnatal depression among women in Indian communities.

PubMed

Jain, Anita; Levy, David

2013-01-01

A woman's cultural and social context affects her experience of postnatal depression. In this literature review, the authors explore questions regarding normal and abnormal postnatal experiences of Indian women with consideration to cross-cultural perspectives. Although postnatal distress or sadness is recognized among many cultures, it is constructed as a transient state in some cultures and as an illness in others. A major challenge for health care providers in Western countries like the United Kingdom and Australia is to develop culturally sensitive approaches to postnatal care for migrant mothers.

Adrenocorticotropic hormone affects nonapoptotic cell death of undifferentiated germ cells in the fetal mouse testis: in vivo study by exo utero transplantation of corticotropic tumor cells into embryos.

PubMed

Nimura, Masayuki; Udagawa, Jun; Otani, Hiroki

2008-06-01

Adrenocorticotropic hormone (ACTH) has been suggested to have possible roles in the fetal testes, one of the organs that express its specific receptors, melanocortin type 2 and 5 receptors (MC2R and MC5R), during the fetal period. We investigated the effect of ACTH on the cells in the testis cord of the fetal mouse testis by inducing ACTH-secreting AtT20 tumor cells in mouse fetuses. We first identified that mouse testicular germ cells at embryonic day (E) 16.5 and E18.5 spermatogonia were entirely CDH1 (E-cadherin)-positive by immunohistochemistry. We next performed AtT20-cell transplantation into the mouse fetus at E12.5, and analyzed ACTH effects on the development of fetal male mouse germ cells that express MC2R and MC5R at E16.5 and E18.5. The spermatogonia in the testis of AtT20-implanted embryos exhibited morphological changes, including pyknotic nuclei and swollen cytoplasm. In the AtT20-implanted embryos, the number of spermatogonia per unit area of the testis cord was significantly lower, but there were more pyknotic spermatogonia than in the controls. Single-stranded DNA-positive (apoptotic) and histone H3-positive (mitotic) spermatogonia were rarely observed and their numbers did not significantly differ in the two groups. Anti-Müllerian hormone (AMH)-positive Sertoli cells, another cell type that constitutes the fetal testis cord but does not express MC2R or MC5R, showed no apparent morphological changes compared with controls, nor were their numbers in the two groups significantly different between the two groups. These results suggest that ACTH, via MC2R and/or MC5R, may be involved in the nonapoptotic cell death of fetal mouse spermatogonia that is observed during the normal perinatal period.

Hanging drop cultures of human testis and testis cancer samples: a model used to investigate activin treatment effects in a preserved niche.

PubMed

Jørgensen, A; Young, J; Nielsen, J E; Joensen, U N; Toft, B G; Rajpert-De Meyts, E; Loveland, K L

2014-05-13

Testicular germ cell tumours of young adults, seminoma or non-seminomas, are preceded by a pre-invasive precursor, carcinoma in situ (CIS), understood to arise through differentiation arrest of embryonic germ cells. Knowledge about the malignant transformation of germ cells is currently limited by the lack of experimental models. The aim of this study was to establish an experimental tissue culture model to maintain normal and malignant germ cells within their niche and allow investigation of treatment effects. Human testis and testis cancer specimens from orchidectomies were cultured in 'hanging drops' and effects of activin A and follistatin treatment were investigated in seminoma cultures. Testis fragments with normal spermatogenesis or CIS cells were cultured for 14 days with sustained proliferation of germ cells and CIS cells and without increased apoptosis. Seminoma cultures survived 7 days, with proliferating cells detectable during the first 5 days. Activin A treatment significantly reduced KIT transcript and protein levels in seminoma cultures, thereby demonstrating a specific treatment response. Hanging drop cultures of human testis and testis cancer samples can be employed to delineate mechanisms governing growth of normal, CIS and tumorigenic germ cells retained within their niche.

[Electrophysiological characteristics of hippocampal postnatal early development mediated by AMPA receptors in rats].

PubMed

Chen, Xue-Yi; Zhang, Ai-Feng; Zhao, Wen; Gao, Yu-Dan; Duan, Hong-Mei; Hao, Peng; Yang, Zhao-Yang; Li, Xiao-Guang

2018-04-25

The present study was aimed to investigate the electrophysiological characteristics of hippocampal postnatal early development mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in rats. Forty-eight Wistar rats were divided into postnatal 0.5-, 1-, 2- and 3-month groups (n = 12). Spontaneous excitatory postsynaptic currents (sEPSCs) and field excitatory postsynaptic potentials (fEPSPs) mediated by AMPA receptors were recorded to evaluate the changes in the intrinsic membrane properties of hippocampal CA1 pyramidal neurons by using patch-clamp and MED64 planar microelectrode array technique respectively. The results showed that, during the period of postnatal 0.5-3 months, some of the intrinsic membrane properties of hippocampal CA1 pyramidal neurons, such as the membrane capacitance (Cm) and the resting membrane potential (RMP), showed no significant changes, while the membrane input resistance (Rin) and the time constant (τ) of the cells were decreased significantly. The amplitude, frequency and kinetics (both rise and decay times) of sEPSCs were significantly increased during the period of postnatal 0.5-1 month, but they were all decreased during the period of postnatal 1-3 months. In addition, the range of evoked fEPSPs in hippocamal CA1 region was significantly expanded, but the fEPSP amplitudes were decreased significantly during the period of postnatal 0.5-3 months. Furthermore, the evoked fEPSPs could be significantly inhibited by extracellular application of the AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). These results suggest that AMPA receptor may act as a major type of excitatory receptor to regulate synaptic transmission and connections during the early stage of hippocampal postnatal development, which promotes the development and functional maturation of hippocampus in rats.

Germ cell tumors: Insights from the Drosophila ovary and the mouse testis

PubMed Central

Salz, Helen K.; Dawson, Emily P.; Heaney, Jason D.

2017-01-01

SUMMARY Ovarian and testicular germ cell tumors of young adults are thought to arise from defects in germ cell development, but the molecular mechanisms underlying malignant transformation are poorly understood. In this review, we focus on the biology of germ cell tumor formation in the Drosophila ovary and the mouse testis, for which the evidence supports common underlying mechanisms such as blocking initiation into the differentiation pathway, impaired lineage progression, and sexual identity instability. We then discuss how these concepts inform our understanding of the disease in humans. PMID:28079292

Maternal anxiety and infants' hippocampal development: timing matters.

PubMed

Qiu, A; Rifkin-Graboi, A; Chen, H; Chong, Y-S; Kwek, K; Gluckman, P D; Fortier, M V; Meaney, M J

2013-09-24

Exposure to maternal anxiety predicts offspring brain development. However, because children's brains are commonly assessed years after birth, the timing of such maternal influences in humans is unclear. This study aimed to examine the consequences of antenatal and postnatal exposure to maternal anxiety upon early infant development of the hippocampus, a key structure for stress regulation. A total of 175 neonates underwent magnetic resonance imaging (MRI) at birth and among them 35 had repeated scans at 6 months of age. Maternal anxiety was assessed using the State-Trait Anxiety Inventory (STAI) at week 26 of pregnancy and 3 months after delivery. Regression analyses showed that antenatal maternal anxiety did not influence bilateral hippocampal volume at birth. However, children of mothers reporting increased anxiety during pregnancy showed slower growth of both the left and right hippocampus over the first 6 months of life. This effect of antenatal maternal anxiety upon right hippocampal growth became statistically stronger when controlling for postnatal maternal anxiety. Furthermore, a strong positive association between postnatal maternal anxiety and right hippocampal growth was detected, whereas a strong negative association between postnatal maternal anxiety and the left hippocampal volume at 6 months of life was found. Hence, the postnatal growth of bilateral hippocampi shows distinct responses to postnatal maternal anxiety. The size of the left hippocampus during early development is likely to reflect the influence of the exposure to perinatal maternal anxiety, whereas right hippocampal growth is constrained by antenatal maternal anxiety, but enhanced in response to increased postnatal maternal anxiety.

Timing and Duration of Drug Exposure Affects Outcomes of a Drug-Nutrient Interaction During Ontogeny.

PubMed

Ling, Binbing; Aziz, Caroline; Wojnarowicz, Chris; Olkowski, Andrew; Alcorn, Jane

2010-10-14

Significant drug-nutrient interactions are possible when drugs and nutrients share the same absorption and disposition mechanisms. During postnatal development, the outcomes of drug-nutrient interactions may change with postnatal age since these processes undergo ontogenesis through the postnatal period. Our study investigated the dependence of a significant drug-nutrient interaction (cefepime-carnitine) on the timing and duration of drug exposure relative to postnatal age. Rat pups were administered cefepime (5 mg/kg) twice daily subcutaneously according to different dosing schedules (postnatal day 1-4, 1-8, 8-11, 8-20, or 1-20). Cefepime significantly reduced serum and heart L-carnitine levels in postnatal day 1-4, 1-8 and 8-11 groups and caused severe degenerative changes in ventricular myocardium in these groups. Cefepime also altered the ontogeny of several key L-carnitine homeostasis pathways. The qualitative and quantitative changes in levels of hepatic γ-butyrobetaine hydroxylase mRNA and activity, hepatic trimethyllysine hydroxlase mRNA, intestinal organic cation/carnitine transporter (Octn) mRNA, and renal Octn2 mRNA depended on when during postnatal development the cefepime exposure occurred and duration of exposure. Despite lower levels of heart L-carnitine in earlier postnatal groups, levels of carnitine palmitoyltransferase mRNA and activity, heart Octn2 mRNA and ATP levels in all treatment groups remained unchanged with cefepime exposure. However, changes in other high energy phosphate substrates were noted and reductions in the phosphocreatine/ATP ratio were found in rat pups with normal serum L-carnitine levels. In summary, our data suggest a significant drug-nutrient transport interaction in developing neonates, the nature of which depends on the timing and duration of exposure relative to postnatal age.

Timing and Duration of Drug Exposure Affects Outcomes of a Drug-Nutrient Interaction During Ontogeny

PubMed Central

Ling, Binbing; Aziz, Caroline; Wojnarowicz, Chris; Olkowski, Andrew; Alcorn, Jane

2010-01-01

Significant drug-nutrient interactions are possible when drugs and nutrients share the same absorption and disposition mechanisms. During postnatal development, the outcomes of drug-nutrient interactions may change with postnatal age since these processes undergo ontogenesis through the postnatal period. Our study investigated the dependence of a significant drug-nutrient interaction (cefepime-carnitine) on the timing and duration of drug exposure relative to postnatal age. Rat pups were administered cefepime (5 mg/kg) twice daily subcutaneously according to different dosing schedules (postnatal day 1-4, 1-8, 8-11, 8-20, or 1-20). Cefepime significantly reduced serum and heart L-carnitine levels in postnatal day 1-4, 1-8 and 8-11 groups and caused severe degenerative changes in ventricular myocardium in these groups. Cefepime also altered the ontogeny of several key L-carnitine homeostasis pathways. The qualitative and quantitative changes in levels of hepatic γ-butyrobetaine hydroxylase mRNA and activity, hepatic trimethyllysine hydroxlase mRNA, intestinal organic cation/carnitine transporter (Octn) mRNA, and renal Octn2 mRNA depended on when during postnatal development the cefepime exposure occurred and duration of exposure. Despite lower levels of heart L-carnitine in earlier postnatal groups, levels of carnitine palmitoyltransferase mRNA and activity, heart Octn2 mRNA and ATP levels in all treatment groups remained unchanged with cefepime exposure. However, changes in other high energy phosphate substrates were noted and reductions in the phosphocreatine/ATP ratio were found in rat pups with normal serum L-carnitine levels. In summary, our data suggest a significant drug-nutrient transport interaction in developing neonates, the nature of which depends on the timing and duration of exposure relative to postnatal age. PMID:27721360

SUBSTANCE-ABUSING MOTHERS IN RESIDENTIAL TREATMENT WITH THEIR BABIES: IMPORTANCE OF PRE- AND POSTNATAL MATERNAL REFLECTIVE FUNCTIONING

PubMed Central

Pajulo, Marjukka; Pyykkönen, Nina; Kalland, Mirjam; Sinkkonen, Jari; Helenius, Hans; Punamäki, Raija-Leena; Suchman, Nancy

2012-01-01

A residential treatment program has been developed specifically for substance-abusing pregnant and parenting women in Finland, focusing on simultaneously supporting maternal abstinence from substances and the mother–baby relationship. The aims of the study are to explore maternal pre- and postnatal reflective functioning and its association with background factors, maternal exposure to trauma, and psychiatric symptoms, postnatal interaction, child development, and later child foster care placement. Participants were 34 mother–baby pairs living in three residential program units during the pre- to postnatal period. We employed self-report questionnaires on background, trauma history, and psychiatric symptoms (Brief Symptom Inventory: L.R. Derogatis, 1993; Edinburgh Postnatal Depression Scale: J.L. Cox, J.M. Holden, & R. Sagovsky, 1987; Traumatic Antecedents Questionnaire: B. Van der Kolk, 2003), videotaped mother–child interactions coded for sensitivity, control, and unresponsiveness (Care Index for Infants and Toddlers: P. Crittenden, 2003); a standardized test of child development (Bayley Scales of Infant Development-II: N. Bayley, 1993); and semistructured interviews for maternal reflective functioning (Pregnancy Interview: A. Slade, E. Bernbach, J. Grienenberger, D.W. Levy, & A. Locker, 2002; Parent Development Interview: A. Slade et al., 2005). Pre- and postnatal maternal reflective functioning (RF) was on average low, but varied considerably across participants. Average RF increased significantly during the intervention. Increase in RF level was found to be associated with type of abused substance and maternal trauma history. Mothers who showed lower postnatal RF levels relapsed to substance use more often after completing a residential treatment period, and their children were more likely to be placed in foster care. The intensive focus on maternal RF is an important direction in the development of efficacious treatment for this very high risk population. PMID:22899872

Secreted Frizzled-related protein 1 (sFRP1) regulates spermatid adhesion in the testis via dephosphorylation of focal adhesion kinase and the nectin-3 adhesion protein complex

PubMed Central

Wong, Elissa W. P.; Lee, Will M.; Cheng, C. Yan

2013-01-01

Development of spermatozoa in adult mammalian testis during spermatogenesis involves extensive cell migration and differentiation. Spermatogonia that reside at the basal compartment of the seminiferous epithelium differentiate into more advanced germ cell types that migrate toward the apical compartment until elongated spermatids are released into the tubule lumen during spermiation. Apical ectoplasmic specialization (ES; a testis-specific anchoring junction) is the only cell junction that anchors and maintains the polarity of elongating/elongated spermatids (step 8–19 spermatids) in the epithelium. Little is known regarding the signaling pathways that trigger the disassembly of the apical ES at spermiation. Here, we show that secreted Frizzled-related protein 1 (sFRP1), a putative tumor suppressor gene that is frequently down-regulated in multiple carcinomas, is a crucial regulatory protein for spermiation. The expression of sFRP1 is tightly regulated in adult rat testis to control spermatid adhesion and sperm release at spermiation. Down-regulation of sFRP1 during testicular development was found to coincide with the onset of the first wave of spermiation at approximately age 45 d postpartum, implying that sFRP1 might be correlated with elongated spermatid adhesion conferred by the apical ES before spermiation. Indeed, administration of sFRP1 recombinant protein to the testis in vivo delayed spermiation, which was accompanied by down-regulation of phosphorylated (p)-focal adhesion kinase (FAK)-Tyr397 and retention of nectin-3 adhesion protein at the apical ES. To further investigate the functional relationship between p-FAK-Tyr397 and localization of nectin-3, we overexpressed sFRP1 using lentiviral vectors in the Sertoli-germ cell coculture system. Consistent with the in vivo findings, overexpression of sFRP1 induced down-regulation of p-FAK-Tyr397, leading to a decline in phosphorylation of nectin-3. In summary, this report highlights the critical role of sFRP1 in regulating spermiation via its effects on the FAK signaling and retention of nectin-3 adhesion complex at the apical ES.—Wong, E. W. P., Lee, W. M., Cheng, C. Y. Secreted Frizzled-related protein 1 (sFRP1) regulates spermatid adhesion in the testis via dephosphorylation of focal adhesion kinase and the nectin-3 adhesion protein complex. PMID:23073828

An Ancient Transcription Factor Initiates the Burst of piRNA Production During Early Meiosis in Mouse Testes

PubMed Central

Li, Xin Zhiguo; Roy, Christian K.; Dong, Xianjun; Bolcun-Filas, Ewelina; Wang, Jie; Han, Bo W.; Xu, Jia; Moore, Melissa J.; Schimenti, John C.; Weng, Zhiping; Zamore, Phillip D.

2013-01-01

SUMMARY Animal germ cells produce PIWI-interacting RNAs (piRNAs), small silencing RNAs that suppress transposons and enable gamete maturation. Mammalian transposon-silencing piRNAs accumulate early in spermatogenesis, whereas pachytene piRNAs are produced later during post-natal spermatogenesis and account for >95% of all piRNAs in the adult mouse testis. Mutants defective for pachytene piRNA pathway proteins fail to produce mature sperm, but neither the piRNA precursor transcripts nor the trigger for pachytene piRNA production is known. Here, we show that the transcription factor A-MYB initiates pachytene piRNA production. A-MYB drives transcription of both pachytene piRNA precursor RNAs and the mRNAs for core piRNA biogenesis factors, including MIWI, the protein through which pachytene piRNAs function. A-MYB regulation of piRNA pathway proteins and piRNA genes creates a coherent feed-forward loop that ensures the robust accumulation of pachytene piRNAs. This regulatory circuit, which can be detected in rooster testes, likely predates the divergence of birds and mammals. PMID:23523368

Concerns about the widespread use of rodent models for human risk assessments of endocrine disruptors

PubMed Central

Habert, René; Muczynski, Vincent; Grisin, Tiphany; Moison, Delphine; Messiaen, Sébastien; Frydman, René; Benachi, Alexandra; Delbes, Géraldine; Lambrot, Romain; Lehraiki, Abdelali; N'Tumba-Byn, Thierry; Guerquin, Marie-Justine; Levacher, Christine; Rouiller-Fabre, Virginie; Livera, Gabriel

2014-01-01

Fetal testis is a major target of endocrine disruptors (EDs). During the last 20 years, we have developed an organotypic culture system that maintains the function of the different fetal testis cell types and have used this approach as a toxicological test to evaluate the effects of various compounds on gametogenesis and steroidogenesis in rat, mouse and human testes. We named this test rat, mouse and human fetal testis assay. With this approach, we compared the effects of six potential EDs ((mono-(2-ethylhexyl) phthalate (MEHP), cadmium, depleted uranium, diethylstilboestrol (DES), bisphenol A (BPA) and metformin) and one signalling molecule (retinoic acid (RA)) on the function of rat, mouse and human fetal testis at a comparable developmental stage. We found that the response is similar in humans and rodents for only one third of our analyses. For instance, RA and MEHP have similar negative effects on gametogenesis in the three species. For another third of our analyses, the threshold efficient concentrations that disturb gametogenesis and/or steroidogenesis differ as a function of the species. For instance, BPA and metformin have similar negative effects on steroidogenesis in human and rodents, but at different threshold doses. For the last third of our analyses, the qualitative response is species specific. For instance, MEHP and DES affect steroidogenesis in rodents, but not in human fetal testis. These species differences raise concerns about the extrapolation of data obtained in rodents to human health risk assessment and highlight the need of rigorous comparisons of the effects in human and rodent models, when assessing ED risk. PMID:24497529

Transcriptome analysis reveals differentially expressed genes associated with germ cell and gonad development in the Southern bluefin tuna (Thunnus maccoyii).

PubMed

Bar, Ido; Cummins, Scott; Elizur, Abigail

2016-03-10

Controlling and managing the breeding of bluefin tuna (Thunnus spp.) in captivity is an imperative step towards obtaining a sustainable supply of these fish in aquaculture production systems. Germ cell transplantation (GCT) is an innovative technology for the production of inter-species surrogates, by transplanting undifferentiated germ cells derived from a donor species into larvae of a host species. The transplanted surrogates will then grow and mature to produce donor-derived seed, thus providing a simpler alternative to maintaining large-bodied broodstock such as the bluefin tuna. Implementation of GCT for new species requires the development of molecular tools to follow the fate of the transplanted germ cells. These tools are based on key reproductive and germ cell-specific genes. RNA-Sequencing (RNA-Seq) provides a rapid, cost-effective method for high throughput gene identification in non-model species. This study utilized RNA-Seq to identify key genes expressed in the gonads of Southern bluefin tuna (Thunnus maccoyii, SBT) and their specific expression patterns in male and female gonad cells. Key genes involved in the reproductive molecular pathway and specifically, germ cell development in gonads, were identified using analysis of RNA-Seq transcriptomes of male and female SBT gonad cells. Expression profiles of transcripts from ovary and testis cells were compared, as well as testis germ cell-enriched fraction prepared with Percoll gradient, as used in GCT studies. Ovary cells demonstrated over-expression of genes related to stem cell maintenance, while in testis cells, transcripts encoding for reproduction-associated receptors, sex steroids and hormone synthesis and signaling genes were over-expressed. Within the testis cells, the Percoll-enriched fraction showed over-expression of genes that are related to post-meiosis germ cell populations. Gonad development and germ cell related genes were identified from SBT gonads and their expression patterns in ovary and testis cells were determined. These expression patterns correlate with the reproductive developmental stage of the sampled fish. The majority of the genes described in this study were sequenced for the first time in T. maccoyii. The wealth of SBT gonadal and germ cell-related gene sequences made publicly available by this study provides an extensive resource for further GCT and reproductive molecular biology studies of this commercially valuable fish.

Effects of a simulated microgravity model on cell structure and function in rat testis and epididymis

NASA Technical Reports Server (NTRS)

Hadley, Jill A.; Hall, Joseph C.; O'Brien, Ami; Ball, Richard

1992-01-01

The effect of simulated microgravity on the structure and function of the testis and epididymis cells was investigated in rats subjected to 7 days of tail suspension. Results of a histological examination revealed presence of disorganized seminiferous tubules and accumulation of large multinucleated cells and spermatids in the lumen of the epididymis. In addition, decreases in the content of testis protein and in testosterone levels in the testis, the interstitial fluid, and the epididymis were observed.

Carboxyhemoglobin Formation in Preterm Infants Is Related to the Subsequent Development of Bronchopulmonary Dysplasia

PubMed Central

Tokuriki, Shuko; Okuno, Takashi; Ohta, Genrei

2015-01-01

Objective. To evaluate the usefulness of carboxyhemoglobin (CO-Hb) levels as a biomarker to predict the development and severity of bronchopulmonary dysplasia (BPD). Methods. Twenty-five infants born at <33 wk of gestational age or with a birth weight of <1,500 g were enrolled. CO-Hb levels were measured between postnatal days 5 and 8, 12 and 15, 19 and 22, and 26 and 29. Urinary levels of 8-hydroxydeoxyguanosine (8-OHdG), advanced oxidation protein products, and Nε-(hexanoyl) lysine were measured between postnatal days 5 and 8 and 26 and 29. Receiver operating characteristic (ROC) analysis was used to compare the biomarkers' predictive values. Results. Compared with infants in the no-or-mild BPD group, infants with moderate-to-severe BPD exhibited higher CO-Hb levels during the early postnatal period and higher 8-OHdG levels between postnatal days 5 and 8. Using ROC analysis to predict the development of moderate-to-severe BPD, the area under the curve (AUC) for CO-Hb levels between postnatal days 5 and 8 was higher than AUCs for the urinary markers. Conclusions. CO-Hb levels during the early postnatal period may serve as a practical marker for evaluating oxidative stress and the severity of subsequently developing BPD. PMID:26294808

Carboxyhemoglobin Formation in Preterm Infants Is Related to the Subsequent Development of Bronchopulmonary Dysplasia.

PubMed

Tokuriki, Shuko; Okuno, Takashi; Ohta, Genrei; Ohshima, Yusei

2015-01-01

To evaluate the usefulness of carboxyhemoglobin (CO-Hb) levels as a biomarker to predict the development and severity of bronchopulmonary dysplasia (BPD). Twenty-five infants born at <33 wk of gestational age or with a birth weight of <1,500 g were enrolled. CO-Hb levels were measured between postnatal days 5 and 8, 12 and 15, 19 and 22, and 26 and 29. Urinary levels of 8-hydroxydeoxyguanosine (8-OHdG), advanced oxidation protein products, and Nε-(hexanoyl) lysine were measured between postnatal days 5 and 8 and 26 and 29. Receiver operating characteristic (ROC) analysis was used to compare the biomarkers' predictive values. Compared with infants in the no-or-mild BPD group, infants with moderate-to-severe BPD exhibited higher CO-Hb levels during the early postnatal period and higher 8-OHdG levels between postnatal days 5 and 8. Using ROC analysis to predict the development of moderate-to-severe BPD, the area under the curve (AUC) for CO-Hb levels between postnatal days 5 and 8 was higher than AUCs for the urinary markers. CO-Hb levels during the early postnatal period may serve as a practical marker for evaluating oxidative stress and the severity of subsequently developing BPD.

Misuse of ultrasound for palpable undescended testis by primary care providers: A prospective study

PubMed Central

Wong, Nathan C.; Bansal, Rahul K.; Lorenzo, Armando J.; DeMaria, Jorge; Braga, Luis H.

2015-01-01

Introduction: Although previous evidence has shown that ultrasound is unreliable to diagnose undescended testis, many primary care providers (PCP) continue to misuse it. We assessed the performance of ultrasound as a diagnostic tool for palpable undescended testis, as well as the diagnostic agreement between PCP and pediatric urologists. Methods: We performed a prospective observational cohort study between 2011 and 2013 for consecutive boys referred with a diagnosis of undescended testis to our tertiary pediatric hospital. Patients referred without an ultrasound and those with non-palpable testes were excluded. Data on referring diagnosis, pediatric urology examination and ultrasound reports were analyzed. Results: Our study consisted of 339 boys. Of these, patients without an ultrasound (n = 132) and those with non-palpable testes (n = 38) were excluded. In the end, there were 169 pateints in this study. Ultrasound was performed in 50% of referred boys showing 256 undescended testis. The mean age at time of referral was 45 months. When ultrasound was compared to physical examination by the pediatric urologist, agreement was only 34%. The performance of ultrasound for palpable undescended testis was: sensitivity = 100%; specificity = 16%; positive predictive value = 34%; negative predictive value = 100%; positive likelihood ratio = 1.2; and negative likelihood ratio = 0. Diagnosis of undescended testis by PCP was confirmed by physical examination in 30% of cases, with 70% re-diagnosed with normal or retractile testes. Conclusion: Ultrasound performed poorly to assess for palpable undescended testis in boys and should not be used. Although the study has important limitations, there is an increasing need for education and evidence-based guidelines for PCP in the management of undescended testis. PMID:26788226

HISTOLOGICAL AND HISTOPATHOLOGICAL EVALUATION OF THE TESTIS

EPA Science Inventory

This book, the first to describe how the testis is evaluated in research and toxicology testing settings, is a resource for individuals who wish to perform a systematic evaluation of the testis. he book contains 728 illustrations and drawings. The book begins with a description o...

Testisimmune privilege - Assumptions versus facts

PubMed Central

Kaur, G.; Mital, P.; Dufour, J.M.

2013-01-01

The testis has long enjoyed a reputation as an immunologically privileged site based on its ability to protect auto-antigenic germ cells and provide an optimal environment for the extended survival of transplanted allo- or xeno-grafts. Exploration of the role of anatomical, physiological, immunological and cellular components in testis immune privilege revealed that the tolerogenic environment of the testis is a result of the immunomodulatory factors expressed or secreted by testicular cells (mainly Sertoli cells, peritubular myoid cells, Leydig cells, and resident macrophages). The blood-testis barrier/Sertoli cell barrier, is also important to seclude advanced germ cells but its requirement in testis immune privilege needs further investigation. Testicular immune privilege is not permanent, as an effective immune response can be mounted against transplanted tissue, and bacterial/viral infections in the testis can be effectively eliminated. Overall, the cellular components control the fate of the immune response and can shift the response from immunodestructive to immunoprotective, resulting in immune privilege. PMID:25309630

Early-life stress impacts the developing hippocampus and primes seizure occurrence: cellular, molecular, and epigenetic mechanisms

PubMed Central

Huang, Li-Tung

2014-01-01

Early-life stress includes prenatal, postnatal, and adolescence stress. Early-life stress can affect the development of the hypothalamic-pituitary-adrenal (HPA) axis, and cause cellular and molecular changes in the developing hippocampus that can result in neurobehavioral changes later in life. Epidemiological data implicate stress as a cause of seizures in both children and adults. Emerging evidence indicates that both prenatal and postnatal stress can prime the developing brain for seizures and an increase in epileptogenesis. This article reviews the cellular and molecular changes encountered during prenatal and postnatal stress, and assesses the possible link between these changes and increases in seizure occurrence and epileptogenesis in the developing hippocampus. In addititon, the priming effect of prenatal and postnatal stress for seizures and epileptogenesis is discussed. Finally, the roles of epigenetic modifications in hippocampus and HPA axis programming, early-life stress, and epilepsy are discussed. PMID:24574961

Association between Prenatal and Postnatal Psychological Distress and Toddler Cognitive Development: A Systematic Review

PubMed Central

2015-01-01

Purpose Maternal psychological distress is one of the most common perinatal complications, affecting up to 25% of pregnant and postpartum women. Research exploring the association between prenatal and postnatal distress and toddler cognitive development has not been systematically compiled. The objective of this systematic review was to determine the association between prenatal and postnatal psychological distress and toddler cognitive development. Methods Articles were included if: a) they were observational studies published in English; b) the exposure was prenatal or postnatal psychological distress; c) cognitive development was assessed from 13 to 36 months; d) the sample was recruited in developed countries; and e) exposed and unexposed women were included. A university-based librarian conducted a search of electronic databases (Embase, CINAHL, Eric, PsycInfo, Medline) (January, 1990-March, 2014). We searched gray literature, reference lists, and relevant journals. Two reviewers independently evaluated titles/abstracts for inclusion, and quality using the Scottish Intercollegiate Guideline Network appraisal tool for observational studies. One reviewer extracted data using a standardized form. Results Thirteen of 2448 studies were included. There is evidence of an association between prenatal and postnatal distress and cognitive development. While variable effect sizes were reported for postnatal associations, most studies reported medium effect sizes for the association between prenatal psychological distress and cognitive development. Too few studies were available to determine the influence of the timing of prenatal exposure on cognitive outcomes. Conclusion Findings support the need for early identification and treatment of perinatal mental health problems as a potential strategy for optimizing toddler cognitive development. PMID:25996151

Association between Prenatal and Postnatal Psychological Distress and Toddler Cognitive Development: A Systematic Review.

PubMed

Kingston, Dawn; McDonald, Sheila; Austin, Marie-Paule; Tough, Suzanne

2015-01-01

Maternal psychological distress is one of the most common perinatal complications, affecting up to 25% of pregnant and postpartum women. Research exploring the association between prenatal and postnatal distress and toddler cognitive development has not been systematically compiled. The objective of this systematic review was to determine the association between prenatal and postnatal psychological distress and toddler cognitive development. Articles were included if: a) they were observational studies published in English; b) the exposure was prenatal or postnatal psychological distress; c) cognitive development was assessed from 13 to 36 months; d) the sample was recruited in developed countries; and e) exposed and unexposed women were included. A university-based librarian conducted a search of electronic databases (Embase, CINAHL, Eric, PsycInfo, Medline) (January, 1990-March, 2014). We searched gray literature, reference lists, and relevant journals. Two reviewers independently evaluated titles/abstracts for inclusion, and quality using the Scottish Intercollegiate Guideline Network appraisal tool for observational studies. One reviewer extracted data using a standardized form. Thirteen of 2448 studies were included. There is evidence of an association between prenatal and postnatal distress and cognitive development. While variable effect sizes were reported for postnatal associations, most studies reported medium effect sizes for the association between prenatal psychological distress and cognitive development. Too few studies were available to determine the influence of the timing of prenatal exposure on cognitive outcomes. Findings support the need for early identification and treatment of perinatal mental health problems as a potential strategy for optimizing toddler cognitive development.

Proteomic characterization of histone variants in the mouse testis by mass spectrometry-based top-down analysis.

PubMed

Kwak, Ho-Geun; Dohmae, Naoshi

2016-11-15

Various histones, including testis-specific histones, exist during spermatogenesis and some of them have been reported to play a key role in chromatin remodeling. Mass spectrometry (MS)-based characterization has become the important step to understand histone structures. Although individual histones or partial histone variant groups have been characterized, the comprehensive analysis of histone variants has not yet been conducted in the mouse testis. Here, we present the comprehensive separation and characterization of histone variants from mouse testes by a top-down approach using MS. Histone variants were successfully separated on a reversed phase column using high performance liquid chromatography (HPLC) with an ion-pairing reagent. Increasing concentrations of testis-specific histones were observed in the mouse testis and some somatic histones increased in the epididymis. Specifically, the increase of mass abundance in H3.2 in the epididymis was inversely proportional to the decrease in H3t in the testis, which was approximately 80%. The top-down characterization of intact histone variants in the mouse testis was performed using LC-MS/MS. The masses of separated histone variants and their expected post-translation modifications were calculated by performing deconvolution with information taken from the database. TH2A, TH2B and H3t were characterized by MS/MS fragmentation. Our approach provides comprehensive knowledge for identification of histone variants in the mouse testis that will contribute to the structural and functional research of histone variants during spermatogenesis.

Characteristics of PCR-SSCP and RAPD-HPCE methods for identifying authentication of Penis et testis cervi in Traditional Chinese Medicine based on cytochrome b gene.

PubMed

Li, Mingcheng; Gao, Lijun; Qu, Li; Sun, Jingyu; Yuan, Guangxin; Xia, Wei; Niu, Jiamu; Fu, Guilian; Zhang, Lihua

2016-07-01

The use of Penis et testis cervi, as a kind of precious Traditional Chinese Medicine (TCM), which is derived from dry deer's testis and penis, has been recorded for many years in China. There are abundant species of deer in China, the Penis et testis from species of Cervus Nippon and Cervus elaphusL were authentic, others species were defined as adulterant (different subspecies of deer) or counterfeits (different species). Identification of their origins or authenticity becomes a key in controlling the herbal products. A modified column chromatography was used to extract mitochondrial DNA of dried deer's testis and penis from sika deer (C. Nippon) and red deer (C. elaphusL) in addition to adulterants and counterfeits. Column chromatography requires for a short time to extract mitochondrial DNA of high purity with little damage of DNA molecules, which provides the primary structure of guarantee for the specific PCR; PCR-SSCP method showed a clear intra-specific difference among patterns of single-chain fragments, and completely differentiate Penis et testis origins from C. Nippon and C. elaphusL. RAPD-HPCE was based on the standard electropherograms to compute a control spectrum curve as similarity reference (R) among different samples. The similarity analysis indicated that there were significant inter-species differences among Penis et testis' adulterant or counterfeits. Both techniques provide a fast, simple, and accurate way to directly identify among inter-species or intra-species of Penis et testis.

[Effects of electromagnetic pulses on apoptosis and TGF-β3 expression of mouse testis tissue].

PubMed

Luo, Yaning; Ding, Guirong; Chen, Yongbin; Xu, Shenglong; Wang, Xiaowu

2014-04-01

To investigate the effects of electromagnetic pulses (EMP) on the apoptosis and transforming growth factor beta 3 (TGF-β3) expression of mouse testis tissue. Thirty-two male BALB/c mice were randomly and equally divided into one control group and three EMP treated groups, which were whole-body exposed to EMP at 200 kV/m with 100, 200, and 400 pulses, respectively. The control group received no treatment. The pathological changes and cell apoptosis in testis tissue were analyzed by TUNEL assay. The mRNA expression of TGF-β3 in testis tissue was determined by RT-PCR, and the protein expression of TGF-β3 was determined by immunohistochemistry and Western blot. No obvious pathological changes were found in testis tissue after EMP exposure at 200 kV/m with 100 and 200 pulses. However, after EMP exposure with 400 pulses, degeneration and shedding of testis tissue, accompanied by significant increase in apoptosis rate (P < 0.05), was observed. The RT-PCR, immunohistochemistry, and Western blot showed that the expression of TGF-β3 mRNA and protein increased significantly after EMP exposure with 400 pulses as compared with that of the control group (P < 0.05). EMP exposure at 200 kV/m with 400 pulses increases the incidence of apoptosis and expression of TGF-β3 in mouse testis tissue, which is potentially one of the mechanisms by which EMP increases blood-testis barrier permeability in mice.

A single-dose live-attenuated vaccine prevents Zika virus pregnancy transmission and testis damage.

PubMed

Shan, Chao; Muruato, Antonio E; Jagger, Brett W; Richner, Justin; Nunes, Bruno T D; Medeiros, Daniele B A; Xie, Xuping; Nunes, Jannyce G C; Morabito, Kaitlyn M; Kong, Wing-Pui; Pierson, Theodore C; Barrett, Alan D; Weaver, Scott C; Rossi, Shannan L; Vasconcelos, Pedro F C; Graham, Barney S; Diamond, Michael S; Shi, Pei-Yong

2017-09-22

Zika virus infection during pregnancy can cause congenital abnormities or fetal demise. The persistence of Zika virus in the male reproductive system poses a risk of sexual transmission. Here we demonstrate that live-attenuated Zika virus vaccine candidates containing deletions in the 3' untranslated region of the Zika virus genome (ZIKV-3'UTR-LAV) prevent viral transmission during pregnancy and testis damage in mice, as well as infection of nonhuman primates. After a single-dose vaccination, pregnant mice challenged with Zika virus at embryonic day 6 and evaluated at embryonic day 13 show markedly diminished levels of viral RNA in maternal, placental, and fetal tissues. Vaccinated male mice challenged with Zika virus were protected against testis infection, injury, and oligospermia. A single immunization of rhesus macaques elicited a rapid and robust antibody response, conferring complete protection upon challenge. Furthermore, the ZIKV-3'UTR-LAV vaccine candidates have a desirable safety profile. These results suggest that further development of ZIKV-3'UTR-LAV is warranted for humans.Zika virus infection can result in congenital disorders and cause disease in adults, and there is currently no approved vaccine. Here Shan et al. show that a single dose of a live-attenuated Zika vaccine prevents infection, testis damage and transmission to the fetus during pregnancy in different animal models.

Prenatal maternal restraint stress exposure alters the reproductive hormone profile and testis development of the rat male offspring.

PubMed

Pallarés, María Eugenia; Adrover, Ezequiela; Baier, Carlos Javier; Bourguignon, Nadia S; Monteleone, Melisa C; Brocco, Marcela A; González-Calvar, Silvia I; Antonelli, Marta C

2013-07-01

Several studies have demonstrated that the presence of stressors during pregnancy induces adverse effects on the neuroendocrine system of the offspring later in life. In the present work, we investigated the effects of early programming on the male reproductive system, employing a prenatal stress (PS) paradigm. This study found that when pregnant dams were placed in a plastic restrainer three times a day during the last week of pregnancy, the offspring showed reduced anogenital distance and delayed testicular descent. Serum luteinising hormone (LH) and follicle-stimulating hormone (FSH) levels were decreased at postnatal day (PND) 28 and testosterone was decreased at PND 75. Increased testosterone plus dihydrotestosterone (T + DHT) concentrations correlated with increased testicular 5α Reductase-1 (5αR-1) mRNA expression at PND 28. Moreover, PS accelerated spermatogenesis at PND 35 and 60, and increased mean seminiferous tubule diameter in pubertal offspring and reduced Leydig cell number was observed at PND 35 and 60. PS offspring had increased androgen receptor (AR) mRNA level at PND 28, and at PND 35 had increased the numbers of Sertoli cells immunopositive for AR. Overall, the results confirm that stress during gestation can induce long-term effects on the male offspring reproductive system. Of particular interest is the pre-pubertal imbalance of circulating hormones that probably trigger accelerated testicular development, followed by an increase in total androgens and a decrease in testosterone concentration during adulthood. Exposure to an unfavourable intrauterine environment might prepare for harsh external conditions by triggering early puberty, increasing reproductive potential.

[Prospective study on the impact of infantile cytomegalovirus infection on growth and development of infants].

PubMed

2010-05-01

To understand the situation of postnatal cytomegalovirus (CMV) infection in Beijing and its impact on infant. From November 2004 to March 2008, a multicenter cohort study on maternal, neonatal and infantile CMV infection was carried out in four hospitals in Beijing. Two hundred and ten infants without congenital infections were enrolled into this study. Their serum IgG antibody to CMV was determined at the age of 1 year. According to the results of CMV DNA at 12 weeks of age and the CMV IgG results at 1 year of age, they were divided into three groups, perinatal infection group, postnatal infection group and postnatal non-infection group. The information of their mothers, the data of their growth and development at 1 year of age, development quotient, their eyes and their auditory function were analyzed. The risk factors of the postnatal cytomegalovirus infection were analyzed by multi-factorial logistic regression. Of the 210 infants, 42 had perinatal infection, 98 had postnatal infection and 70 had no infection. The postnatal cytomegalovirus infection rate was 46.40%, taken into account the congenital infection rate and perinatal infection rate, the total cytomegalovirus infection rate was 66.85% at 1 year of age. The clinical manifestation, developmental status and the quotient of development from three groups at birth and at 1 year of age were analyzed. No significant difference was found. In postnatal cytomegalovirus infection group the rates of breast feeding, mixed feeding and formula feeding were 87.76%, 9.18% and 3.06%, respectively; while in no infection group the rates were 61.43%, 21.43% and 17.14%, respectively(chi(2) = 17.040, P < 0.01). CMV infection is present widely in China. Non-breast feeding is an important protective factor. Postnatal cytomegalovirus infection in infants had no significant impact on the health and development of infants.

Effects of the antiandrogens, vinclozolin and cyproterone acetate on gonadal development in the Japanese medaka (Oryzias latipes).

PubMed

Kiparissis, Yiannis; Metcalfe, Tracy L; Balch, Gordon C; Metcalfe, Chris D

2003-05-29

This study was focused on determining the effects of exposure to antiandrogens on the gonadal development of Japanese medaka (Oryzias latipes). Test compounds included the fungicide, vinclozolin and the clinical antiandrogen, cyproterone acetate. Newly hatched medaka were exposed to aqueous solutions of vinclozolin (2500 microg/l) and the vinclozolin fungicide formulation, Ronilan (1000 and 5000 microg/l) and cyproterone acetate (1 and 10 microg/l), for 3 months. Histological evaluation of the gonadal tissues of exposed fish indicated that the 5000 microg/l concentration of the vinclozolin formulation (Ronilan) induced a low incidence of intersex (i.e. testis-ova) and the 2500 microg/l concentration of vinclozolin-affected spermatogenesis in males. Also, the vinclozolin treatments induced moderate ovarian atresia. Cyproterone acetate also induced a low incidence of testis-ova, but in contrast to the vinclozolin treatment the amount of ovarian tissue in the testis-ova was equal to or greater than the amount of testicular tissue. In the cyproterone acetate treatments, both oogenesis and spermatogenesis were moderately inhibited at all test concentrations. The results of this study indicate that antiandrogens have the potential to alter testicular development and gametogenesis in fish. However, research is needed to determine the mechanisms by which antiandrogens affect fish.

Interaction of oligomeric breast cancer resistant protein (BCRP) with adjudin: a male contraceptive with anti-cancer activity.

PubMed

Cheng, Yan Ho; Jenardhanan, Pranitha; Mathur, Premendu P; Qian, Xiaojing; Xia, Weiliang; Silvestrini, Bruno; Cheng, Chuen Yan

2014-01-01

Breast cancer resistant protein (BCRP, ABCG2) is an ATP-binding cassette (ABC) transporter, which together with two other ABC efflux drug pumps, namely P-glycoprotein (P-gp, ABCB1) and multidrug resistance-related protein 1 (MRP1, ABCC1) is the most important multidrug resistance protein foun d in eukaryotic cells including cells in the testis. However, unlike P-gp and MRP1, which are components of the Sertoli cell blood-testis barrier (BTB), BCRP is not expressed at the BTB in rodents and human testes. Instead, BCRP is expressed by peritubular myoid cells and endothelial cells of the lymphatic vessel in the tunica propria, residing outside the BTB. As such, the testis is equipped with two levels of defense against xenobiotics or drugs, preventing these harmful substances from entering the adluminal compartment to perturb meiosis and post-meiotic spermatid development: one at the level of the BTB conferred by P-gp and MRP1 and one at the tunica propria conferred by BCRP. The presence of drug transporters at the tunica propria as well as at the Sertoli cell BTB thus poses significant obstacles in developing non-hormonal contraceptives if these drugs (e.g., adjudin) exert their effects in germ cells behind the BTB, such as in the adluminal (apical) compartment of the seminiferous epithelium. Herein, we summarize recent findings pertinent to adjudin, a non-hormonal male contraceptive, and molecular interactions of adjudin with BCRP so that this information can be helpful to devise delivery strategies to evade BCRP in the tunica propria to improve its bioavailability in the testis.

Effects of dietary omega-3/omega-6 fatty acid ratios on reproduction in the young breeder rooster.

PubMed

Feng, Yun; Ding, Yu; Liu, Juan; Tian, Ye; Yang, Yanzhou; Guan, Shuluan; Zhang, Cheng

2015-03-21

Polyunsaturated fatty acids (PUFAs) are necessary for the body's metabolism, growth and development. Although PUFAs play an important role in the regulation of reproduction, their role in testis development in the rooster is unknown. The present study was conducted to investigate the effects of omega-3/omega-6 (n-3/n-6, PUFAs) ratios on reproductive performance in young breeder roosters. Plasma levels of reproductive hormones, testis development, and reproductive hormone receptor and StAR mRNA expression were also assessed. Although PUFAs (n-3/n-6: 1/4.15) had no significant effect on the testis index (P > 0.05), the spermatogonial development and germ cell layers were increased. Moreover, serum levels of hormones (GnRH, FSH, LH and T) on day 35 were also significantly increased by PUFAs (n-3/n-6: 1/4.15). To investigate whether PUFAs regulate the expression of hormone receptors and StAR, real time-PCR was used to measure GnRHR, FSHR, LHR and StAR mRNA levels. PUFAs significantly increased the mRNA levels of all of these genes. These results indicate that PUFAs enhance the reproductive performance of young roosters by increasing hormone secretion and function, the latter by up-regulating receptor expression. These findings provide a sound basis for a balanced n-3/n-6 PUFA ratio being beneficial to young rooster reproduction.

Hanging drop cultures of human testis and testis cancer samples: a model used to investigate activin treatment effects in a preserved niche

PubMed Central

Jørgensen, A; Young, J; Nielsen, J E; Joensen, U N; Toft, B G; Rajpert-De Meyts, E; Loveland, K L

2014-01-01

Background: Testicular germ cell tumours of young adults, seminoma or non-seminomas, are preceded by a pre-invasive precursor, carcinoma in situ (CIS), understood to arise through differentiation arrest of embryonic germ cells. Knowledge about the malignant transformation of germ cells is currently limited by the lack of experimental models. The aim of this study was to establish an experimental tissue culture model to maintain normal and malignant germ cells within their niche and allow investigation of treatment effects. Methods: Human testis and testis cancer specimens from orchidectomies were cultured in ‘hanging drops' and effects of activin A and follistatin treatment were investigated in seminoma cultures. Results: Testis fragments with normal spermatogenesis or CIS cells were cultured for 14 days with sustained proliferation of germ cells and CIS cells and without increased apoptosis. Seminoma cultures survived 7 days, with proliferating cells detectable during the first 5 days. Activin A treatment significantly reduced KIT transcript and protein levels in seminoma cultures, thereby demonstrating a specific treatment response. Conclusions: Hanging drop cultures of human testis and testis cancer samples can be employed to delineate mechanisms governing growth of normal, CIS and tumorigenic germ cells retained within their niche. PMID:24781282

From antenatal to postnatal depression: associated factors and mitigating influences.

PubMed

Redshaw, Maggie; Henderson, Jane

2013-06-01

Postnatal depression has a serious impact on new mothers and their children and families. Risk factors identified include a history of depression, multiparity, and young age. The study aimed to investigate factors associated with experiencing antenatal depression and developing subsequent postnatal depression. The study utilized survey data from 5332 women about their experience and well-being during pregnancy, in labor, and postnatally up to 3 months. Prespecified sociodemographic and clinical variables were tabulated against the incidence of antenatal depression and postnatal depression. Binary logistic regression was used to estimate the effects of the principal underlying variables. Risk factors for antenatal depression were multiparity, black and minority ethnic (BME) status, physical or mental health problems, living in a deprived area, and unplanned pregnancy. Different factors for postnatal depression were evident among women who had experienced antenatal depression: multiparity and BME status were protective, whereas being left alone in labor and experiencing poor postnatal health increased the risk of postnatal depression. This study confirms previous research on risk factors for antenatal depression and stresses the importance of continuous support in labor and vigilance in the postnatal period regarding the potential ill effects of continuing postnatal health problems.

Anger in the context of postnatal depression: An integrative review.

PubMed

Ou, Christine H; Hall, Wendy A

2018-05-20

Contrary to social constructions of new motherhood as a joyous time, mothers may experience postnatal depression and anger. Although postnatal depression has been thoroughly studied, the expression of maternal anger in the context of postnatal depression is conceptually unclear. This integrative review investigated the framing of anger in the context of postnatal depression. After undertaking a search of CINAHL, Ovid-Medline, PsycInfo, and Web of Science, we identified qualitative (n = 7) and quantitative (n = 17) papers that addressed maternal anger and postnatal depression. We analyzed the data by developing themes. Our review indicated that anger was a salient mood disturbance for some postnatally depressed women with themes integrated as: (i) anger accompanying depression, (ii) powerlessness as a component of depression and anger, and (iii) anger occurring as a result of expectations being violated. Our findings indicate that anger can coexist with women's postnatal depression. Anger can be expressed toward the self and toward children and family members with negative relationship effects. We recommend that health care providers and researchers consider anger in the context of postnatal mood disturbances. © 2018 Wiley Periodicals, Inc.

Predictors of postnatal mother-infant bonding: the role of antenatal bonding, maternal substance use and mental health.

PubMed

Rossen, Larissa; Hutchinson, Delyse; Wilson, Judy; Burns, Lucy; A Olsson, Craig; Allsop, Steve; J Elliott, Elizabeth; Jacobs, Sue; Macdonald, Jacqueline A; Mattick, Richard P

2016-08-01

The emotional bond that a mother feels towards her baby is critical to social, emotional and cognitive development. Maternal health and wellbeing through pregnancy and antenatal bonding also play a key role in determining bonding postnatally, but the extent to which these relationships may be disrupted by poor mental health or substance use is unclear. This study aimed to examine the extent to which mother-fetal bonding, substance use and mental health through pregnancy predicted postnatal mother-infant bonding at 8 weeks. Participants were 372 women recruited from three metropolitan hospitals in Australia. Data was collected during trimesters one, two and three of pregnancy and 8 weeks postnatal using the Maternal Antenatal Attachment Scale (MAAS), Maternal Postnatal Attachment Scale (MPAS), the Edinburgh Antenatal and Postnatal Depression Scale (EPDS), the Depression and Anxiety Scales (DASS-21), frequency and quantity of substance use (caffeine, alcohol and tobacco) as well as a range of demographic and postnatal information. Higher antenatal bonding predicted higher postnatal bonding at all pregnancy time-points in a fully adjusted regression model. Maternal depressive symptoms in trimesters two and three and stress in trimester two were inversely related to poorer mother-infant bonding 8 weeks postnatally. This study extends previous work on the mother's felt bond to her developing child by drawing on a large sample of women and documenting the pattern of this bond at three time points in pregnancy and at 8 weeks postnatally. Utilising multiple antenatal waves allowed precision in isolating the relationships in pregnancy and at key intervention points. Investigating methods to enhance bonding and intervene in pregnancy is needed. It is also important to assess maternal mental health through pregnancy.

Activation of GABA-A receptors during postnatal brain development increases anxiety- and depression-related behaviors in a time- and dose-dependent manner in adult mice.

PubMed

Salari, Ali-Akbar; Bakhtiari, Amir; Homberg, Judith R

2015-08-01

Disturbances of the gamma-amino butyric acid-ergic (GABAergic) system during postnatal development can have long-lasting consequences for later life behavior, like the individual's response to stress. However, it is unclear which postnatal windows of sensitivity to GABA-ergic modulations are associated with what later-life behavioral outcomes. Therefore, we sought to determine whether neonatal activation of the GABA-A receptor during two postnatal periods, an early window (postnatal day 3-5) and a late window (postnatal day 14-16), can affect anxiety- and depression-related behaviors in male mice in later life. To this end, mice were treated with either saline or muscimol (50, 100, 200, 300 and 500μg/kg) during the early and late postnatal periods. An additional group of mice was treated with the GABA-A receptor antagonist bicuculline+muscimol. When grown to adulthood male mice were exposed to behavioral tests to measure anxiety- and depression-related behaviors. Baseline and stress-induced corticosterone (CORT) levels were also measured. The results indicate that early postnatal and to a lesser extent later postnatal exposure to the GABA-A receptor agonist muscimol increased anxiety-like behavior and stress-induced CORT levels in adults. Moreover, the early postnatal treatment with muscimol increased depression-like behavior with increasing baseline CORT levels. The anxiogenic and depression-like later-life consequences could be antagonized by bicuculline. Our findings suggest that GABA-A receptor signaling during early-life can influence anxiety- and depression-related behaviors in a time- and dose-dependent manner in later life. Our findings help to increase insight in the developmental mechanisms contributing to stress-related disorders. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Nodavirus Colonizes and Replicates in the Testis of Gilthead Seabream and European Sea Bass Modulating Its Immune and Reproductive Functions

PubMed Central

Valero, Yulema; Arizcun, Marta; Esteban, M. Ángeles; Bandín, Isabel; Olveira, José G.; Patel, Sonal; Cuesta, Alberto; Chaves-Pozo, Elena

2015-01-01

Viruses are threatening pathogens for fish aquaculture. Some of them are transmitted through gonad fluids or gametes as occurs with nervous necrosis virus (NNV). In order to be transmitted through the gonad, the virus should colonize and replicate inside some cell types of this tissue and avoid the subsequent immune response locally. However, whether NNV colonizes the gonad, the cell types that are infected, and how the immune response in the gonad is regulated has never been studied. We have demonstrated for the first time the presence and localization of NNV into the testis after an experimental infection in the European sea bass (Dicentrarchus labrax), and in the gilthead seabream (Sparus aurata), a very susceptible and an asymptomatic host fish species, respectively. Thus, we localized in the testis viral RNA in both species using in situ PCR and viral proteins in gilthead seabream by immunohistochemistry, suggesting that males might also transmit the virus. In addition, we were able to isolate infective particles from the testis of both species demonstrating that NNV colonizes and replicates into the testis of both species. Blood contamination of the tissues sampled was discarded by completely fish bleeding, furthermore the in situ PCR and immunocytochemistry techniques never showed staining in blood vessels or cells. Moreover, we also determined how the immune and reproductive functions are affected comparing the effects in the testis with those found in the brain, the main target tissue of the virus. Interestingly, NNV triggered the immune response in the European sea bass but not in the gilthead seabream testis. Regarding reproductive functions, NNV infection alters 17β-estradiol and 11-ketotestosterone production and the potential sensitivity of brain and testis to these hormones, whereas there is no disruption of testicular functions according to several reproductive parameters. Moreover, we have also studied the NNV infection of the testis in vitro to assess local responses. Our in vitro results show that the changes observed on the expression of immune and reproductive genes in the testis of both species are different to those observed upon in vivo infections in most of the cases. PMID:26691348

Androgen imprinting of the brain in animal models and humans with intersex disorders: review and recommendations.

PubMed

Hrabovszky, Zoltan; Hutson, John M

2002-11-01

Psychosexual development, gender assignment and surgical treatment in patients with intersex are controversial issues in the medical literature. Some groups are of the opinion that gender identity and sexual orientation are determined prenatally secondary to the fetal hormonal environment causing irreversible development of the nervous system. We reviewed the evidence in animal and human studies to determine the possible role of early postnatal androgen production in gender development. An extensive literature review was performed of data from animal experiments and human studies. RESULTS Many animal studies show that adding or removing hormonal stimulus in early postnatal life can profoundly alter gender behavior of the adult animal. Human case studies show that late intervention is unable to reverse gender orientation from male to female. Most studies have not permitted testing of whether early gender assignment and treatment as female with suppression/ablation of postnatal androgen production leads to improved concordance of the gender identity and sex of rearing. Animal studies support a role for postnatal androgens in brain/behavior development with human studies neither completely supportive nor antagonistic. Therefore, gender assignment in infants with intersex should be made with the possibility in mind that postnatal testicular hormones at ages 1 to 6 months may affect gender identity. A case-control study is required to test the hypothesis that postnatal androgen exposure may convert ambisexual brain functions to committed male behavior patterns.

Aspiration and tetracycline sclerotherapy of primary vaginal hydrocoele of testis in adults.

PubMed

Ali, Johar; Anwar, Waqas; Akbar, Mohammad; Akbar, Syed Ali; Zafar, Arshad

2008-01-01

Primary Vaginal Hydrocoele of Testis is a common condition which is primarily treated surgically. Many patients with Hydrocoele of testis are either not willing or are unfit for surgery. This study was done to know the safety, efficacy and out come of tetracycline induced sclerotherapy of Primary Vaginal Hydrocoele of Testis in adults. This quasi experimental study was done in Shahina Jamil Hospital, attached with Frontier Medical College and Ayub Teaching Hospital, Abbottabad from March 2006 to April, 2007. Thirty-seven patients with primary vaginal hydrocoele were included in the study. Aspiration and instillation of Tetracycline was done after spermatic cord block with 2% lignocaine. Procedure time, Peri and Post-procedure complications, number of injections for cure and patients' satisfaction with the procedure were recorded. Patients were discharged home 3 to 4 hours after the procedure and followed up after one week, one month, three months and six months. Direct admission and re-admissions were recorded. The mean age of patients was 47 years. Mean procedure time was 45 minutes. All patients were cured. Mild postoprocedure pain occurred in 12 (40%), moderate pain in 14 (46%) patients and severe pain in 4 (13.3%) patients. No patient developed haematoma or local infection. One patient (3.3%) had micturition problem. Two (6.6%) patients had minimal recurrence. One injection was sufficient for cure in all patients. 28 (93%) patients were satisfied while 2 (6.6%) patients were not satisfied with this procedure. No patient was admitted in the hospital after the procedure. Aspiration and injection of tetracycline in Primary vaginal Hydrocoele of Testis in adults is safe, effective and very economical procedure.

Breast cancer resistance protein regulates apical ectoplasmic specialization dynamics stage specifically in the rat testis

PubMed Central

Qian, Xiaojing; Mruk, Dolores D.; Wong, Elissa W. P.

2013-01-01

Drug transporters determine the bioavailability of drugs in the testis behind the blood-testis barrier (BTB). Thus, they are crucial for male contraceptive development if these drugs (e.g., adjudin) exert their effects behind the BTB. Herein breast cancer resistance protein (Bcrp), an efflux drug transporter, was found to be expressed by both Sertoli and germ cells. Interestingly, Bcrp was not a component of the Sertoli cell BTB. Instead, it was highly expressed by peritubular myoid cells at the tunica propria and also endothelial cells of the microvessels in the interstitium at all stages of the epithelial cycle. Unexpectedly, Bcrp was found to be expressed at the Sertoli-step 18–19 spermatid interface but limited to stage VI-early VIII tubules, and an integrated component of the apical ectoplasmic specialization (apical ES). Apparently, Bcrp is being used by late-stage spermatids to safeguard their completion of spermiogenesis by preventing harmful drugs to enter these cells while they transform to spermatozoa. Also, the association of Bcrp with actin, Eps8 (epidermal growth factor receptor pathway substrate 8, an actin barbed end capping and bundling protein), and Arp3 (actin-related protein 3, a component of the Arp2/3 complex known to induce branched actin polymerization) at the apical ES suggest that Bcrp may be involved in regulating the organization of actin filament bundles at the site. Indeed, a knockdown of Bcrp by RNAi in the testis perturbed the apical ES function, disrupting spermatid polarity and adhesion. In summary, Bcrp is a regulator of the F-actin-rich apical ES in the testis. PMID:23403943

Morphofunctional evaluation of the testis, duration of spermatogenesis and spermatogenic efficiency in the Japanese fancy mouse (Mus musculus molossinus).

PubMed

Costa, Guilherme M J; Leal, Marcelo C; França, Luiz R

2017-08-01

Japanese fancy mouse, mini mouse or pet mouse are common names used to refer to strains of mice that present with different colour varieties and coat types. Although many genetic studies that involve spotting phenotype based on the coat have been performed in these mice, there are no reports of quantitative data in the literature regarding testis structure and spermatogenic efficiency. Hence, in this study we researched testis function and spermatogenesis in the adult Japanese fancy mouse. The following values of 68 ± 6 mg and 0.94 ± 0.1% were obtained as mean testis weight and gonadosomatic index, respectively. In comparison with other investigated mice strains, the fancy mouse Leydig cell individual size was much smaller, resulting in higher numbers of these cells per gram of testis. As found for laboratory mice strains, as a result of the development of the acrosomic system, 12 stages of the seminiferous epithelium cycle have been described in this study. The combined frequencies of pre-meiotic and post-meiotic stages were respectively 24% and 64% and very similar to the laboratory mice. The more differentiated germ cell types marked at 1 h or 9 days after tritiated thymidine administration were preleptotene/leptotene and pachytene spermatocytes at the same stage (VIII). The mean duration of one spermatogenic cycle was 8.8 ± 0.01 days and the total length of spermatogenesis lasted 37.8 ± 0.01 days (4.5 cycles). A high number of germ cell apoptosis was evident during meiosis, resulting in lower Sertoli cell and spermatogenic efficiencies, when compared with laboratory mice strains.

[Triorchidism: which therapy?

PubMed

Piro, Eugenia; Abati, Laura; Zocca, Veronica; Brugnoni, Marta; D'Alessio, Antonio

2017-06-23

Polyorchidism is an anomaly characterized by more than two gonads; triorchidism is the most common variant. Its management is controversial, mostly when surgical treatment is occasional. CB, 14 year-old, came to the hospital due to right-sided testicular torsion. During surgery, testis was rotated and the contralateral testis, which presented as an anatomically continuum with a gonadic structure similar to the other testes but with a smaller diameter, was fixed. We performed biopsy on both left testes and decided to preserve the supernumerary one. Following the anatomic and functional classification of polyorchidism by Singer, preservation is justified on the grounds of the presence of a supernumerary testis that drains into the epididymis of the normal testis, merging into one single deferent duct (Singer Type 1). At biopsy, both testes had a valid spermatogenic asset. The diagnostic follow-up at 6 and 12 months did not show any pathological alteration. Diagnosis of polyorchidism is occasional. Its treatment varies depending on the site, dimension, and anatomy of the drainage system of the supernumerary testis. If the supernumerary testis is preserved, a standardized diagnostic follow-up is recommended.

Novel noncoding RNA from human Y distal heterochromatic block (Yq12) generates testis-specific chimeric CDC2L2

PubMed Central

Jehan, Zeenath; Vallinayagam, Sambandam; Tiwari, Shrish; Pradhan, Suman; Singh, Lalji; Suresh, Amritha; Reddy, Hemakumar M.; Ahuja, Y.R.; Jesudasan, Rachel A.

2007-01-01

The human Y chromosome, because it is enriched in repetitive DNA, has been very intractable to genetic and molecular analyses. There is no previous evidence for developmental stage- and testis-specific transcription from the male-specific region of the Y (MSY). Here, we present evidence for the first time for a developmental stage- and testis-specific transcription from MSY distal heterochromatic block. We isolated two novel RNAs, which localize to Yq12 in multiple copies, show testis-specific expression, and lack active X-homologs. Experimental evidence shows that one of the above Yq12 noncoding RNAs (ncRNAs) trans-splices with CDC2L2 mRNA from chromosome 1p36.3 locus to generate a testis-specific chimeric β sv13 isoform. This 67-nt 5′UTR provided by the Yq12 transcript contains within it a Y box protein-binding CCAAT motif, indicating translational regulation of the β sv13 isoform in testis. This is also the first report of trans-splicing between a Y chromosomal and an autosomal transcript. PMID:17095710

Deregulated Cardiac Specific MicroRNAs in Postnatal Heart Growth.

PubMed

Yu, Pujiao; Wang, Hongbao; Xie, Yuan; Zhou, Jinzhe; Yao, Jianhua; Che, Lin

2016-01-01

The heart is recognized as an organ that is terminally differentiated by adulthood. However, during the process of human development, the heart is the first organ with function in the embryo and grows rapidly during the postnatal period. MicroRNAs (miRNAs, miRs), as regulators of gene expression, play important roles during the development of multiple systems. However, the role of miRNAs in postnatal heart growth is still unclear. In this study, by using qRT-PCR, we compared the expression of seven cardiac- or muscle-specific miRNAs that may be related to heart development in heart tissue from mice at postnatal days 0, 3, 8, and 14. Four miRNAs-miR-1a-3p, miR-133b-3p, miR-208b-3p, and miR-206-3p-were significantly decreased while miR-208a-3p was upregulated during the postnatal heart growth period. Based on these results, GeneSpring GX was used to predict potential downstream targets by performing a 3-way comparison of predictions from the miRWalk, PITA, and microRNAorg databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to identify potential functional annotations and signaling pathways related to postnatal heart growth. This study describes expression changes of cardiac- and muscle-specific miRNAs during postnatal heart growth and may provide new therapeutic targets for cardiovascular diseases.

Pentacle gold-copper alloy nanocrystals: a new system for entering male germ cells in vitro and in vivo

NASA Astrophysics Data System (ADS)

Lin, Yu; He, Rong; Sun, Liping; Yang, Yushan; Li, Wenqing; Sun, Fei

2016-12-01

Gold-based nanocrystals have attracted considerable attention for drug delivery and biological applications due to their distinct shapes. However, overcoming biological barriers is a hard and inevitable problem, which restricts medical applications of nanomaterials in vivo. Seeking for an efficient transportation to penetrate biological barriers is a common need. There are three barriers: blood-testis barrier, blood-placenta barrier, and blood-brain barrier. Here, we pay close attention to the blood-testis barrier. We found that the pentacle gold-copper alloy nanocrystals not only could enter GC-2 cells in vitro in a short time, but also could overcome the blood-testis barrier and enter male germ cells in vivo. Furthermore, we demonstrated that the entrance efficiency would become much higher in the development stages. The results also suggested that the pentacle gold-copper alloy nanocrystals could easier enter to germ cells in the pathological condition. This system could be a new method for theranostics in the reproductive system.

Identification of a testis-enriched heat shock protein and fourteen members of Hsp70 family in the swamp eel.

PubMed

He, Yan; Luo, Majing; Yi, Minhan; Sheng, Yue; Cheng, Yibin; Zhou, Rongjia; Cheng, Hanhua

2013-01-01

Gonad differentiation is one of the most important developmental events in vertebrates. Some heat shock proteins are associated with gonad development. Heat shock protein 70 (Hsp70) in the teleost fish and its roles in sex differentiation are poorly understood. We have identified a testis-enriched heat shock protein Hspa8b2 in the swamp eel using Western blot analysis and Mass Spectrometry (MS). Fourteen Hsp70 family genes were further identified in this species based on transcriptome information. The phylogenetic tree of Hsp70 family was constructed using the Maximum Likelihood method and their expression patterns in the swamp eel gonads were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). There are fourteen gene members in the Hsp70 family in the swamp eel genome. Hsp70 family, particularly Hspa8, has expanded in the species. One of the family members Hspa8b2 is predominantly expressed in testis of the swamp eel.

Structural and quantitative expression analyses of HERV gene family in human tissues.

PubMed

Ahn, Kung; Kim, Heui-Soo

2009-08-31

Human endogenous retroviruses (HERVs) have been implicated in the pathogenesis of several human diseases as multi-copy members in the human genome. Their gene expression profiling could provide us with important insights into the pathogenic relationship between HERVs and cancer. In this study, we have evaluated the genomic structure and quantitatively determined the expression patterns in the env gene of a variety of HERV family members located on six specific loci by the RetroTector 10 program, as well as real-time RT-PCR amplification. The env gene transcripts evidenced significant differences in the human tumor/normal adjacent tissues (colon, liver, uterus, lung and testis). As compared to the adjacent normal tissues, high levels of expression were noted in testis tumor tissues for HERV-K, in liver and lung tumor tissues for HERV-R, in liver, lung, and testis tumor tissues for HERV-H, and in colon and liver tumor tissues for HERV-P. These data warrant further studies with larger groups of patients to develop biomarkers for specific human cancers.

Temporary Depletion of Microglia during the Early Postnatal Period Induces Lasting Sex-Dependent and Sex-Independent Effects on Behavior in Rats

PubMed Central

2016-01-01

Abstract Microglia are the primary immune cells of the brain and function in multiple ways to facilitate proper brain development. However, our current understanding of how these cells influence the later expression of normal behaviors is lacking. Using the laboratory rat, we administered liposomal clodronate centrally to selectively deplete microglia in the developing postnatal brain. We then assessed a range of developmental, juvenile, and adult behaviors. Liposomal clodronate treatment on postnatal days 0, 2, and 4 depleted microglia with recovery by about 10 days of age and induced a hyperlocomotive phenotype, observable in the second postnatal week. Temporary microglia depletion also increased juvenile locomotion in the open field test and decreased anxiety-like behaviors in the open field and elevated plus maze. These same rats displayed reductions in predator odor–induced avoidance behavior, but increased their risk assessment behaviors compared with vehicle-treated controls. In adulthood, postnatal microglia depletion resulted in significant deficits in male-specific sex behaviors. Using factor analysis, we identified two underlying traits—behavioral disinhibition and locomotion—as being significantly altered by postnatal microglia depletion. These findings further implicate microglia as being critically important to the development of juvenile and adult behavior. PMID:27957532

Lipogenesis and lipid peroxidation in rat testes after long-term treatment with sucrose and tannic acid in drinking water.

PubMed

Mašek, T; Starčević, K

2017-05-01

We studied the influence of long-term treatment with sucrose and tannic acid in drinking water on the fatty acid profile and lipid peroxidation in rat testes. Male Wistar rats were supplemented with sucrose (30% w/v) or with sucrose and tannic acid (sucrose 30% w/v, tannic acid 0.1% w/v) in drinking water. The treatment with sucrose elevated blood glucose levels in the plasma (p < .05) and decreased the testis weight (p < .05) and testis index (p < .05) of the rats. Sucrose treatment increased monounsaturated fatty acids (MUFA) and C22:6n3, and decreased n6 fatty acids in testis tissue. Lipid peroxidation was significantly increased after sucrose administration in plasma (p < .05) and testis tissue (p < .01). The addition of tannic acid led to the decrease in lipid peroxidation in the plasma (p < .05) and testis (p < .05), a further increase in MUFA and decrease in n6 fatty acids. In conclusion, sucrose significantly altered the testis fatty acid profile with an increase in MUFA and C22:6n3, and a decrease in n6 fatty acids. Tannic acid attenuated oxidative stress and hyperglycaemia, but it did not improve pathological changes in the fatty acid composition of the testis. © 2016 Blackwell Verlag GmbH.

Dynamic changes in DNA demethylation in the tree shrew (Tupaia belangeri chinensis) brain during postnatal development and aging.

PubMed

Wei, Shu; Hua, Hai-Rong; Chen, Qian-Quan; Zhang, Ying; Chen, Fei; Li, Shu-Qing; Li, Fan; Li, Jia-Li

2017-03-18

Brain development and aging are associated with alterations in multiple epigenetic systems, including DNA methylation and demethylation patterns. Here, we observed that the levels of the 5-hydroxymethylcytosine (5hmC) ten-eleven translocation (TET) enzyme-mediated active DNA demethylation products were dynamically changed and involved in postnatal brain development and aging in tree shrews ( Tupaia belangeri chinensis ). The levels of 5hmC in multiple anatomic structures showed a gradual increase throughout postnatal development, whereas a significant decrease in 5hmC was found in several brain regions in aged tree shrews, including in the prefrontal cortex and hippocampus, but not the cerebellum. Active changes in Tet mRNA levels indicated that TET2 and TET3 predominantly contributed to the changes in 5hmC levels. Our findings provide new insight into the dynamic changes in 5hmC levels in tree shrew brains during postnatal development and aging processes.

Mode of action for reproductive and hepatic toxicity inferred from a genomic study of triazole antifungals.

PubMed

Goetz, Amber K; Dix, David J

2009-08-01

The mode of action for the reproductive toxicity of some triazole antifungals has been characterized as an increase in serum testosterone and hepatic response, and reduced insemination and fertility indices. In order to refine our mechanistic understanding of these potential modes of action, gene expression profiling was conducted on liver and testis from male Wistar Han IGS rats exposed to myclobutanil (500, 2000 ppm), propiconazole (500, 2500 ppm), or triadimefon (500, 1800 ppm) from gestation day six to postnatal day 92. Gene expression profiles indicated that all three triazoles significantly perturbed the fatty acid, steroid, and xenobiotic metabolism pathways in the male rat liver. In addition, triadimefon modulated expression of genes in the liver from the sterol biosynthesis pathway. Although expression of individual genes were affected, there were no common pathways modulated by all three triazoles in the testis. The pathways identified in the liver included numerous genes involved in phase I-III metabolism (Aldh1a1, Cyp1a1, Cyp2b2, Cyp3a1, Cyp3a2, Slco1a4, Udpgtr2), fatty acid metabolism (Cyp4a10, Pcx, Ppap2b), and steroid metabolism (Ugt1a1, Ugt2a1) for which expression was altered by the triazoles. These differentially expressed genes form part of a network involving lipid, sterol, and steroid homeostatic pathways regulated by the constitutive androstane (CAR), pregnane X (PXR), peroxisome proliferator-activated alpha, and other nuclear receptors in liver. These relatively high dose and long-term exposures to triazole antifungals appeared to perturb fatty acid and steroid metabolism in the male rat liver predominantly through the CAR and PXR signaling pathways. These toxicogenomic effects describe a plausible series of key events contributing to the disruption in steroid homeostasis and reproductive toxicity of select triazole antifungals.

Knockdown of the GnRH-II receptor in the porcine testis impairs the biosynthesis of 10 gonadal steroids

USDA-ARS?s Scientific Manuscript database

The second mammalian GnRH isoform (GnRH-II) and its cognate receptor (GnRHR-II) are poor modulators of gonadotropin secretion in swine. However, both are abundantly produced within the porcine testis suggesting an autocrine/paracrine role. Within the boar testis, GnRHR-II immunolocalizes to the plas...

Supplementation with fish oil and coconut fat prevents prenatal stress-induced changes in early postnatal development.

PubMed

Borsonelo, Elizabethe C; Suchecki, Deborah; Calil, Helena Maria; Galduróz, José Carlos F

2011-08-01

Adequate development of the central nervous system depends on prenatal and postnatal factors. On one hand, prenatal stress (PNS) has been implicated in impaired development of the offspring. On other hand, nutritional factors during pregnancy and lactation can influence fetal and postnatal growth. This study assessed the postnatal development of rat offspring exposed to PNS, which consisted of restraint and bright lights, 3 times/day, from days 14 to 20 of pregnancy, whose mothers were fed different diets during pregnancy and lactation: regular diet, diet supplemented with coconut fat or fish oil. When pregnancy was confirmed, they were distributed into control (CTL) or PNS groups. At birth, PNS males and females weighed less than those in the group CTL. At 21 days of age, this alteration was no longer observed with fish oil and coconut fat groups. PNS and coconut fat diet induced increased locomotor activity in 13 day old male and female pups, and this effect was prevented by fish oil supplementation only in females. In conclusion, postnatal development from birth to weaning was influenced by PNS and diet and some of those alterations were prevented by coconut fat and fish oil. Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.

Avian infectious bronchitis virus: a possible cause of reduced fertility in the rooster.

PubMed

Boltz, David A; Nakai, Masaaki; Bahra, Janice M

2004-12-01

The formation of epididymal stones in the rooster epididymis is a widespread problem that has detrimental effects on sperm production and fertility. The cause of epididymal stones is unknown, but an infectious agent, the avian infectious bronchitis virus (AIBV), has been implicated. The goal of this study was to determine if administering the live attenuated AIBV vaccine to male chicks increases the incidence of stones in the epididymal region of the adult rooster. Specific pathogen free (SPF) Leghorn roosters were divided into two groups: a vaccine-free group (n = 7) and a group vaccinated with AIBV (n = 12). The vaccine was administered orally at 2, 4, 10, and 14 wk of age. Blood was drawn weekly to monitor antibodies to AIBV. At 26 wk of age, blood was obtained to determine testosterone concentrations, and reproductive tracts were removed to analyze daily sperm production and to detect epididymal stones. Nine of 12 vaccinated roosters developed stones, whereas those not given the vaccine did not develop stones. Serum testosterone concentrations were significantly (P < 0.05) reduced in vaccinated roosters with epididymal stones (3.6 +/- 0.30 ng/ml) when compared with nonvaccinated roosters that did not have epididymal stones (7.0 +/- 1.63 ng/ml). Testis weight was significantly (P < 0.05) reduced in vaccinated roosters with epididymal stones (12.1 +/- 0.76 g), as compared with nonvaccinated roosters without epididymal stones (15.2 +/- 0.81 g). Daily sperm production was significantly (P < 0.05) decreased in vaccinated roosters with epididymal stones (5.03 +/- 0.31 x 10(8) sperm/testis/day) when compared with nonvaccinated roosters without epididymal stones (7.43 +/- 0.52 x 10(8) sperm/testis/day). Comparing daily sperm production on a per gram basis, vaccinated roosters with epididymal stones had 4.38 +/- 0.14 x 10(7) sperm/g of testis, which was significantly (P < 0.05) smaller than nonvaccinated roosters without epididymal stones, which had 5.17 +/- 0.17 x 10(7) sperm/g of testis. We conclude that the use of a live attenuated AIBV vaccine increases the incidence of epididymal stones in roosters, resulting in decreased sperm production and decreased serum testosterone concentrations.

Gene discovery in the hamster: a comparative genomics approach for gene annotation by sequencing of hamster testis cDNAs

PubMed Central

Oduru, Sreedhar; Campbell, Janee L; Karri, SriTulasi; Hendry, William J; Khan, Shafiq A; Williams, Simon C

2003-01-01

Background Complete genome annotation will likely be achieved through a combination of computer-based analysis of available genome sequences combined with direct experimental characterization of expressed regions of individual genomes. We have utilized a comparative genomics approach involving the sequencing of randomly selected hamster testis cDNAs to begin to identify genes not previously annotated on the human, mouse, rat and Fugu (pufferfish) genomes. Results 735 distinct sequences were analyzed for their relatedness to known sequences in public databases. Eight of these sequences were derived from previously unidentified genes and expression of these genes in testis was confirmed by Northern blotting. The genomic locations of each sequence were mapped in human, mouse, rat and pufferfish, where applicable, and the structure of their cognate genes was derived using computer-based predictions, genomic comparisons and analysis of uncharacterized cDNA sequences from human and macaque. Conclusion The use of a comparative genomics approach resulted in the identification of eight cDNAs that correspond to previously uncharacterized genes in the human genome. The proteins encoded by these genes included a new member of the kinesin superfamily, a SET/MYND-domain protein, and six proteins for which no specific function could be predicted. Each gene was expressed primarily in testis, suggesting that they may play roles in the development and/or function of testicular cells. PMID:12783626

[Perineal ectopic testis: report of four paediatric cases].

PubMed

Jlidi, Said; Echaieb, Anis; Ghorbel, Sofiene; Khemakhem, Rachid; Ben Khalifa, Sonia; Chaouachi, Béji

2004-09-01

Perineal ectopic testis is a rare congenital malformation in which the testis is abnormally situated between the penoscrotal raphe and the genitofemoral fold. The authors report four new cases in children aged 2 months, 6 months, 2 years and 5 years. The abnormality was associated with an inguinal hernia in one case. The diagnosis was based on the presence of an empty scrotum or perineal swelling. Treatment, via an inguinal incision, consisted of orchidopexy in a dartos pouch with a favourable course in every case. The aetiopathogenesis of perineal ectopic testis is controversial. It can be easily diagnosed by palpation of the testis in the perineal region. Orchidopexy in a dartos pouch must be performed early, and does not raise any particular problems because of the sufficient length of the spermatic cord. The functional prognosis, always difficult to define, appears to be identical to that of other sites.

A case of adenocarcinoma of the rete testis accompanied by focal adenomatous hyperplasia

PubMed Central

2013-01-01

Abstract Adenocarcinoma of the rete testis is very rare. There is still little knowledge about its etiology and pathogenesis. Herein, we present a case of rete testis adenocarcinoma in a 36-year-old Chinese male. The tumor was predominantly composed of irregular small tubules and papillary structures with cuboidal or polygonal cells. In peripheral area of the tumor, the remaining normal rete testis and adenomatous hyperplasia of the rete testis could also be seen, indicating the possible relationship between adenomatous hyperplasia and adenocarcinoma. In addition, the patient underwent a left hydrocelectomy because of the existence of hydrocele 3 years ago. But, it is unclear whether hydrocele and hydrocelectomy is its cause or just the early clinical presentation of the adenocarcinoma. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6757609119625499 PMID:23800084

Specialized rules of gene transcription in male germ cells: the CREM paradigm.

PubMed

Monaco, Lucia; Kotaja, Noora; Fienga, Giulia; Hogeveen, Kevin; Kolthur, Ullas S; Kimmins, Sarah; Brancorsini, Stefano; Macho, Betina; Sassone-Corsi, Paolo

2004-12-01

Specialized transcription complexes that coordinate the differentiation programme of spermatogenesis have been found in germ cells, which display specific differences in the components of the general transcription machinery. The TATA-binding protein family and its associated cofactors, for example, show upregulated expression in testis. In this physiological context, transcriptional control mediated by the activator cAMP response element modulator (CREM) represents an established paradigm. Somatic cell activation by CREM requires its phosphorylation at a unique regulatory site (Ser117) and subsequent interaction with the ubiquitous coactivator CREB-binding protein. In testis, CREM transcriptional activity is controlled through interaction with a tissue-specific partner, activator of CREM in the testis (ACT), which confers a powerful, phosphorylation-independent activation capacity. The function of ACT was found to be regulated by the testis-specific kinesin KIF17b. Here we discuss some aspects of the testis-specific transcription machinery, whose function is essential for the process of spermatogenesis.

Interaction of Oligomeric Breast Cancer Resistant Protein (BCRP) with Adjudin: A Male Contraceptive with Anti-Cancer Activity

PubMed Central

Cheng, Yan Ho; Jenardhanan, Pranitha; Mathur, Premendu P.; Qian, Xiaojing; Xia, Weiliang; Silvestrini, Bruno; Cheng, Chuen Yan

2016-01-01

Breast cancer resistant protein (BCRP, ABCG2) is an ATP-binding cassette (ABC) transporter, which together with two other ABC efflux drug pumps, namely P-glycoprotein (P-gp, ABCB1) and multidrug resistance-related protein 1 (MRP1, ABCC1) is the most important multidrug resistance protein found in eukaryotic cells including cells in the testis. However, unlike P-gp and MRP1, which are components of the Sertoli cell blood-testis barrier (BTB), BCRP is not expressed at the BTB in rodents and human testes. Instead, BCRP is expressed by peritubular myoid cells and endothelial cells of the lymphatic vessel in the tunica propria, residing outside the BTB. As such, the testis is equipped with two levels of defense against xenobiotics or drugs, preventing these harmful substances from entering the adluminal compartment to perturb meiosis and post-meiotic spermatid development: one at the level of the BTB conferred by P-gp and MRP1 and one at the tunica propria conferred by BCRP. The presence of drug transporters at the tunica propria as well as at the Sertoli cell BTB thus poses significant obstacles in developing non-hormonal contraceptives if these drugs (e.g., adjudin) exert their effects in germ cells behind the BTB, such as in the adluminal (apical) compartment of the seminiferous epithelium. Herein, we summarize recent findings pertinent to adjudin, a non-hormonal male contraceptive, and molecular interactions of adjudin with BCRP so that this information can be helpful to devise delivery strategies to evade BCRP in the tunica propria to improve its bioavailability in the testis. PMID:25620224

Effect of maternal excessive sodium intake on postnatal brain development in rat offspring.

PubMed

Shin, Jung-a; Ahn, Young-mo; Lee, Hye-ah; Park, Hyesook; Kim, Young-ju; Lee, Hwa-young

2015-04-01

Postnatal brain development is affected by the in utero environment. Modern people usually have a high sodium intake. The aim of this study was to investigate the effect of sodium hyperingestion during pregnancy on the postnatal brain development of rat offspring. The sodium-overloaded rats received 1.8% NaCl in their drinking water for 7 days during the last week of gestation. Their body weight, urine, and blood levels of sodium and other parameters were measured. Some rats were sacrificed at pregnancy day 22 and the weight and length of the placenta and foetus were measured. The cerebral cortex and hippocampus were obtained from their offspring at postnatal day 1 and at postnatal weeks 1, 2, 4, and 8. Western blot analyses were conducted with brain tissue lysates. The sodium-overloaded animals had decreased weight gain in the last week of gestation as well as decreased food intake, increased water intake, urine volume, urine sodium, and serum sodium. There were no differences in placental weight and length. The foetuses of sodium-overloaded rats showed decreased body weight and size, and this difference was maintained postnatally for 2 weeks. In the cerebral cortex and hippocampus of the offspring, the protein levels of myelin basic protein, calmodulin/calcium-dependent protein kinase II, and brain-derived neurotrophic factor were decreased or aberrantly expressed. The present data suggest that increased sodium intake during pregnancy affects the brain development of the offspring.

Loss of p300 and CBP disrupts histone acetylation at the mouse Sry promoter and causes XY gonadal sex reversal

PubMed Central

Carré, Gwenn-Aël; Siggers, Pam; Xipolita, Marilena; Brindle, Paul; Lutz, Beat; Wells, Sara; Greenfield, Andy

2018-01-01

Abstract CREB-binding protein (CBP, CREBBP, KAT3A) and its closely related paralogue p300 (EP300, KAT3B), together termed p300/CBP, are histone/lysine acetyl-transferases that control gene expression by modifying chromatin-associated proteins. Here, we report roles for both of these chromatin-modifying enzymes in mouse sex determination, the process by which the embryonic gonad develops into a testis or an ovary. By targeting gene ablation to embryonic gonadal somatic cells using an inducible Cre line, we show that gonads lacking either gene exhibit major abnormalities of XY gonad development at 14.5 dpc, including partial sex reversal. Embryos lacking three out of four functional copies of p300/Cbp exhibit complete XY gonadal sex reversal and have greatly reduced expression of the key testis-determining genes Sry and Sox9. An analysis of histone acetylation at the Sry promoter in mutant gonads at 11.5 dpc shows a reduction in levels of the positive histone mark H3K27Ac. Our data suggest a role for CBP/p300 in testis determination mediated by control of histone acetylation at the Sry locus and reveal a novel element in the epigenetic control of Sry and mammalian sex determination. They also suggest possible novel causes of human disorders of sex development (DSD). PMID:29145650

Early postnatal exposure to isoflurane causes cognitive deficits and disrupts development of newborn hippocampal neurons via activation of the mTOR pathway

PubMed Central

Lim, Sanghee; Kwak, Minhye; Gray, Christy D.; Xu, Michael; Choi, Jun H.; Junn, Sue; Kim, Jieun; Xu, Jing; Schaefer, Michele; Johns, Roger A.; Song, Hongjun; Ming, Guo-Li; Mintz, C. David

2017-01-01

Clinical and preclinical studies indicate that early postnatal exposure to anesthetics can lead to lasting deficits in learning and other cognitive processes. The mechanism underlying this phenomenon has not been clarified and there is no treatment currently available. Recent evidence suggests that anesthetics might cause persistent deficits in cognitive function by disrupting key events in brain development. The hippocampus, a brain region that is critical for learning and memory, contains a large number of neurons that develop in the early postnatal period, which are thus vulnerable to perturbation by anesthetic exposure. Using an in vivo mouse model we demonstrate abnormal development of dendrite arbors and dendritic spines in newly generated dentate gyrus granule cell neurons of the hippocampus after a clinically relevant isoflurane anesthesia exposure conducted at an early postnatal age. Furthermore, we find that isoflurane causes a sustained increase in activity in the mechanistic target of rapamycin pathway, and that inhibition of this pathway with rapamycin not only reverses the observed changes in neuronal development, but also substantially improves performance on behavioral tasks of spatial learning and memory that are impaired by isoflurane exposure. We conclude that isoflurane disrupts the development of hippocampal neurons generated in the early postnatal period by activating a well-defined neurodevelopmental disease pathway and that this phenotype can be reversed by pharmacologic inhibition. PMID:28683067

A blood-testis barrier restricting passage from blood into rete testis fluid but not into lymph

PubMed Central

Setchell, B. P.; Voglmayr, J. K.; Waites, G. M. H.

1969-01-01

1. A permeability barrier in or around the seminiferous tubules of rams has been demonstrated by studying the rate of passage of a variety of substances from blood plasma into fluid collected from the rete testis and into testicular lymph. 2. All substances studied passed readily into testicular lymph. 3. Tritiated water, urea, ethanol and bicarbonate in rete testis fluid equilibrated with blood plasma within 3 hr; Na+, K+, Rb+, Cl-, I-, CNS-, creatinine and galactose entered slowly and p-aminohippurate (PAH), glutamate, iodinated albumin, inulin and [51Cr]EDTA did not appear in rete testis fluid at all. 4. Rubidium was excluded relative to iodoantipyrine from the testes of control and hypophysectomized rats and from rat testes heated to 37, 40, 43 and 45° C; no such exclusion was seen in testes of rats which had been given cadmium chloride 5 months earlier so as to destroy the seminiferous tubules. 5. It is suggested that this permeability barrier will regulate the access to the seminiferous epithelium of some constituents of blood plasma, isolate the germinal cells immunologically and help to maintain the concentration differences between rete testis fluid and lymph or blood plasma. PMID:4973530

PAGE-1, an X chromosome-linked GAGE-like gene that is expressed in normal and neoplastic prostate, testis, and uterus

PubMed Central

Brinkmann, Ulrich; Vasmatzis, George; Lee, Byungkook; Yerushalmi, Noga; Essand, Magnus; Pastan, Ira

1998-01-01

We have used a combination of computerized database mining and experimental expression analyses to identify a gene that is preferentially expressed in normal male and female reproductive tissues, prostate, testis, fallopian tube, uterus, and placenta, as well as in prostate cancer, testicular cancer, and uterine cancer. This gene is located on the human X chromosome, and it is homologous to a family of genes encoding GAGE-like proteins. GAGE proteins are expressed in a variety of tumors and in testis. We designate the novel gene PAGE-1 because the expression pattern in the Cancer Genome Anatomy Project libraries indicates that it is predominantly expressed in normal and neoplastic prostate. Further database analysis indicates the presence of other genes with high homology to PAGE-1, which were found in cDNA libraries derived from testis, pooled libraries (with testis), and in a germ cell tumor library. The expression of PAGE-1 in normal and malignant prostate, testicular, and uterine tissues makes it a possible target for the diagnosis and possibly for the vaccine-based therapy of neoplasms of prostate, testis, and uterus. PMID:9724777

PAGE-1, an X chromosome-linked GAGE-like gene that is expressed in normal and neoplastic prostate, testis, and uterus.

PubMed

Brinkmann, U; Vasmatzis, G; Lee, B; Yerushalmi, N; Essand, M; Pastan, I

1998-09-01

We have used a combination of computerized database mining and experimental expression analyses to identify a gene that is preferentially expressed in normal male and female reproductive tissues, prostate, testis, fallopian tube, uterus, and placenta, as well as in prostate cancer, testicular cancer, and uterine cancer. This gene is located on the human X chromosome, and it is homologous to a family of genes encoding GAGE-like proteins. GAGE proteins are expressed in a variety of tumors and in testis. We designate the novel gene PAGE-1 because the expression pattern in the Cancer Genome Anatomy Project libraries indicates that it is predominantly expressed in normal and neoplastic prostate. Further database analysis indicates the presence of other genes with high homology to PAGE-1, which were found in cDNA libraries derived from testis, pooled libraries (with testis), and in a germ cell tumor library. The expression of PAGE-1 in normal and malignant prostate, testicular, and uterine tissues makes it a possible target for the diagnosis and possibly for the vaccine-based therapy of neoplasms of prostate, testis, and uterus.

Cystic dysplasia of the testis: a very rare paediatric tumor of the testis.

PubMed

Eberli, Daniel; Gretener, Heini; Dommann-Scherrer, Corina; Pestalozzi, Dietegen; Fehr, Jean-Luc

2002-01-01

To describe a case of cystic dysplasia of the testis (CDT), an uncommon cause of scrotal swelling in the pediatric patient. Clinic, therapy, fertility, and radiographic and pathologic findings are discussed and the 30 previously reported cases are reviewed. A 9-year-old boy presented with asymptomatic scrotal swelling. A scrotal ultrasound showed a multicystic scrotal mass in the rete testis and an ipsilateral renal agenesis. The growth in size of the mass forced the authors to perform an operative exploration. Intraoperative findings included a multicystic mass in the rete testis of the right testicle. Testicle-sparing total removal of the multicystic mass was performed and the pathologic examination revealed a benign, multilobulated configuration of the cysts in the region of the rete testis. These findings were similar to those found in previously reported cases of CDT. Ipsilateral renal agenesis is the most common associated anomaly. As a pathogenetic factor, mal-junction of the Wolffian duct in the 5th week of gestation is most creditable. CDT is a rare cause of pediatric scrotal mass. When feasible, a testicle-sparing approach should be considered and all patients should undergo evaluation for associated urologic anomalies.

A new bioluminescent imaging technology for studying oxidative stress in the testis and its impacts on fertility.

PubMed

Ma, Qixiang; Shao, Haozhen; Feng, Yanyan; Zhang, Linpeng; Li, Pengshou; Hu, Xiaowei; Ma, Zhitao; Lou, Hua; Zeng, Xianwei; Luo, Guangbin

2018-05-24

Excessive oxidative stress (OS) leads to cellular dysfunctions and cell death and constitutes a major cause of male infertility. However, the etiologies of increased reactive oxygen species (ROS) in male infertility is not fully understood. One major limitation is the lack of an in vivo imaging system that can be used to effectively study the impact of excessive ROS in the testis. Recently, we discovered that the hepatocellular carcinoma reporter (HCR) mice previously generated in our laboratory also expressed luciferase in the spermatids of the testis. The goal of the current study is to use the HCR mice to detect OS in the testis and to investigate the potential use of this new system in studying OS-induced male infertility. Bioluminescence imaging (BLI) was performed in HCR mice that were treated with peroxy caged luciferin-1 (PCL-1), an OS reporter, to establish a new mouse model for in vivo monitoring of the OS status inside the male reproductive tract. Subsequently, the effect of acetaminophen (APAP) overdose on the OS inside the testis and male fertility were determined. Lastly, APAP was co-administered with glutathione, an antioxidant reagent, to test if the HCR mice can serve as a model for the effective and rapid assessment of the potency of individual agents in modifying the OS inside the mouse testis. The OS level in the testis in the HCR mice was readily detected by BLI. The use of this new model led to the discovery that APAP caused a sudden rise of OS in the testis and was a potent toxicant for the male reproductive system. Moreover, administration of glutathione was effective in preventing the APAP-induced elevation of OS and in ameliorating all of the OS-induced anomalies in the testis. The HCR mice represent an excellent model for monitoring OS change in the mouse testis by real time BLI. APAP is a potent male reproductive toxicant and APAP-treated mice represent a valid model for OS-induced male infertility. This model can be used to study OS-induced damage in male reproductive tract and in assessing the effects of therapeutic agents on the relative levels of OS and male fertility. Copyright © 2018 Elsevier Inc. All rights reserved.

Effects of Trans-Resveratrol on hyperglycemia-induced abnormal spermatogenesis, DNA damage and alterations in poly (ADP-ribose) polymerase signaling in rat testis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abdelali, Ala

Diabetes induces oxidative stress, DNA damage and alters several intracellular signaling pathways in organ systems. This study investigated modulatory effects of Trans-Resveratrol on type 1 diabetes mellitus (T1DM)-induced abnormal spermatogenesis, DNA damage and alterations in poly (ADP-ribose) polymerase (PARP) signaling in rat testis. Trans-Resveratrol administration (5mg/kg/day, ip) to Streptozotocin-induced T1DM adult male Wistar rats from day 22–42 resulted in recovery of induced oxidative stress, abnormal spermatogenesis and inhibited DNA synthesis, and led to mitigation of 8-hydroxy-2'-deoxyguanosine formation in the testis and spermatozoa, and DNA double-strand breaks in the testis. Trans-Resveratrol aggravated T1DM-induced up-regulation of aminoacyl tRNA synthetase complex-interacting multifunctional proteinmore » 2 expression; however, it did not modify the up-regulated total PARP and down-regulated PARP1 expressions, but recovered the decreased SirT1 (Sirtuin 1) levels in T1DM rat testis. Trans-Resveratrol, when given alone, reduced the poly (ADP-ribosyl)ation (pADPr) process in the testis due to an increase in PAR glycohydrolase activity, but when given to T1DM rats it did not affect the pADPr levels. T1DM with or without Trans-Resveratrol did not induce nuclear translocation of apoptosis-inducing factor and the formation of 50 kb DNA breaks, suggesting to the lack of caspase-3-independent cell death called parthanatos. T1DM with or without Trans-Resveratrol did not increase necrotic cell death in the testis. Primary spermatocytes, Sertoli cells, Leydig cells and intra-testicular vessels showed the expression of PARP pathway related proteins. In conclusion, Trans-Resveratrol mitigates T1DM-induced sperm abnormality and DNA damage, but does not significantly modulate PARP signaling pathway, except the SirT1 expression, in the rat testis. - Highlights: • Resveratrol inhibits diabetes-induced abnormal sperm morphogenesis • Resveratrol recovers diabetes-induced DNA damage in testis and spermatozoa • Resveratrol does not normalize diabetes-induced increase in total PARP • Resveratrol does not modulate diabetes-induced decrease in PARP1 • Resveratrol normalizes diabetes-induced decrease in SirT1 levels in testis.« less

Effect of vitamin E supplement in diet on antioxidant ability of testis in Boer goat.

PubMed

Hong, Zhu; Hailing, Luo; Hui, Meng; Guijie, Zhang; Leyan, Yan; Dubing, Yue

2010-01-01

The aim of this study was to evaluate the supplementation of Vitamin E in diet on the antioxidant capacity of testis in Boer goat. Twenty-four healthy, Boer male kids of similar body weight (BW) were selected at 3 months of age from the kid flock. Kids were born from does treated with simultaneous flushing and artificial insemination technology. The Boer kids were divided into four groups randomly, supplemented with 0, 80, 320 and 880 IU kid(-1)d(-1) Vitamin E, which were labeled as Groups 1, 2, 3 and 4, respectively, for 150 days (5 months). Blood samples were collected at the 15th-, 30th-, 60th-, 90th-, 120th-, and 150th-day during the experimental period, and the serums were used to determine Vitamin E content. Three Boer goats in each group were slaughtered at the age of eight months at the end of the experiment. Liver and testis were collected to test the Vitamin E content and the antioxidant capacity of testis. Results showed that the content of Vitamin E in serum, liver and testis increased with the increasing addition of Vitamin E. However, the content of Vitamin E in the serum, liver and testis, in the control, was significantly lower than in Groups 2 and 3, respectively, but there was no significant difference between the control Group and Group 4. When high levels of Vitamin E (880 IU kid(-1)d(-1)) were added, contents of Vitamin E in serum, liver and testis were decreased and compared with the controls. Adding a low level (80 IU kid(-1)d(-1)) of Vitamin E can increase activity of total anti-oxidation competence (T-AOC) and superoxide dismutase (SOD), and decrease content of nitric oxide (NO) in testis. MDA (malondialdehyde) content was decreased significantly in Group 3 (P<0.05). Supplementing a low level (80 IU kid(-1)d(-1)) and middle level (320 IU kid(-1)d(-1)) of Vitamin E decreased activity of nitric oxide syntha (NOS) in testis (P<0.05). Vitamin E can increase activity of GSH-PX (glutathione peroxidase). These results indicate that supplementing Vitamin E protects testis from damage by preoxidation.

Intestinal absorption and renal reabsorption of calcium throughout postnatal development

PubMed Central

Beggs, Megan R

2017-01-01

Calcium is vital for many physiological functions including bone mineralization. Postnatal deposition of calcium into bone is greatest in infancy and continues through childhood and adolescence until peek mineral density is reached in early adulthood. Thereafter, bone mineral density remains static until it eventually declines in later life. A positive calcium balance, i.e. more calcium absorbed than excreted, is crucial to bone deposition during growth and thus to peek bone mineral density. Dietary calcium is absorbed from the intestine into the blood. It is then filtered by the renal glomerulus and either reabsorbed by the tubule or excreted in the urine. Calcium can be (re)absorbed across intestinal and renal epithelia via both transcellular and paracellular pathways. Current evidence suggests that significant intestinal and renal calcium transport changes occur throughout development. However, the molecular details of these alterations are incompletely delineated. Here we first briefly review the current model of calcium transport in the intestine and renal tubule in the adult. Then, we describe what is known with regard to calcium handling through postnatal development, and how alterations may aid in mediating a positive calcium balance. The role of transcellular and paracellular calcium transport pathways and the contribution of specific intestinal and tubular segments vary with age. However, the current literature highlights knowledge gaps in how specifically intestinal and renal calcium (re)absorption occurs early in postnatal development. Future research should clarify the specific changes in calcium transport throughout early postnatal development including mediators of these alterations enabling appropriate bone mineralization. Impact statement This mini review outlines the current state of knowledge pertaining to the molecules and mechanisms maintaining a positive calcium balance throughout postnatal development. This process is essential to achieving optimal bone mineral density in early adulthood, thereby lowering the lifetime risk of osteoporosis. PMID:28346014

Conserved form and function of the germinal epithelium through 500 million years of vertebrate evolution.

PubMed

Grier, Harry J; Uribe, Mari Carmen; Lo Nostro, Fabiana L; Mims, Steven D; Parenti, Lynne R

2016-08-01

The germinal epithelium, i.e., the site of germ cell production in males and females, has maintained a constant form and function throughout 500 million years of vertebrate evolution. The distinguishing characteristic of germinal epithelia among all vertebrates, males, and females, is the presence of germ cells among somatic epithelial cells. The somatic epithelial cells, Sertoli cells in males or follicle (granulosa) cells in females, encompass and isolate germ cells. Morphology of all vertebrate germinal epithelia conforms to the standard definition of an epithelium: epithelial cells are interconnected, border a body surface or lumen, are avascular and are supported by a basement membrane. Variation in morphology of gonads, which develop from the germinal epithelium, is correlated with the evolution of reproductive modes. In hagfishes, lampreys, and elasmobranchs, the germinal epithelia of males produce spermatocysts. A major rearrangement of testis morphology diagnoses osteichthyans: the spermatocysts are arranged in tubules or lobules. In protogynous (female to male) sex reversal in teleost fishes, female germinal epithelial cells (prefollicle cells) and oogonia transform into the first male somatic cells (Sertoli cells) and spermatogonia in the developing testis lobules. This common origin of cell types from the germinal epithelium in fishes with protogynous sex reversal supports the homology of Sertoli cells and follicle cells. Spermatogenesis in amphibians develops within spermatocysts in testis lobules. In amniotes vertebrates, the testis is composed of seminiferous tubules wherein spermatogenesis occurs radially. Emerging research indicates that some mammals do not have lifetime determinate fecundity. The fact emerged that germinal epithelia occur in the gonads of all vertebrates examined herein of both sexes and has the same form and function across all vertebrate taxa. Continued study of the form and function of the germinal epithelium in vertebrates will increasingly clarify our understanding of vertebrate reproduction. J. Morphol. 277:1014-1044, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Couple comorbidity and correlates of postnatal depressive symptoms in mothers and fathers in the first two weeks following delivery.

PubMed

Anding, Jana Eos; Röhrle, Bernd; Grieshop, Melita; Schücking, Beate; Christiansen, Hanna

2016-01-15

Postnatal depression affects a significant number of parents; however, its co-occurrence in mothers and fathers has not been studied extensively. Identifying predictors and correlates of postnatal depressive symptoms can help develop effective interventions. Questionnaires on several socio-demographic and psychosocial factors were administered to 276 couples within two weeks after birth. Depressive symptoms in mothers and fathers were assessed using the Edinburgh Postnatal Depression Scale (EPDS). After calculating the correlation coefficient between mothers and fathers' EPDS scores, univariate and multivariate linear regression analyses were performed to identify significant correlates of postnatal depressive symptoms in mothers and fathers. Prevalence of maternal and paternal postnatal depressive symptoms was 15.9% (EPDS>12) and 5.4% (EPDS>10), respectively. There was a moderate positive correlation between mothers and fathers' EPDS scores (r=.30, p<.001). Multivariate analyses indicated that parental stress was the strongest predictor for maternal and paternal postnatal depressive symptoms. Pregnancy- and birth-related distress and partners' EPDS scores were also associated with depressive symptoms in both parents. Relationship satisfaction was only inversely related with fathers' EPDS scores, while mothers' EPDS scores were additionally associated with critical life events, history of childhood violence, and birth-related physiological complaints. Since information about participation rates (those who declined) is unavailable, we cannot rule out sampling bias. Further, some psychosocial factors were assessed using single items. Since co-occurrence of depressive symptoms in mothers and fathers is high, developing and evaluating postnatal depression interventions for couples may be beneficial. Interventions to reduce parenting stress may help prevent parental postnatal depression. Copyright © 2015 Elsevier B.V. All rights reserved.

Widespread neuronal degeneration in rats following oral administration of methylmercury during the postnatal developing phase: a model of fetal-type minamata disease.

PubMed

Sakamoto, M; Wakabayashi, K; Kakita, A; Hitoshi Takahashi; Adachi, T; Nakano, A

1998-02-16

The neurotoxicity of methylmercury (MeHg) treatment during the postnatal developing phase in rats was studied. Rats on postnatal day 1 were orally administered 5 mg/kg/day methylmercury chloride (MMC) for more than 30 consecutive days. Body weight loss began 26 days after MMC was administered, and severe paralysis of the hind-limbs and unsteadiness appeared subsequently. Histopathologically, the widespread neuronal degeneration was observed in the cerebral neocortex, neostriatum, red nucleus, brainstem, cerebellum and spinal dorsal root ganglia on day 32. The widespread distribution of the lesions was quite similar to that in fetal cases of MeHg intoxication in Minamata, Japan. These findings suggest that MMC treatment during the postnatal development phase in rats produce a good model of fetal-type Minamata disease. Copyright 1998 Elsevier Science B.V.

Fetal and post-natal lung defects reveal a novel and required role for Fgf8 in lung development

PubMed Central

Yu, Shibin; Poe, Bryan; Schwarz, Margaret; Elliot, Sarah; Albertine, Kurt H.; Fenton, Stephen; Garg, Vidu; Moon, Anne M.

2016-01-01

The fibroblast growth factor, FGF8, has been shown to be essential for vertebrate cardiovascular, craniofacial, brain and limb development. Here we report that Fgf8 function is required for normal progression through the late fetal stages of lung development that culminate in alveolar formation. Budding, lobation and branching morphogenesis are unaffected in early stage Fgf8 hypomorphic and conditional mutant lungs. Excess proliferation during fetal development disrupts distal airspace formation, mesenchymal and vascular remodeling, and Type I epithelial cell differentiation resulting in postnatal respiratory failure and death. Our findings reveal a previously unknown, critical role for Fgf8 function in fetal lung development and suggest that this factor may also contribute to postnatal alveologenesis. Given the high number of premature infants with alveolar dysgenesis and lung dysplasia, and the accumulating evidence that short-term benefits of available therapies may be outweighed by long term detrimental effects on postnatal alveologenesis, the therapeutic implications of identifying a factor or pathway that can be targeted to stimulate normal alveolar development are profound. PMID:20727874

Cognition and behavioural development in early childhood: the role of birth weight and postnatal growth.

PubMed

Huang, Cheng; Martorell, Reynaldo; Ren, Aiguo; Li, Zhiwen

2013-02-01

We evaluate the relative importance of birth weight and postnatal growth for cognition and behavioural development in 8389 Chinese children, 4-7 years of age. Method Weight was the only size measure available at birth. Weight, height, head circumference and intelligence quotient (IQ) were measured between 4 and 7 years of age. Z-scores of birth weight and postnatal conditional weight gain to 4-7 years, as well as height and head circumference at 4-7 years of age, were the exposure variables. Z-scores of weight at 4-7 years were regressed on birth weight Z-scores, and the residual was used as the measure of postnatal conditional weight gain. The outcomes were child's IQ, measured by the Chinese Wechsler Young Children Scale of Intelligence, as well as internalizing behavioural problems, externalizing behavioural problems and other behavioural problems, evaluated by the Child Behavior Checklist 4-18. Multivariate regressions were conducted to investigate the relationship of birth weight and postnatal growth variables with the outcomes, separately for preterm children and term children. Both birth weight and postnatal weight gain were associated with IQ among term children; 1 unit increment in Z-score of birth weight (∼450 g) was associated with an increase of 1.60 [Confidence interval (CI): 1.18-2.02; P < 0.001] points in IQ, and 1 unit increment in conditional postnatal weight was associated with an increase of 0.46 (CI: 0.06-0.86; P = 0.02) points in IQ, after adjustment for confounders; similar patterns were observed when Z-scores of postnatal height and head circumference at age 4-7 years were used as alternative measurements of postnatal growth. Effect sizes of relationships with IQ were smaller than 0.1 of a standard deviation in all cases. Neither birth weight nor postnatal growth indicators were associated with behavioural outcomes among term children. In preterm children, neither birth weight nor postnatal growth measures were associated with IQ or behavioural outcomes. Both birth weight and postnatal growth were associated with IQ but not behavioural outcomes for Chinese term children aged 4-7 years, but the effect sizes were small. No relation between either birth weight or postnatal growth and cognition or behavioural outcomes was observed among preterm children aged 4-7 years.

Chronic pain has a negative impact on sexuality in testis cancer survivors.

PubMed

Pühse, Gerald; Wachsmuth, Julia Urte; Kemper, Sebastian; Husstedt, Ingo W; Evers, Stefan; Kliesch, Sabine

2012-01-01

Testis cancer is a disease that directly affects a man's sense of masculinity and involves treatments compromising sexual function. The aim of this study was to investigate the prevalence of sexual dysfunction and the influence of chronic pain on sexuality in long-term testis cancer survivors. Thus, we examined 539 patients after they had one testis removed because of a testicular germ cell tumor. Having completed oncologic therapy, all patients received a detailed questionnaire asking about the occurrence and clinical presentation of testis pain before and after orchiectomy. In addition, items from the abridged International Index of Erectile Function and Brief Sexual Function Inventory were used to gain precise information on individual sexual function. Overall, 34.5% of our testicular cancer survivors complained of reduced sexual desire, and sexual activity was reduced in 41.6%. Erectile dysfunction was present in up to 31.5% of patients. In 24.4%, the ability to maintain an erection during intercourse was impaired. Ejaculatory disorders (premature, delayed, retrograde, or anejaculation) occurred in 84.9% of our testis cancer survivors. A total of 32.4% of our participants experienced a reduced intensity of orgasm, and 95.4% experienced reduced overall sexual satisfaction. There was a significant correlation between the occurrence of chronic pain symptoms and the relative frequency and intensity of erectile dysfunction, inability to maintain an erection, ejaculation disorders, and reduced intensity of orgasm. In conclusion, chronic pain has a negative impact on sexuality in testis cancer survivors.

An essential role for IGF2 in cartilage development and glucose metabolism during postnatal long bone growth.

PubMed

Uchimura, Tomoya; Hollander, Judith M; Nakamura, Daisy S; Liu, Zhiyi; Rosen, Clifford J; Georgakoudi, Irene; Zeng, Li

2017-10-01

Postnatal bone growth involves a dramatic increase in length and girth. Intriguingly, this period of growth is independent of growth hormone and the underlying mechanism is poorly understood. Recently, an IGF2 mutation was identified in humans with early postnatal growth restriction. Here, we show that IGF2 is essential for longitudinal and appositional murine postnatal bone development, which involves proper timing of chondrocyte maturation and perichondrial cell differentiation and survival. Importantly, the Igf2 null mouse model does not represent a simple delay of growth but instead uncoordinated growth plate development. Furthermore, biochemical and two-photon imaging analyses identified elevated and imbalanced glucose metabolism in the Igf2 null mouse. Attenuation of glycolysis rescued the mutant phenotype of premature cartilage maturation, thereby indicating that IGF2 controls bone growth by regulating glucose metabolism in chondrocytes. This work links glucose metabolism with cartilage development and provides insight into the fundamental understanding of human growth abnormalities. © 2017. Published by The Company of Biologists Ltd.

Maternal Postnatal Depression and the Development of Depression in Offspring up to 16 Years of Age

ERIC Educational Resources Information Center

Murray, Lynne; Arteche, Adriane; Fearon, Pasco; Halligan, Sarah; Goodyer, Ian; Cooper, Peter

2011-01-01

Objective: The aim of this study was to determine the developmental risk pathway to depression by 16 years in offspring of postnatally depressed mothers. Method: This was a prospective longitudinal study of offspring of postnatally depressed and nondepressed mothers; child and family assessments were made from infancy to 16 years. A total of 702…

Maternal postnatal mental health and later emotional-behavioural development of children: the mediating role of parenting behaviour.

PubMed

Giallo, R; Cooklin, A; Wade, C; D'Esposito, F; Nicholson, J M

2014-05-01

Maternal postnatal mental health difficulties have been associated with poor outcomes for children. One mechanism by which parent mental health can impact on children's outcomes is via its effects on parenting behaviour. The longitudinal relationships between maternal postnatal distress, parenting warmth, hostility and child well-being at age seven were examined for 2200 families participating in a population-based longitudinal study of Australian children. The relationship between postnatal distress and children's later emotional-behavioural development was mediated by parenting hostility, but not parenting warmth, even after accounting for concurrent maternal mental health. Postnatal distress was more strongly associated with lower parenting warmth for mothers without a past history of depression compared with mothers with a past history of depression. These findings underscore the contribution of early maternal well-being to later parenting and child outcomes, highlighting the importance of mental health and parenting support in the early parenting years. Implications for policy and practice are discussed. © 2013 John Wiley & Sons Ltd.

A systematic approach towards the development of quality indicators for postnatal care after discharge in Flanders, Belgium.

PubMed

Helsloot, Kaat; Walraevens, Mieke; Besauw, Saskia Van; Van Parys, An-Sofie; Devos, Hanne; Holsbeeck, Ann Van; Roelens, Kristien

2017-05-01

to develop a set of quality indicators for postnatal care after discharge from the hospital, using a systematic approach. key elements of qualitative postnatal care were defined by performing a systematic review and the literature was searched for potential indicators (step 1). The potential indicators were evaluated by five criteria (validity, reliability, sensitivity, feasibility and acceptability) and by making use of the 'Appraisal of Guidelines for Research and Evaluation', the AIRE-instrument (step 2). In a modified Delphi-survey, the quality indicators were presented to a panel of experts in the field of postnatal care using an online tool (step 3). The final results led to a Flemish model of postnatal care (step 4). Flanders, Belgium PARTICIPANTS: health care professionals, representatives of health care organisations and policy makers with expertise in the field of postnatal care. after analysis 57 research articles, 10 reviews, one book and eight other documents resulted in 150 potential quality indicators in seven critical care domains. Quality assessment of the indicators resulted in 58 concept quality indicators which were presented to an expert-panel of health care professionals. After two Delphi-rounds, 30 quality indicators (six structure, 17 process, and seven outcome indicators) were found appropriate to monitor and improve the quality of postnatal care after discharge from the hospital. KEY CONCLUSIONS AND IMPLICATIONS FOR CLINICAL PRACTICE: the quality indicators resulted in a Flemish model of qualitative postnatal care that was implemented by health authorities as a minimum standard in the context of shortened length of stay. Postnatal care should be adjusted to a flexible length of stay and start in pregnancy with an individualised care plan that follows mother and new-born throughout pregnancy, childbirth and postnatal period. Criteria for discharge and local protocols about the organisation and content of care are essential to facilitate continuity of care. Copyright © 2017 Elsevier Ltd. All rights reserved.

Germ cell tumors: Insights from the Drosophila ovary and the mouse testis.

PubMed

Salz, Helen K; Dawson, Emily P; Heaney, Jason D

2017-03-01

Ovarian and testicular germ cell tumors of young adults are thought to arise from defects in germ cell development, but the molecular mechanisms underlying malignant transformation are poorly understood. In this review, we focus on the biology of germ cell tumor formation in the Drosophila ovary and the mouse testis, for which evidence supports common underlying mechanisms, such as blocking initiation into the differentiation pathway, impaired lineage progression, and sexual identity instability. We then discuss how these concepts inform our understanding of the disease in humans. Mol. Reprod. Dev. 84: 200-211, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

The Postnatal Development of Spinal Sensory Processing

NASA Astrophysics Data System (ADS)

Fitzgerald, Maria; Jennings, Ernest

1999-07-01

The mechanisms by which infants and children process pain should be viewed within the context of a developing sensory nervous system. The study of the neurophysiological properties and connectivity of sensory neurons in the developing spinal cord dorsal horn of the intact postnatal rat has shed light on the way in which the newborn central nervous system analyzes cutaneous innocuous and noxious stimuli. The receptive field properties and evoked activity of newborn dorsal horn cells to single repetitive and persistent innocuous and noxious inputs are developmentally regulated and reflect the maturation of excitatory transmission within the spinal cord. These changes will have an important influence on pain processing in the postnatal period.

Canine cryptorchism and subsequent testicular neoplasia: case-control study with epidemiologic update.

PubMed

Hayes, H M; Wilson, G P; Pendergrass, T W; Cox, V S

1985-08-01

A retrospective study of 2,912 cryptorchid dogs identified 14 breeds with significantly high risk. Among six distinct closely interrelated breed groups (e.g., toy, miniature, and standard poodles), the risk in the smaller breed was always greater than that in the larger relative, suggesting that genetically influenced maldescent could be, in part, related to physical size or the rate of growth of the involved structures. Testicular tumors were diagnosed in 5.7% of the cryptorchid dogs; half had only Sertoli cell tumors, one-third had only seminomas. The relative risk for Sertoli cell tumor or seminoma was not directly related to a familial risk for cryptorchism. Using the health experience of a control population composed of male dogs with anal sac disease (N = 4,184), there is an estimated relative risk of 9.2 in cryptorchid dogs to develop a testis tumor (95% confidence interval, 5.9-14.3) and 4.2 in dogs with inguinal hernia (95% confidence interval, 1.8-9.5). Considering that the anatomical development of the genital tract, testis descent, and tunic relationships in dog are very similar to that in man, and that the associations of cryptorchism and inguinal hernia with testis neoplasms are also similar, the dog should be an excellent model system to further investigate the causes of human cryptorchism.

Spontaneous CD4+ and CD8+ T‐cell responses directed against cancer testis antigens are present in the peripheral blood of testicular cancer patients

PubMed Central

Pearce, Hayden; Hutton, Paul; Chaudhri, Shalini; Porfiri, Emilio; Patel, Prashant; Viney, Richard

2017-01-01

Cancer/testis antigen (CTAg) expression is restricted to spermatogenic cells in an immune‐privileged site within the testis. However, these proteins are expressed aberrantly by malignant cells and T‐cell responses against CTAgs develop in many cancer patients. We investigated the prevalence, magnitude and phenotype of CTAg‐specific T cells in the blood of patients with testicular germ cell tumors (TGCTs). CD8+ and CD4+ T‐cell responses against MAGE‐A family antigens were present in 44% (20/45) of patients’ samples assayed by ex vivo IFN‐γ ELISPOT. The presence of MAGE‐specific CD8+ T cells was further determined following short‐term in vitro expansion through the use of pMHC‐I multimers containing known immunogenic peptides. Longitudinal analysis revealed that the frequency of MAGE‐specific T cells decreased by 89% following orchidectomy suggesting that persistence of tumor antigen is required to sustain CTAg‐specific T‐cell immunity. Notably, this decrease correlated with a decline in the global effector/memory T‐cell pool following treatment. Spontaneous T‐cell immunity against CTAg proteins therefore develops in many patients with testicular cancer and may play an important role in the excellent clinical outcome of patients with this tumor subtype. PMID:28555838

Recent advances of in vitro culture systems for spermatogonial stem cells in mammals.

PubMed

Sahare, Mahesh G; Suyatno; Imai, Hiroshi

2018-04-01

Spermatogonial stem cells (SSCs) in the mammalian testis are unipotent stem cells for spermatozoa. They show unique cell characteristics as stem cells and germ cells after being isolated from the testis and cultured in vitro. This review introduces recent progress in the development of culture systems for the establishment of SSC lines in mammalian species, including humans. Based on the published reports, the isolation and purification of SSCs, identification and characteristics of SSCs, and culture system for mice, humans, and domestic animals have been summarized. In mice, cell lines from SSCs are established and can be reprogrammed to show pluripotent stem cell potency that is similar to embryonic stem cells. However, it is difficult to establish cell lines for animals other than mice because of the dearth of understanding about species-specific requirements for growth factors and mechanisms supporting the self-renewal of cultured SSCs. Among the factors that are associated with the development of culture systems, the enrichment of SSCs that are isolated from the testis and the combination of growth factors are essential. Providing an example of SSC culture in cattle, a rational consideration was made about how it can be possible to establish cell lines from neonatal and immature testes.

Backdoor pathway for dihydrotestosterone biosynthesis: implications for normal and abnormal human sex development.

PubMed

Fukami, Maki; Homma, Keiko; Hasegawa, Tomonobu; Ogata, Tsutomu

2013-04-01

We review the current knowledge about the "backdoor" pathway for the biosynthesis of dihydrotestosterone (DHT). While DHT is produced from cholesterol through the conventional "frontdoor" pathway via testosterone, recent studies have provided compelling evidence for the presence of an alternative "backdoor" pathway to DHT without testosterone intermediacy. This backdoor pathway is known to exist in the tammar wallaby pouch young testis and the immature mouse testis, and has been suggested to be present in the human as well. Indeed, molecular analysis has identified pathologic mutations of genes involved in the backdoor pathway in genetic male patients with undermasculinized external genitalia, and urine steroid profile analysis has argued for the relevance of the activated backdoor pathway to abnormal virilization in genetic females with cytochrome P450 oxidoreductase deficiency and 21-hydroxylase deficiency. It is likely that the backdoor pathway is primarily operating in the fetal testis in a physiological condition to produce a sufficient amount of DHT for male sex development, and that the backdoor pathway is driven with a possible interaction between fetal and permanent adrenals in pathologic conditions with increased 17-hydroxyprogesterone levels. These findings provide novel insights into androgen biosynthesis in both physiological and pathological conditions. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

Characterisation of ATRX, DMRT1, DMRT7 and WT1 in the platypus (Ornithorhynchus anatinus).

PubMed

Tsend-Ayush, Enkhjargal; Lim, Shu Ly; Pask, Andrew J; Hamdan, Diana Demiyah Mohd; Renfree, Marilyn B; Grützner, Frank

2009-01-01

One of the most puzzling aspects of monotreme reproductive biology is how they determine sex in the absence of the SRY gene that triggers testis development in most other mammals. Although monotremes share a XX female/XY male sex chromosome system with other mammals, their sex chromosomes show homology to the chicken Z chromosome, including the DMRT1 gene, which is a dosage-dependent sex determination gene in birds. In addition, monotremes feature an extraordinary multiple sex chromosome system. However, no sex determination gene has been identified as yet on any of the five X or five Y chromosomes and there is very little knowledge about the conservation and function of other known genes in the monotreme sex determination and differentiation pathway. We have analysed the expression pattern of four evolutionarily conserved genes that are important at different stages of sexual development in therian mammals. DMRT1 is a conserved sex-determination gene that is upregulated in the male developing gonad in vertebrates, while DMRT7 is a mammal-specific spermatogenesis gene. ATRX, a chromatin remodelling protein, lies on the therian X but there is a testis-expressed Y-copy in marsupials. However, in monotremes, the ATRX orthologue is autosomal. WT1 is an evolutionarily conserved gene essential for early gonadal formation in both sexes and later in testis development. We show that these four genes in the adult platypus have the same expression pattern as in other mammals, suggesting that they have a conserved role in sexual development independent of genomic location.

Mosaic analysis of gene function in postnatal mouse brain development by using virus-based Cre recombination.

PubMed

Gibson, Daniel A; Ma, Le

2011-08-01

Normal brain function relies not only on embryonic development when major neuronal pathways are established, but also on postnatal development when neural circuits are matured and refined. Misregulation at this stage may lead to neurological and psychiatric disorders such as autism and schizophrenia. Many genes have been studied in the prenatal brain and found crucial to many developmental processes. However, their function in the postnatal brain is largely unknown, partly because their deletion in mice often leads to lethality during neonatal development, and partly because their requirement in early development hampers the postnatal analysis. To overcome these obstacles, floxed alleles of these genes are currently being generated in mice. When combined with transgenic alleles that express Cre recombinase in specific cell types, conditional deletion can be achieved to study gene function in the postnatal brain. However, this method requires additional alleles and extra time (3-6 months) to generate the mice with appropriate genotypes, thereby limiting the expansion of the genetic analysis to a large scale in the mouse brain. Here we demonstrate a complementary approach that uses virally-expressed Cre to study these floxed alleles rapidly and systematically in postnatal brain development. By injecting recombinant adeno-associated viruses (rAAVs) encoding Cre into the neonatal brain, we are able to delete the gene of interest in different regions of the brain. By controlling the viral titer and coexpressing a fluorescent protein marker, we can simultaneously achieve mosaic gene inactivation and sparse neuronal labeling. This method bypasses the requirement of many genes in early development, and allows us to study their cell autonomous function in many critical processes in postnatal brain development, including axonal and dendritic growth, branching, and tiling, as well as synapse formation and refinement. This method has been used successfully in our own lab (unpublished results) and others, and can be extended to other viruses, such as lentivirus, as well as to the expression of shRNA or dominant active proteins. Furthermore, by combining this technique with electrophysiology as well as recently-developed optical imaging tools, this method provides a new strategy to study how genetic pathways influence neural circuit development and function in mice and rats.

Disorders of Sex Development with Testicular Differentiation in SRY-Negative 46,XX Individuals: Clinical and Genetic Aspects.

PubMed

Grinspon, Romina P; Rey, Rodolfo A

2016-01-01

Virilisation of the XX foetus is the result of androgen excess, resulting most frequently from congenital adrenal hyperplasia in individuals with typical ovarian differentiation. In rare cases, 46,XX gonads may differentiate into testes, a condition known as 46,XX testicular disorders of sex development (DSD), or give rise to the coexistence of ovarian and testicular tissue, a condition known as 46,XX ovotesticular DSD. Testicular tissue differentiation may be due to the translocation of SRY to the X chromosome or an autosome. In the absence of SRY, overexpression of other pro-testis genes, e.g. SOX family genes, or failure of pro-ovarian/anti-testis genes, such as WNT4 and RSPO1, may underlie the development of testicular tissue. Recent experimental and clinical evidence giving insight into SRY-negative 46,XX testicular or ovotesticular DSD is discussed. © 2016 S. Karger AG, Basel.

Changes in fine structure of pericytes and novel desmin-immunopositive perivascular cells during postnatal development in rat anterior pituitary gland.

PubMed

Jindatip, Depicha; Fujiwara, Ken; Horiguchi, Kotaro; Tsukada, Takehiro; Kouki, Tom; Yashiro, Takashi

2013-09-01

Pericytes are perivascular cells associated with capillaries. We previously demonstrated that pericytes, identified by desmin immunohistochemistry, produce type I and III collagens in the anterior pituitary gland of adult rats. In addition, we recently used desmin immunoelectron microscopy to characterize a novel type of perivascular cell, dubbed a desmin-immunopositive perivascular cell, in the anterior pituitary. These two types of perivascular cells differ in fine structure. The present study attempted to characterize the morphological features of pituitary pericytes and novel desmin-immunopositive perivascular cells during postnatal development, in particular their role in collagen synthesis. Desmin immunostaining revealed numerous perivascular cells at postnatal day 5 (P5) and P10. Transmission electron microscopy showed differences in the fine structure of the two cell types, starting at P5. Pericytes had well-developed rough endoplasmic reticulum and Golgi apparatus at P5 and P10. The novel desmin-immunopositive perivascular cells exhibited dilated cisternae of rough endoplasmic reticulum at P5-P30. In addition, during early postnatal development in the gland, a number of type I and III collagen-expressing cells were observed, as were high expression levels of these collagen mRNAs. We conclude that pituitary pericytes and novel desmin-immunopositive perivascular cells contain well-developed cell organelles and that they actively synthesize collagens during the early postnatal period.

Disproportionate cardiac hypertrophy during early postnatal development in infants born preterm.

PubMed

Aye, Christina Y L; Lewandowski, Adam J; Lamata, Pablo; Upton, Ross; Davis, Esther; Ohuma, Eric O; Kenworthy, Yvonne; Boardman, Henry; Wopperer, Samuel; Packham, Alice; Adwani, Satish; McCormick, Kenny; Papageorghiou, Aris T; Leeson, Paul

2017-07-01

BackgroundAdults born very preterm have increased cardiac mass and reduced function. We investigated whether a hypertrophic phenomenon occurs in later preterm infants and when this occurs during early development.MethodsCardiac ultrasound was performed on 392 infants (33% preterm at mean gestation 34±2 weeks). Scans were performed during fetal development in 137, at birth and 3 months of postnatal age in 200, and during both fetal and postnatal development in 55. Cardiac morphology and function was quantified and computational models created to identify geometric changes.ResultsAt birth, preterm offspring had reduced cardiac mass and volume relative to body size with a more globular heart. By 3 months, ventricular shape had normalized but both left and right ventricular mass relative to body size were significantly higher than expected for postmenstrual age (left 57.8±41.9 vs. 27.3±29.4%, P<0.001; right 39.3±38.1 vs. 16.6±40.8, P=0.002). Greater changes were associated with lower gestational age at birth (left P<0.001; right P=0.001).ConclusionPreterm offspring, including those born in late gestation, have a disproportionate increase in ventricular mass from birth up to 3 months of postnatal age. These differences were not present before birth. Early postnatal development may provide a window for interventions relevant to long-term cardiovascular health.

Disproportionate cardiac hypertrophy during early postnatal development in infants born preterm

PubMed Central

Aye, Christina Y L; Lewandowski, Adam J; Lamata, Pablo; Upton, Ross; Davis, Esther; Ohuma, Eric O; Kenworthy, Yvonne; Boardman, Henry; Wopperer, Samuel; Packham, Alice; Adwani, Satish; McCormick, Kenny; Papageorghiou, Aris T; Leeson, Paul

2017-01-01

Background Adults born very preterm have increased cardiac mass and reduced function. We investigated whether a hypertrophic phenomenon occurs in later preterm infants and when this occurs during early development. Methods Cardiac ultrasound was performed on 392 infants (33% preterm at mean gestation 34±2 weeks). Scans were performed during fetal development in 137, at birth and 3 months of postnatal age in 200, and during both fetal and postnatal development in 55. Cardiac morphology and function was quantified and computational models created to identify geometric changes. Results At birth, preterm offspring had reduced cardiac mass and volume relative to body size with a more globular heart. By 3 months, ventricular shape had normalized but both left and right ventricular mass relative to body size were significantly higher than expected for postmenstrual age (left 57.8±41.9 vs. 27.3±29.4%, P<0.001; right 39.3±38.1 vs. 16.6±40.8, P=0.002). Greater changes were associated with lower gestational age at birth (left P<0.001; right P=0.001). Conclusion Preterm offspring, including those born in late gestation, have a disproportionate increase in ventricular mass from birth up to 3 months of postnatal age. These differences were not present before birth. Early postnatal development may provide a window for interventions relevant to long-term cardiovascular health. PMID:28399117

Postnatal proteasome inhibition induces neurodegeneration and cognitive deficiencies in adult mice: a new model of neurodevelopment syndrome.

PubMed

Romero-Granados, Rocío; Fontán-Lozano, Ángela; Aguilar-Montilla, Francisco Javier; Carrión, Ángel Manuel

2011-01-01

Defects in the ubiquitin-proteasome system have been related to aging and the development of neurodegenerative disease, although the effects of deficient proteasome activity during early postnatal development are poorly understood. Accordingly, we have assessed how proteasome dysfunction during early postnatal development, induced by administering proteasome inhibitors daily during the first 10 days of life, affects the behaviour of adult mice. We found that this regime of exposure to the proteasome inhibitors MG132 or lactacystin did not produce significant behavioural or morphological changes in the first 15 days of life. However, towards the end of the treatment with proteasome inhibitors, there was a loss of mitochondrial markers and activity, and an increase in DNA oxidation. On reaching adulthood, the memory of mice that were injected with proteasome inhibitors postnatally was impaired in hippocampal and amygdala-dependent tasks, and they suffered motor dysfunction and imbalance. These behavioural deficiencies were correlated with neuronal loss in the hippocampus, amygdala and brainstem, and with diminished adult neurogenesis. Accordingly, impairing proteasome activity at early postnatal ages appears to cause morphological and behavioural alterations in adult mice that resemble those associated with certain neurodegenerative diseases and/or syndromes of mental retardation.

Blueberry extracts protect testis from hypobaric hypoxia induced oxidative stress in rats.

PubMed

Zepeda, Andrea; Aguayo, Luis G; Fuentealba, Jorge; Figueroa, Carolina; Acevedo, Alejandro; Salgado, Perla; Calaf, Gloria M; Farías, Jorge

2012-01-01

Exposure to hypobaric hypoxia causes oxidative damage to male rat reproductive function. The aim of this study was to evaluate the protective effect of a blueberry extract (BB-4) in testis of rats exposed to hypobaric hypoxia. Morphometric analysis, cellular DNA fragmentation, glutathione reductase (GR), and superoxide dismutase (SOD) activities were evaluated. Our results showed that supplementation of BB-4 reduced lipid peroxidation, decreased apoptosis, and increased GR and SOD activities in rat testis under hypobaric hypoxia conditions (P < 0.05). Therefore, this study demonstrates that blueberry extract significantly reduced the harmful effects of oxidative stress caused by hypobaric hypoxia in rat testis by affecting glutathione reductase and superoxide dismutase activities.

Post-natal myogenic and adipogenic developmental

PubMed Central

Konings, Gonda; van Weeghel, Michel; van den Hoogenhof, Maarten MG; Gijbels, Marion; van Erk, Arie; Schoonderwoerd, Kees; van den Bosch, Bianca; Dahlmans, Vivian; Calis, Chantal; Houten, Sander M; Misteli, Tom

2011-01-01

A-type lamins are a major component of the nuclear lamina. Mutations in the LMNA gene, which encodes the A-type lamins A and C, cause a set of phenotypically diverse diseases collectively called laminopathies. While adult LMNA null mice show various symptoms typically associated with laminopathies, the effect of loss of lamin A/C on early post-natal development is poorly understood. Here we developed a novel LMNA null mouse (LMNAGT−/−) based on genetrap technology and analyzed its early post-natal development. We detect LMNA transcripts in heart, the outflow tract, dorsal aorta, liver and somites during early embryonic development. Loss of A-type lamins results in severe growth retardation and developmental defects of the heart, including impaired myocyte hypertrophy, skeletal muscle hypotrophy, decreased amounts of subcutaneous adipose tissue and impaired ex vivo adipogenic differentiation. These defects cause death at 2 to 3 weeks post partum associated with muscle weakness and metabolic complications, but without the occurrence of dilated cardiomyopathy or an obvious progeroid phenotype. Our results indicate that defective early post-natal development critically contributes to the disease phenotypes in adult laminopathies. PMID:21818413

Homeodomain interacting protein kinase 2 regulates postnatal development of enteric dopaminergic neurons and glia via BMP signaling.

PubMed

Chalazonitis, Alcmène; Tang, Amy A; Shang, Yulei; Pham, Tuan D; Hsieh, Ivy; Setlik, Wanda; Gershon, Michael D; Huang, Eric J

2011-09-28

Trophic factor signaling is important for the migration, differentiation, and survival of enteric neurons during development. The mechanisms that regulate the maturation of enteric neurons in postnatal life, however, are poorly understood. Here, we show that transcriptional cofactor HIPK2 (homeodomain interacting protein kinase 2) is required for the maturation of enteric neurons and for regulating gliogenesis during postnatal development. Mice lacking HIPK2 display a spectrum of gastrointestinal (GI) phenotypes, including distention of colon and slowed GI transit time. Although loss of HIPK2 does not affect the enteric neurons in prenatal development, a progressive loss of enteric neurons occurs during postnatal life in Hipk2(-/-) mutant mice that preferentially affects the dopaminergic population of neurons in the caudal region of the intestine. The mechanism by which HIPK2 regulates postnatal enteric neuron development appears to involve the response of enteric neurons to bone morphogenetic proteins (BMPs). Specifically, compared to wild type mice, a larger proportion of enteric neurons in Hipk2(-/-) mutants have an abnormally high level of phosphorylated Smad1/5/8. Consistent with the ability of BMP signaling to promote gliogenesis, Hipk2(-/-) mutants show a significant increase in glia in the enteric nervous system. In addition, numbers of autophagosomes are increased in enteric neurons in Hipk2(-/-) mutants, and synaptic maturation is arrested. These results reveal a new role for HIPK2 as an important transcriptional cofactor that regulates the BMP signaling pathway in the maintenance of enteric neurons and glia, and further suggest that HIPK2 and its associated signaling mechanisms may be therapeutically altered to promote postnatal neuronal maturation.

Educating the European Citizen in the Global Age: Engaging with the Post-National and Identifying a Research Agenda

ERIC Educational Resources Information Center

Marshall, Harriet

2009-01-01

In recent decades there have been increased calls for UK schools to develop a more European and global orientation in their pedagogy and curriculum, and to equip children and young people with post-national knowledge, skills, and dispositions. This paper examines some key problems in post-national conceptions of citizenship education, in order to…

Lipidomics reveals dramatic lipid compositional changes in the maturing postnatal lung

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dautel, Sydney E.; Kyle, Jennifer E.; Clair, Geremy

Lung immaturity is a major cause of morbidity and mortality in premature infants. Understanding the molecular mechanisms driving normal lung development could provide insights on how to ameliorate disrupted development. While transcriptomic and proteomic analyses of normal lung development have been previously reported, characterization of changes in the lipidome is lacking. Lipids play significant roles in the lung, such as dipalmitoylcholine in pulmonary surfactant; however, many of the roles of specific lipid species in normal lung development, as well as in disease states, are not well defined. In this study, we used liquid chromatography-mass spectrometry (LC-MS/MS) to investigate the murinemore » lipidome during normal postnatal lung development. Lipidomics analysis of lungs from post-natal day 7, day 14 and 6-8 week mice (adult) identified 928 unique lipids across 21 lipid subclasses, with dramatic alterations in the lipidome across developmental stages. Our data confirmed previously recognized aspects of post-natal lung development and revealed several insights, including in sphingolipid-mediated apoptosis, inflammation and energy storage/usage. Complementary proteomics, metabolomics and chemical imaging corroborated these observations. Finally, this multi-omic view provides a unique resource and deeper insight into normal pulmonary development.« less

Lipidomics reveals dramatic lipid compositional changes in the maturing postnatal lung

DOE PAGES

Dautel, Sydney E.; Kyle, Jennifer E.; Clair, Geremy; ...

2017-02-01

Lung immaturity is a major cause of morbidity and mortality in premature infants. Understanding the molecular mechanisms driving normal lung development could provide insights on how to ameliorate disrupted development. While transcriptomic and proteomic analyses of normal lung development have been previously reported, characterization of changes in the lipidome is lacking. Lipids play significant roles in the lung, such as dipalmitoylcholine in pulmonary surfactant; however, many of the roles of specific lipid species in normal lung development, as well as in disease states, are not well defined. In this study, we used liquid chromatography-mass spectrometry (LC-MS/MS) to investigate the murinemore » lipidome during normal postnatal lung development. Lipidomics analysis of lungs from post-natal day 7, day 14 and 6-8 week mice (adult) identified 928 unique lipids across 21 lipid subclasses, with dramatic alterations in the lipidome across developmental stages. Our data confirmed previously recognized aspects of post-natal lung development and revealed several insights, including in sphingolipid-mediated apoptosis, inflammation and energy storage/usage. Complementary proteomics, metabolomics and chemical imaging corroborated these observations. Finally, this multi-omic view provides a unique resource and deeper insight into normal pulmonary development.« less

Transgenerational Epigenetic Programming of the Embryonic Testis Transcriptome

PubMed Central

Anway, Matthew D.; Rekow, Stephen S.; Skinner, Michael K.

2008-01-01

Embryonic exposure to the endocrine disruptor vinclozolin during gonadal sex determination appears to promote an epigenetic reprogramming of the male germ-line that is associated with transgenerational adult onset disease states. Transgenerational effects on the embryonic day 16 (E16) testis demonstrated reproducible changes in the testis transcriptome for multiple generations (F1-F3). The expression of 196 genes were found to be influenced, with the majority of gene expression being decreased or silenced. Dramatic changes in the gene expression of methyltransferases during gonadal sex determination were observed in the F1 and F2 vinclozolin generation (E16) embryonic testis, but the majority returned to control generation levels by the F3 generation. The most dramatic effects were on the germ-line associated Dnmt3A and Dnmt3L isoforms. Observations demonstrate that an embryonic exposure to vinclozolin appears to promote an epigenetic reprogramming of the male germ-line that correlates with transgenerational alterations in the testis transcriptome in subsequent generations. PMID:18042343

Oct4-GFP expression during transformation of gonocytes into spermatogonial stem cells in the perinatal mouse testis.

PubMed

Li, Ruili; Vannitamby, Amanda; Zhang, Jian-Guo; Fehmel, Emma L; Southwell, Bridget R; Hutson, John M

2015-12-01

In cryptorchidism perinatal failure to switch off Oct4, a germ cell (GC) marker, may lead to carcinoma in situ. We aimed to analyze Oct4 expression during mouse gonocyte transformation into spermatogonial stem cells (SSC). Testes from OG2 (Oct4-promoter driven eGFP) mice at embryonic day (E) 17 and postnatal day P0-10 underwent immunohistochemistry and immunoblotting. Antibodies against MVH, AMH, Ki67, and c-Kit were visualized by confocal microscopy. Numbers of Oct4-GFP(+) GC and Oct4-GFP(-) GC/tubule were counted using ImageJ. Data were analyzed using nonparametric one-way ANOVA. GC from E17-P4 were Oct4-GFP(+). Numbers of Oct4-GFP(-) GC/tubule increased from P6-10, whereas Oct4-GFP(+) GC/tubule numbers remained similar between P6 and P10. Sertoli cells proliferated from E17-P10, whereas GC only proliferated from P2. Gonocytes (Oct4-GFP(+)/c-Kit(-)) central in tubules migrated to the basement membrane to become prospermatogonia (Oct4-GFP(+)/c-Kit(-)) and then SSC (Oct4-GFP(+)/c-Kit(+)) from day 4 and further developed into Oct4-GFP(-)/c-Kit(+) at P6. In Oct4-GFP mice both centrally located gonocytes and prospermatogonia located at the tubular basement membrane were Oct4-GFP(+)/c-Kit(-) before further developing into SSC (Oct4-GFP(+)/c-Kit(+)). This indicates that Oct4 is important in gonocyte transformation into SSC. Understanding this process will aid GC tumor diagnostics and fertility potential in boys with UDT undergoing orchidopexy. Copyright © 2015 Elsevier Inc. All rights reserved.

Expression of the estrogen receptor GPER by testicular peritubular cells is linked to sexual maturation and male fertility

PubMed Central

Sandner, F; Welter, H; Schwarzer, JU; Köhn, FM; Urbanski, HF; Mayerhofer, A

2014-01-01

Besides the two nuclear estrogen receptors (ESR1/ESR2), the G protein-coupled estrogen receptor (GPER) was described in the human testis but little is known about testicular GPER during development or male infertility. We performed an immunohistochemical analysis using human and rhesus monkey testicular samples. The results obtained in adult primate testes showed GPER in interstitial and vascular cells as well as in the smooth muscle-like peritubular cells, which build the wall of seminiferous tubules. Expression of GPER was also found in cultured human testicular peritubular cells (HPTCs) by Western blotting and RT-PCR/sequencing. Furthermore, as seen in time-lapse videos of cultured cells, addition of a specific GPER agonist (G1) significantly reduced the numbers of HTPCs within 24 h. A GPER antagonist (G15) prevented this action, implying a role for GPER related to the control of cell proliferation or cell death of peritubular cells. Peritubular cell functions and their phenotype change, for example, during postnatal development and in cases of male infertility. The study of non-human primate samples revealed that GPER in peritubular cells was detectable only from the time of puberty onwards, while in samples from infantile and prepubertal monkeys only interstitial cells showed immunopositive staining. In testicular biopsies of men with mixed atrophy a reduction or loss of immunoreactive GPER was found in peritubular cells surrounding those tubules, in which spermatogenesis was impaired. In other cases of impaired spermatogenesis, namely when the tubular wall was fibrotically remodeled, a complete loss of GPER was seen. Thus, the observed inverse relation between the state of fertility and GPER expression by peritubular cells implies that the regulation of primate testicular peritubular cells by estrogens is mediated by GPER in both, health and disease. PMID:25052196

Testicular cells exhibit similar molecular responses to cigarette smoke condensate ex vivo and in vivo.

PubMed

Esakky, Prabagaran; Hansen, Deborah A; Drury, Andrea M; Felder, Paul; Cusumano, Andrew; Moley, Kelle H

2018-01-01

Male exposure to cigarette smoke is associated with seminal defects and with congenital anomalies and childhood cancers in offspring. In mice, paternal exposure to cigarette smoke condensate (CSC) causes molecular defects in germ cells and phenotypic effects in their offspring. Here we used an ex vivo testicular explant model and in vivo exposure to determine the concentration at which CSC impairs spermatogenesis and offspring development. We explanted testis tissue at postnatal day (P)5.5 and cultured it until P11.5. Assessment of growth parameters by analyzing expression of cell-specific markers revealed that the explant system maintained structural and functional integrity. We exposed the P5.5 to -11.5 explants to various concentrations (40-160 µg/ml) of CSC and confirmed that nicotine in the CSC was metabolized to cotinine. We assessed various growth and differentiation parameters, as well as testosterone production, and observed that many spermatogenesis features were impaired at 160 µg/ml CSC. The same parameters were impaired by a similar CSC concentration in vivo Finally, females mated to males that were exposed to 160 µg/ml CSC neonatally had increased rates of pup resorption. We conclude that male exposure to CSC impairs offspring development and that the concentration at which CSC impairs spermatogenesis is similar in vivo and ex vivo. Given that the concentrations of CSC we used contained similar doses of nicotine as human smokers are exposed to, we argue that our model mimics human male reproductive effects of smoking.-Esakky, P., Hansen, D. A., Drury, A. M., Felder, P., Cusumano, A., Moley, K. H. Testicular cells exhibit similar molecular responses to cigarette smoke condensate ex vivo and in vivo . © FASEB.

Critical androgen-sensitive periods of rat penis and clitoris development.

PubMed

Welsh, Michelle; MacLeod, David J; Walker, Marion; Smith, Lee B; Sharpe, Richard M

2010-02-01

Androgen control of penis development/growth is unclear. In rats, androgen action in a foetal 'masculinisation programming window' (MPW; e15.5-e18.5)' predetermines penile length and hypospadias occurrence. This has implications for humans (e.g. micropenis). Our studies aimed to establish in rats when androgen action/administration affects development/growth of the penis and if deficits in MPW androgen action were rescuable postnatally. Thus, pregnant rats were treated with flutamide during the MPW +/- postnatal testosterone propionate (TP) treatment. To assess penile growth responsiveness, rats were treated with TP in various time windows (late foetal, neonatal through early puberty, puberty onset, or combinations thereof). Phallus length, weight, and morphology, hypospadias and anogenital distance (AGD) were measured in mid-puberty (d25) or adulthood (d90) in males and females, plus serum testosterone in adult males. MPW flutamide exposure reduced adult penile length and induced hypospadias dose-dependently; this was not rescued by postnatal TP treatment. In normal rats, foetal (e14.5-e21.5) TP exposure did not affect male penis size but increased female clitoral size. In males, TP exposure from postnatal d1-24 or at puberty (d15-24), increased penile length at d25, but not ultimately in adulthood. Foetal + postnatal TP (e14-postnatal d24) increased penile size at d25 but reduced it at d90 (due to reduced endogenous testosterone). In females, this treatment caused the biggest increase in adult clitoral size but, unlike in males, phallus size was unaffected by TP during puberty (d15-24). Postnatal TP treatment advanced penile histology at d25 to more resemble adult histology. AGD strongly correlated with final penis length. It is concluded that adult penile size depends critically on androgen action during the MPW but subsequent growth depends on later androgen exposure. Foetal and/or postnatal TP exposure does not increase adult penile size above its 'predetermined' length though its growth towards this maximum is advanced by peripubertal TP treatment.

Male reproductive toxicity of CrVI: In-utero exposure to CrVI at the critical window of testis differentiation represses the expression of Sertoli cell tight junction proteins and hormone receptors in adult F1 progeny rats.

PubMed

Kumar, Kathiresh M; Aruldhas, Mariajoseph Michael; Banu, Sheerin L; Sadasivam, Balaji; Vengatesh, Ganapathy; Ganesh, Karthik M; Navaneethabalakrishnan, Shobana; Navin, Ajith Kumar; Michael, Felicia Mary; Venkatachalam, Sankar; Stanley, Jone A; Ramachandran, Ilangovan; Banu, Sakhila K; Akbarsha, Mohammad Abdulkader

2017-04-01

The effect of gestational exposure to CrVI (occupational/environmental pollutant and target to Sertoli cells(SC)) was tested in a rat model during the testicular differentiation from the bipotential gonad may interrupt spermatogenesis by disrupting SC tight junctions(TJ) and it's proteins and hormone receptors. Pregnant Wistar rats were exposed to 50/100/200ppm CrVI through drinking water during embryonic days 9-14. On Postnatal day 120, testes were subjected to ion exchange chromatographic analysis and revealed increased level of CrIII in SCs and germ cells, serum and testicular interstitial fluid(TIF). Microscopic analyses showed seminiferous tubules atrophy and disruption of SC TJ, which also recorded decreased testosterone in TIF. mRNA and Protein expression analyses attested decreased level of Fshr, Ar, occludin and claudin-11 in SCs. Immunofluorescent detection revealed weak signal of TJ proteins. Taken together, we concluded that gestational exposure to CrVI interferes with the expression of SC TJ proteins due to attenuated expression of hormone receptors. Copyright © 2017 Elsevier Inc. All rights reserved.

Essential role of citron kinase in cytokinesis of spermatogenic precursors.

PubMed

Cunto, Ferdinando Di; Imarisio, Sara; Camera, Paola; Boitani, Carla; Altruda, Fiorella; Silengo, Lorenzo

2002-12-15

During spermatogenesis, the first morphological indication of spermatogonia differentiation is incomplete cytokinesis, followed by the assembly of stable intercellular cytoplasmic communications. This distinctive feature of differentiating male germ cells has been highly conserved during evolution, suggesting that regulation of the cytokinesis endgame is a crucial aspect of spermatogenesis. However, the molecular mechanisms underlying testis-specific regulation of cytokinesis are still largely unknown. Citron kinase is a myotonin-related protein acting downstream of the GTPase Rho in cytokinesis control. We previously reported that Citron kinase knockout mice are affected by a complex neurological syndrome caused by cytokinesis block and apoptosis of specific neuronal precursors. In this report we show that, in addition, these mice display a dramatic testicular impairment, with embryonic and postnatal loss of undifferentiated germ cells and complete absence of mature spermatocytes. By contrast, the ovaries of mutant females appear essentially normal. Developmental analysis revealed that the cellular depletion observed in mutant testes is caused by increased apoptosis of undifferentiated and differentiating precursors. The same cells display a severe cytokinesis defect, resulting in the production of multinucleated cells and apoptosis. Our data indicate that Citron kinase is specifically required for cytokinesis of the male germ line.

Does testis weight decline towards the Subarctic? A case study on the common frog, Rana temporaria

NASA Astrophysics Data System (ADS)

Hettyey, Attila; Laurila, Anssi; Herczeg, Gábor; Jönsson, K. Ingemar; Kovács, Tibor; Merilä, Juha

2005-04-01

Interpopulation comparisons of variation in resource availability and in allocation patterns along altitudinal and latitudinal gradients allow insights into the mechanisms shaping the life history of animals. Patterns of between-population differences in female life history traits have been studied intensively across a wide range of taxa, but similar investigations in males have remained scarce. To study if testis weight—a measure of reproductive investment—varies on a geographical scale in anurans, we focussed on the variation in relative testis weight (RelTW) and asymmetry in 22 populations of the common frog Rana temporaria along a 1,600-km latitudinal transect across the Scandinavian peninsula. We found that RelTW decreased towards the north. Body mass and body length both had independent positive effects on testes mass. We found evidence for directional asymmetry (DA) in testis weight with the right testis being larger than the left. The level of DA in testis weight was not related to latitude, but both body mass and testes mass had independent positive effects on asymmetry. We discuss the northwards decrease in RelTW in terms of a decreased reproductive investment as a possible consequence of harsher environmental conditions, and perhaps also, weaker sexual selection in the north than in the south.

High doses of nandrolone decanoate reduce volume of testis and length of seminiferous tubules in rats.

PubMed

Noorafshan, Ali; Karbalay-Doust, Saied; Ardekani, Fakhrodin Mesbah

2005-02-01

Anabolic-androgenic steroid (AAS) compounds rank among the drugs most widely abused with the goal of improving athletic ability, appearance, or muscle mass. It has been shown that these compounds have adverse effects on human and animal physiology and sperm quality, but quantitative structural changes of the testis have received less attention. The present study was conducted to evaluate the effects of nandrolone decanoate, which is one of the AAS compounds, on testis weight and volume, diameter and length of seminiferous tubules in rats by unbiased stereological methods. Adult rats were divided into three groups. The first comprised control rats; the second and third groups received low and high doses of nandrolone decanoate for 14 weeks. The rats were then left untreated for 14 weeks. After removal of the testis, stereological study of these tissues showed that the mean volume of testis and length of the seminiferous tubules in the animals that received high doses of nandrolone decanoate were reduced approximately 32% (p<0.01) and approximately 31% (p<0.04), respectively, in comparison with the control group. It can be concluded that the high doses of nandrolone decanoate produce structural changes in the rat testis that remain 14 weeks after stopping injection of the drug.

Slower postnatal motor development in infants of mothers with latent toxoplasmosis during the first 18 months of life.

PubMed

Kaňková, Sárka; Sulc, Jan; Křivohlavá, Romana; Kuběna, Aleš; Flegr, Jaroslav

2012-11-01

Toxoplasmosis, a zoonosis caused by a protozoan, Toxoplasma gondii, is probably the most widespread human parasitosis in developed countries. Pregnant women with latent toxoplasmosis have seemingly younger fetuses especially in the 16th week of gestation, which suggests that fetuses of Toxoplasma-infected mothers have slower rates of development in the first trimester of pregnancy. In the present retrospective cohort study, we analyzed data on postnatal motor development of infants from 331 questionnaire respondents including 53 Toxoplasma-infected mothers to search for signs of early postnatal development disorders. During the first year of life, a slower postnatal motor development was observed in infants of mothers with latent toxoplasmosis. These infants significantly later developed the ability to control the head position (p=0.039), to roll from supine to prone position (p=0.022) and were slightly later to begin crawling (p=0.059). Our results are compatible with the hypothesis that the difference in the rates of prenatal and early postnatal development between children of Toxoplasma-negative and Toxoplasma-positive mothers might be caused by a decreased stringency of embryo quality control in partly immunosuppressed Toxoplasma-positive mothers resulting in a higher proportion of infants with genetic or developmental disorders in offspring. However, because of relatively low return rate of questionnaires and an associated risk of a sieve effect, our results should be considered as preliminary and performing a large scale prospective study in the future is critically needed. Copyright © 2012 Elsevier Ltd. All rights reserved.

Regulation of microglial development: a novel role for thyroid hormone.

PubMed

Lima, F R; Gervais, A; Colin, C; Izembart, M; Neto, V M; Mallat, M

2001-03-15

The postnatal development of rat microglia is marked by an important increase in the number of microglial cells and the growth of their ramified processes. We studied the role of thyroid hormone in microglial development. The distribution and morphology of microglial cells stained with isolectin B4 or monoclonal antibody ED1 were analyzed in cortical and subcortical forebrain regions of developing rats rendered hypothyroid by prenatal and postnatal treatment with methyl-thiouracil. Microglial processes were markedly less abundant in hypothyroid pups than in age-matched normal animals, from postnatal day 4 up to the end of the third postnatal week of life. A delay in process extension and a decrease in the density of microglial cell bodies, as shown by cell counts in the developing cingulate cortex of normal and hypothyroid animals, were responsible for these differences. Conversely, neonatal rat hyperthyroidism, induced by daily injections of 3,5,3'-triiodothyronine (T3), accelerated the extension of microglial processes and increased the density of cortical microglial cell bodies above physiological levels during the first postnatal week of life. Reverse transcription-PCR and immunological analyses indicated that cultured cortical ameboid microglial cells expressed the alpha1 and beta1 isoforms of nuclear thyroid hormone receptors. Consistent with the trophic and morphogenetic effects of thyroid hormone observed in situ, T3 favored the survival of cultured purified microglial cells and the growth of their processes. These results demonstrate that thyroid hormone promotes the growth and morphological differentiation of microglia during development.

Roles of piRNAs in microcystin-leucine-arginine (MC-LR) induced reproductive toxicity in testis on male offspring.

PubMed

Zhang, Ling; Zhang, Hui; Zhang, Huan; Benson, Mikael; Han, Xiaodong; Li, Dongmei

2017-07-01

In the present study, we evaluated the toxic effects on the testis of the male offspring of MC-LR exposure during fetal and lactational periods. Pregnant females were distributed into two experimental groups: control group and MC-LR group which were exposed to 0 and 10 μg/L of MC-LR, respectively, through drinking water separately during fetal and lactational periods. At the age of 30 days after birth, the male offspring were euthanized. The body weight, testis index, and histomorphology change were observed and the global changes of piwi-interacting RNA (piRNA) expression were evaluated. The results revealed that MC-LR was found in the testis of male offspring, body weight and testis index decreased significantly, and testicular tissue structure was damaged in the MC-LR group. In addition, the exposure to MC-LR resulted in an altered piRNA expression profile and an increase of the cell apoptosis and a decrease of the cell proliferation in the testis of the male offspring. It was reasonable to speculate that the toxic effects on reproductive system of the male offspring in MC-LR group might be mediated by piRNAs through the regulation of the target genes. As far as we are aware, this is the first report showing that MC-LR could play a role in disorder of proliferative and cell apoptosis in the testis of the male offspring by the maternal transmission effect of toxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Use of testicular sperm for intracytoplasmic sperm injection in men with high sperm DNA fragmentation: a SWOT analysis

PubMed Central

Esteves, Sandro C; Roque, Matheus; Garrido, Nicolás

2018-01-01

Spermatozoa retrieved from the testis of men with high levels of sperm DNA fragmentation (SDF) in the neat semen tend to have better DNA quality. Given the negative impact of SDF on the outcomes of Assisted Reproductive Technology (ART), an increased interest has emerged about the use of testicular sperm for intracytoplasmic sperm injection (Testi-ICSI). In this article, we used a SWOT (strengths, weaknesses, opportunities, and threats) analysis to summarize the advantages and drawbacks of this intervention. The rationale of Testi-ICSI is bypass posttesticular DNA fragmentation caused by oxidative stress during sperm transit through the epididymis. Hence, oocyte fertilization by genomically intact testicular spermatozoa may be optimized, thus increasing the chances of creating a normal embryonic genome and the likelihood of achieving a live birth, as recently demonstrated in men with high SDF. However, there is still limited evidence as regards the clinical efficacy of Testi-ICSI, thus creating opportunities for further confirmatory clinical research as well as investigation of Testi-ICSI in clinical scenarios other than high SDF. Furthermore, Testi-ICSI can be compared to other laboratory preparation methods for deselecting sperm with damaged DNA. At present, the available literature supports the use of testicular sperm when performing ICSI in infertile couples whose male partners have posttesticular SDF. Due to inherent risks of sperm retrieval, Testi-ICSI should be offered when less invasive treatments for alleviating DNA damage have failed. A call for continuous monitoring is nonetheless required concerning the health of generated offspring and the potential complications of sperm retrieval. PMID:28440264

Use of testicular sperm for intracytoplasmic sperm injection in men with high sperm DNA fragmentation: a SWOT analysis.

PubMed

Esteves, Sandro C; Roque, Matheus; Garrido, Nicolás

2018-01-01

Spermatozoa retrieved from the testis of men with high levels of sperm DNA fragmentation (SDF) in the neat semen tend to have better DNA quality. Given the negative impact of SDF on the outcomes of Assisted Reproductive Technology (ART), an increased interest has emerged about the use of testicular sperm for intracytoplasmic sperm injection (Testi-ICSI). In this article, we used a SWOT (strengths, weaknesses, opportunities, and threats) analysis to summarize the advantages and drawbacks of this intervention. The rationale of Testi-ICSI is bypass posttesticular DNA fragmentation caused by oxidative stress during sperm transit through the epididymis. Hence, oocyte fertilization by genomically intact testicular spermatozoa may be optimized, thus increasing the chances of creating a normal embryonic genome and the likelihood of achieving a live birth, as recently demonstrated in men with high SDF. However, there is still limited evidence as regards the clinical efficacy of Testi-ICSI, thus creating opportunities for further confirmatory clinical research as well as investigation of Testi-ICSI in clinical scenarios other than high SDF. Furthermore, Testi-ICSI can be compared to other laboratory preparation methods for deselecting sperm with damaged DNA. At present, the available literature supports the use of testicular sperm when performing ICSI in infertile couples whose male partners have posttesticular SDF. Due to inherent risks of sperm retrieval, Testi-ICSI should be offered when less invasive treatments for alleviating DNA damage have failed. A call for continuous monitoring is nonetheless required concerning the health of generated offspring and the potential complications of sperm retrieval.

Replacement of serum with ocular fluid for cryopreservation of immature testes.

PubMed

Pothana, Lavanya; Devi, Lalitha; Venna, Naresh Kumar; Pentakota, Niharika; Varma, Vivek Phani; Jose, Jedy; Goel, Sandeep

2016-12-01

Cryopreservation of immature testis is a feasible approach for germplasm preservation of male animals. Combinations of dimethyl sulfoxide (DMSO) and foetal bovine serum (FBS) are used for testis cryopreservation. However, an alternative to FBS is needed, because FBS is expensive. Buffalo ocular fluid (BuOF), a slaughter house by-product, could be an economical option. The objective of the present study was to assess whether BuOF can replace FBS for cryopreservation of immature mouse (Mus musculus), rat (Rattus norvegicus), and buffalo (Bubalus bubalis) testes. Results showed that rodent and buffalo testes frozen in DMSO (10% for rodents and 20% for buffalo) with 20% FBS or BuOF had similar numbers of viable and DNA-damaged cells (P > 0.05). The expression of cell proliferation- (PCNA) and apoptosis-specific proteins (Annexin V and BAX/BCL2 ratio) were also comparable in mouse and buffalo testes frozen in DMSO with FBS or BuOF (P > 0.05). Interestingly, rat testis frozen in DMSO with BuOF had lower expression of Annexin V protein than testis frozen in DMSO with FBS (P < 0.05). The percentage of meiotic germ cells (pachytene-stage spermatocytes) in xenografts from testis frozen either in DMSO with BuOF or FBS did not significantly differ in rats or buffalo (P > 0.05). These findings provide evidence that BuOF has potential to replace FBS for cryopreservation of immature rodent and buffalo testis. Further investigation is needed to explore whether BuOF can replace FBS for testis cryopreservation of other species. Copyright © 2016 Elsevier Inc. All rights reserved.

Histopathological effects of boldenone in cattle.

PubMed

Groot, M J; Biolatti, B

2004-03-01

Histopathology of male cattle previously found positive for béta-boldenone in urine in the Netherlands and in Italy was studied. The animals were derived from practice and several weeks had passed after the finding of béta-boldenone before the animals were examined. The animals consisted of 34 male veal calves and one finishing bull. In the prostate gland hypersecretion, cyst formation (45%) and hyperplasia of the urethral epithelium was observed, in the bulbo-urethral gland similar alterations were present. The testis showed reduced development and degeneration of the germinal epithelium (70%), leading to debris and syncytial cell formation in the lumina. Stromal proliferation was evident. In some animals the liver was sampled and showed periportal fibrosis, bile duct proliferation and sometimes necrosis. The bull also showed degeneration of the germinal epithelium of the testis and absence of sperm production, the prostate gland showed some secretion and had an atrophic appearance. It is concluded that béta-boldenone may lead to degeneration of the germinal epithelium of the testis and hypersecretion and cyst formation in the prostate and bulbo-urethral gland, which alterations may heal in time.

Effects of flutamide and finasteride on rat testicular descent.

PubMed

Spencer, J R; Torrado, T; Sanchez, R S; Vaughan, E D; Imperato-McGinley, J

1991-08-01

The endocrine control of descent of the testis in mammalian species is poorly understood. The androgen dependency of testicular descent was studied in the rat using an antiandrogen (flutamide) and an inhibitor of the enzyme 5 alpha-reductase (finasteride). Androgen receptor blockade inhibited testicular descent more effectively than inhibition of 5 alpha-reductase activity. Moreover, its inhibitory effect was limited to the outgrowth phase of the gubernaculum testis, particularly the earliest stages of outgrowth. Gubernacular size was also significantly reduced in fetuses exposed to flutamide during the outgrowth period. In contrast, androgen receptor blockade or 5 alpha-reductase inhibition applied after the initiation of gubernacular outgrowth or during the regression phase did not affect testicular descent. Successful inhibition of the development of epididymis and vas by prenatal flutamide did not correlate with ipsilateral testicular maldescent, suggesting that an intact epididymis is not required for descent of the testis. Plasma androgen assays confirmed significant inhibition of dihydrotestosterone formation in finasteride-treated rats. These data suggest that androgens, primarily testosterone, are required during the early phases of gubernacular outgrowth for subsequent successful completion of testicular descent.

Identification of human candidate genes for male infertility by digital differential display.

PubMed

Olesen, C; Hansen, C; Bendsen, E; Byskov, A G; Schwinger, E; Lopez-Pajares, I; Jensen, P K; Kristoffersson, U; Schubert, R; Van Assche, E; Wahlstroem, J; Lespinasse, J; Tommerup, N

2001-01-01

Evidence for the importance of genetic factors in male fertility is accumulating. In the literature and the Mendelian Cytogenetics Network database, 265 cases of infertile males with balanced reciprocal translocations have been described. The candidacy for infertility of 14 testis-expressed transcripts (TETs) were examined by comparing their chromosomal mapping position to the position of balanced reciprocal translocation breakpoints found in the 265 infertile males. The 14 TETs were selected by using digital differential display (electronic subtraction) to search for apparently testis-specific transcripts in the TIGR database. The testis specificity of the 14 TETs was further examined by reverse transcription-polymerase chain reaction (RT-PCR) on adult and fetal tissues showing that four TETs (TET1 to TET4) were testis-expressed only, six TETs (TET5 to TET10) appeared to be differentially expressed and the remaining four TETs (TET11 to TET14) were ubiquitously expressed. Interestingly, the two tesis expressed-only transcripts, TET1 and TET2, mapped to chromosomal regions where seven and six translocation breakpoints have been reported in infertile males respectively. Furthermore, one ubiquitously, but predominantly testis-expressed, transcript, TET11, mapped to 1p32-33, where 13 translocation breakpoints have been found in infertile males. Interestingly, the mouse mutation, skeletal fusions with sterility, sks, maps to the syntenic region in the mouse genome. Another transcript, TET7, was the human homologue of rat Tpx-1, which functions in the specific interaction of spermatogenic cells with Sertoli cells. TPX-1 maps to 6p21 where three cases of chromosomal breakpoints in infertile males have been reported. Finally, TET8 was a novel transcript which in the fetal stage is testis-specific, but in the adult is expressed in multiple tissues, including testis. We named this novel transcript fetal and adult testis-expressed transcript (FATE).

Germ cell survival and differentiation after xenotransplantation of testis tissue from three endangered species: Iberian lynx (Lynx pardinus), Cuvier's gazelle (Gazella cuvieri) and Mohor gazelle (G. dama mhorr).

PubMed

Arregui, Lucía; Dobrinski, Ina; Roldan, Eduardo R S

2014-01-01

The use of assisted reproductive techniques for endangered species is a major goal for conservation. One of these techniques, testis tissue xenografting, allows for the development of spermatozoa from animals that die before reaching sexual maturity. To assess the potential use of this technique with endangered species, testis tissue from six Iberian lynxes (one fetus, two perinatal cubs, two 6-month-old and one 2-year-old lynx), two Cuvier's gazelle fetuses and one 8-month-old Mohor gazelle were transplanted ectopically into nude mice. Tissue from the lynx fetus, perinatal cubs and 2-year-old donors degenerated, whereas spermatogonia were present in 15% of seminiferous tubules more than 70 weeks after grafting in transplanted testis tissue from 6-month-old donors. Seminal vesicle weights (indicative of testosterone production) increased over time in mice transplanted with tissue from 6-month-old lynxes. Progression of spermatogenesis was observed in xenografts from gazelles and was donor age dependent. Tissue from Cuvier's gazelle fetuses contained spermatocytes 40 weeks after grafting. Finally, round spermatids were found 28 weeks after transplantation in grafts from the 8-month-old Mohor gazelle. This is the first time that xenotransplantation of testicular tissue has been performed with an endangered felid and the first successful xenotransplantation in an endangered species. Our results open important options for the preservation of biological diversity.

A meta-analysis of nutrition interventions on mental development of children under-two in low- and middle-income countries.

PubMed

Larson, Leila Margaret; Yousafzai, Aisha K

2017-01-01

Interventions to improve nutritional status of young children in low- and middle-income countries (LMIC) may have the added benefit of improving their mental and motor development. This meta-analysis updates and goes beyond previous ones by answering two important questions: (1) do prenatal and postnatal nutritional inputs improve mental development, and (2) are effects on mental development associated with two theoretically interesting mediators namely physical growth and motor development? The meta-analysis of articles on Medline, PsycINFO, Global Health and Embase was limited to randomized trials in LMICs, with mental development of children from birth to age two years as an outcome. The initial yield of 2689 studies was reduced to 33; 12 received a global quality rating of strong. Of the 10 prenatal and 23 postnatal nutrition interventions, the majority used zinc, iron/folic acid, vitamin A or multiple micronutrients, with a few evaluating macronutrients. The weighted mean effect size, Cohen's d (95% CI) for prenatal and postnatal nutrition interventions on mental development was 0.042 (-0.0084, 0.092) and 0.076 (0.019, 0.13), respectively. Postnatal supplements consisting of macronutrients yielded an effect size d (95% CI) of 0.14 (0.0067, 0.27), multiple micronutrients 0.082 (-0.012, 0.18) and single micronutrients 0.058 (-0.0015, 0.12). Motor development, but not growth status, effect sizes were significantly associated with mental development in postnatal interventions. In summary, nutrition interventions had small effects on mental development. Future studies might have greater effect if they addressed macronutrient deficiencies combined with child stimulation and hygiene and sanitation interventions. © 2015 John Wiley & Sons Ltd.

Cognition and behavioural development in early childhood: the role of birth weight and postnatal growth

PubMed Central

Huang, Cheng; Martorell, Reynaldo; Ren, Aiguo; Li, Zhiwen

2013-01-01

Background We evaluate the relative importance of birth weight and postnatal growth for cognition and behavioural development in 8389 Chinese children, 4–7 years of age. Method Weight was the only size measure available at birth. Weight, height, head circumference and intelligence quotient (IQ) were measured between 4 and 7 years of age. Z-scores of birth weight and postnatal conditional weight gain to 4–7 years, as well as height and head circumference at 4–7 years of age, were the exposure variables. Z-scores of weight at 4–7 years were regressed on birth weight Z-scores, and the residual was used as the measure of postnatal conditional weight gain. The outcomes were child’s IQ, measured by the Chinese Wechsler Young Children Scale of Intelligence, as well as internalizing behavioural problems, externalizing behavioural problems and other behavioural problems, evaluated by the Child Behavior Checklist 4–18. Multivariate regressions were conducted to investigate the relationship of birth weight and postnatal growth variables with the outcomes, separately for preterm children and term children. Results Both birth weight and postnatal weight gain were associated with IQ among term children; 1 unit increment in Z-score of birth weight (∼450 g) was associated with an increase of 1.60 [Confidence interval (CI): 1.18–2.02; P < 0.001] points in IQ, and 1 unit increment in conditional postnatal weight was associated with an increase of 0.46 (CI: 0.06–0.86; P = 0.02) points in IQ, after adjustment for confounders; similar patterns were observed when Z-scores of postnatal height and head circumference at age 4–7 years were used as alternative measurements of postnatal growth. Effect sizes of relationships with IQ were smaller than 0.1 of a standard deviation in all cases. Neither birth weight nor postnatal growth indicators were associated with behavioural outcomes among term children. In preterm children, neither birth weight nor postnatal growth measures were associated with IQ or behavioural outcomes. Conclusions Both birth weight and postnatal growth were associated with IQ but not behavioural outcomes for Chinese term children aged 4–7 years, but the effect sizes were small. No relation between either birth weight or postnatal growth and cognition or behavioural outcomes was observed among preterm children aged 4–7 years. PMID:23243117

The development of two postnatal health instruments: one for mothers (M-PHI) and one for fathers (F-PHI) to measure health during the first year of parenting.

PubMed

Jones, G L; Morrell, C J; Cooke, J M; Speier, D; Anumba, D; Stewart-Brown, S

2011-09-01

To develop and psychometrically evaluate two questionnaires measuring both positive and negative postnatal health of mothers (M-PHI) and fathers (F-PHI) during the first year of parenting. The M-PHI and the F-PHI were developed in four stages. Stage 1: Postnatal women's focus group (M-PHI) and postnatal fathers' postal questionnaire (F-PHI); Stage 2: Qualitative interviews; Stage 3: Pilot postal survey and main postal survey; and Stage 4: Test-retest postal survey. The M-PHI consisted of a 29-item core questionnaire with six main scales and five conditional scales. The F-PHI consisted of a 27-item questionnaire with six main scales. All scales achieved good internal reliability (Cronbach's α 0.66-0.87 for M-PHI, 0.72-0.90 for F-PHI). Intraclass correlation coefficients demonstrated high test-retest reliability (0.60-0.88). Correlation coefficients supported the criterion validity of the M-PHI and the F-PHI when tested against the Short-Form-12 (SF-12), Edinburgh Postnatal Depression Scale (EPDS) and the Warwick and Edinburgh Mental Well-Being Scale (WEMWBS). The M-PHI and F-PHI are valid, reliable, parent-generated instruments. These unique instruments will be invaluable for practitioners wishing to promote family-centred care and for trialists and other researchers requiring a validated instrument to measure both positive and negative health during the first postnatal year, as to date no such measurement has existed.

Postnatally acquired cytomegalovirus infection via breast milk: effects on hearing and development in preterm infants.

PubMed

Vollmer, Brigitte; Seibold-Weiger, Karin; Schmitz-Salue, Christine; Hamprecht, Klaus; Goelz, Rangmar; Krageloh-Mann, Ingeborg; Speer, Christian P

2004-04-01

In preterm infants there is a high risk of transmission of cytomegalovirus (CMV) via breast milk from seropositive mothers with reactivation of the virus during lactation. There is little information about the long term sequel of early postnatally acquired CMV infection in pre-term infants. This study aimed to investigate whether there was an increased frequency of impaired neurodevelopmental outcome and sensorineural hearing loss in preterm infants with postnatally acquired CMV infection through transmission by CMV-positive breast milk. Twenty-two preterm infants [median birth weight, 1020 g (range, 600 to 1870 g); median gestational age, 27.6 weeks (range, 23.6 to 32 weeks] with early postnatally acquired CMV infection by breast-feeding (onset of viruria between Days 23 and 190 postnatally) were compared with 22 CMV-negative preterm infants individually matched for gestational age, birth weight, gender, intracranial hemorrhage and duration of ventilation. At 2 to 4.5 years of age, follow-up assessments were conducted consisting of neurologic examination, neurodevelopmental assessment and detailed audiologic tests. None of the children had sensorineural hearing loss. There was no difference between the groups with regard to neurologic, speech and language or motor development. The results of this study suggest that early postnatally acquired CMV infection via CMV-positive breast milk does not have a negative effect on neurodevelopment and hearing in this group of patients. Because we studied a small number of infants, further follow-up studies are warranted in preterm infants with early postnatally acquired CMV infection.

Dmrt1 is necessary for male sexual development in zebrafish

PubMed Central

Webster, Kaitlyn A.; Schach, Ursula; Ordaz, Angel; Steinfeld, Jocelyn S.; Draper, Bruce W.; Siegfried, Kellee R.

2018-01-01

The dmrt1 (doublesex and mab-3 related transcription factor 1) gene is a key regulator of sex determination and/or gonadal sex differentiation across metazoan animals. This is unusual given that sex determination genes are typically not well conserved. The mechanisms by which zebrafish sex is determined have remained elusive due to the lack of sex chromosomes and the complex polygenic nature of sex determination in domesticated strains. To investigate the role of dmrt1 in zebrafish sex determination and gonad development, we isolated mutations disrupting this gene. We found that the majority of dmrt1 mutant fish develop as fertile females suggesting a complete male-to-female sex reversal in mutant animals that would have otherwise developed as males. A small percentage of mutant animals became males, but were sterile and displayed testicular dysgenesis. Therefore zebrafish dmrt1 functions in male sex determination and testis development. Mutant males had aberrant gonadal development at the onset of gonadal sex-differentiation, displaying reduced oocyte apoptosis followed by development of intersex gonads and failed testis morphogenesis and spermatogenesis. By contrast, female ovaries developed normally. We found that Dmrt1 is necessary for normal transcriptional regulation of the amh (anti-Müllerian hormone) and foxl2 (forkhead box L2) genes, which are thought to be important for male or female sexual development respectively. Interestingly, we identified one dmrt1 mutant allele that cooperates with a linked segregation distorter locus to generate an apparent XY sex determination mechanism. We conclude that dmrt1 is dispensable for ovary development but necessary for testis development in zebrafish, and that dmrt1 promotes male development by transcriptionally regulating male and female genes as has been described in other animals. Furthermore, the strong sex-ratio bias caused by dmrt1 reduction-of-function points to potential mechanisms through which sex chromosomes may evolve. PMID:27940159

Fusion Imaging: A Novel Staging Modality in Testis Cancer

DTIC Science & Technology

2010-01-01

the anatomic precision of computed tomography. To the best of our knowledge, this represents the first study of the effectiveness using fusion...imaging in evaluation of patients with testis cancer. Methods: A prospective study of 49 patients presenting to Walter Reed Army Medical Center with...incidence of testis cancer has been increasing at an annual rate of 3%, leading to a doubling in cases world-wide over the last 40 years. With the advent

Gestational form of Selenium in Free-Choice Mineral Mixes Affects Transcriptome Profiles of the Neonatal Calf Testis, Including those of Steroidogenic and Spermatogenic Pathways.

PubMed

Cerny, K L; Garbacik, S; Skees, C; Burris, W R; Matthews, J C; Bridges, P J

2016-01-01

In areas where soils are deficient in Selenium (Se), dietary supplementation of this trace mineral directly to cattle is recommended. Because Se status affects testosterone synthesis and frequency of sperm abnormalities, and the form of Se supplemented to cows affects tissue-specific gene expression, the objective of this study was to determine whether the form of Se consumed by cows during gestation would affect the expression of mRNAs that regulate steroidogenesis and/or spermatogenesis in the neonatal calf testis. Twenty-four predominantly Angus cows were assigned randomly to have individual, ad libitum, access of a mineral mix containing 35 ppm of Se in free-choice vitamin-mineral mixes as either inorganic (ISe), organic (OSe), or a 50/50 mix of ISe and OSe (MIX), starting 4 months prior to breeding and continuing throughout gestation. Thirteen male calves were born over a 3-month period (ISe, n = 5; OSe, n = 4; MIX, n = 4), castrated within 2 days of birth, and extracted testis RNA subjected to transcriptomal analysis by microarray (Affymetrix Bovine 1.0 ST arrays) and targeted gene expression analysis by real-time reverse-transcription PCR (RT-PCR) of mRNAs encoding proteins known to affect steroidogenesis and/or spermatogenesis. The form of dam Se affected (P < 0.05) the expression of 853 annotated genes, including 17 mRNAs putatively regulating steroidogenesis and/or spermatogenesis. Targeted RT-PCR analysis indicated that the expression of mRNA encoding proteins CYP2S1 (cytochrome P450, family 2, subfamily S, polypeptide 1), HSD17B7 (hydroxysteroid (17β) dehydrogenase 7), SULT1E1 (sulfotransferase family 1E, estrogen preferring, member 1), LDHA (lactate dehydrogenase A), CDK5R1 (cyclin-dependent kinase 5, regulatory subunit 1), and LEP (leptin) was affected (P < 0.05) by form of Se consumed by dams of developing bull calves, while AKR1C4 (aldo-keto reductase family 1, member C4) and CCND2 (cyclin D2) tended (P < 0.09) to be affected. Our results indicate that form of Se fed to dams during gestation affected the transcriptome of the neonatal calf testis. If these profiles are maintained throughout maturation, then the form of Se fed to dams may impact bull fertility and the development of Se form-dependent mineral mixes that target gestational development of the testis are warranted.

Combined Leydig cell and Sertoli cell dysfunction in 46,XX males lacking the sex determining region Y gene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Turner, B.; Vordermark, J.S.; Fechner, P.Y.

1995-07-03

We have evaluated 3 individuals with a rare form of 46,XX sex reversal. All of them had ambiguous external genitalia and mixed wolffian and muellerian structures, indicating both Leydig cell and Sertoli cell dysfunction, similar to that of patients with true hermaphroditism. However, gonadal tissue was not ovotesticular but testicular with varying degrees of dysgenesis. SRY sequences were absent in genomic DNA from peripheral leukocytes in all 3 subjects. Y centromere sequences were also absent, indicating that testis development did not occur because of a low level mosaicism of Y-bearing cells. The subjects in this report demonstrate that there ismore » a continuum in the extent of the testis determination in SRY-negative 46,XX sex reversal, ranging from nearly normal to minimal testicular development. 20 refs.« less

Thyroid hormone actions on male reproductive system of teleost fish.

PubMed

Tovo-Neto, Aldo; da Silva Rodrigues, Maira; Habibi, Hamid R; Nóbrega, Rafael Henrique

2018-04-17

Thyroid hormones (THs) play important roles in the regulation of many biological processes of vertebrates, such as growth, metabolism, morphogenesis and reproduction. An increasing number of studies have been focused on the involvement of THs in the male reproductive system of vertebrates, in particular of fish. Therefore, this mini-review aims to summarize the main findings on THs role in male reproductive system of fish, focusing on sex differentiation, testicular development and spermatogenesis. The existing data in the literature have demonstrated that THs exert their roles at the different levels of the hypothalamic-pituitary-gonadal (HPG) axis. In general a positive correlation has been shown between THs and fish reproductive status; where THs are associated with testicular development, growth and maturation. Recently, the molecular mechanisms underlying the role of THs in spermatogenesis have been unraveled in zebrafish testis. THs promote germ cell proliferation and differentiation by increasing a stimulatory growth factor of spermatogenesis produced by Sertoli cells. In addition, THs enhanced the gonadotropin-induced androgen release in zebrafish testis. Next to their functions in the adult testis, THs are involved in the gonadal sex differentiation through modulating sex-related gene expression, and testicular development via regulation of Sertoli cell proliferation. In conclusion, this mini-review showed that THs modulate the male reproductive system during the different life stages of fish. The physiological and molecular mechanisms showed a link between the thyroid and reproduction, suggesting a possibly co-evolution and interdependence of these two systems. Copyright © 2018 Elsevier Inc. All rights reserved.

Successful xenogeneic germ cell transplantation from Jundia catfish (Rhamdia quelen) into adult Nile tilapia (Oreochromis niloticus) testes.

PubMed

Silva, M A; Costa, G M J; Lacerda, S M S N; Brandão-Dias, P F P; Kalapothakis, E; Silva Júnior, A F; Alvarenga, E R; França, L R

2016-05-01

Fish germ cell transplantation presents several important potential applications for aquaculture, including the preservation of germplasm from endangered fish species with high genetic and commercial values. Using this technique in studies developed in our laboratory with adult male Nile tilapias (Oreochromis niloticus), all the necessary procedures were successfully established, allowing the production of functional sperm and healthy progeny approximately 2months after allogeneic transplantation. In the present study, we evaluated the viability of the adult Nile tilapia testis to generate sperm after xenogeneic transplant of germ cells from sexually mature Jundia catfish (Rhamdia quelen) that belong to a different taxonomic order. Therefore, in order to investigate at different time-periods post-transplantation, the presence and development of donor PKH26 labeled catfish germ cells were followed in the tilapia seminiferous tubules. From 7 to 20days post-transplantation, only PKH26 labeled spermatogonia were observed, whereas spermatocytes at different stages of development were found at 70days. Germ cell transplantation success and progression of spermatogenesis were indicated by the presence of labeled PKH26 spermatids and sperm on days 90 and 120 post-transplantation, respectively. Confirming the presence of the catfish genetic material in the tilapia testis, all recipient tilapias evaluated (n=8) showed the genetic markers evaluated. Therefore, we demonstrated for the first time that the adult Nile tilapia testis offers the functional conditions for development of spermatogenesis with sperm production from a fish species belonging to a different order, which provides an important new venue for aquaculture advancement. Copyright © 2016 Elsevier Inc. All rights reserved.

ARX/Arx is expressed in germ cells during spermatogenesis in both marsupial and mouse.

PubMed

Yu, Hongshi; Pask, Andrew J; Hu, Yanqiu; Shaw, Geoff; Renfree, Marilyn B

2014-03-01

The X-linked aristaless gene, ARX, is essential for the development of the gonads, forebrain, olfactory bulb, pancreas, and skeletal muscle in mice and humans. Mutations cause neurological diseases, often accompanied by ambiguous genitalia. There are a disproportionately high number of testis and brain genes on the human and mouse X chromosomes. It is still unknown whether the X chromosome accrued these genes during its evolution or whether genes that find themselves on the X chromosome evolve such roles. ARX was originally autosomal in mammals and remains so in marsupials, whereas in eutherian mammals it translocated to the X chromosome. In this study, we examined autosomal ARX in tammars and compared it with the X-linked Arx in mice. We detected ARX mRNA in the neural cells of the forebrain, midbrain and hindbrain, and olfactory bulbs in developing tammars, consistent with the expression in mice. ARX was detected by RT-PCR and mRNA in situ hybridization in the developing tammar wallaby gonads of both sexes, suggestive of a role in sexual development as in mice. We also detected ARX/Arx mRNA in the adult testis in both tammars and mice, suggesting a potential novel role for ARX/Arx in spermiogenesis. ARX transcripts were predominantly observed in round spermatids. Arx mRNA localization distributions in the mouse adult testis suggest that it escaped meiotic sex chromosome inactivation during spermatogenesis. Our findings suggest that ARX in the therian mammal ancestor already played a role in male reproduction before it was recruited to the X chromosome in eutherians.

Extensive alternative splicing transitions during postnatal skeletal muscle development are required for calcium handling functions

PubMed Central

Brinegar, Amy E; Xia, Zheng; Loehr, James Anthony; Li, Wei; Rodney, George Gerald

2017-01-01

Postnatal development of skeletal muscle is a highly dynamic period of tissue remodeling. Here, we used RNA-seq to identify transcriptome changes from late embryonic to adult mouse muscle and demonstrate that alternative splicing developmental transitions impact muscle physiology. The first 2 weeks after birth are particularly dynamic for differential gene expression and alternative splicing transitions, and calcium-handling functions are significantly enriched among genes that undergo alternative splicing. We focused on the postnatal splicing transitions of the three calcineurin A genes, calcium-dependent phosphatases that regulate multiple aspects of muscle biology. Redirected splicing of calcineurin A to the fetal isoforms in adult muscle and in differentiated C2C12 slows the timing of muscle relaxation, promotes nuclear localization of calcineurin target Nfatc3, and/or affects expression of Nfatc transcription targets. The results demonstrate a previously unknown specificity of calcineurin isoforms as well as the broader impact of alternative splicing during muscle postnatal development. PMID:28826478

Determinants of postnatal care non-utilization among women in Nigeria.

PubMed

Somefun, Oluwaseyi Dolapo; Ibisomi, Latifat

2016-01-11

Although, there are several programs in place in Nigeria to ensure maternal and child health, maternal and neonatal mortality rates remain high with maternal mortality rates being 576/100,000 and neonatal mortality rates at 37/1000 live births (NDHS, 2013). While there are many studies on the utilization of maternal health services such as antenatal care and skilled delivery at birth, studies on postnatal care are limited. Therefore, the aim of this study is to examine the factors associated with the non-utilization of postnatal care among mothers in Nigeria using the Nigeria Demographic and Health Survey (NDHS) 2013. For analysis, the postnatal care uptake for 19,418 children born in the 5 years preceding the survey was considered. The dependent variable was a composite variable derived from a list of questions on postnatal care. A multinomial logistic regression model was applied to examine the adjusted and unadjusted determinants of non-utilization of postnatal care. Results from this study showed that 63% of the mothers of the 19,418 children did not utilize postnatal care services in the period examined. About 42% of the study population between 25 and 34 years did not utilize postnatal care and 61% of the women who did not utilize postnatal care had no education. Results from multinomial logistic regression show that antenatal care use, distance, education, place of delivery, region and wealth status are significantly associated with the non-utilization of postnatal care services. This study revealed the low uptake of postnatal care service in Nigeria. To increase mothers' utilization of postnatal care services and improve maternal and child health in Nigeria, interventions should be targeted at women in remote areas who don't have access to services and developing mobile clinics. In addition, it is crucial that steps should be taken on educating women. This would have a significant influence on their perceptions about the use of postnatal care services in Nigeria.

Diversification of intrinsic motoneuron electrical properties during normal development and botulinum toxin-induced muscle paralysis in early postnatal mice.

PubMed

Nakanishi, S T; Whelan, P J

2010-05-01

During early postnatal development, between birth and postnatal days 8-11, mice start to achieve weight-bearing locomotion. In association with the progression of weight-bearing locomotion there are presumed developmental changes in the intrinsic electrical properties of spinal -motoneurons. However, these developmental changes in the properties of -motoneuron properties have not been systematically explored in mice. Here, data are presented documenting the developmental changes of selected intrinsic motoneuron electrical properties, including statistically significant changes in action potential half-width, intrinsic excitability and diversity (quantified as coefficient of variation) of rheobase current, afterhyperpolarization half-decay time, and input resistance. In various adult mammalian preparations, the maintenance of intrinsic motoneuron electrical properties is dependent on activity and/or transmission-sensitive motoneuron-muscle interactions. In this study, we show that botulinum toxin-induced muscle paralysis led to statistically significant changes in the normal development of intrinsic motoneuron electrical properties in the postnatal mouse. This suggests that muscle activity during early neonatal life contributes to the development of normal motoneuron electrical properties.

Early life exposure to environmental tobacco smoke alters immune response to asbestos via a shift in inflammatory phenotype resulting in increased disease development.

PubMed

Brown, Traci Ann; Holian, Andrij; Pinkerton, Kent E; Lee, Joong Won; Cho, Yoon Hee

2016-07-01

Asbestos in combination with tobacco smoke exposure reportedly leads to more severe physiological consequences than asbestos alone; limited data also show an increased disease risk due to environmental tobacco smoke (ETS) exposure. Environmental influences during gestation and early lung development can result in physiological changes that alter risk for disease development throughout an individual's lifetime. Therefore, maternal lifestyle may impact the ability of offspring to subsequently respond to environmental insults and alter overall disease susceptibility. In this study, we examined the effects of exposure to ETS in utero and during early postnatal development on asbestos-related inflammation and disease in adulthood. ETS exposure in utero appeared to shift inflammation towards a Th2 phenotype, via suppression of Th1 inflammatory cytokine production. This effect was further pronounced in mice exposed to ETS in utero and during early postnatal development. In utero ETS exposure led to increased collagen deposition, a marker of fibrotic disease, when the offspring was later exposed to asbestos, which was further increased with additional ETS exposure during early postnatal development. These data suggest that ETS exposure in utero alters the immune responses and leads to greater disease development after asbestos exposure, which is further exacerbated when exposure to ETS continues during early postnatal development.

FGF-2 signal promotes proliferation of cerebellar progenitor cells and their oligodendrocytic differentiation at early postnatal stage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Naruse, Masae; Shibasaki, Koji; Ishizaki, Yasuki, E-mail: yasukiishizaki@gunma-u.ac.jp

The origins and developmental regulation of cerebellar oligodendrocytes are largely unknown, although some hypotheses of embryonic origins have been suggested. Neural stem cells exist in the white matter of postnatal cerebellum, but it is unclear whether these neural stem cells generate oligodendrocytes at postnatal stages. We previously showed that cerebellar progenitor cells, including neural stem cells, widely express CD44 at around postnatal day 3. In the present study, we showed that CD44-positive cells prepared from the postnatal day 3 cerebellum gave rise to neurospheres, while CD44-negative cells prepared from the same cerebellum did not. These neurospheres differentiated mainly into oligodendrocytesmore » and astrocytes, suggesting that CD44-positive neural stem/progenitor cells might generate oligodendrocytes in postnatal cerebellum. We cultured CD44-positive cells from the postnatal day 3 cerebellum in the presence of signaling molecules known as mitogens or inductive differentiation factors for oligodendrocyte progenitor cells. Of these, only FGF-2 promoted survival and proliferation of CD44-positive cells, and these cells differentiated into O4+ oligodendrocytes. Furthermore, we examined the effect of FGF-2 on cerebellar oligodendrocyte development ex vivo. FGF-2 enhanced proliferation of oligodendrocyte progenitor cells and increased the number of O4+ and CC1+ oligodendrocytes in slice cultures. These results suggest that CD44-positive cells might be a source of cerebellar oligodendrocytes and that FGF-2 plays important roles in their development at an early postnatal stage. - Highlights: • CD44 is expressed in cerebellar neural stem/progenitor cells at postnatal day 3 (P3). • FGF-2 promoted proliferation of CD44-positive progenitor cells from P3 cerebellum. • FGF-2 promoted oligodendrocytic differentiation of CD44-positive progenitor cells. • FGF-2 increased the number of oligodendrocytes in P3 cerebellar slice culture.« less

Retinoic Acid Signalling and the Control of Meiotic Entry in the Human Fetal Gonad

PubMed Central

Kinnell, Hazel L.; Anderson, Richard A.; Saunders, Philippa T. K.

2011-01-01

The development of mammalian fetal germ cells along oogenic or spermatogenic fate trajectories is dictated by signals from the surrounding gonadal environment. Germ cells in the fetal testis enter mitotic arrest, whilst those in the fetal ovary undergo sex-specific entry into meiosis, the initiation of which is thought to be mediated by selective exposure of fetal ovarian germ cells to mesonephros-derived retinoic acid (RA). Aspects of this model are hard to reconcile with the spatiotemporal pattern of germ cell differentiation in the human fetal ovary, however. We have therefore examined the expression of components of the RA synthesis, metabolism and signalling pathways, and their downstream effectors and inhibitors in germ cells around the time of the initiation of meiosis in the human fetal gonad. Expression of the three RA-synthesising enzymes, ALDH1A1, 2 and 3 in the fetal ovary and testis was equal to or greater than that in the mesonephros at 8–9 weeks gestation, indicating an intrinsic capacity within the gonad to synthesise RA. Using immunohistochemistry to detect RA receptors RARα, β and RXRα, we find germ cells to be the predominant target of RA signalling in the fetal human ovary, but also reveal widespread receptor nuclear localization indicative of signalling in the testis, suggesting that human fetal testicular germ cells are not efficiently shielded from RA by the action of the RA-metabolising enzyme CYP26B1. Consistent with this, expression of CYP26B1 was greater in the human fetal ovary than testis, although the sexually-dimorphic expression patterns of the germ cell-intrinsic regulators of meiotic initiation, STRA8 and NANOS2, appear conserved. Finally, we demonstrate that RA induces a two-fold increase in STRA8 expression in cultures of human fetal testis, but is not sufficient to cause widespread meiosis-associated gene expression. Together, these data indicate that while local production of RA within the fetal ovary may be important in regulating the onset of meiosis in the human fetal ovary, mechanisms other than CYP26B1-mediated metabolism of RA may exist to inhibit the entry of germ cells into meiosis in the human fetal testis. PMID:21674038

[Male pseudohermaphroditism].

PubMed

Fukutani, K

1997-11-01

Male pseudohermaphroditism is a condition of sex differentiation disorders in which the gonads are tests, but the genital ducts and/or external genitalia are incompletely masculinized. This syndrome is caused by a failure of the sequential process in embryonal development of the testis. In the presence of functioning testis the Müllerian ducts regress, while the mesonephric ducts and urogenital sinus differentiate into the internal and external male genitalia. Male pseudohermaphroditism is classified to subtypes according to etiological factors: (1) testicular unresponsiveness to hCG and LH; (2) defect in testosterone biosynthesis; (3) end-organ resistance to androgen; (4) defects in the intracellular metabolism of testosterone; (5) aberrations in testicular organogenesis; (6) defects in anti-Müllerian hormone.

Design, modelling and preliminary characterisation of microneedle-based electrodes for tissue electroporation in vivo

NASA Astrophysics Data System (ADS)

O'Mahony, Conor; Houlihan, Ruth; Grygoryev, Konstantin; Ning, Zhenfei; Williams, John; Moore, Tom

2016-10-01

We analysed the use of microneedle-based electrodes to enhance electroporation of mouse testis with DNA vectors for production of transgenic mice. Different microneedle formats were developed and tested, and we ultimately used electrodes based on arrays of 500 μm tall microneedles. In a series of experiments involving injection of a DNA vector expressing Green Fluorescent Protein (GFP) and electroporation using microneedle electrodes and a commercially available voltage supply, we compared the performance of flat and microneedle electrodes by measuring GFP expression at various timepoints after electroporation. Our main finding, supported by both experimental and simulated data, is that needles significantly enhanced electroporation of testis.

Distributional map of the terminal and sub-terminal sugar residues of the glycoconjugates in the prepubertal and postpubertal testis of a subject affected by complete androgen insensitivity syndrome (Morris's syndrome): lectin histochemical study.

PubMed

Gheri, G; Vannelli, G B; Marini, M; Zappoli Thyrion, G D; Gheri, R G; Sgambati, E

2004-01-01

In the present research we have investigated the distribution of the sugar residues of the glycoconjugates in the prepubertal and postpubertal testes of a subject with Morris's syndrome (CAIS, Complete Androgen Insensitivity Syndrome). For this purpose a battery of six horseradish peroxidase-conjugated lectins was used (SBA, PNA, WGA, ConA, LTA and UEAI). We have obtained a complete distributional map of the terminal and sub-terminal oligosaccharides in the tunica albuginea, interstitial tissue, lamina propria of the seminiferous tubules, Leydig cells, Sertoli cells, spermatogonia, mastocytes and endothelial cells. Furthermore the present study has shown that a large amount of sugar residues were detectable in the prepubertal and postpubertal testes but that some differences exist with particular regard to the Sertoli cells. The Sertoli cells and the Leydig cells of the retained prepubertal testis of the patient affected by Morris's syndrome were characterized by the presence of alpha-L-fucose, which was absent in the retained prepubertal testis of the normal subjects. Comparing the results on the postpubertal testis with those obtained on the same aged testis of healthy subjects we have demonstrated that alpha-L-fucose in the Sertoli and Leydig cells and D-galactose-N-acetyl-D-galactosamine in the Leydig cells are a unique feature of the subject affected by Morris's syndrome. D-galactose (ss1,3)-N-acetyl-D-galactosamine and sialic acid, which are present in the Leydig cells of the normal testis were never observed in the same cells of the postpubertal testis of the CAIS patient.

Protective effects of polyunsatutared fatty acids supplementation against testicular damage induced by intermittent hypobaric hypoxia in rats.

PubMed

Castillo, Rodrigo L; Zepeda, Andrea B; Short, Stefania E; Figueroa, Elías; Bustos-Obregon, Eduardo; Farías, Jorge G

2015-01-23

Intermittent hypobaric hypoxia (IHH) induces changes in the redox status and structure in rat testis. These effects may be present in people at high altitudes, such as athletes and miners. Polyunsaturated fatty acids (PUFA) can be effective in counteracting these oxidative modifications due to their antioxidants properties. The aim of the work was to test whether PUFA supplementation attenuates oxidative damage in testis by reinforcing the antioxidant defense system. The animals were divided into four groups (7 rats per group): normobaric normoxia (~750 tor; pO2 156 mmHg; Nx); Nx + PUFA, supplemented with PUFA (DHA: EPA = 3:1; 0.3 g kg(-1) of body weight per day); hypoxic hypoxia (~428 tor; pO2 90 mmHg; Hx) and, Hx + PUFA. The hypoxic groups were exposed in 4 cycles to 96 h of HH followed by 96 h of normobaric normoxia for 32 days. Total antioxidant capacity (FRAP) and lipid peroxidation (malondialdehyde, MDA) in plasma and reduced (GSH)/oxidized glutathione (GSSG) ratio, tissue lipid peroxidation (TBARS) and antioxidant enzymes activity were assessed at the end of the study in testis. Also, SIRTUIN 1 and HIF-1 protein expression in testis were determined. IHH increased lipid peroxidation in plasma and HIF-1 protein levels in testis. In addition, IHH reduced FRAP levels in plasma, antioxidant enzymes activities and SIRTUIN 1 protein levels in testis. PUFA supplementation attenuated these effects, inducing the increases in FRAP, in the antioxidant enzymes activity and HIF-1 levels. These results suggest that the IHH model induces a prooxidant status in plasma and testis. The molecular protective effect of PUFA may involve the induction of an antioxidant mechanism.

Stage-specific expression of DDX4 and c-kit at different developmental stages of the porcine testis.

PubMed

Lee, Ran; Lee, Won-Young; Park, Hyun-Jung; Ha, Woo-Tae; Woo, Jae-Seok; Chung, Hak-Jae; Lee, Ji-Heon; Hong, Kwonho; Song, Hyuk

2018-03-01

Spermatogenesis begins with spermatogonial stem cells (SSCs), which are located in the basement membrane of the adult testes. Previous studies have described specific biomarkers for undifferentiated porcine spermatogonia or SSCs; however, these markers are not sufficient to understand spermatogenesis at different developmental stages. The objective of this study was characterize the expression of DEAD-Box polypeptide 4 (DDX4, also known as VASA) and tyrosine-protein kinase kit (c-kit), as potential markers of male germ cells in the porcine testis. In porcine testis tissue at prepubertal stages (5, 30, and 60 days), DDX4 and c-kit protein expression was detected in the most undifferentiated spermatogonia, which also express protein gene product 9.5 (PGP9.5). However, in porcine testis tissues from pubertal and postpubertal stages (90, 120, and 150 days), DDX4 and c-kit were not detected in PGP9.5-positive undifferentiated spermatogonia. The DDX4 expression pattern was similar to that of c-kit in the porcine testis. In adult porcine testes, DDX4-expressing cells were located on the lumenal side, compared to synaptonemal complex protein 3-positive primary spermatocytes, but DDX-4 was not co-expressed with acrosin, a known acrosome marker. In addition, DDX4 was detected in PGP9.5-expressing porcine SSCs in culture. Based on our results, we suggest that DDX4 and c-kit are putative markers of undifferentiated spermatogonia in the prepubertal porcine testis. While in the postpubertal porcine testis, they are markers of differentiated spermatocytes. These findings may facilitate future studies of porcine spermatogenesis. Copyright © 2018 Elsevier B.V. All rights reserved.

Maternal deprivation decelerates postnatal morphological lung development of F344 rats.

PubMed

Hupa, Katharina Luise; Schmiedl, Andreas; Pabst, Reinhard; Von Hörsten, Stephan; Stephan, Michael

2014-02-01

Intensive medical care at premature born infants is often associated with separation of neonates from their mothers. Here, early artificial prolonged separation of rat pups from their dams (Maternal Deprivation, MD) was used to study potential impact on morphological lung maturation. Furthermore, we investigated the influence of an endogenous deficiency of the neuropeptide-cleaving dipeptidyl peptidase IV (DPP4), since the effects of MD are known to be partly mediated via neuropeptidergic effects, hypothesizing that MD will lead to a retardation of postnatal lung development, DPP4-dependendly. We used wild type and CD26/DPP4 deficient rats. For MD, the dam was placed each day into a separate cage for 2 h, while the pups remained in the nest on their own. Morphological lung maturation and cell proliferation at the postnatal days 7, 10, 14, and 21 were determined morphometrically. Maternally deprived wild types showed a retarded postnatal lung development compared with untreated controls in both substrains. During alveolarization, an increased thickness of alveolar septa and a decreased surface of septa about 50% were found. At the end of the morphological lung maturation, the surface of the alveolar septa was decreased at about 25% and the septal thickness remained increased about 20%. The proliferation rate was also decreased about 50% on day 14. However, the MD induced effects were less pronounced in DPP4-deficient rats, due to a significant deceleration already induced by DPP4-deficiency. Thus, MD as a model for postnatal stress experience influences remarkably postnatal development of rats, which is significantly modulated by the DPP4-system. Copyright © 2013 Wiley Periodicals, Inc.

SCG postnatal remodelling--hypertrophy and neuron number stability--in Spix's yellow-toothed cavies (Galea spixii).

PubMed

Ladd, Aliny A B Lobo; Ladd, Fernando V Lobo; da Silva, Andrea A P; Oliveira, Moacir F; de Souza, Romeu R; Coppi, Antonio A

2012-04-01

Whilst a fall in neuron numbers seems a common pattern during postnatal development, several authors have nonetheless reported an increase in neuron number, which may be associated with any one of a number of possible processes encapsulating either neurogenesis or late maturation and incomplete differentiation. Recent publications have thus added further fuel to the notion that a postnatal neurogenesis may indeed exist in sympathetic ganglia. In the light of these uncertainties surrounding the effects exerted by postnatal development on the number of superior cervical ganglion (SCG) neurons, we have used state-of-the-art design-based stereology to investigate the quantitative structure of SCG at four distinct timepoints after birth, viz., 1-3 days, 1 month, 12 months and 36 months. The main effects exerted by ageing on the SCG structure were: (i) a 77% increase in ganglion volume; (ii) stability in the total number of the whole population of SCG nerve cells (no change--either increase or decrease) during post-natal development; (iii) a higher proportion of uninucleate neurons to binucleate neurons only in newborn animals; (iv) a 130% increase in the volume of uninucleate cell bodies; and (v) the presence of BrdU positive neurons in animals at all ages. At the time of writing our results support the idea that neurogenesis takes place in the SCG of preás, albeit it warrants confirmation by further markers. We also hypothesise that a portfolio of other mechanisms: cell repair, maturation, differentiation and death may be equally intertwined and implicated in the numerical stability of SCG neurons during postnatal development. Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.

Thrombospondin-2 Expression During Retinal Vascular Development and Neovascularization.

PubMed

Fei, Ping; Palenski, Tammy L; Wang, Shoujian; Gurel, Zafer; Hankenson, Kurt D; Sorenson, Christine M; Sheibani, Nader

2015-09-01

To determine thrombospondin-2 (TSP2) expression and its impact on postnatal retinal vascular development and retinal neovascularization. The TSP2-deficient (TSP2(-/-)) mice and a line of TSP2 reporter mice were used to assess the expression of TSP2 during postnatal retinal vascular development and neovascularization. The postnatal retinal vascularization was evaluated using immunostaining of wholemount retinas prepared at different postnatal days by collagen IV staining and/or TSP2 promoter driven green fluorescent protein (GFP) expression. The organization of astrocytes was evaluated by glial fibrillary acidic protein (GFAP) staining. Retinal vascular densities were determined using trypsin digestion preparation of wholemount retinas at 3- and 6-weeks of age. Retinal neovascularization was assessed during the oxygen-induced ischemic retinopathy (OIR). Choroidal neovascularization (CNV) was assessed using laser-induced CNV. Using the TSP2-GFP reporter mice, we observed significant expression of TSP2 mRNA in retinas of postnatal day 5 (P5) mice, which increased by P7 and remained high up to P42. Similar results were observed in retinal wholemount preparations, and western blotting for GFP with the highest level of GFP was observed at P21. In contrast to high level of mRNA at P42, the GFP fluorescence or protein level was dramatically downregulated. The primary retinal vasculature developed at a faster rate in TSP2(-/-) mice compared with TSP2(+/+) mice up to P5. However, the developing retinal vasculature in TSP2(+/+) mice caught up with that of TSP2(-/-) mice after P7. No significant differences in retinal vascular density were observed at 3- or 6-weeks of age. TSP2(-/-) mice also exhibited a similar sensitivity to the hyperoxia-mediated vessel obliteration and similar level of neovascularization during OIR as TSP2(+/+) mice. Lack of TSP2 expression minimally affected laser-induced CNV compared with TSP2(+/+) mice. Lack of TSP2 expression was associated with enhanced retinal vascularization during early postnatal days but not at late postnatal times, and minimally affected retinal and CNV. However, the utility of TSP2 as a potential therapeutic target for inhibition of ocular neovascularization awaits further investigation.

Retinal dehydrogenase gene expression in stomach and small intestine of rats during postnatal development and in vitamin A deficiency.

PubMed

Bhat, P V

1998-04-17

Retinal dehydrogenase (RALDH) catalyzes the oxidation of retinal to all-trans and 9-cis retinoic acid, which function as ligands controlling RAR and RXR nuclear receptor-signaling pathways. We have recently shown the expression of RALDH transcript in the stomach and small intestine by reverse transcription polymerase chain reaction [Bhat, P.V., Labrecque J., Dumas, F., Lacroix, A. and Yoshida, A. (1995) Gene 166, 303-306]. We have examined RALDH expression in the stomach and small intestine before and during postnatal development and in vitamin A deficiency by assaying for mRNA levels and protein as well as for enzyme activity. In -2 day fetuses, RALDH expression was high in the small intestine, whereas RALDH protein was not detectable in the stomach. However, expression of RALDH was seen in the stomach after birth, and gradually increased with age and reached the highest level at postnatal day 42. In the intestine, RALDH expression decreased postnatally. Vitamin A deficiency up-regulated RALDH expression in the stomach and small intestine, and administration of retinoids down-regulated the RALDH expression in these tissues. These results show the differential expression of RALDH in the stomach and small intestine during postnatal development, and that vitamin A status regulates the expression of RALDH gene in these tissues.

Morphological and Surgical Overview of Adolescent Testis Affected by Varicocele

PubMed Central

Santoro, Giuseppe

2013-01-01

Varicocele is a common pathology of the testis frequently associated with infertility. For its management, a fine morphological study of the testis, both macroscopically and microscopically, and an accurate choice of surgical procedure are mandatory. The present review focuses its attention on the anatomic substrates of adolescent varicocele and its pathophysiologic modifications. The comprehensive assessment of all the reported alterations should be considered by the clinician before deciding the type of treatment and the timing. PMID:24348160

Effects of vitamin E on reproductive hormones and testis structure in chronic dioxin-treated mice.

PubMed

Yin, Hai-Ping; Xu, Jian-Ping; Zhou, Xian-Qing; Wang, Ying

2012-03-01

The purpose of this study was to investigate the effects of vitamin E on reproductive hormones and testis structure in mice treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Five experimental groups of a combination of TCDD and vitamin E were designed as follows: 0 ng/kg/d and 0 mg/kg/d (control group), 100 ng/kg/d and 0 mg/kg/d (Group I), 100 ng/kg/d and 20 mg/kg/d (Group II), 100 ng/kg/d and 100 mg/kg/d (Group III), and 100 ng/kg/d and 500 mg/kg/d (Group IV) respectively. Vitamin E and TCDD were given by oral gavage for 7 weeks. The results demonstrated that TCDD decreased the levels of brain gonadotropin releasing hormone (GnRH), testis luteinizing hormone (LH) and follicle stimulating hormone (FSH), serum testosterone and testis spermatozoa number, and damaged testis structure. Vitamin E at 20 mg/kg alleviated the decrease of GnRH; vitamin E at 20, 100, and 500 mg/kg antagonized the decline of LH and FSH; vitamin E at 20 and 100 mg/kg reversed the decrease of testosterone and spermatozoa number; and vitamin E at 100 mg/kg decreased the damage of the testis structure caused by TCDD. The results indicate that vitamin E antagonizes the reproductive endocrine toxicity and alleviates the changes in testicular structure caused by TCDD.

Protective effect of Zingiber officinale extract on rat testis after cyclophosphamide treatment.

PubMed

Mohammadi, F; Nikzad, H; Taghizadeh, M; Taherian, A; Azami-Tameh, A; Hosseini, S M; Moravveji, A

2014-08-01

Decreasing the side effects of chemotherapy in testis has been the subjects of many studies. In this study, the protective effects of Zingiber officinale extract on rat testis were investigated after chemotherapy with cyclophosphamide. Histological and biochemical parameters were compared in cyclophosphamide-treated rats with or without ginger extract intake. Wistar male rats were randomly divided into four groups each 10. The control group received a single injection of 1 ml isotonic saline intraperitoneally. The Cyclophosphamide (CP) group received a single dose of cyclophosphamide (100 mg kg(-1) BW) intraperitoneally. CP + 300 and CP + 600 groups received orally 300 or 600 mg of ginger extract, respectively, for a period of 6 weeks after cyclophosphamide injection. The morphologic and histological structure of the testis was compared in different groups of the rats. Also, factors like malondialdehyde, reactive oxygen species, total antioxidant capacity and testosterone level were assessed in blood serum as well. Our results showed that although ginger extract could not change testis weight, malondialdehyde (MDA) and ROS, but antioxidant and testosterone levels in serum were increased significantly. Also, an obvious improved histological change was seen in CP + 300 and CP + 600 groups in comparison with CP group. These protective effects of ginger on rat testis after cyclophosphamide treatment could be attributed to the higher serum level of antioxidants. © 2013 Blackwell Verlag GmbH.

A WEB-BASED SURVEY OF MOTHER-INFANT BOND, ATTACHMENT EXPERIENCES, AND METACOGNITION IN POSTTRAUMATIC STRESS FOLLOWING CHILDBIRTH.

PubMed

Williams, Charlotte; Patricia Taylor, Emily; Schwannauer, Matthias

2016-05-01

Postnatal depression is linked to adverse outcomes for parent and child, with metacognition and parenting experiences key variables in the development and maintenance of depression. The attachment between mother and infant is especially vulnerable to the effects of untreated postnatal depression. Despite high levels of reported postnatal stress symptoms, less attention has been given the relationship between attachment, metacognition, and postnatal traumatic symptoms in the context of birth trauma. This study tested several hypotheses regarding the relationships between recalled parenting experiences, metacognition, postnatal symptoms of posttraumatic stress disorder and depression and perceptions of the mother-infant bond, confirming and extending upon metacognitive and mentalization theories. A Web-based, cross-sectional, self-report questionnaire design was employed in an analog sample of new mothers. Participants were 502 women recruited via open-access Web sites associated with birth organizations. Structural equation modeling was employed for the principal analysis. Metacognition fully mediated the relationship between recalled parenting experiences and postnatal psychological outcomes. Posttraumatic stress was indirectly associated with maternal perceptions of the bond, with this relationship mediated by depression. Metacognition may have a key role in postnatal psychological distress. Where postnatal depression or traumatic birth experiences are identified, screening for posttraumatic stress is strongly indicated. © 2016 Michigan Association for Infant Mental Health.

Free radicals in adolescent varicocele testis.

PubMed

Romeo, Carmelo; Santoro, Giuseppe

2014-01-01

We examine the relationship between the structure and function of the testis and the oxidative and nitrosative stress, determined by an excessive production of free radicals and/or decreased availability of antioxidant defenses, which occur in the testis of adolescents affected by varicocele. Moreover, the effects of surgical treatment on oxidative stress were provided. We conducted a PubMed and Medline search between 1980 and 2014 using "adolescent," "varicocele," "free radicals," "oxidative and nitrosative stress," "testis," and "seminiferous tubules" as keywords. Cross-references were checked in each of the studies, and relevant articles were retrieved. We conclude that increased concentration of free radicals, generated by conditions of hypoxia, hyperthermia, and hormonal dysfunction observed in adolescent affected by varicocele, can harm germ cells directly or indirectly by influencing nonspermatogenic cells and basal lamina. With regard to few available data in current literature, further clinical trials on the pre- and postoperative ROS and RNS levels together with morphological studies of the cellular component of the testis are fundamental for complete comprehension of the role played by free radicals in the pathogenesis of adolescent varicocele and could justify its pharmacological treatment with antioxidants.

Oxidative alterations induced by D-aspartic acid in prepubertal rat testis in vitro: a mechanistic study.

PubMed

Chandrashekar, K N; Muralidhara

2008-07-01

The objective of the present study was to investigate the oxidative induction response following in vitro treatment with D-aspartic acid (DA) in prepubertal rat testis (homogenates, explants, and cell suspensions). In all three preparations, DA enhanced (P<0.001) lipid peroxidation, manifest as increased reactive oxygen species (ROS) and malondialdehyde (MDA). Further, DA-induced oxidative induction was potentiated (P<0.001) in the presence of iron (5 microM) and 3-amino triazole and mercaptosuccinate (P<0.001), known inhibitors of the peroxide metabolizing enzymes, catalase and glutathione peroxidase, respectively. Testis homogenates exposed to L-arginine (LA) per se had reduced (P<0.001) endogenous levels of ROS and MDA; furthermore, pre-incubation with L-arginine markedly suppressed (P<0.001) DA-induced oxidative induction, suggesting an antagonistic action, perhaps due to LA-derived nitric oxide. In conclusion, DA caused significant oxidative induction in prepubertal rat testis, but this action was abrogated by L-arginine. The relevance of this phenomenon in vivo merits further study, as both of these molecules have specific physiological functions in the testis.

Effect of sildenafil citrate (Viagra) and ethanol on the Albino rat testis: a scanning electron microscopic approach.

PubMed

Sivasankaran, T G; Udayakumar, R; Elanchezhiyan, C; Sabhanayakam, Selvi

2008-02-01

The effects of sildenafil citrate with ethanol on the rat testis was studied using scanning electron microscopy. Male Albino rats were divided into 8 groups, each being treated for a maximum of 45 days as follows. In the 4 short-term treatment groups, control rats were administered normal saline orally, whereas experimental animals were fed sildenafil citrate (Viagra) 1 microg/g with 18% ethanol (5 g/kg body weight), which was given orally as a single dose. After 1, 2.5, 4 and 24h the rats were killed. In the 4 long-term treatment groups, daily continuous doses of drug and ethanol with a single dosage were given for 15, 30 and 45 days and the animals killed 4h after the last dosage. Changes in the testis were compared with the normal healthy rat testis. The use of a scanning electron microscope for evaluation of the changes in the testis is more suitable for observation of the surface and morphological shapes of the tissue structures.

Operations-oriented performance measures for freeway management systems : final report.

DOT National Transportation Integrated Search

2008-12-01

This report describes the second and final year activities of the project titled Using Operations-Oriented Performance Measures to Support Freeway Management Systems. Work activities included developing a prototype system architecture for testi...

Postnatal Erythropoietin Mitigates Impaired Cerebral Cortical Development Following Subplate Loss from Prenatal Hypoxia–Ischemia

PubMed Central

Jantzie, Lauren L.; Corbett, Christopher J.; Firl, Daniel J.; Robinson, Shenandoah

2015-01-01

Preterm birth impacts brain development and leads to chronic deficits including cognitive delay, behavioral problems, and epilepsy. Premature loss of the subplate, a transient subcortical layer that guides development of the cerebral cortex and axonal refinement, has been implicated in these neurological disorders. Subplate neurons influence postnatal upregulation of the potassium chloride co-transporter KCC2 and maturation of γ-amino-butyric acid A receptor (GABAAR) subunits. We hypothesized that prenatal transient systemic hypoxia–ischemia (TSHI) in Sprague–Dawley rats that mimic brain injury from extreme prematurity in humans would cause premature subplate loss and affect cortical layer IV development. Further, we predicted that the neuroprotective agent erythropoietin (EPO) could attenuate the injury. Prenatal TSHI induced subplate neuronal loss via apoptosis. TSHI impaired cortical layer IV postnatal upregulation of KCC2 and GABAAR subunits, and postnatal EPO treatment mitigated the loss (n ≥ 8). To specifically address how subplate loss affects cortical development, we used in vitro mechanical subplate ablation in slice cultures (n ≥ 3) and found EPO treatment attenuates KCC2 loss. Together, these results show that subplate loss contributes to impaired cerebral development, and EPO treatment diminishes the damage. Limitation of premature subplate loss and the resultant impaired cortical development may minimize cerebral deficits suffered by extremely preterm infants. PMID:24722771

A structure-based extracellular matrix expansion mechanism of fibrous tissue growth.

PubMed

Kalson, Nicholas S; Lu, Yinhui; Taylor, Susan H; Starborg, Tobias; Holmes, David F; Kadler, Karl E

2015-05-20

Embryonic growth occurs predominately by an increase in cell number; little is known about growth mechanisms later in development when fibrous tissues account for the bulk of adult vertebrate mass. We present a model for fibrous tissue growth based on 3D-electron microscopy of mouse tendon. We show that the number of collagen fibrils increases during embryonic development and then remains constant during postnatal growth. Embryonic growth was explained predominately by increases in fibril number and length. Postnatal growth arose predominately from increases in fibril length and diameter. A helical crimp structure was established in embryogenesis, and persisted postnatally. The data support a model where the shape and size of tendon is determined by the number and position of embryonic fibroblasts. The collagen fibrils that these cells synthesise provide a template for postnatal growth by structure-based matrix expansion. The model has important implications for growth of other fibrous tissues and fibrosis.

Dioxin-induced retardation of development through a reduction in the expression of pituitary hormones and possible involvement of an aryl hydrocarbon receptor in this defect: A comparative study using two strains of mice with different sensitivities to dioxin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takeda, Tomoki; Taura, Junki; Hattori, Yukiko

We have previously revealed that treating pregnant rats with 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD) reduces the expression of gonadotropins and growth hormone (GH) in the fetal and neonatal pituitary. A change in gonadotropin expression impairs the testicular expression of steroidogenic proteins in perinatal pups, and imprint defects in sexual behavior after reaching maturity. In this study, we examined whether TCDD also affects the expression of gonadotropin and GH in mice using C57BL/6J and DBA/2J strains which express the aryl hydrocarbon receptor (Ahr) exhibiting a different affinity for TCDD. When pregnant C57BL/6J mice at gestational day (GD) 12 were given oral TCDD (0.2–20 μg/kg),more » all doses significantly attenuated the pituitary expression of gonadotropin mRNAs in fetuses at GD18. On the other hand, in DBA/2J mice, a much higher dose of TCDD (20 μg/kg) was needed to produce a significant attenuation. Such reduction in the C57BL/6J strain continued until at least postnatal day (PND) 4. In agreement with this, TCDD reduced the testicular expression of steroidogenic proteins in C57BL/6J neonates at PND2 and 4, although the same did not occur in the fetal testis and ovary. Furthermore, TCDD reduced the perinatal expression of GH, litter size and the body weight of newborn pups only in the C57BL/6J strain. These results suggest that 1) also in mice, maternal exposure to TCDD attenuates gonadotropin-regulated steroidogenesis and GH expression leading to the impairment of pup development and sexual immaturity; and 2) Ahr activation during the late fetal and early postnatal stages is required for these defects. - Highlights: • The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on mouse growth was studied. • TCDD reduced the levels of luteinizing hormone and growth hormone in perinatal pups. • Maternal exposure to TCDD also attenuated testicular steroidogenesis in pups. • The above effects of TCDD were more pronounced in C57BL/6J than in DBA/2J strain. • TCDD seems to disturb pup maturation by activating aryl hydrocarbon receptor.« less

Magnetic resonance angiography for the nonpalpable testis: a cost and cancer risk analysis.

PubMed

Eggener, S E; Lotan, Y; Cheng, E Y

2005-05-01

For the unilateral nonpalpable testis standard management is open surgical or laparoscopic exploration. An ideal imaging technique would reliably identify testicular nubbins and safely allow children to forgo surgical exploration without compromising future health or fertility. Our goal was to perform a cost and risk analysis of magnetic resonance angiography (MRA) for unilateral nonpalpable cryptorchid testes. A search of the English medical literature revealed 3 studies addressing the usefulness of MRA for the nonpalpable testicle. We performed a meta-analysis and applied the results to a hypothetical set of patients using historical testicular localization data. Analysis was then performed using 3 different management protocols-MRA with removal of testicular nubbin tissue, MRA with observation of testicular nubbin tissue and diagnostic laparoscopy. A cancer risk and cost analysis was then performed. MRA with observation of testicular nubbin tissue results in 29% of patients avoiding surgery without any increased cost of care. Among the 29% of boys with testicular nubbins left in situ and observed the highest estimated risk was 1 in 300 of cancer developing, and 1 in 5,300 of dying of cancer. A protocol using MRA with observation of inguinal nubbins results in nearly a third of boys avoiding surgical intervention at a similar cost to standard care without any significant increased risk of development of testis cancer.

Spontaneous CD4+ and CD8+ T-cell responses directed against cancer testis antigens are present in the peripheral blood of testicular cancer patients.

PubMed

Pearce, Hayden; Hutton, Paul; Chaudhri, Shalini; Porfiri, Emilio; Patel, Prashant; Viney, Richard; Moss, Paul

2017-07-01

Cancer/testis antigen (CTAg) expression is restricted to spermatogenic cells in an immune-privileged site within the testis. However, these proteins are expressed aberrantly by malignant cells and T-cell responses against CTAgs develop in many cancer patients. We investigated the prevalence, magnitude and phenotype of CTAg-specific T cells in the blood of patients with testicular germ cell tumors (TGCTs). CD8 + and CD4 + T-cell responses against MAGE-A family antigens were present in 44% (20/45) of patients' samples assayed by ex vivo IFN-γ ELISPOT. The presence of MAGE-specific CD8 + T cells was further determined following short-term in vitro expansion through the use of pMHC-I multimers containing known immunogenic peptides. Longitudinal analysis revealed that the frequency of MAGE-specific T cells decreased by 89% following orchidectomy suggesting that persistence of tumor antigen is required to sustain CTAg-specific T-cell immunity. Notably, this decrease correlated with a decline in the global effector/memory T-cell pool following treatment. Spontaneous T-cell immunity against CTAg proteins therefore develops in many patients with testicular cancer and may play an important role in the excellent clinical outcome of patients with this tumor subtype. © 2017 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Neurobehavioral Development of Common Marmoset Monkeys

PubMed Central

Schultz-Darken, Nancy; Braun, Katarina M.; Emborg, Marina E.

2016-01-01

Common marmoset (Callithrix jacchus) monkeys are a resource for biomedical research and their use is predicted to increase due to the suitability of this species for transgenic approaches. Identification of abnormal neurodevelopment due to genetic modification relies upon the comparison with validated patterns of normal behavior defined by unbiased methods. As scientists unfamiliar with nonhuman primate development are interested to apply genomic editing techniques in marmosets, it would be beneficial to the field that the investigators use validated methods of postnatal evaluation that are age and species appropriate. This review aims to analyze current available data on marmoset physical and behavioral postnatal development, describe the methods used and discuss next steps to better understand and evaluate marmoset normal and abnormal postnatal neurodevelopment PMID:26502294

Integrity of the blood-testis barrier in healthy men after suppression of spermatogenesis with testosterone and levonorgestrel.

PubMed

Ilani, Niloufar; Armanious, Nancy; Lue, Yan-He; Swerdloff, Ronald S; Baravarian, Sima; Adler, Alex; Tsang, Christina; Jia, Yue; Cui, Yu-Gui; Wang, Xing-Hai; Zhou, Zuo-Min; Sha, Jia-Hao; Wang, Christina

2012-12-01

Do exogenous male hormonal contraceptives that suppress intratesticular testosterone and spermatogenesis interfere with the blood-testis barrier integrity in men? When spermatogenesis was suppressed by testosterone alone or combined with levonorgestrel (LNG) treatment in men, the structural appearance of Sertoli cell tight junctions remained intact in the human testis. Testosterone promotes the integrity of the blood-testis barrier. Intratesticular androgen deprivation induced by exogenous testosterone plus a progestin to suppress spermatogenesis in a contraceptive regimen may disturb the structural and functional integrity of the blood-testis barrier. Testicular biopsies were obtained from a sub-study of a randomized clinical trial of 36 healthy Chinese men who were treated for 18 weeks and followed for at least a 12-week recovery period. Healthy Chinese male volunteers (27-48 years) were randomized to two treatment groups (n = 18/group) for 18 weeks: (1) testosterone undecanoate (TU) 1000 mg i.m. injection followed by a 500 mg injection every 6 weeks and (2) TU + LNG 250 μg orally daily. Blood samples were obtained from all participants before and during treatment and at the end of the recovery phase. Open testicular biopsies for this study were obtained from four men before treatment and from four men in each of the TU and TU + LNG groups at 2 and 9 weeks of treatment. The presence of antisperm antibodies was checked in the archived serum samples of the subjects at baseline, during treatment and at the end of the recovery period. Stored testicular biopsy samples from cynomolgus monkeys treated with either sub-cutaneous testosterone or placebo for 12 weeks were used for additional protein expression studies. Expression of blood-testis barrier associated proteins quantified by immunohistochemistry (claudin 3, claudin 11, junctional adhesion molecule-A, zonula occludens-1) remained unchanged despite a significant decrease in the numbers of pachytene spermatocytes and round spermatids in the seminiferous tubules at 9 weeks in the TU + LNG group. This was confirmed by immunoblots showing a lack of quantitative change in these tight junction proteins in monkeys after testosterone treatment. There were no increases in serum antisperm antibodies in the volunteers during the study. The duration of the study was short and the long-term effects of male hormonal contraceptive treatments on the integrity of the blood-testis barrier remain to be determined. This study supports the safety of male hormonal contraceptive treatment and does not corroborate the previous findings of disturbed immunological integrity of the blood-testis barrier from animal studies such as androgen receptor knockout mice and exogenous hormonal treatment in rats. The study was supported by grants from the Contraceptive Research and Development Program and the Mellon Foundation (MFG-02-64, MFG-03-67), Endocrine, Metabolism and Nutrition Training Grant (T32 DK007571), the Clinical and Translational Science Institute at Los Angeles Biomedical and Harbor-UCLA Medical Center (UL1RR033176 and UL1TR000124) and the Los Angeles Biomedical Research Institute Summer High School Student Program.

Deletion of neurturin impairs development of cholinergic nerves and heart rate control in postnatal mouse hearts.

PubMed

Downs, Anthony M; Jalloh, Hawa B; Prater, Kayla J; Fregoso, Santiago P; Bond, Cherie E; Hampton, Thomas G; Hoover, Donald B

2016-05-01

The neurotrophic factor neurturin is required for normal cholinergic innervation of adult mouse heart and bradycardic responses to vagal stimulation. Our goals were to determine effects of neurturin deletion on development of cardiac chronotropic and dromotropic functions, vagal baroreflex response, and cholinergic nerve density in nodal regions of postnatal mice. Experiments were performed on postnatal C57BL/6 wild-type (WT) and neurturin knockout (KO) mice. Serial electrocardiograms were recorded noninvasively from conscious pups using an ECGenie apparatus. Mice were treated with atenolol to evaluate and block sympathetic effects on heart rate (HR) and phenylephrine (PE) to stimulate the baroreflex. Immunohistochemistry was used to label cholinergic nerves in paraffin sections. WT and KO mice showed similar age-dependent increases in HR and decreases in PR interval between postnatal days (P) 2.5 and 21. Treatment with atenolol reduced HR significantly in WT and KO pups at P7.5. PE caused a reflex bradycardia that was significantly smaller in KO pups. Cholinergic nerve density was significantly less in nodal regions of P7.5 KO mice. We conclude that cholinergic nerves have minimal influence on developmental changes in HR and PR, QRS, and QTc intervals in mouse pups. However, cholinergic nerves mediate reflex bradycardia by 1 week postnatally. Deletion of neurturin impairs cholinergic innervation of the heart and the vagal efferent component of the baroreflex early during postnatal development. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

MEAL PARAMETERS AND VAGAL GASTROINTESTINAL AFFERENTS IN MICE THAT EXPERIENCED EARLY POSTNATAL OVERNUTRITION

PubMed Central

Biddinger, Jessica E.; Fox, Edward A.

2010-01-01

Early postnatal overnutrition results in a predisposition to develop obesity due in part to hypothalamic and sympathetic dysfunction. Potential involvement of another major regulatory system component - the vagus nerve - has not been examined. Moreover, feeding disturbances have rarely been investigated prior to development of obesity when confounds due to obesity are minimized. To examine these issues, litters were culled on the day of birth to create small litters (SL; overnutrition), or normal-size litters (NL; normal nutrition). Body weight, fat pad weight, meal patterns, and vagal sensory duodenal innervation were compared between SL and NL adult mice prior to development of obesity. Meal patterns were studied 18 hour/day for 3 weeks using a balanced diet. Then vagal mechanoreceptors were labeled using anterograde transport of wheatgerm agglutinin-horseradish peroxidase injected into the nodose ganglion and their density and morphology were examined. Between postnatal day 1 and weaning, body weight of SL mice was greater than for NL mice. By young adulthood it was similar in both groups, whereas SL fat pad weight was greater in males, suggesting postnatal overnutrition produced a predisposition to obesity. SL mice exhibited increased food intake, decreased satiety ratio, and increased first meal rate (following mild food deprivation) compared to NL mice, suggesting postnatal overnutrition disrupted satiety. The density and structure of intestinal IGLEs appeared similar in SL and NL mice. Thus, although a vagal role cannot be excluded, our meal parameter and anatomical findings provided no evidence for significant postnatal overnutrition effects on vagal gastrointestinal afferents. PMID:20403369

Meal parameters and vagal gastrointestinal afferents in mice that experienced early postnatal overnutrition.

PubMed

Biddinger, Jessica E; Fox, Edward A

2010-08-04

Early postnatal overnutrition results in a predisposition to develop obesity due in part to hypothalamic and sympathetic dysfunction. Potential involvement of another major regulatory system component--the vagus nerve--has not been examined. Moreover, feeding disturbances have rarely been investigated prior to development of obesity when confounds due to obesity are minimized. To examine these issues, litters were culled on the day of birth to create small litters (SL; overnutrition), or normal size litters (NL; normal nutrition). Body weight, fat pad weight, meal patterns, and vagal sensory duodenal innervation were compared between SL and NL adult mice prior to development of obesity. Meal patterns were studied 18 h/day for 3 weeks using a balanced diet. Then vagal mechanoreceptors were labeled using anterograde transport of wheatgerm agglutinin-horseradish peroxidase injected into the nodose ganglion and their density and morphology were examined. Between postnatal day 1 and weaning, body weight of SL mice was greater than for NL mice. By young adulthood it was similar in both groups, whereas SL fat pad weight was greater in males, suggesting postnatal overnutrition produced a predisposition to obesity. SL mice exhibited increased food intake, decreased satiety ratio, and increased first meal rate (following mild food deprivation) compared to NL mice, suggesting postnatal overnutrition disrupted satiety. The density and structure of intestinal IGLEs appeared similar in SL and NL mice. Thus, although a vagal role cannot be excluded, our meal parameter and anatomical findings provided no evidence for significant postnatal overnutrition effects on vagal gastrointestinal afferents. Copyright 2010 Elsevier Inc. All rights reserved.

Juvenile granulosa cell tumor of the testis: case report and review of literature.

PubMed

Nieto, Nieves; Torres-Valdivieso, Maria José; Aguado, Pablo; Mateos, Maria Elena; López-Pérez, Jesús; Melero, Carmen; Vivanco, José Luis; Gómez, Andrés

2002-01-01

Juvenile granulosa cell tumor of the testis is an infrequent tumor of the gonadal stroma characteristic of the pediatric age. It usually appears as a scrotal mass and less frequently as an abdominal or inguinal mass. It may be associated with ambiguous genitalia and/or abnormal sex chromosomes. The recommended treatment is orchiectomy alone because local recurrence or metastasis have never been observed. We describe a patient with a juvenile granulosa cell tumor of the testis and review the literature.

Irinotecan metabolite SN38 results in germ cell loss in the testis but not in the ovary of prepubertal mice.

PubMed

Lopes, Federica; Smith, Rowena; Nash, Sophie; Mitchell, Rod T; Spears, Norah

2016-11-01

Does the Irinotecan metabolite 7-ethyl-10-hydroxycamptothecan (SN38) damage the gonads of male and female prepubertal mice? The Irinotecan metabolite SN38 reduces germ cell numbers within the seminiferous tubules of mouse testes at concentrations that are relevant to cancer patients, while in contrast it has little if any effect on the female germ cell population. Little is known about the role of the chemotherapeutic agent Irinotecan on female fertility, with only one article to date reporting menopausal symptoms in perimenopausal women treated with Irinotecan, while no data are available either on adult male fertility or on the impact of Irinotecan on the subsequent fertility of prepubertal cancer patients, female or male. Male and female gonads were obtained from postnatal day 5 C57BL/6 mice and exposed in vitro to a range of concentrations of the Irinotecan metabolite SN38: 0.002, 0.01, 0.05, 0.1 or 1 µg ml -1 for the testis and 0.1, 1, 2.5 or 5 µg ml -1 for the ovary, with treated gonads compared to control gonads not exposed to SN38. SN38 was dissolved in 0.5% dimethyl sulfoxide, with controls exposed to the same concentration of diluent. The number of testis fragments used for each analysis ranged between 3 and 9 per treatment group, while the number of ovaries used for each analysis ranged between 4 and 12 per treatment group. Neonatal mouse gonads were developed in vitro, with tissue analysed at the end of the 4-6 day culture period, following immunofluorescence or hematoxylin and eosin staining. Statistical analyses were performed using one-way ANOVA followed by Bonferroni post-hoc test for normally distributed data and Kruskal-Wallis test followed by Dunns post-test for non-parametric data. Abnormal testis morphology was observed when tissues were exposed to SN38, with a smaller seminiferous tubule diameter at the highest concentration of SN38 (1 µg ml -1 , p < 0.001 versus control) and increased number of Sertoli cell-only tubules at the two highest concentrations of SN38 (0.1 µg ml -1 , p < 0.001; 1 µg ml -1 , p < 0.0001, both versus control). Within seminiferous tubules, a dose response decrease was observed in both germ cell number (mouse vasa homologue (MVH)-positive cells) and in proliferating cell number (bromodeoxyuridine (BrdU)-positive cells), with significance reached at the two highest concentrations of SN38 (0.1 µg ml -1 , p < 0.01 for both; 1 µg ml -1 , p < 0.001-MVH, p < 0.01-BrdU; all versus control). No change was seen in protein expression of the apoptotic marker cleaved caspase 3. Double immunofluorescence showed that occasional proliferating germ cells were present in treated testes, even after exposure to the highest drug concentration. When prepubertal ovaries were treated with SN38, no effect was seen on germ cell number, apoptosis or cell proliferation, even after exposure to the highest drug concentrations. As with any study using in vitro experiments with an experimental animal model, caution is required when extrapolating the present findings to humans. Differences between human and mouse spermatogonial development also need to be considered when assessing the effect of chemotherapeutic exposure. However, the prepubertal testes and ovaries used in the present studies contain germ cell populations that are representative of those found in prepubertal patients, and experimental tissues were exposed to drug concentrations within the range found in patient plasma. Our findings demonstrate that the prepubertal mouse ovary is relatively insensitive to exposure to the Irinotecan metabolite SN38, while it induces a marked dose-dependent sensitivity in the testicular germ cell population. The study identifies the importance of further investigation to identify the risk of infertility in young male cancer patients treated with Irinotecan. None. Work supported by Medical Research Grant (MRC) grant G1002118 and Children with Cancer UK grant 15-198. The authors declare that there is no conflict of interest that could prejudice the impartiality of the present research. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

Choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and MEK expression in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Jianhai

Fluoride is known to cause male reproductive toxicity, and the elucidation of its underlying mechanisms is an ongoing research focus in reproductive toxicology and epidemiology. Choline, an essential nutrient, has been extensively studied for its benefits in nervous system yet was rarely discussed for its prospective effect in male reproductive system. This study aims to explore the potential protective role of choline against NaF-induced male reproductive toxicity via MAPK pathway. The male mice were administrated by 150 mg/L NaF in drinking water, 5.75 g/kg choline in diet, and their combination respectively from maternal gestation to postnatal 15 weeks. The resultsmore » showed that fluoride exposure reduced body weight growth, lowered sperm count and survival percentages, altered testicular histology, down-regulated the mRNA expressions of NGF, Ras, Raf, and MEK genes in testes, as well as significantly decreased the expressions of both NGF and phosphor-MEK proteins in testes. Examination of data from choline-treated mice revealed that choline supplementation ameliorated these fluoride-induced changes. Taken together, our findings suggest that choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and phosphor-MEK expression. The suitable dosage and supplementation periods of choline await further exploration. - Highlights: • Fluoride exposure altered the growth and development, sperm count and sperm survival percentages, testicular histology • Fluoride exposure decreased NGF, Ras, and Mek mRNA and NGF and p-MEK protein expressions in testis of mice. • Choline supplementation diminishes fluoride-induced testicular toxicity.« less

Copy number variation of two separate regulatory regions upstream of SOX9 causes isolated 46,XY or 46,XX disorder of sex development.

PubMed

Kim, Gwang-Jin; Sock, Elisabeth; Buchberger, Astrid; Just, Walter; Denzer, Friederike; Hoepffner, Wolfgang; German, James; Cole, Trevor; Mann, Jillian; Seguin, John H; Zipf, William; Costigan, Colm; Schmiady, Hardi; Rostásy, Moritz; Kramer, Mildred; Kaltenbach, Simon; Rösler, Bernd; Georg, Ina; Troppmann, Elke; Teichmann, Anne-Christin; Salfelder, Anika; Widholz, Sebastian A; Wieacker, Peter; Hiort, Olaf; Camerino, Giovanna; Radi, Orietta; Wegner, Michael; Arnold, Hans-Henning; Scherer, Gerd

2015-04-01

SOX9 mutations cause the skeletal malformation syndrome campomelic dysplasia in combination with XY sex reversal. Studies in mice indicate that SOX9 acts as a testis-inducing transcription factor downstream of SRY, triggering Sertoli cell and testis differentiation. An SRY-dependent testis-specific enhancer for Sox9 has been identified only in mice. A previous study has implicated copy number variations (CNVs) of a 78 kb region 517-595 kb upstream of SOX9 in the aetiology of both 46,XY and 46,XX disorders of sex development (DSD). We wanted to better define this region for both disorders. By CNV analysis, we identified SOX9 upstream duplications in three cases of SRY-negative 46,XX DSD, which together with previously reported duplications define a 68 kb region, 516-584 kb upstream of SOX9, designated XXSR (XX sex reversal region). More importantly, we identified heterozygous deletions in four families with SRY-positive 46,XY DSD without skeletal phenotype, which define a 32.5 kb interval 607.1-639.6 kb upstream of SOX9, designated XY sex reversal region (XYSR). To localise the suspected testis-specific enhancer, XYSR subfragments were tested in cell transfection and transgenic experiments. While transgenic experiments remained inconclusive, a 1.9 kb SRY-responsive subfragment drove expression specifically in Sertoli-like cells. Our results indicate that isolated 46,XY and 46,XX DSD can be assigned to two separate regulatory regions, XYSR and XXSR, far upstream of SOX9. The 1.9 kb SRY-responsive subfragment from the XYSR might constitute the core of the Sertoli-cell enhancer of human SOX9, representing the so far missing link in the genetic cascade of male sex determination. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Actin nucleator Spire 1 is a regulator of ectoplasmic specialization in the testis.

PubMed

Wen, Qing; Li, Nan; Xiao, Xiang; Lui, Wing-Yee; Chu, Darren S; Wong, Chris K C; Lian, Qingquan; Ge, Renshan; Lee, Will M; Silvestrini, Bruno; Cheng, C Yan

2018-02-12

Germ cell differentiation during the epithelial cycle of spermatogenesis is accompanied by extensive remodeling at the Sertoli cell-cell and Sertoli cell-spermatid interface to accommodate the transport of preleptotene spermatocytes and developing spermatids across the blood-testis barrier (BTB) and the adluminal compartment of the seminiferous epithelium, respectively. The unique cell junction in the testis is the actin-rich ectoplasmic specialization (ES) designated basal ES at the Sertoli cell-cell interface, and the apical ES at the Sertoli-spermatid interface. Since ES dynamics (i.e., disassembly, reassembly and stabilization) are supported by actin microfilaments, which rapidly converts between their bundled and unbundled/branched configuration to confer plasticity to the ES, it is logical to speculate that actin nucleation proteins play a crucial role to ES dynamics. Herein, we reported findings that Spire 1, an actin nucleator known to polymerize actins into long stretches of linear microfilaments in cells, is an important regulator of ES dynamics. Its knockdown by RNAi in Sertoli cells cultured in vitro was found to impede the Sertoli cell tight junction (TJ)-permeability barrier through changes in the organization of F-actin across Sertoli cell cytosol. Unexpectedly, Spire 1 knockdown also perturbed microtubule (MT) organization in Sertoli cells cultured in vitro. Biochemical studies using cultured Sertoli cells and specific F-actin vs. MT polymerization assays supported the notion that a transient loss of Spire 1 by RNAi disrupted Sertoli cell actin and MT polymerization and bundling activities. These findings in vitro were reproduced in studies in vivo by RNAi using Spire 1-specific siRNA duplexes to transfect testes with Polyplus in vivo-jetPEI as a transfection medium with high transfection efficiency. Spire 1 knockdown in the testis led to gross disruption of F-actin and MT organization across the seminiferous epithelium, thereby impeding the transport of spermatids and phagosomes across the epithelium and perturbing spermatogenesis. In summary, Spire 1 is an ES regulator to support germ cell development during spermatogenesis.

A critical developmental role for tgfbr2 in myogenic cell lineages is revealed in mice expressing SM22-Cre, not SMMHC-Cre.

PubMed

Frutkin, Andrew D; Shi, Haikun; Otsuka, Goro; Levéen, Per; Karlsson, Stefan; Dichek, David A

2006-10-01

Smooth muscle cell (SMC)-specific deletion of transforming growth factor beta (TGF-beta) signaling would help elucidate the mechanisms through which TGF-beta signaling contributes to vascular development and disease. We attempted to generate mice with SMC-specific deletion of TGF-beta signaling by mating mice with a conditional ("floxed") allele for the type II TGF-beta receptor (tgfbr2flox) to mice with SMC-targeted expression of Cre recombinase. We bred male mice transgenic for smooth muscle myosin heavy chain (SMMHC)-Cre with females carrying tgfbr2flox. Surprisingly, SMMHC-Cre mice recombined tgfbr2flox at low levels in SMC and at high levels in the testis. Recombination of tgfbr2flox in testis correlated with high-level expression of SMMHC-Cre in testis and germline transmission of tgfbr2null. In contrast, mice expressing Cre from a SM22alpha promoter (SM22-Cre) efficiently recombined tgfbr2flox in vascular and visceral SMC and the heart, but not in testis. Use of the R26R reporter allele confirmed that Cre-mediated recombination in vascular SMC was inefficient for SMMHC-Cre mice and highly efficient for SM22-Cre mice. Breedings that introduced the SM22-Cre allele into tgfbr2flox/flox zygotes in order to generate adult mice that are hemizygous for SM22-Cre and homozygous for tgfbr2flox- and would have conversion of tgfbr2flox/flox to tgfbr2null/null in SMC-produced no live SM22-Cre : tgfbr2flox/flox pups (P<0.001). We conclude: (1) "SMC-targeted" Cre lines vary significantly in specificity and efficiency of Cre expression; (2) TGF-beta signaling in the subset of cells that express SM22alpha is required for normal development; (3) generation of adult mice with absent TGF-beta signaling in SMC remains a challenge.

Developmental regulation of inhibitory synaptic currents in the dorsal motor nucleus of the vagus in the rat

PubMed Central

Anselmi, Laura; Travagli, R. Alberto

2016-01-01

Prior immunohistochemical studies have demonstrated that at early postnatal time points, central vagal neurons receive both glycinergic and GABAergic inhibitory inputs. Functional studies have demonstrated, however, that adult vagal efferent motoneurons receive only inhibitory GABAergic synaptic inputs, suggesting loss of glycinergic inhibitory neurotransmission during postnatal development. The purpose of the present study was to test the hypothesis that the loss of glycinergic inhibitory synapses occurs in the immediate postnatal period. Whole cell patch-clamp recordings were made from dorsal motor nucleus of the vagus (DMV) neurons from postnatal days 1–30, and the effects of the GABAA receptor antagonist bicuculline (1–10 μM) and the glycine receptor antagonist strychnine (1 μM) on miniature inhibitory postsynaptic current (mIPSC) properties were examined. While the baseline frequency of mIPSCs was not altered by maturation, perfusion with bicuculline either abolished mIPSCs altogether or decreased mIPSC frequency and decay constant in the majority of neurons at all time points. In contrast, while strychnine had no effect on mIPSC frequency, its actions to increase current decay time declined during postnatal maturation. These data suggest that in early postnatal development, DMV neurons receive both GABAergic and glycinergic synaptic inputs. Glycinergic neurotransmission appears to decline by the second postnatal week, and adult neurons receive principally GABAergic inhibitory inputs. Disruption of this developmental switch from GABA-glycine to purely GABAergic transmission in response to early life events may, therefore, lead to adverse consequences in vagal efferent control of visceral functions. PMID:27440241

Critical androgen-sensitive periods of rat penis and clitoris development

PubMed Central

Welsh, Michelle; MacLeod, David J; Walker, Marion; Smith, Lee B; Sharpe, Richard M

2010-01-01

Androgen control of penis development/growth is unclear. In rats, androgen action in a foetal ‘masculinisation programming window’ (MPW; e15.5–e18.5)’ predetermines penile length and hypospadias occurrence. This has implications for humans (e.g. micropenis). Our studies aimed to establish in rats when androgen action/administration affects development/growth of the penis and if deficits in MPW androgen action were rescuable postnatally. Thus, pregnant rats were treated with flutamide during the MPW ± postnatal testosterone propionate (TP) treatment. To assess penile growth responsiveness, rats were treated with TP in various time windows (late foetal, neonatal through early puberty, puberty onset, or combinations thereof). Phallus length, weight, and morphology, hypospadias and anogenital distance (AGD) were measured in mid-puberty (d25) or adulthood (d90) in males and females, plus serum testosterone in adult males. MPW flutamide exposure reduced adult penile length and induced hypospadias dose-dependently; this was not rescued by postnatal TP treatment. In normal rats, foetal (e14.5–e21.5) TP exposure did not affect male penis size but increased female clitoral size. In males, TP exposure from postnatal d1–24 or at puberty (d15–24), increased penile length at d25, but not ultimately in adulthood. Foetal + postnatal TP (e14–postnatal d24) increased penile size at d25 but reduced it at d90 (due to reduced endogenous testosterone). In females, this treatment caused the biggest increase in adult clitoral size but, unlike in males, phallus size was unaffected by TP during puberty (d15–24). Postnatal TP treatment advanced penile histology at d25 to more resemble adult histology. AGD strongly correlated with final penis length. It is concluded that adult penile size depends critically on androgen action during the MPW but subsequent growth depends on later androgen exposure. Foetal and/or postnatal TP exposure does not increase adult penile size above its ‘predetermined’ length though its growth towards this maximum is advanced by peripubertal TP treatment. PMID:19656234

Maternal Bonding through Pregnancy and Postnatal: Findings from an Australian Longitudinal Study.

PubMed

Rossen, Larissa; Hutchinson, Delyse; Wilson, Judy; Burns, Lucinda; Allsop, Steve; Elliott, Elizabeth J; Jacobs, Sue; Macdonald, Jacqui A; Olsson, Craig; Mattick, Richard P

2017-07-01

Background  Mother-infant bonding provides the foundation for secure attachment through the lifespan and organizes many facets of infant social-emotional development, including later parenting. Aims  To describe maternal bonding to offspring across the pregnancy and postnatal periods, and to examine a broad range of sociodemographic and psychosocial predictors of the maternal-offspring bond. Methods  Data were drawn from a sample of 372 pregnant women participating in an Australian population-based longitudinal study of postnatal health and development. Participants completed maternal bonding questionnaires at each trimester and 8 weeks postnatal. Data were collected on a range of sociodemographic and psychosocial factors. Results  Bonding increased significantly through pregnancy, in quality and intensity. Regression analyses indicated that stronger antenatal bonding at all time points (trimesters 1 through 3) predicted stronger postnatal bonding. Older maternal age, birth mother being born in a non-English speaking country, mother not working full time, being a first-time mother, breast-feeding problems, and baby's crying behavior all predicted poorer bonding at 8 weeks postpartum. Conclusion  These novel findings have important implications for pregnant women and their infant offspring, and for health care professionals working in perinatal services. Importantly, interventions to strengthen maternal-fetal bonding would be beneficial during pregnancy to enhance postnatal bonding and infant health outcomes. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

White tea intake prevents prediabetes-induced metabolic dysfunctions in testis and epididymis preserving sperm quality.

PubMed

Dias, Tânia R; Alves, Marco G; Rato, Luís; Casal, Susana; Silva, Branca M; Oliveira, Pedro F

2016-11-01

Prediabetes has been associated with alterations in male reproductive tract, especially in testis and epididymis. Moreover, in vitro studies described a promising action of tea (Camellia sinensis L.) against metabolic dysfunctions. Herein, we hypothesized that white tea (WTEA) ingestion by prediabetic animals could ameliorate the metabolic alterations induced by the disease in testicular and epididymal tissues, preserving sperm quality. WTEA infusion was prepared and its phytochemical profile was evaluated by 1 H-NMR. A streptozotocin-induced prediabetic rat model was developed and three experimental groups were defined: control, prediabetic (PreDM) and prediabetic drinking WTEA (PreDM+WTEA). Metabolic profiles of testis and epididymis were evaluated by determining the metabolites content ( 1 H-NMR), protein levels (western blot) and enzymatic activities of key metabolic intervenient. The quality of spermatozoa from cauda epididymis was also assessed. Prediabetes increased glucose transporter 3 protein levels and decreased lactate dehydrogenase activity in testis, resulting in a lower lactate content. WTEA ingestion led to a metabolic adaptation to restore testicular lactate content. Concerning epididymis, prediabetes decreased the protein levels of several metabolic intervenient, resulting in decreased lactate and alanine content. WTEA consumption restored most of the evidenced alterations, however, not lactate content. WTEA also improved epididymal sperm motility and restored sperm viability. Prediabetes strongly affected testicular and epididymal metabolic status and most of these alterations were restored by WTEA consumption, resulting in the improvement of sperm quality. Our results suggest that WTEA consumption can be a cost-effective strategy to improve prediabetes-induced reproductive dysfunction. Copyright © 2016 Elsevier Inc. All rights reserved.

Duration of spermatogenesis and daily sperm production in the jaguar (Panthera onca).

PubMed

Costa, G M J; Chiarini-Garcia, H; Morato, R G; Alvarenga, R L L S; França, L R

2008-10-15

The jaguar, like most wild felids, is an endangered species. Since there are few data regarding reproductive biology for this species, our main goal was to investigate basic aspects of the testis and spermatogenesis. Four adult male jaguars were utilized; to determine the duration of spermatogenesis, two animals received an intratesticular injection of H(3)-thymidine. Mean (+/-SEM) testis weight and the gonadosomatic index were 17.7+/-2.2g and 0.05+/-0.01%, respectively, whereas the seminiferous tubules and the Leydig cells volume density were 74.7+/-3.8 and 16.7+/-1.6%. Eight stages of spermatogenesis were characterized, according to the tubular morphology system and acrosome development. Each spermatogenic cycle and the entire spermatogenic process (based on 4.5 cycles) lasted approximately 12.8+/-0.01 and 57.7+/-0.07 d. The number of Sertoli and Leydig cells per gram of testis was 29+/-4 x 10(6) and 107+/-12 x 10(6). Based on the number of round spermatids per pachytene spermatocyte (2.8+/-0.3:1; meiotic index); significant cell loss (30%) occurred during the two meiotic divisions. There were approximately eight spermatids for each Sertoli cell (Sertoli cell efficiency), whereas the daily sperm production per gram of testis was 16.9+/-1.2 x 10(6). We expect that in the near future, the knowledge obtained in the present investigation will facilitate, utilizing germ cell transplantation, preservation of the germinal epithelium and the ability to generate sperm from jaguars in testes of domestic cats.

Perinatal development of conjugative enzyme systems.

PubMed Central

Lucier, G W

1976-01-01

The problems and priorities involved in studying the role of conjugagive enzymes in developmental pharmacology are discussed and evaluated. The relative rates of UDP glucuronyltransferase and beta-glucuronidase were studied during perinatal development in hepatic and extrahepatic tissues to determine the net balance of glucuronidation or deglucuronidation at different developmental stages. In general, deglucuronidation predominated over glucuronidation in fetal tissues whereas the converse was evident in adults. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), an extremely toxic contaminant of some organochlorine compounds, was shown to be a potent inducer of some hepatic and extrahepatic drug-metabolizing enzymes. TCDD, administered during gestation, induced the postnatal activities of p-nitrophenol glucuronyltransferase and benzpyrene hydroxylase in rats. Foster mother experiments revealed that the postnatal induction was caused primarily by newborn exposure to TCDD in the mother's milk. Tissue distribution experiments with TCDD-14C confirmed these findings. Although TCDD induced non-steroid glucuronidation, no significant effects were evident on the postnatal development of steroid glucuronidation. The synthetic estrogen diethylstilbestrol (DES) is metabolized primarily by glucuronidation. The postnatal development of DES glucuronidation, like the steroid pathway, was not affected by gestational TCDD treatment. The fetal distribution of DES and DES-glucuronide, at different stages of development, correlated well with the perinatal development of steroid glucuronyltransferase activity. PMID:829487

Evaluation of gene expression profiles and pathways underlying postnatal development in mouse sclera.

PubMed

Lim, Wan'E; Kwan, Jia Lin; Goh, Liang Kee; Beuerman, Roger W; Barathi, Veluchamy A

2012-01-01

The aim of this study was to identify the genes and pathways underlying the growth of the mouse sclera during postnatal development. Total RNA was isolated from each of 30 single mouse sclera (n=30, 6 sclera each from 1-, 2-, 3-, 6-, and 8-week-old mice) and reverse-transcribed into cDNA using a T7-N(6) primer. The resulting cDNA was fragmented, labeled with biotin, and hybridized to a Mouse Gene 1.0 ST Array. ANOVA analysis was then performed using Partek Genomic Suite 6.5 beta and differentially expressed transcript clusters were filtered based on a selection criterion of ≥ 2 relative fold change at a false discovery rate of ≤ 5%. Genes identified as involved in the main biologic processes during postnatal scleral development were further confirmed using qPCR. A possible pathway that contributes to the postnatal development of the sclera was investigated using Ingenuity Pathway Analysis software. The hierarchical clustering of all time points showed that they did not cluster according to age. The highest number of differentially expressed transcript clusters was found when week 1 and week 2 old scleral tissues were compared. The peroxisome proliferator- activated receptor gamma coactivator 1-alpha (Ppargc1a) gene was found to be involved in the networks generated using Ingenuity Pathway Studio (IPA) from the differentially expressed transcript cluster lists of week 2 versus 1, week 3 versus 2, week 6 versus 3, and week 8 versus 6. The gene expression of Ppargc1a varied during scleral growth from week 1 to 2, week 2 to 3, week 3 to 6, and week 6 to 8 and was found to interact with a different set of genes at different scleral growth stages. Therefore, this indicated that Ppargc1a might play a role in scleral growth during postnatal weeks 1 to 8. Gene expression of eye diseases should be studied as early as postnatal weeks 1-2 to ensure that any changes in gene expression pattern during disease development are detected. In addition, we propose that Ppargc1a might play a role in regulating postnatal scleral development by interacting with a different set of genes at different scleral growth stages.

Evaluation of gene expression profiles and pathways underlying postnatal development in mouse sclera

PubMed Central

Lim, Wan’E.; Kwan, Jia Lin; Goh, Liang Kee; Beuerman, Roger W.

2012-01-01

Purpose The aim of this study was to identify the genes and pathways underlying the growth of the mouse sclera during postnatal development. Methods Total RNA was isolated from each of 30 single mouse sclera (n=30, 6 sclera each from 1-, 2-, 3-, 6-, and 8-week-old mice) and reverse-transcribed into cDNA using a T7-N6 primer. The resulting cDNA was fragmented, labeled with biotin, and hybridized to a Mouse Gene 1.0 ST Array. ANOVA analysis was then performed using Partek Genomic Suite 6.5 beta and differentially expressed transcript clusters were filtered based on a selection criterion of ≥2 relative fold change at a false discovery rate of ≤5%. Genes identified as involved in the main biologic processes during postnatal scleral development were further confirmed using qPCR. A possible pathway that contributes to the postnatal development of the sclera was investigated using Ingenuity Pathway Analysis software. Results The hierarchical clustering of all time points showed that they did not cluster according to age. The highest number of differentially expressed transcript clusters was found when week 1 and week 2 old scleral tissues were compared. The peroxisome proliferator- activated receptor gamma coactivator 1-alpha (Ppargc1a) gene was found to be involved in the networks generated using Ingenuity Pathway Studio (IPA) from the differentially expressed transcript cluster lists of week 2 versus 1, week 3 versus 2, week 6 versus 3, and week 8 versus 6. The gene expression of Ppargc1a varied during scleral growth from week 1 to 2, week 2 to 3, week 3 to 6, and week 6 to 8 and was found to interact with a different set of genes at different scleral growth stages. Therefore, this indicated that Ppargc1a might play a role in scleral growth during postnatal weeks 1 to 8. Conclusions Gene expression of eye diseases should be studied as early as postnatal weeks 1–2 to ensure that any changes in gene expression pattern during disease development are detected. In addition, we propose that Ppargc1a might play a role in regulating postnatal scleral development by interacting with a different set of genes at different scleral growth stages. PMID:22736935

Coexistence of Trisomy 13 and SRY (-) XX Ovotesticular Disorder of Sex Development.

PubMed

Ürel Demir, Gizem; Doğan, Özlem Akgün; Şimşek Kiper, Pelin Özlem; Utine, Gülen Eda; Boduroğlu, Koray; Gucer, Safak; Alikaşifoğlu, Mehmet

2017-12-01

Ovotesticular disorder of sex development (OT-DSD) is a rare disorder of sexual differentiation characterized by the presence of both testicular and ovarian tissue in an individual and the majority of cases have been reported with 46,XX karyotype. In 46,XX cases, testicular differentiation may occur due to the translocation of SRY to the X chromosome or to an autosome. Herein, we present a female newborn with a combination of trisomy 13 and SRY (-) XX OT-DSD. Trisomy 13 is a relatively common and well-known chromosomal disorder in which disorders of sexual differentiation are not frequent. In the absence of SRY, overexpression of pro-testis genes, or decreased expression of pro-ovarian/anti-testis genes have been suggested as underlying mechanisms of testicular formation. The findings in this patient were suggestive of an underlying genomic disorder associated with FGF9 and/or SPRY2.

New frontiers in nonhormonal male contraception

PubMed Central

Cheng, C. Yan; Mruk, Dolores D.

2015-01-01

The world’s population is nearing 6.8 billion, and we are in need of a male contraceptive that is safe, effective, reversible and affordable. Hormonal approaches, which employ different formulations of testosterone administered in combination with other hormones, have shown considerable promise in clinical trials, and they are currently at the forefront of research and development. However, the long-term effects of using hormones throughout a male’s reproductive life for contraception are unknown, and it may take decades before this information becomes available. Because of this, many investigators are aiming to bring a nonhormonal male contraceptive to the consumer market. Indeed, there are several distinct but feasible avenues in which fertility can be regulated without affecting the hypothalamus-pituitary-testis axis. In this review, we discuss several approaches for fertility control involving the testis that one day may lead to the development of a nonhormonal male contraceptive. PMID:20933122

New frontiers in nonhormonal male contraception.

PubMed

Cheng, C Yan; Mruk, Dolores D

2010-11-01

The world's population is nearing 6.8 billion, and we are in need of a male contraceptive that is safe, effective, reversible and affordable. Hormonal approaches, which employ different formulations of testosterone administered in combination with other hormones, have shown considerable promise in clinical trials, and they are currently at the forefront of research and development. However, the long-term effects of using hormones throughout a male's reproductive life for contraception are unknown, and it may take decades before this information becomes available. Because of this, many investigators are aiming to bring a nonhormonal male contraceptive to the consumer market. Indeed, there are several distinct but feasible avenues in which fertility can be regulated without affecting the hypothalamus-pituitary-testis axis. In this review, we discuss several approaches for fertility control involving the testis that one day may lead to the development of a nonhormonal male contraceptive. Copyright © 2010 Elsevier Inc. All rights reserved.

Development and clinical application of a new testicular prosthesis

PubMed Central

Ning, Ye; Cai, Zhikang; Chen, Huixing; Ping, Ping; Li, Peng; Wang, Zhong; Li, Zheng

2011-01-01

A new type of testicular prosthesis made of silastic with an elliptical shape to mimic a normal testis was developed by our team and submitted for patenting in China. The prosthesis was produced in different sizes to imitate the normal testis of the patient. To investigate the effects and safety of the testicular prosthesis, 20 patients receiving testicular prosthesis implantation were recruited for this study. Follow-up after 6 months revealed no complications in the patients. All the patients answered that they were satisfied with their body image and the position of the implants, 19 patients were satisfied with the size and 16 patients were satisfied with the weight. These results show that the testicular prosthesis used in this study can meet patient's expectations. Patients undergoing orchiectomy should be offered the option to receive a testicular prosthesis implantation. The dimensions and weight of the available prosthetic implants should be further addressed to improve patient satisfaction. PMID:21927041

Immunolocalization of NR1, NR2A, and PSD-95 in rat hippocampal subregions during postnatal development.

PubMed

Ling, Wei; Chang, Lirong; Song, Yizhi; Lu, Tao; Jiang, Yuhua; Li, Youxiang; Wu, Yan

2012-05-01

Although the expression of NMDARs and synaptic-associated proteins has been widely studied, the temporospatial distribution of NMDAR subunits and synaptic proteins in different hippocampal subregions during postnatal development still lacks detailed information, and the relationship between NR1 or NR2 subunits and PSD-95 family proteins is controversial. In this study, we used immunofluorescent staining to assess NR1 or NR2A and PSD-95 expressions and the relationship between them in CA1, CA3, and DG of rat hippocampus on postnatal (P) days: P0, P4, P7, P10, P14, P21, P28, P56. The results showed that from P0 to P56, NR1, NR2A, and PSD-95 expressions increased gradually, and the time points of their expression peak differed in CA1, CA3, and DG during postnatal development. Interestingly, although the expression of PSD-95 was positively correlated to both NR1 and NR2A, the NR1 and PSD-95 coexpressed puncta were greatest in CA3, while NR2A and PSD-95 coexpressed puncta were greatest in CA1, compared to other subregions. Surprisingly, at P21, among different strata of CA1, the area of highest expression of NR2A was dramatically changed from stratum pyramidale to stratum polymorphum and stratum moleculare, and returned to stratum pyramidale gradually on the later observed days again, indicating that P21 may be one critical timepoint during postnatal development in CA1. The specific temporospatial distribution pattern of NR1, NR2A, and PSD-95 might be related to the different physiological functions during postnatal development. Discovering the alteration of the relationship between PSD-95 and NMDAR subunits expression may be helpful for understanding mechanisms and therapy of neurodegenerative diseases. Copyright © 2011 Elsevier GmbH. All rights reserved.

A statewide review of postnatal care in private hospitals in Victoria, Australia.

PubMed

Rayner, Jo-Anne; McLachlan, Helen L; Forster, Della A; Peters, Louise; Yelland, Jane

2010-05-28

Concerns have been raised in Australia and internationally regarding the quality and effectiveness of hospital postnatal care, although Australian women receiving postnatal care in the private maternity sector rate their satisfaction with care more highly than women receiving public maternity care. In Victoria, Australia, two-thirds of women receive their maternity care in the public sector and the remainder in private health care sector. A statewide review of public hospital postnatal care in Victoria from the perspective of care providers found many barriers to care provision including the busyness of postnatal wards, inadequate staffing and priority being given to other episodes of care; however the study did not include private hospitals. The aim of this study was replicate the review in the private sector, to explore the structure and organisation of postnatal care in private hospitals and identify those aspects of care potentially impacting on women's experiences and maternal and infant care. This provides a more complete overview of the organisational structures and processes in postnatal care in all Victorian hospitals from the perspective of care providers. A mixed method design was used. A structured postal survey was sent to all Victorian private hospitals (n = 19) and key informant interviews were undertaken with selected clinical midwives, maternity unit managers and obstetricians (n = 11). Survey data were analysed using descriptive statistics and interview data analysed thematically. Private hospital care providers report that postnatal care is provided in very busy environments, and that meeting the aims of postnatal care (breastfeeding support, education of parents and facilitating rest and recovery for women following birth) was difficult in the context of increased acuity of postnatal care; prioritising of other areas over postnatal care; high midwife-to-woman ratios; and the number and frequency of visitors. These findings were similar to the public review. Organisational differences in postnatal care were found between the two sectors: private hospitals are more likely to have a separate postnatal care unit with single rooms and can accommodate partners' over-night; very few have a policy of infant rooming-in; and most have well-baby nurseries. Private hospitals are also more likely to employ staff other than midwives, have fewer core postnatal staff and have a greater dependence on casual and bank staff to provide postnatal care. There are similarities and differences in the organisation and provision of private postnatal care compared to postnatal care in public hospitals. Key differences between the two sectors relate to the organisational and aesthetic aspects of service provision rather than the delivery of postnatal care. The key messages emerging from both reviews is the need to review and monitor the adequacy of staffing levels and to develop alternative approaches to postnatal care to improve this episode of care for women and care providers alike. We also recommend further research to provide a greater evidence-base for postnatal care provision.

Anchoring Junctions As Drug Targets: Role in Contraceptive Development

PubMed Central

Mruk, Dolores D.; Silvestrini, Bruno; Cheng, C. Yan

2010-01-01

In multicellular organisms, cell-cell interactions are mediated in part by cell junctions, which underlie tissue architecture. Throughout spermatogenesis, for instance, preleptotene leptotene spermatocytes residing in the basal compartment of the seminiferous epithelium must traverse the blood-testis barrier to enter the adluminal compartment for continued development. At the same time, germ cells must also remain attached to Sertoli cells, and numerous studies have reported extensive restructuring at the Sertoli-Sertoli and Sertoli-germ cell interface during germ cell movement across the seminiferous epithelium. Furthermore, the proteins and signaling cascades that regulate adhesion between testicular cells have been largely delineated. These findings have unveiled a number of potential “druggable” targets that can be used to induce premature release of germ cells from the seminiferous epithelium, resulting in transient infertility. Herein, we discuss a novel approach with the aim of developing a nonhormonal male contraceptive for future human use, one that involves perturbing adhesion between Sertoli and germ cells in the testis. PMID:18483144

Tooth-bone morphogenesis during postnatal stages of mouse first molar development

PubMed Central

Lungová, Vlasta; Radlanski, Ralf J; Tucker, Abigail S; Renz, Herbert; Míšek, Ivan; Matalová, Eva

2011-01-01

The first mouse molar (M1) is the most common model for odontogenesis, with research particularly focused on prenatal development. However, the functional dentition forms postnatally, when the histogenesis and morphogenesis of the tooth is completed, the roots form and the tooth physically anchors into the jaw. In this work, M1 was studied from birth to eruption, assessing morphogenesis, proliferation and apoptosis, and correlating these with remodeling of the surrounding bony tissue. The M1 completed crown formation between postnatal (P) days 0–2, and the development of the tooth root was initiated at P4. From P2 until P12, cell proliferation in the dental epithelium reduced and shifted downward to the apical region of the forming root. In contrast, proliferation was maintained or increased in the mesenchymal cells of the dental follicle. At later stages, before tooth eruption (P20), cell proliferation suddenly ceased. This withdrawal from the cell cycle correlated with tooth mineralization and mesenchymal differentiation. Apoptosis was observed during all stages of M1 postnatal morphogenesis, playing a role in the removal of cells such as osteoblasts in the mandibular region and working together with osteoclasts to remodel the bone around the developing tooth. At more advanced developmental stages, apoptotic cells and bodies accumulated in the cell layers above the tooth cusps, in the path of eruption. Three-dimensional reconstruction of the developing postnatal tooth and bone indicates that the alveolar crypts form by resorption underneath the primordia, whereas the ridges form by active bone growth between the teeth and roots to form a functional complex. PMID:21418206

Intestinal microbiota influence the early postnatal development of the enteric nervous system.

PubMed

Collins, J; Borojevic, R; Verdu, E F; Huizinga, J D; Ratcliffe, E M

2014-01-01

Normal gastrointestinal function depends on an intact and coordinated enteric nervous system (ENS). While the ENS is formed during fetal life, plasticity persists in the postnatal period during which the gastrointestinal tract is colonized by bacteria. We tested the hypothesis that colonization of the bowel by intestinal microbiota influences the postnatal development of the ENS. The development of the ENS was studied in whole mount preparations of duodenum, jejunum, and ileum of specific pathogen-free (SPF), germ-free (GF), and altered Schaedler flora (ASF) NIH Swiss mice at postnatal day 3 (P3). The frequency and amplitude of circular muscle contractions were measured in intestinal segments using spatiotemporal mapping of video recorded spontaneous contractile activity with and without exposure to lidocaine and N-nitro-L-arginine (NOLA). Immunolabeling with antibodies to PGP9.5 revealed significant abnormalities in the myenteric plexi of GF jejunum and ileum, but not duodenum, characterized by a decrease in nerve density, a decrease in the number of neurons per ganglion, and an increase in the proportion of myenteric nitrergic neurons. Frequency of amplitude of muscle contractions were significantly decreased in the jejunum and ileum of GF mice and were unaffected by exposure to lidocaine, while NOLA enhanced contractile frequency in the GF jejunum and ileum. These findings suggest that early exposure to intestinal bacteria is essential for the postnatal development of the ENS in the mid to distal small intestine. Future studies are needed to investigate the mechanisms by which enteric microbiota interact with the developing ENS. © 2013 John Wiley & Sons Ltd.

The Role of Endothelin System in Renal Structure and Function during the Postnatal Development of the Rat Kidney.

PubMed

Albertoni Borghese, María F; Ortiz, María C; Balonga, Sabrina; Moreira Szokalo, Rocío; Majowicz, Mónica P

2016-01-01

Renal development in rodents, unlike in humans, continues during early postnatal period. We aimed to evaluate whether the pharmacological inhibition of Endothelin system during this period affects renal development, both at structural and functional level in male and female rats. Newborn rats were treated orally from postnatal day 1 to 20 with vehicle or bosentan (Actelion, 20 mg/kg/day), a dual endothelin receptor antagonist (ERA). The animals were divided in 4 groups: control males, control females, ERA males and ERA females. At day 21, we evaluated renal function, determined the glomerular number by a maceration method and by morphometric analysis and evaluated possible structural renal alterations by three methods: 〈alpha〉-Smooth muscle actin (α-SMA) immunohistochemistry, Masson's trichrome and Sirius red staining. The pharmacological inhibition of Endothelin system with a dual ERA during the early postnatal period of the rat did not leads to renal damage in the kidneys of male and female rats. However, ERA administration decreased the number of glomeruli, the juxtamedullary filtration surface area and the glomerular filtration rate and increased the proteinuria. These effects could predispose to hypertension or renal diseases in the adulthood. On the other hand, these effects were more pronounced in male rats, suggesting that there are sex differences that could be greater later in life. These results provide evidence that Endothelin has an important role in rat renal postnatal development. However these results do not imply that the same could happen in humans, since human renal development is complete at birth.

Early life exposure to environmental tobacco smoke alters immune response to asbestos via a shift in inflammatory phenotype resulting in increased disease development

PubMed Central

Brown, Traci A.; Holian, Andrij; Pinkerton, Kent E.; Lee, Joong Won; Cho, Yoon Hee

2016-01-01

Asbestos in combination with tobacco smoke exposure reportedly leads to more severe physiological consequences than asbestos alone; limited data also show an increased disease risk due to environmental tobacco smoke (ETS) exposure. Environmental influences during gestation and early lung development can result in physiological changes that alter risk for disease development throughout an individual’s lifetime. Therefore, maternal lifestyle may impact the ability of offspring to subsequently respond to environmental insults and alter overall disease susceptibility. In this study, we examined the effects of exposure to ETS in utero and during early postnatal development on asbestos-related inflammation and disease in adulthood. ETS exposure in utero appeared to shift inflammation towards a Th2 phenotype, via suppression of Th1 inflammatory cytokine production. This effect was further pronounced in mice exposed to ETS in utero and during early postnatal development. In utero ETS exposure led to increased collagen deposition, a marker of fibrotic disease, when the offspring was later exposed to asbestos, which was further increased with additional ETS exposure during early postnatal development. These data suggest that ETS exposure in utero alters the immune responses and leads to greater disease development after asbestos exposure, which is further exacerbated when exposure to ETS continues during early postnatal development. PMID:27138493

Expression of the neurotransmitter-synthesizing enzyme glutamic acid decarboxylase in male germ cells.

PubMed

Persson, H; Pelto-Huikko, M; Metsis, M; Söder, O; Brene, S; Skog, S; Hökfelt, T; Ritzén, E M

1990-09-01

The gene encoding glutamic acid decarboxylase (GAD), the key enzyme in the synthesis of the inhibitory neurotransmitter gamma-aminobutyric acid, is shown to be expressed in the testis of several different species. Nucleotide sequence analysis of a cDNA clone isolated from the human testis confirmed the presence of GAD mRNA in the testis. The major GAD mRNA in the testis was 2.5 kilobases. Smaller amounts of a 3.7-kilobase mRNA with the same size as GAD mRNA in the brain was also detected in the testis. In situ hybridization using a GAD-specific probe revealed GAD mRNA expressing spermatocytes and spermatids located in the middle part of rat seminiferous tubules. Studies on the ontogeny of GAD mRNA expression showed low levels of GAD mRNA in testes of prepubertal rats, with increasing levels as sexual maturation is reached, compatible with GAD mRNA expression in germ cells. In agreement with this, fractionation of cells from the rat seminiferous epithelium followed by Northern (RNA) blot analysis showed the highest levels of GAD mRNA associated with spermatocytes and spermatids. Evidence for the presence of GAD protein in the rat testis was obtained from the demonstration of GAD-like immunoreactivity in seminiferous tubules, predominantly at a position where spermatids and spermatozoa are found. Furthermore, GAD-like immunoreactivity was seen in the midpiece of ejaculated human spermatozoa, the part that is responsible for generating energy for spermatozoan motility.

Expression of the neurotransmitter-synthesizing enzyme glutamic acid decarboxylase in male germ cells.

PubMed Central

Persson, H; Pelto-Huikko, M; Metsis, M; Söder, O; Brene, S; Skog, S; Hökfelt, T; Ritzén, E M

1990-01-01

The gene encoding glutamic acid decarboxylase (GAD), the key enzyme in the synthesis of the inhibitory neurotransmitter gamma-aminobutyric acid, is shown to be expressed in the testis of several different species. Nucleotide sequence analysis of a cDNA clone isolated from the human testis confirmed the presence of GAD mRNA in the testis. The major GAD mRNA in the testis was 2.5 kilobases. Smaller amounts of a 3.7-kilobase mRNA with the same size as GAD mRNA in the brain was also detected in the testis. In situ hybridization using a GAD-specific probe revealed GAD mRNA expressing spermatocytes and spermatids located in the middle part of rat seminiferous tubules. Studies on the ontogeny of GAD mRNA expression showed low levels of GAD mRNA in testes of prepubertal rats, with increasing levels as sexual maturation is reached, compatible with GAD mRNA expression in germ cells. In agreement with this, fractionation of cells from the rat seminiferous epithelium followed by Northern (RNA) blot analysis showed the highest levels of GAD mRNA associated with spermatocytes and spermatids. Evidence for the presence of GAD protein in the rat testis was obtained from the demonstration of GAD-like immunoreactivity in seminiferous tubules, predominantly at a position where spermatids and spermatozoa are found. Furthermore, GAD-like immunoreactivity was seen in the midpiece of ejaculated human spermatozoa, the part that is responsible for generating energy for spermatozoan motility. Images PMID:1697032

Tissue-Specific Transcriptomics in the Field Cricket Teleogryllus oceanicus

PubMed Central

Bailey, Nathan W.; Veltsos, Paris; Tan, Yew-Foon; Millar, A. Harvey; Ritchie, Michael G.; Simmons, Leigh W.

2013-01-01

Field crickets (family Gryllidae) frequently are used in studies of behavioral genetics, sexual selection, and sexual conflict, but there have been no studies of transcriptomic differences among different tissue types. We evaluated transcriptome variation among testis, accessory gland, and the remaining whole-body preparations from males of the field cricket, Teleogryllus oceanicus. Non-normalized cDNA libraries from each tissue were sequenced on the Roche 454 platform, and a master assembly was constructed using testis, accessory gland, and whole-body preparations. A total of 940,200 reads were assembled into 41,962 contigs, to which 36,856 singletons (reads not assembled into a contig) were added to provide a total of 78,818 sequences used in annotation analysis. A total of 59,072 sequences (75%) were unique to one of the three tissues. Testis tissue had the greatest proportion of tissue-specific sequences (62.6%), followed by general body (56.43%) and accessory gland tissue (44.16%). We tested the hypothesis that tissues expressing gene products expected to evolve rapidly as a result of sexual selection—testis and accessory gland—would yield a smaller proportion of BLASTx matches to homologous genes in the model organism Drosophila melanogaster compared with whole-body tissue. Uniquely expressed sequences in both testis and accessory gland showed a significantly lower rate of matching to annotated D. melanogaster genes compared with those from general body tissue. These results correspond with empirical evidence that genes expressed in testis and accessory gland tissue are rapidly evolving targets of selection. PMID:23390599

Tissue-specific transcriptomics in the field cricket Teleogryllus oceanicus.

PubMed

Bailey, Nathan W; Veltsos, Paris; Tan, Yew-Foon; Millar, A Harvey; Ritchie, Michael G; Simmons, Leigh W

2013-02-01

Field crickets (family Gryllidae) frequently are used in studies of behavioral genetics, sexual selection, and sexual conflict, but there have been no studies of transcriptomic differences among different tissue types. We evaluated transcriptome variation among testis, accessory gland, and the remaining whole-body preparations from males of the field cricket, Teleogryllus oceanicus. Non-normalized cDNA libraries from each tissue were sequenced on the Roche 454 platform, and a master assembly was constructed using testis, accessory gland, and whole-body preparations. A total of 940,200 reads were assembled into 41,962 contigs, to which 36,856 singletons (reads not assembled into a contig) were added to provide a total of 78,818 sequences used in annotation analysis. A total of 59,072 sequences (75%) were unique to one of the three tissues. Testis tissue had the greatest proportion of tissue-specific sequences (62.6%), followed by general body (56.43%) and accessory gland tissue (44.16%). We tested the hypothesis that tissues expressing gene products expected to evolve rapidly as a result of sexual selection--testis and accessory gland--would yield a smaller proportion of BLASTx matches to homologous genes in the model organism Drosophila melanogaster compared with whole-body tissue. Uniquely expressed sequences in both testis and accessory gland showed a significantly lower rate of matching to annotated D. melanogaster genes compared with those from general body tissue. These results correspond with empirical evidence that genes expressed in testis and accessory gland tissue are rapidly evolving targets of selection.

High androgen receptor immunoexpression in human "Sertoli cell only" testis.

PubMed

Loukil, L Hadjkacem; Boudawara, T Sellami; Ayadi, I; Bahloul, A; Jlidi, R; Ayadi, H; Keskes, L Ammar

2005-01-01

Our purpose was to evaluate cellular androgen receptor (AR) distribution and intensity of immunostaining in the human azoospermic testis. Thirty six biopsy specimens from azoospermic men were immunostained, using a monoclonal antibody of human AR. The localization and the intensity of AR immunostaining was evaluated in Sertoli Cell Only (SCO) testis (G1, n = 21), in spermatogenesis arrest testis (G2, n = 11) and in histologically normal testis (G3, n = 4). We found an AR immunostaining in Sertoli, peritubular myoid and Leydig cells, but not in germ cells. The intensity of the immunostaining varied substantially between biopsy specimens of different patients. Sertoli and Leydig cells AR immunostaining (score and intensity) in SCO group was higher than in the other groups. For Sertoli cells, the score means of AR immunoreactivity were 20 +/- 2.36, 10.18 +/- 1.0 and 1 +/- 1, for G1, G2 and G3 groups, respectively. For Leydig cells, the score means were 10.24 +/- 1.37, 6 +/- 0.71 and 0, for G1, G2 and G3 groups, respectively. We found significant differences between G1 and G2 (p = 0.0008), between G1 and G3 (p = 1.54 10-7) and G2 and G3 (p = 0.00032). These results suggest that in the testis AR is located exclusively in somatic cells and its expression is higher in SCO syndrome than in normal and in arrest spermatogenesis testes.

HSP86 and HSP84 exhibit cellular specificity of expression and co-precipitate with an HSP70 family member in the murine testis

NASA Technical Reports Server (NTRS)

Gruppi, C. M.; Wolgemuth, D. J.

1993-01-01

This study extends to the protein level our previous observations, which had established the stage and cellular specificity of expression of hsp86 and hsp84 in the murine testis in the absence of exogenous stress. Immunoblot analysis was used to demonstrate that HSP86 protein was present throughout testicular development and that its levels increased with the appearance of differentiating germ cells. HSP86 was most abundant in the germ cell population and was present at significantly lower levels in the somatic cells. By contrast, the HSP84 protein was detected in the somatic cells of the testis rather than in germ cells. The steady-state levels of HSP86 and HSP84 paralleled the pattern of the expression of their respective mRNAs, suggesting that regulation at the level of translation was not a major mechanism controlling hsp90 gene expression in testicular cells. Immunoprecipitation analysis revealed that a 70-kDa protein coprecipitated with the HSP86/HSP84 proteins in testicular homogenates. This protein was identified as an HSP70 family member by immunoblot analysis, suggesting that HSP70 and HSP90 family members interact in testicular cells.

Maturation of Cerebellar Purkinje Cell Population Activity during Postnatal Refinement of Climbing Fiber Network.

PubMed

Good, Jean-Marc; Mahoney, Michael; Miyazaki, Taisuke; Tanaka, Kenji F; Sakimura, Kenji; Watanabe, Masahiko; Kitamura, Kazuo; Kano, Masanobu

2017-11-21

Neural circuits undergo massive refinements during postnatal development. In the developing cerebellum, the climbing fiber (CF) to Purkinje cell (PC) network is drastically reshaped by eliminating early-formed redundant CF to PC synapses. To investigate the impact of CF network refinement on PC population activity during postnatal development, we monitored spontaneous CF responses in neighboring PCs and the activity of populations of nearby CF terminals using in vivo two-photon calcium imaging. Population activity is highly synchronized in newborn mice, and the degree of synchrony gradually declines during the first postnatal week in PCs and, to a lesser extent, in CF terminals. Knockout mice lacking P/Q-type voltage-gated calcium channel or glutamate receptor δ2, in which CF network refinement is severely impaired, exhibit an abnormally high level of synchrony in PC population activity. These results suggest that CF network refinement is a structural basis for developmental desynchronization and maturation of PC population activity. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Maternal Pre- and Postnatal Mental Health Trajectories and Child Mental Health and Development: Prospective Study in a Normative and Formerly Infertile Sample

ERIC Educational Resources Information Center

Vanska, Mervi; Punamaki, Raija-Leena; Tolvanen, Asko; Lindblom, Jallu; Flykt, Marjo; Unkila-Kallio, Leila; Tiitinen, Aila; Repokari, Leena; Sinkkonen, Jari; Tulppala, Maija

2011-01-01

Pregnancy and early motherhood involve uncertainty and change, which can evoke mental health problems. We identified maternal mental health trajectories in pre- and postnatal period, and examined their association with later child mental health and development. Finnish mothers reported psychological distress (General Health Questionnaire [GHQ-36])…

Mitochondrial dysfunction in alveolar and white matter developmental failure in premature infants

PubMed Central

Ten, Vadim S.

2017-01-01

At birth, some organs in premature infants are not developed enough to meet challenges of the extra-uterine life. Although growth and maturation continues after premature birth, postnatal organ development may become sluggish or even arrested, leading to organ dysfunction. There is no clear mechanistic concept of this postnatal organ developmental failure in premature neonates. This review introduces a concept-forming hypothesis: Mitochondrial bioenergetic dysfunction is a fundamental mechanism of organs maturation failure in premature infants. Data collected in support of this hypothesis are relevant to two major diseases of prematurity: white matter injury and broncho-pulmonary dysplasia. In these diseases, totally different clinical manifestations are defined by the same biological process, developmental failure of the main functional units—alveoli in the lungs and axonal myelination in the brain. Although molecular pathways regulating alveolar and white matter maturation differ, proper bioenergetic support of growth and maturation remains critical biological requirement for any actively developing organ. Literature analysis suggests that successful postnatal pulmonary and white matter development highly depends on mitochondrial function which can be inhibited by sublethal postnatal stress. In premature infants, sublethal stress results mostly in organ maturation failure without excessive cellular demise. PMID:27901512

Mitochondrial dysfunction in alveolar and white matter developmental failure in premature infants.

PubMed

Ten, Vadim S

2017-02-01

At birth, some organs in premature infants are not developed enough to meet challenges of the extra-uterine life. Although growth and maturation continues after premature birth, postnatal organ development may become sluggish or even arrested, leading to organ dysfunction. There is no clear mechanistic concept of this postnatal organ developmental failure in premature neonates. This review introduces a concept-forming hypothesis: Mitochondrial bioenergetic dysfunction is a fundamental mechanism of organs maturation failure in premature infants. Data collected in support of this hypothesis are relevant to two major diseases of prematurity: white matter injury and broncho-pulmonary dysplasia. In these diseases, totally different clinical manifestations are defined by the same biological process, developmental failure of the main functional units-alveoli in the lungs and axonal myelination in the brain. Although molecular pathways regulating alveolar and white matter maturation differ, proper bioenergetic support of growth and maturation remains critical biological requirement for any actively developing organ. Literature analysis suggests that successful postnatal pulmonary and white matter development highly depends on mitochondrial function which can be inhibited by sublethal postnatal stress. In premature infants, sublethal stress results mostly in organ maturation failure without excessive cellular demise.

Characterization and expression of cyp19a gene in the Chinese giant salamander Andrias davidianus.

PubMed

Hu, Qiaomu; Xiao, Hanbing; Tian, HaiFeng; Meng, Yan

2016-02-01

We cloned the full length cyp19a of Chinese giant salamander Andrias davidianus, determined its distribution in tissues and developing gonads, and analyzed the CpG methylation pattern of the cyp19a promoter. The results revealed isoforms of 1706 bp (G arom) and 1698 bp (B arom) in length, differing in the 5' flanking region, both encoding 502 amino acids. The G arom gene was observed mainly in the ovary and kidney, with little in other investigated tissues, while B arom expression was high in the brain, ovary, testis, and pituitary, with low or undetected expression in other examined tissues. Total aromatase expression was high in the ovary; moderate in the kidney, brain, testis, and pituitary; and low in the remaining tissues. G arom expression was significantly higher in the ovary than in the testis and gradually decreased with maturation of the salamander. A single injection of methyltestosterone or letrozole resulted in ovarian G arom expression decreasing over a 12-96 h period. A 1366 bp sequence of the cyp19a promoter was cloned and shown to be conserved in selected species. CpG methylation level was negatively correlated with cyp19a expression in the examined tissues and developing ovaries. Five and three CpG methylation sites positively correlated with DNA methylation levels in tissues and developing ovary, suggesting that they play an important role in regulating cyp19a expression. The aromatase gene showed two isoforms with distinct expression patterns, and the promoter methylation level at specific CpG sites was associated with variation in expression profiles of tissues and developing ovaries. Copyright © 2015 Elsevier Inc. All rights reserved.

Cellular and Hormonal Disruption of Fetal Testis Development in Sheep Reared on Pasture Treated with Sewage Sludge

PubMed Central

Paul, Catriona; Rhind, Stewart M.; Kyle, Carol E.; Scott, Hayley; McKinnell, Chris; Sharpe, Richard M.

2005-01-01

The purpose of this study was to evaluate whether experimental exposure of pregnant sheep to a mixture of environmental chemicals added to pasture as sewage sludge (n = 9 treated animals) exerted effects on fetal testis development or function; application of sewage sludge was undertaken so as to maximize exposure of the ewes to its contents. Control ewes (n = 9) were reared on pasture treated with an equivalent amount of inorganic nitrogenous fertilizer. Treatment had no effect on body weight of ewes, but it reduced body weight by 12–15% in male (n = 12) and female (n = 8) fetuses on gestation day 110. In treated male fetuses (n = 11), testis weight was significantly reduced (32%), as were the numbers of Sertoli cells (34% reduction), Leydig cells (37% reduction), and gonocytes (44% reduction), compared with control fetuses (n = 8). Fetal blood levels of testosterone and inhibin A were also reduced (36% and 38%, respectively) in treated compared with control fetuses, whereas blood levels of luteinizing hormone and follicle-stimulating hormone were unchanged. Based on immunoexpression of anti-Müllerian hormone, cytochrome P450 side chain cleavage enzyme, and Leydig cell cytoplasmic volume, we conclude that the hormone changes in treated male fetuses probably result from the reduction in somatic cell numbers. This reduction could result from fetal growth restriction in male fetuses and/or from the lowered testosterone action; reduced immunoexpression of α-smooth muscle actin in peritubular cells and of androgen receptor in testes of treated animals supports the latter possibility. These findings indicate that exposure of the developing male sheep fetus to real-world mixtures of environmental chemicals can result in major attenuation of testicular development and hormonal function, which may have consequences in adulthood. PMID:16263515

[Expression and localization of transmembrane protein CMTM2 in human testis and sperm].

PubMed

Zhang, X W; Lan, K; Yang, W B; Li, Q; Zhao, Y P; Yin, H Q; Kite, B; Bai, W J; Xu, T

2017-08-18

To study the expression of transmembrane protein CMTM2 in the testis and sperm of adult males and to approach the potential function of the protein in the male reproductive system. The expression of CMTM2 in human testis and sperm was confirmed by Western blot. Immunohistochemical staining was used for detecting CMTM2 localization in the testis tissue, TRITC-CMTM2 and FITC-Hoechst double immunofluorescence staining was performed to examine the subcellular localization of CMTM2 in the human sperm before and after acrosome reaction, that is, immunofluorescent staining was used for detecting CMTM2 localization in both the testis and sperm before and after the acrosome reaction. CMTM2 was presented in both human testis and sperm. In the testis, CMTM2 immunoreactive particles were observed mainly in the membrane of the different stages of spermatogenic cells. In the human sperm, its immunoreactivity was restrictively localized to the posterior head where sperm-egg fusion occurred, and the CMTM2 localization was not affected by sperm acrosome reaction. CMTM2 was widely expressed in seminiferous tubules of the human testis, mainly in the cell membranes of spermatogenic cells, which was consistent with the previous reports. The immunofluorescence performed on frozen human testis slides showed similar findings with immunohistochemistry, which gave weight to the localization of CMTM2 in the cell membranes of spermatogenic cells at different stages. TRITC-CMTM2 and FITC-Hoechst double immunofluorescence staining was performed to examine the subcellular localization of CMTM2 in the human sperm before and after acrosome reaction. CMTM2 was localized at the posterior head of sperm before and after acrosome reaction. The localization and expression of CMTM2 were not affected by sperm acrosome reaction. Expression of CMTM2 in the male reproductive system of the adult human exhibits cell- and region-specific patterns, which suggests that they may play an important role in spermatogenesis and sperm-egg fusion. The expression of CMTM2 in the male reproductive system of the adult human exhibits cell- and region-specific patterns, which suggests that they may play an important role in spermatogenesis and sperm-egg fusion. However, it still remains to be further elucidated about the definite role of CMTM2 in male reproductive system and the process of spermatogenesis. And in vitro fertilization experiments are needed to confirm the role of CMTM2 in fertilization in future.

Sexual behavior and testis morphology in the BACHD rat model

PubMed Central

Novati, Arianna; Yu-Taeger, Libo; Gonzalez Menendez, Irene; Quintanilla Martinez, Leticia

2018-01-01

Background Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by a mutation in the huntingtin (HTT) gene, which results in brain neurodegeneration and peripheral pathology affecting different organs including testis. Patients with HD suffer from motor and cognitive impairment, and multiple psychiatric symptoms. Among behavioral abnormalities in HD, sexual disturbances have often been reported, but scarcely investigated in animal models. The BACHD rat model of HD carries the human full-length mutated HTT (mHTT) genomic sequence with 97 CAG-CAA repeats and displays HD-like alterations at neuropathological and behavioral level. Objective This study aims to phenotype the BACHD rats’ sexual behavior and performance as well as testis morphology because alterations in these aspects have been associated to HD. Methods Two rat cohorts at the age of 3 and 7 months were subjected to mating tests to assess different parameters of sexual behavior. Histological analyses for testis morphology were performed in different rat cohorts at 1.5, 7 and 12 months of age whereas immunohistochemical analyses were carried out at 7 and 12 months of age to visualize the presence of mHTT in testicular tissue. Furthermore, western blot analyses were used to assess HTT and mHTT expression levels in striatum and testis at three months of age. Results At 3 months, BACHD rats showed a decreased time exploring the female anogenital area (AGA), decreased latency to mount, increased number of intromissions and ejaculations and enhanced hit rate. At 7 months, all sexual parameters were comparable between genotypes with the exception that BACHD rats explored the AGA less than wild type rats. Testis analyses did not reveal any morphological alteration at any of the examined ages, but showed presence of mHTT limited to Sertoli cells in transgenic rats at both 7 and 12 months. BACHD rat HTT and mHTT expression levels in testis were lower than striatum at 3 months of age. Conclusions The testis phenotype in the BACHD rat model does not mimic the changes observed in human HD testis. The altered sexual behavior in BACHD rats at three months of age could be to a certain extent representative of and share common underlying pathways with some of the sexual disturbances in HD patients. Further investigating the biological causes of the sexual phenotype in BACHD rats may therefore contribute to clarifying the mechanisms at the base of sexual behavior changes in HD. PMID:29883458

Expression analysis of cancer-testis genes in prostate cancer reveals candidates for immunotherapy.

PubMed

Faramarzi, Sepideh; Ghafouri-Fard, Soudeh

2017-09-01

Prostate cancer is a prevalent disorder among men with a heterogeneous etiological background. Several molecular events and signaling perturbations have been found in this disorder. Among genes whose expressions have been altered during the prostate cancer development are cancer-testis antigens (CTAs). This group of antigens has limited expression in the normal adult tissues but aberrant expression in cancers. This property provides them the possibility to be used as cancer biomarkers and immunotherapeutic targets. Several CTAs have been shown to be immunogenic in prostate cancer patients and some of the have entered clinical trials. Based on the preliminary data obtained from these trials, it is expected that CTA-based therapeutic options are beneficial for at least a subset of prostate cancer patients.

Congenital intra-abdominal bilateral juvenile granulosa cell tumors of the testis associated with constitutional loss of material from chromosome 4.

PubMed

Yu, David C; Pathak, Bhavana; Vargas, Sara O; Javid, Patrick J; Hisama, Fuki M; Wilson, Jay M; Linden, Bradley C

2011-01-01

Juvenile granulosa cell tumor (JGCT) is an uncommon gonadal stromal tumor that occurs rarely in the testis. We report a newborn boy with bilateral intra-abdominal JGCT presenting with abdominal distention and respiratory distress at birth. He was taken to the operating room emergently, and 2 large masses connected by gubernacula to the inguinal canals were resected. Associated abnormalities included a constitutional chromosome 4 abnormality, polymicrogyria, and renal cysts. This report describes a rare presentation of JGCT with abdominal compression and expands the literature to include bilateral testicular involvement. Additionally, it is the 1st report of JGCT associated with a chromosome 4 abnormality, highlighting a genetic region that may be important in JGCT development.

Expression of the Wilms' tumor gene WT1 in the murine urogenital system.

PubMed

Pelletier, J; Schalling, M; Buckler, A J; Rogers, A; Haber, D A; Housman, D

1991-08-01

The Wilms' tumor gene WT1 is a recessive oncogene that encodes a putative transcription factor implicated in nephrogenesis during kidney development. In this report we analyze expression of WT1 in the murine urogenital system. WT1 is expressed in non-germ-cell components of the testis and ovaries in both young and adult mice. In situ mRNA hybridization studies demonstrate that WT1 is expressed in the granulosa and epithelial cells of ovaries, the Sertoli cells of the testis, and in the uterine wall. In addition to the 3.1-kb WT1 transcript detected by Northern blotting of RNA from kidney, uterus, and gonads, there is an approximately 2.5-kb WT1-related mRNA species in testis. The levels of WT1 mRNA in the gonads are among the highest observed, surpassing amounts detected in the embryonic kidney. During development, these levels are differentially regulated, depending on the sexual differentiation of the gonad. Expression of WT1 mRNA in the female reproductive system does not fluctuate significantly from days 4 to 40 postpartum. In contrast, WT1 mRNA levels in the tesis increase steadily after birth, reaching their highest expression levels at day 8 postpartum and decreasing slightly as the animal matures. Expression of WT1 in the gonads is detectable as early as 12.5 days postcoitum (p.c.). As an initial step toward exploring the tissue-specific expression of WT1, DNA elements upstream of WT1 were cloned and sequenced. Three putative transcription initiation sites, utilized in testis, ovaries, and uterus, were mapped by S1 nuclease protection assays. The sequences surrounding these sites have a high G + C content, and typical upstream CCAAT and TATAA boxes are not present. These studies allowed us to identify the translation initiation site for WT1 protein synthesis. We have also used an epitope-tagging protocol to demonstrate that WT1 is a nuclear protein, consistent with its role as a transcription factor. Our results demonstrate regulation of WT1 expression during development of the gonads, implicate WT1 in genitourinary development, and provide a molecular framework toward understanding genitourinary defects observed among hereditary cases of Wilms' tumor.

De novo Transcriptome Analysis of Portunus trituberculatus Ovary and Testis by RNA-Seq: Identification of Genes Involved in Gonadal Development

PubMed Central

Meng, Xian-liang; Liu, Ping; Jia, Fu-long; Li, Jian; Gao, Bao-Quan

2015-01-01

The swimming crab Portunus trituberculatus is a commercially important crab species in East Asia countries. Gonadal development is a physiological process of great significance to the reproduction as well as commercial seed production for P. trituberculatus. However, little is currently known about the molecular mechanisms governing the developmental processes of gonads in this species. To open avenues of molecular research on P. trituberculatus gonadal development, Illumina paired-end sequencing technology was employed to develop deep-coverage transcriptome sequencing data for its gonads. Illumina sequencing generated 58,429,148 and 70,474,978 high-quality reads from the ovary and testis cDNA library, respectively. All these reads were assembled into 54,960 unigenes with an average sequence length of 879 bp, of which 12,340 unigenes (22.45% of the total) matched sequences in GenBank non-redundant database. Based on our transcriptome analysis as well as published literature, a number of candidate genes potentially involved in the regulation of gonadal development of P. trituberculatus were identified, such as FAOMeT, mPRγ, PGMRC1, PGDS, PGER4, 3β-HSD and 17β-HSDs. Differential expression analysis generated 5,919 differentially expressed genes between ovary and testis, among which many genes related to gametogenesis and several genes previously reported to be critical in differentiation and development of gonads were found, including Foxl2, Wnt4, Fst, Fem-1 and Sox9. Furthermore, 28,534 SSRs and 111,646 high-quality SNPs were identified in this transcriptome dataset. This work represents the first transcriptome analysis of P. trituberculatus gonads using the next generation sequencing technology and provides a valuable dataset for understanding molecular mechanisms controlling development of gonads and facilitating future investigation of reproductive biology in this species. The molecular markers obtained in this study will provide a fundamental basis for population genetics and functional genomics in P. trituberculatus and other closely related species. PMID:26042806

Fetal growth from mid- to late pregnancy is associated with infant development: the Generation R Study.

PubMed

Henrichs, Jens; Schenk, Jacqueline J; Barendregt, Charlotte S; Schmidt, Henk G; Steegers, Eric Ap; Hofman, Albert; Jaddoe, Vincent W V; Moll, Henriette A; Verhulst, Frank C; Tiemeier, Henning

2010-07-01

The aim of this study was to investigate within a population-based cohort of 4384 infants (2182 males, 2202 females) whether fetal growth from early pregnancy onwards is related to infant development and whether this potential relationship is independent of postnatal growth. Ultrasound measurements were performed in early, mid-, and late pregnancy. Estimated fetal weight was calculated using head and abdominal circumference and femur length. Infant development was measured with the Minnesota Infant Development Inventory at 12 months (SD 1.1mo, range 10-17mo). Information on postnatal head size and body weight at 7 months was obtained from medical records. After adjusting for potential confounders and for postnatal growth, faster fetal weight gain from mid- to late pregnancy predicted a reduced risk of delayed social development (odds ratio [OR] 0.82; 95% confidence interval [CI] 0.71-0.95, p=0.008), self-help abilities (OR 0.84; 95% CI 0.73-0.98, p=0.023), and overall infant development (OR 0.65; 95% CI 0.49-0.87, p=0.003). Similar findings were observed for fetal head growth from mid- to late pregnancy. Faster fetal growth predicts a lower risk of delayed infant development independent of postnatal growth. These results suggest that reduced fetal growth between mid- and late pregnancy may determine subsequent developmental outcomes.

The effects of microgravity on the development of surface righting in rats

PubMed Central

Walton, Kerry D; Harding, Shannon; Anschel, David; Harris, Ya'el Tobi; Llinás, Rodolfo

2005-01-01

The active interaction of neonatal animals with their environment has been shown to be a decisive factor in the postnatal development of sensory systems, which demonstrates a critical period in their maturation. The direct demonstration of such a dependence on the rearing environment has not been demonstrated for motor system function. Nor has the role of gravity in mammalian motor system development been investigated. Here we report the results of two space flight missions examining the effect of removing gravity on the development of surface righting. Since the essential stimulus that drives this synergy, gravitation, was missing, righting did not occur while the animals were in the microgravity environment. We hypothesize that this absence of contextual motor experience arrested the maturation of the motor tactics for surface righting. Such effects were permanent in rats spending 16 days (from postnatal day (P), P14 to P30), but were transient in animals spending nine days (from P15 to P24) in microgravity. Thus, active, contextual interaction with the environment during a critical period of development is necessary for the postnatal maturation of motor tactics as exemplified by surface righting, and such events must occur within a particular time period. Further, Earth's gravitational field is not assumed by the developing motor system. Rather, postnatal motor system development is appropriate to the gravitational field in which the animal is reared. PMID:15774538

Gestational bisphenol A exposure and testis development.

PubMed

Williams, Cecilia; Bondesson, Maria; Krementsov, Dimitry N; Teuscher, Cory

Virtually all humans are exposed to bisphenol A (BPA). Since BPA can act as a ligand for estrogen receptors, potential hazardous effects of BPA should be evaluated in the context of endogenous estrogenic hormones. Because estrogen is metabolized in the placenta, developing fetuses are normally exposed to very low endogenous estrogen levels. BPA, on the other hand, passes through the placenta and might have distinct adverse consequences during the sensitive stages of fetal development. Testicular gametogenesis and steroidogenesis begin early during fetal development. These processes are sensitive to estrogens and play a role in determining the number of germ stem cells, sperm count, and male hormone levels in adulthood. Although studies have shown a correlation between BPA exposure and perturbed reproduction, a clear consensus has yet to be established as to whether current human gestational BPA exposure results in direct adverse effects on male genital development and reproduction. However, studies in animals and in vitro have provided direct evidence for the ability of BPA exposure to influence male reproductive development. This review discusses the current knowledge of potential effects of BPA exposure on male reproductive health and whether gestational exposure adversely affects testis development.

Outcome of prenatal depression and risk factors associated with persistence in the first postnatal year: prospective study from Rawalpindi, Pakistan.

PubMed

Rahman, Atif; Creed, Francis

2007-06-01

Rates of prenatal and postnatal depression in developing countries are high. Prolonged depression during the postnatal period is associated with impaired infant growth and development. Little is known about the factors predicting the persistence of prenatal depression beyond the first few postnatal months. From a sample of 701 women in a rural sub-district of Pakistan, the Schedule for Clinical Assessment in Neuropsychiatry (SCAN) was used to identify those with ICD-10 depressive disorder in the third trimester of pregnancy (n=160). Depressed women were re-assessed at 3, 6 and 12 months postnatal. Persistently depressed women (depressed at all time points) were compared with the remainder. Psychiatric symptoms, disability and life events were measured using the Self-Reporting Questionnaire (SRQ), Brief Disability Questionnaire (BDQ), and a modified Life Events Checklist. Of 129 mothers who completed follow-up, 73 (56%) were depressed at all points of assessment. These persistently depressed mothers had higher SRQ and BDQ scores prenatally and had experienced more life events in the year preceding the third pregnancy trimester than the mothers whose depressive disorder resolved (none received treatment). Persistent depression was significantly associated also with poverty, having 5 or more children, an uneducated husband and lack of a confidant or friend. On multivariate analysis, higher SRQ score and poverty during pregnancy predicted persistent depression. The sample was from one rural sub-district only. We did not assess the women for physical conditions such as anaemia and thyroid-deficiency. Women who are poor and have more psychological symptoms during pregnancy are more likely to remain depressed one year after giving birth. This study highlights the need for developing mechanisms of early identification and suitable psychosocial interventions to minimise the damaging effects of persistent postnatal depression in poor communities.

Postnatal care: development of a psychometric multidimensional satisfaction questionnaire (the WOMBPNSQ) to assess women's views.

PubMed

Smith, Lindsay F P

2011-10-01

Postnatal care is the neglected area of pregnancy care, despite repeated calls to improve it. Changes would require assessment, which should include women's views. No suitable satisfaction questionnaire exists to enable this. To develop a multidimensional psychometric postnatal satisfaction self-completion instrument. Ten maternity services in south west England from 2006-2009. Sources for questions were literature review, fieldwork, and related published instruments. Principal components analysis with varimax rotation was used to develop the final WOMen's views of Birth Postnatal Satisfaction Questionnaire (WOMBPNSQ) version. Validity and internal reliability were assessed. Questionnaires were mailed 6-8 weeks postnatally (with one reminder). The WOMBPNSQ comprises 36 seven-point Likert questions (13 dimensions including general satisfaction). Of 300 women, 166 (55.3%) replied; of these 155 (95.1 %) were white, 152 (93.8%) were married or cohabiting, 135 (81.3%) gave birth in a consultant unit, 129 (78.6%) had a vaginal delivery; and 100 (60.6%) were multiparous. The 12 specific dimensions were: support from professionals or partner, or social support; care from GP and health visitor; advice on contraception, feeding baby, the mother's health; continuity of care; duration of inpatient stay; home visiting; pain after birth. These have internal reliability (Cronbach's alpha varying from 0.624 to 0.902). Various demographic and clinical characteristics were significantly associated with specific dimensions. WOMBPNSQ could be used to assess existing or planned changes to maternity services or as a screening instrument, which would then enable in-depth qualitative assessment of areas of dissatisfaction. Its convergent validity and test-retest reliability are still to be assessed but are an improvement upon existing postnatal satisfaction questionnaires.

[Strategies for development, follow-up, and assessment of care provided to women in the pregnancy-postnatal cycle].

PubMed

Holanda, Cristyanne Samara Miranda de; Alchieri, João Carlos; Morais, Fátima Raquel Rosado; Maranhão, Técia Maria de Oliveira

2015-06-01

To describe the development of a questionnaire for assessment of prenatal, birth, and postnatal care (Inventário de Avaliação da Assistência ao Pré-natal, Parto e Puerpério, IAAPPP), which was designed taking into consideration the experience of users of a public obstetric service. This mixed methods research was performed in the city of Caicó, state of Rio Grande do Norte, Brazil. The study consisted of two phases: in phase 1, focal groups were organized with 19 users of the health care system for identification of relevant issues for assessment of the pregnancy-postnatal cycle. The first draft of the questionnaire was also designed and tested for validity with seven of the 19 focal group participants; a second draft was produced and retested. In phase 2, the intra-class correlation coefficient was calculated to determine reproducibility. A pilot test was carried out to determine the applicability of the survey and the final version of the IAAPPP was developed. Based on the focal group discussions, the inventory was organized into four domains: 1) socioeconomic information, 2) obstetric history, 3) description of current obstetric experience and 4) assessment of follow-up. Domains 3 and 4 were subdivided into prenatal care, birthcare, postnatal care, and pregnancy-postnatal cycle. The answers of the women who evaluated the instrument for domain 4 were strongly correlated (>0.8), indicating reproducibility of the IAAPPP. The methodological model allowed us to identify needs and demands of women in the pregnancy-postnatal cycle, and allowed us to design a questionnaire that can be applied to other regions with similar sociocultural characteristics.

Microglial numbers attain adult levels after undergoing a rapid decrease in cell number in the third postnatal week.

PubMed

Nikodemova, Maria; Kimyon, Rebecca S; De, Ishani; Small, Alissa L; Collier, Lara S; Watters, Jyoti J

2015-01-15

During postnatal development, microglia, CNS resident innate immune cells, are essential for synaptic pruning, neuronal apoptosis and remodeling. During this period microglia undergo morphological and phenotypic transformations; however, little is known about how microglial number and density is regulated during postnatal CNS development. We found that after an initial increase during the first 14 postnatal days, microglial numbers in mouse brain began declining in the third postnatal week and were reduced by 50% by 6weeks of age; these "adult" levels were maintained until at least 9months of age. Microglial CD11b levels increased, whereas CD45 and ER-MP58 declined between P10 and adulthood, consistent with a maturing microglial phenotype. Our data indicate that both increased microglial apoptosis and a decreased proliferative capacity contribute to the developmental reduction in microglial numbers. We found no correlation between developmental reductions in microglial numbers and brain mRNA levels of Cd200, Cx3Cl1, M-Csf or Il-34. We tested the ability of M-Csf-overexpression, a key growth factor promoting microglial proliferation and survival, to prevent microglial loss in the third postnatal week. Mice overexpressing M-Csf in astrocytes had higher numbers of microglia at all ages tested. However, the developmental decline in microglial numbers still occurred, suggesting that chronically elevated M-CSF is unable to overcome the developmental decrease in microglial numbers. Whereas the identity of the factor(s) regulating microglial number and density during development remains to be determined, it is likely that microglia respond to a "maturation" signal since the reduction in microglial numbers coincides with CNS maturation. Copyright © 2014 Elsevier B.V. All rights reserved.

The role of self-esteem instability in the development of postnatal depression: A prospective study testing a diathesis-stress account.

PubMed

Franck, Erik; Vanderhasselt, Marie-Anne; Goubert, Liesbet; Loeys, Tom; Temmerman, Marleen; De Raedt, Rudi

2016-03-01

Understanding vulnerability factors involved in the development of postnatal depression has important implications for theory and practice. In this prospective study, we investigated whether self-esteem instability during pregnancy would better predict postnatal depressive symptomatology than level of self-esteem. In addition, going beyond former studies, we tested the possible origin of this instability, examining whether day-to-day fluctuations in self-esteem could be explained by fluctuations in mood state, and whether this day-to-day self-esteem reactivity would predict postnatal depressive symptoms. 114 healthy never-depressed women were tested during the late second or third trimester of their gestation (Time 1) and at 12 weeks after delivery (Time 2). Day-to-day levels of self-esteem and depressed mood state were assessed at Time 1. At Time 2, postnatal depressive symptoms were assessed. The results show that, after controlling for initial depressive symptomatology, age and socio-economic status, postnatal depressive symptomatology at 12 weeks after childbirth could be predicted by self-esteem instability and not level of self-esteem. In addition, multi-level analyses demonstrated that these changes in day-to-day levels of self-esteem are associated with changes in day-to-day levels of depressed mood state and that those subjects with greater prenatal self-esteem reactivity upon depressed mood report higher levels of depressive symptoms post-partum. We used paper and pencil day-to-day measures of state self-esteem, which can be subject to bias. These results provide evidence for a diathesis-stress account of postnatal depression, highlighting the importance of a multi-dimensional view of self-esteem and the predictive role of self-esteem instability. Copyright © 2015 Elsevier Ltd. All rights reserved.

Postnatal dietary fatty acid composition permanently affects the structure of hypothalamic pathways controlling energy balance in mice.

PubMed

Schipper, Lidewij; Bouyer, Karine; Oosting, Annemarie; Simerly, Richard B; van der Beek, Eline M

2013-12-01

We previously reported that dietary lipid quality during early life can have long-lasting effects on metabolic health and adiposity. Exposure to a postnatal diet with low dietary omega-6 (n-6) or high omega-3 (n-3) fatty acid (FA) content resulted in reduced body fat accumulation when challenged with a moderate Western-style diet (WSD) beginning in adolescence. We determined whether this programming effect is accompanied by changes in hypothalamic neural projections or modifications in the postnatal leptin surge, which would indicate the altered development of hypothalamic circuits that control energy balance. Neonatal mice were subjected to a control diet (CTR) or experimental diet with altered relative n-6 and n-3 FA contents [ie, a diet with a relative reduction in n-6 fatty acid (LOW n-6) or a diet with a relative increase in n-3 fatty acid (HIGH n-3) compared with the CTR from postnatal day (PN) 2 to 42]. Compared with CTR mice, mice fed a LOW n-6 or HIGH n-3 during postnatal life showed significant reductions in the density of both orexigenic and anorexigenic neural projections to the paraventricular nucleus of the hypothalamus at PN 28. These impairments persisted into adulthood and were still apparent after the WSD challenge between PNs 42 and 98. However, the neuroanatomical changes were not associated with changes in the postnatal leptin surge. Although the exact mechanism remains to be elucidated, our data indicate that the quality of dietary FA during postnatal life affects the development of the central regulatory circuits that control energy balance and may do so through a leptin-independent mechanism.

Insights from Australian parents into educational experiences in the early postnatal period.

PubMed

McKellar, Lois V; Pincombe, Jan I; Henderson, Ann M

2006-12-01

to investigate the provision of parent education during the early postnatal period in order to gain insight that, through stakeholder collaboration, will contribute to the development of innovative strategies to enhance the provision of postnatal education in a contemporary health-care environment. the study comprises the first stage of an action-research project. The first stage of research sought to explore the experiences of mothers and fathers in the early postnatal period by conducting a questionnaire within 4 weeks of the birth of their baby. The data obtained from the questionnaire is to inform an action-research group for stage two of the project. The Children, Youth and Women's Health Service, a large city maternity hospital in South Australia, covering a range of socio-economic strata. 85 parents completed and returned the questionnaire, comprising 52 mothers and 33 fathers. an anonymous self-report questionnaire was purpose designed to provide each parent with an opportunity to reflect on their own experience, with particular emphasis given to the provision of education and support during the early postnatal period. a number of themes emerged, including a window of opportunity during the postnatal hospital stay to provide education and support, despite the reduction in the length of stay; the need for a family-centred approach to maternity services; and the significance of self and social network in the early transition to parenthood. The findings from this stage of the research, combined with a review of the literature, provide insight that will contribute to stage two of the study. At this stage, an action-research group will continue planning to develop specific actions to enhance the provision of education to parents in the early postnatal period. These actions will subsequently be implemented and assessed.

Effects of different levels of dietary selenium on the proliferation of spermatogonial stem cells and antioxidant status in testis of roosters.

PubMed

Shi, Lei; Zhao, Hui; Ren, Youshe; Yao, Xiaolei; Song, Ruigao; Yue, Wenbin

2014-10-01

The objective of this study was to investigate the different levels of dietary Se (from sodium selenite) on the proliferation of SSCs (spermatogonial stem cells) in testis of roosters. Also, the antioxidant status and Se content in blood plasma and testis were evaluated. A total of eighty 12-week-old Hy-Line Variety white roosters at an averaged body weight of 1.38 ± 0.2 kg were selected and randomly divided into four experimental groups. They were fed with the basal diet (0.044 mgSe/kg DM) supplemented with 0 (control), 0.5, 1.0 or 2.0 mgSe/kg DM (from sodium selenite). After the feeding experiment, blood and testis samples were collected for analysis of the antioxidant status and Se concentration. The testis samples were also used to examine the Thy-1 and β1-integrin mRNA expression by RT-PCR and detect the population of SSCs by immunofluorescence analysis. The results show that Se concentration in blood and testis of the animals was progressively increased with the increasing Se level in diet. The highest GSH-Px (glutathione peroxidase) activity and lowest MDA content in blood and testis was obtained in the treatment of 0.5mg/kg. RT-PCR analysis showed that mRNA expression of SSCs markers were significantly lower in the control and 1.0mg/kg groups when compared with that in the treatment of 0.5mg/kg. A similar trend was observed in the population of SSCs analyzed by immunofluorescence assay. These data suggest that dietary Se can influence the population of SSCs of roosters during spermatogenesis and that oxidative stress can modulate SSCs behavior through regulating some key factors during spermatogenesis. Copyright © 2014 Elsevier B.V. All rights reserved.

DEMONSTRATION IN VITRO OF ANAPHYLACTOID RESPONSE OF THE UTERUS AND ILEUM OF GUINEA PIGS INJECTED WITH TESTIS OR SPERM

PubMed Central

Katsh, Seymour

1958-01-01

Female guinea pigs were injected with the following materials: homogenates of guinea pig testis in saline or in adjuvant; suspensions of washed guinea pig sperm in saline or in adjuvant; homogenates of rabbit testis in adjuvant; guinea pig sperm and rabbit sperm in adjuvant. Control animals were not injected or were injected with adjuvant alone. At various times between 15 and 39 days after injection, the animals were sacrificed. Their ilea and uterine horns were removed and tested in vitro for reaction to washed epididymal sperm of the guinea pig, rabbit, or bull. It was found that the animals which were injected with homologous testis or sperm in adjuvant possessed organs which responded strongly to the challenge with homologous sperm. The response was a contracture which began 10 to 30 seconds after the sperm were injected into the bath and lasted for 5 minutes to 4 hours, the longest period of observation. Responses which lasted for periods of 5 minutes to 30 minutes were obtained with the uteri of the animals injected with guinea pig testis in saline or with guinea pig sperm in saline. Animals which were injected with rabbit testis and adjuvant responded to rabbit sperm, and animals injected with guinea pig sperm and rabbit sperm in adjuvant reacted to both gametes. A large proportion of the control animals possessed organs which reacted weakly to the challenge with homologous sperm. Retesting the organ which had contracted following exposure to sperm indicated that desensitization had occurred. Testing with heterologous sperm indicated a species selectivity. The evidence is interpreted to mean that injections of sperm or testis induce a hypersensitivity which is similar in some respects but differs from true anaphylaxis. The findings are discussed from the point of view of the nature of the response and the implications regarding natural immunity to sperm. PMID:13481258

Mineral distributions at the developing tendon enthesis.

PubMed

Schwartz, Andrea G; Pasteris, Jill D; Genin, Guy M; Daulton, Tyrone L; Thomopoulos, Stavros

2012-01-01

Tendon attaches to bone across a functionally graded interface, "the enthesis". A gradient of mineral content is believed to play an important role for dissipation of stress concentrations at mature fibrocartilaginous interfaces. Surgical repair of injured tendon to bone often fails, suggesting that the enthesis does not regenerate in a healing setting. Understanding the development and the micro/nano-meter structure of this unique interface may provide novel insights for the improvement of repair strategies. This study monitored the development of transitional tissue at the murine supraspinatus tendon enthesis, which begins postnatally and is completed by postnatal day 28. The micrometer-scale distribution of mineral across the developing enthesis was studied by X-ray micro-computed tomography and Raman microprobe spectroscopy. Analyzed regions were identified and further studied by histomorphometry. The nanometer-scale distribution of mineral and collagen fibrils at the developing interface was studied using transmission electron microscopy (TEM). A zone (∼20 µm) exhibiting a gradient in mineral relative to collagen was detected at the leading edge of the hard-soft tissue interface as early as postnatal day 7. Nanocharacterization by TEM suggested that this mineral gradient arose from intrinsic surface roughness on the scale of tens of nanometers at the mineralized front. Microcomputed tomography measurements indicated increases in bone mineral density with time. Raman spectroscopy measurements revealed that the mineral-to-collagen ratio on the mineralized side of the interface was constant throughout postnatal development. An increase in the carbonate concentration of the apatite mineral phase over time suggested possible matrix remodeling during postnatal development. Comparison of Raman-based observations of localized mineral content with histomorphological features indicated that development of the graded mineralized interface is linked to endochondral bone formation near the tendon insertion. These conserved and time-varying aspects of interface composition may have important implications for the growth and mechanical stability of the tendon-to-bone attachment throughout development.

Sperm competition and maternal effects differentially influence testis and sperm size in Callosobruchus maculatus.

PubMed

Gay, L; Hosken, D J; Vasudev, R; Tregenza, T; Eady, P E

2009-05-01

The evolutionary factors affecting testis size are well documented, with sperm competition being of major importance. However, the factors affecting sperm length are not well understood; there are no clear theoretical predictions and the empirical evidence is inconsistent. Recently, maternal effects have been implicated in sperm length variation, a finding that may offer insights into its evolution. We investigated potential proximate and microevolutionary factors influencing testis and sperm size in the bruchid beetle Callosobruchus maculatus using a combined approach of an artificial evolution experiment over 90 generations and an environmental effects study. We found that while polyandry seems to select for larger testes, it had no detectable effect on sperm length. Furthermore, population density, a proximate indicator of sperm competition risk, was not significantly associated with sperm length or testis size variation. However, there were strong maternal effects influencing sperm length.

Tzfp represses the androgen receptor in mouse testis.

PubMed

Furu, Kari; Klungland, Arne

2013-01-01

The testis zinc finger protein (Tzfp), also known as Repressor of GATA, belongs to the BTB/POZ zinc finger family of transcription factors and is thought to play a role in spermatogenesis due to its remarkably high expression in testis. Despite many attempts to find the in vivo role of the protein, the molecular function is still largely unknown. Here, we address this issue using a novel mouse model with a disrupted Tzfp gene. Homozygous Tzfp null mice are born at reduced frequency but appear viable and fertile. Sertoli cells in testes lacking Tzfp display an increase in Androgen Receptor (AR) signaling, and several genes in the testis, including Gata1, Aie1 and Fanc, show increased expression. Our results indicate that Tzfp function as a transcriptional regulator and that loss of the protein leads to alterations in AR signaling and reduced number of apoptotic cells in the testicular tubules.

In utero heat stress increases postnatal core body temperature in pigs

USDA-ARS?s Scientific Manuscript database

In utero heat stress (IUHS) negatively impacts postnatal development, but how it alters future body temperature parameters and energetic metabolism is not well-understood. Objectives were to characterize future temperature indices and bioenergetic markers in pigs originating from differing in utero...

Major epigenetic development distinguishing neuronal and non-neuronal cells occurs postnatally in the murine hypothalamus

USDA-ARS?s Scientific Manuscript database

Prenatal and early postnatal environment can persistently alter one's risk of obesity. Environmental effects on hypothalamic developmental epigenetics constitute a likely mechanism underlying such 'developmental programming' of energy balance regulation. To advance our understanding of these process...

Skilled movements require non-apoptotic Bax/Bak pathway-mediated corticospinal circuit reorganization

PubMed Central

Gu, Zirong; Serradj, Najet; Ueno, Masaki; Liang, Mishi; Li, Jie; Baccei, Mark L.; Martin, John H.; Yoshida, Yutaka

2017-01-01

Early postnatal mammals, including human babies, can perform only basic motor tasks. The acquisition of skilled behaviors occurs later, requiring anatomical changes in neural circuitry to support the development of coordinated activation or suppression of functionally related muscle groups. How this circuit reorganization occurs during postnatal development remains poorly understood. Here we explore the connectivity between corticospinal (CS) neurons in the motor cortex and muscles in mice. Using trans-synaptic viral and electrophysiological assays, we identify the early postnatal reorganization of CS circuitry for antagonistic muscle pairs. We further show that this synaptic rearrangement requires the activity-dependent, non-apoptotic Bax/Bak-caspase signaling cascade. Adult Bax/Bak mutant mice exhibit aberrant co-activation of antagonistic muscle pairs and skilled grasping deficits but normal reaching and retrieval behaviors. Our findings reveal key cellular and molecular mechanisms driving postnatal motor circuit reorganization and the resulting impacts on muscle activation patterns and the execution of skilled movements. PMID:28472660

A structure-based extracellular matrix expansion mechanism of fibrous tissue growth

PubMed Central

Kalson, Nicholas S; Lu, Yinhui; Taylor, Susan H; Starborg, Tobias; Holmes, David F; Kadler, Karl E

2015-01-01

Embryonic growth occurs predominately by an increase in cell number; little is known about growth mechanisms later in development when fibrous tissues account for the bulk of adult vertebrate mass. We present a model for fibrous tissue growth based on 3D-electron microscopy of mouse tendon. We show that the number of collagen fibrils increases during embryonic development and then remains constant during postnatal growth. Embryonic growth was explained predominately by increases in fibril number and length. Postnatal growth arose predominately from increases in fibril length and diameter. A helical crimp structure was established in embryogenesis, and persisted postnatally. The data support a model where the shape and size of tendon is determined by the number and position of embryonic fibroblasts. The collagen fibrils that these cells synthesise provide a template for postnatal growth by structure-based matrix expansion. The model has important implications for growth of other fibrous tissues and fibrosis. DOI: http://dx.doi.org/10.7554/eLife.05958.001 PMID:25992598

Undescended testis? How best to teach the physical examination.

PubMed

Zundel, S; Blumenstock, G; Herrmann-Werner, A; Trueck, M; Schmidt, A; Wiechers, S

2016-12-01

Undescended testis in boys is common. Guidelines recommend surgical treatment between the ages of 6 months and 2 years; nevertheless, orchidopexy is frequently performed at later ages. One reason is the belated diagnosis due to a perceived difficulty in the physical examination (PE) and correct localization of the testis. We aimed to find an effective method for teaching the physical examination of the testis in a child. An interdisciplinary team developed teaching sessions, including an educational video and a simulator. Medical students (n = 133) were randomized into three groups: self-study only, video, and video and simulator. The sessions were carried out and quantitative feedback was collected from the teachers and students. The learning achievements of the different groups were assessed with an objective structured clinical examination (OSCE). The differences in mean OSCE results between all three groups were tested using one-way analysis of variance (ANOVA). For multiple pairwise comparisons, a closed testing procedure was performed using unpaired t-tests. The self-study only group acquired the poorest results in the OSCE, with a mean score of 5.1 out of 10. The video-only-group reached a mean of 6.7, and the video-and-simulator group performed best with a mean score of 8.5. The differences between all three groups were found to be statistically significant, with P = 0.007. The attached figure illustrates this data. If analyzed in pairs, this difference was particularly apparent between the groups self-study only vs video and simulator, with P = 0.002. Qualitative feedback revealed doubtful effectiveness for educational videos, but positive reactions to training on a simulator. The poor results of the self-study-only group were in accordance with the literature, where textbook learning was found not to increase OSCE results. The effectiveness of video tutorials remains doubtful; studies focusing on this teaching method are divergent and the present students' feedback supports this data. The effective teaching with the simulator has been proven for other skills (i.e. ultrasound skills). The analyzed cohort for this study was small, and the study should be repeated at different institutions and with larger numbers of students to assure generalizability. Low-fidelity pediatric simulators with palpable testis are available and are able to improve examining skills in medical students. We hope the presented study inspires medical educators in their teaching of the PE of the pediatric testis. Copyright © 2016 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Dietary sodium manipulation during critical periods in development sensitize adult offspring to amphetamines

PubMed Central

McBride, Shawna M.; Culver, Bruce; Flynn, Francis W.

2008-01-01

This study examined critical periods in development to determine when offspring were most susceptible to dietary sodium manipulation leading to amphetamine sensitization. Wistar dams (n = 6–8/group) were fed chow containing low (0.12% NaCl; LN), normal (1% NaCl; NN), or high sodium (4% NaCl; HN) during the prenatal or early postnatal period (birth to 5 wk). Offspring were fed normal chow thereafter until testing at 6 mo. Body weight (BW), blood pressure (BP), fluid intake, salt preference, response to amphetamine, open field behavior, plasma adrenocorticotropin hormone (ACTH), plasma corticosterone (Cort), and adrenal gland weight were measured. BW was similar for all offspring. Offspring from the prenatal and postnatal HN group had increased BP, NaCl intake, and salt preference and decreased water intake relative to NN offspring. Prenatal HN offspring had greater BP than postnatal HN offspring. In response to amphetamine, both prenatal and postnatal LN and HN offspring had increased locomotor behavior compared with NN offspring. In a novel open field environment, locomotion was also increased in prenatal and postnatal LN and HN offspring compared with NN offspring. ACTH and Cort levels 30 min after restraint stress and adrenal gland weight measurement were greater in LN and HN offspring compared with NN offspring. These results indicate that early life experience with low- and high-sodium diets, during the prenatal or early postnatal period, is a stress that produces long-term changes in responsiveness to amphetamines and to subsequent stressors. PMID:18614766

Connexin 43 reboots meiosis and reseals blood-testis barrier following toxicant-mediated aspermatogenesis and barrier disruption.

PubMed

Li, Nan; Mruk, Dolores D; Mok, Ka-Wai; Li, Michelle W M; Wong, Chris K C; Lee, Will M; Han, Daishu; Silvestrini, Bruno; Cheng, C Yan

2016-04-01

Earlier studies have shown that rats treated with an acute dose of 1-(2,4-dichlorobenzyl)-1H-indazole-3-carbohydrazide (adjudin, a male contraceptive under development) causes permanent infertility due to irreversible blood-testis barrier (BTB) disruption even though the population of undifferentiated spermatogonia remains similar to normal rat testes, because spermatogonia fail to differentiate into spermatocytes to enter meiosis. Since other studies have illustrated the significance of connexin 43 (Cx43)-based gap junction in maintaining the homeostasis of BTB in the rat testis and the phenotypes of Sertoli cell-conditional Cx43 knockout mice share many of the similarities of the adjudin-treated rats, we sought to examine if overexpression of Cx43 in these adjudin-treated rats would reseal the disrupted BTB and reinitiate spermatogenesis. A full-length Cx43 cloned into mammalian expression vector pCI-neo was used to transfect testes of adjudin-treated ratsversusempty vector. It was found that overexpression of Cx43 indeed resealed the Sertoli cell tight junction-permeability barrier based on a functionalin vivoassay in tubules displaying signs of meiosis as noted by the presence of round spermatids. Thus, these findings suggest that overexpression of Cx43 reinitiated spermatogenesis at least through the steps of meiosis to generate round spermatids in testes of rats treated with an acute dose of adjudin that led to aspermatogenesis. It was also noted that the round spermatids underwent eventual degeneration with the formation of multinucleated cells following Cx43 overexpression due to the failure of spermiogenesis because no elongating/elongated spermatids were detected in any of the tubules examined. The mechanism by which overexpression of Cx43 reboots meiosis and rescues BTB function was also examined. In summary, overexpression of Cx43 in the testis with aspermatogenesis reboots meiosis and reseals toxicant-induced BTB disruption, even though it fails to support round spermatids to enter spermiogenesis.-Li, N., Mruk, D. D., Mok, K.-W., Li, M. W. M., Wong, C. K. C., Lee, W. M., Han, D., Silvestrini, B., Cheng, C. Y. Connexin 43 reboots meiosis and reseals blood-testis barrier following toxicant-mediated aspermatogenesis and barrier disruption. © FASEB.

Phthalate-Induced Pathology in the Foetal Testis Involves More Than Decreased Testosterone Production

EPA Science Inventory

Foetal exposure to phthalates is known to adversely impact male reproductive development and function. Developmental anomalies of reproductive tract have been attributed to impaired testosterone synthesis. However, species differences in the ability to produce testosterone have...

REPRODUCTIVE TOXICITY OF PHTHALATE ESTERS

EPA Science Inventory

Phthalate esters display several modes of toxicity in mammalian species. In the rat, in utero exposure at relatively low dosage levels disrupts development of the reproductive system of the male rat by altering fetal testis hormone production. This presentation is a review of t...

Transgenerational Effects of Di(2-ethylhexyl) Phthalate in the SD Male Rat

EPA Science Inventory

In the rat, some phthalates alter sexual differentiation at relatively low dosage levels by altering fetal Leydig cell development and hormone synthesis, thereby inducing abnormalities of the testis, gubernacular ligaments, epididymis and other androgen-dependent tissues. In ...

Protective effect of Urtica dioica L against nicotine-induced damage on sperm parameters, testosterone and testis tissue in mice.

PubMed

Jalili, Cyrus; Salahshoor, Mohammad Reza; Naseri, Ali

2014-06-01

Nicotine consumption can decrease fertility drive in males by inducing oxidative stress and DNA damage. Urtica dioica L (U.dioica) is a multipurpose herb in traditional medicine for which some anti-oxidative and anti-inflammatory properties have been identified. The main goal is to investigate whether the U.dioica could inhibit nicotine adverse effects on sperm cells viability, count, motility, and testis histology and testosterone hormone. In this study, hydro-alcoholic extract of U.dioica was prepared and various doses of U.dioica (0, 10, 20, and 50 mg/kg) and U.dioica plus nicotine (0, 10, 20, and 50 mg/kg) were administered intraperitoneally to 56 male mice for 28 consequent days. These mice were randomly assigned to 8 groups (n=7) and sperm parameters (sperm cells viability, count, motility, and morphology), testis and prostate weight, testis histology and testosterone hormone were analyzed and compared. The results indicated that nicotine administration (0.5 mg/kg) significantly decreased testosterone level, count and motility of sperm cells, and testis weight compared to control group (p=0.00). However, increasing the dose of U.dioica significantly boosted motility, count, normal morphology of sperm cells, seminiferous tubules diameter, and testosterone in all groups compared to control (p=0.00) and testis weight in 20 and 50 mg/kg doses in comparison with control group (p=0.00). It seems that U.dioica hydro-alcoholic extract administration could increase the quality of spermatozoa and inhibits nicotine-induced adverse effects on sperm parameters.

Expression of Apg-1, a member of the Hsp110 family, in the human testis and sperm.

PubMed

Nonoguchi, K; Tokuchi, H; Okuno, H; Watanabe, H; Egawa, H; Saito, K; Ogawa, O; Fujita, J

2001-06-01

Apg-1 encodes a heat shock protein belonging to the Hsp110 family and is inducible by a 32 degrees C to 39 degrees C heat shock in somatic cells. In mouse testicular germ cells Apg-1 mRNA is constitutively expressed depending on the developmental stage. As human Apg-1 has recently been identified, the expression of Apg-1 in the human testis and sperm was investigated. Expression and heat-inducibility of Apg-1 in the human testicular germ cell tumor cell line, NEC8, was analyzed. Using an antimouse Apg-1 antibody, expression of Apg-1 in the human testis and sperm was examined by western blotting after confirmation of the specificity of the antibody. The cells expressing Apg-1 in the testis were further determined by immunohistochemistry. Slight induction of Apg-1 mRNA was detected in NEC8 cells after 32 degrees C to 39 degrees C temperature shift. In the human testis, the antibody specifically recognized Apg-1, which was absent in the testis without germ cells (Sertoli-cell-only syndrome) or arrested at spermatogonia. Spermatocytes and spermatids, but not testicular somatic cells, were positively stained with the anti-Apg-1 antibody. By western blot analysis, Apg-1 was detected in the preparation enriched for sperm from normal volunteers and infertile patients, but not from azoospermia patients. Apg-1 is developmentally expressed in human testicular germ cells and sperm, suggesting its role in spermatogenesis and fertilization. Identification of substrates for Apg-1 chaperone activity will help elucidate its function.

[Acceleration of Jingui Shenqi Pill on the testis telomerase activity in mice of Shen-yang deficiency].

PubMed

Xu, Cui-Ping; Zhu, Qing-Jun; Song, Jie; Li, Zhen; Zhang, Dan

2013-02-01

To explore the effects of Jingui Shenqi Pill (JSP) on the testis telomerase activity in mice of Shen-yang deficiency syndrome (SYDS). The SYDS model was prepared in 30 mice by over-fatigue and sexual overstrain. They were randomly divided into the model group and the JSP group, 15 in each group. Another 15 normal male mice were selected as the normal group. Mice in the normal group were fed routinely, with distilled water administered intragastrically at the daily dose of 0.1 mL/10 g. Mice in the model group were also administered intragastrically with distilled water at the daily dose of 0.1 mL/10 g while modeling establishment. Mice in the treatment group were administered intragastrically with JSP suspension at 0.1 mL/10 g (the concentration was 0.241 g/mL). The intervention lasted for 4 weeks. Four weeks later, the testis telomerase activity was detected in the three groups by ELISA. The SYDS model was replicated successfully by over-fatigue and sexual overstrain. JSP could improve the signs of mice of SYDS. Compared with the normal group, the activity of testis telomerase decreased in the model group (P < 0.01). Compared with the model group, the testis telomerase activity markedly increased in the treatment group (P < 0.01). The testis telomerase activity in mice of SYDS caused by over-fatigue and sexual overstrain obviously decreased, when compared with that in mice of the normal group. JSP could recover its activity.

Study of Tnp1, Tekt1, and Plzf Genes Expression During an in vitro Three-Dimensional Neonatal Male Mice Testis Culture

PubMed

Alrahel, Ahmad; Movahedin, Mansoureh; Mazaheri, Zohre; Amidi, Fardin

2018-07-01

In vitro spermatogenesis has a long research history beginning in the early 20th century. This organ culture method was therefore abandoned, and alternative cell culture methods were chosen by many researchers. Here, whether Tnp1, Tekt1, and Plzf, which play a crucial role in spermatogenesis, can be expressed during testis organ culture was assessed. Testes of 10 mouse pups were first removed, and the testis tissue was then separated into smaller pieces of seminiferous tubules. The size of the pieces was arbitrary; approximately 1 mg in weight or 1 mm3 in size when compacted. Afterwards, the testis tissue fragments (1–3) were transferred to the hexahedrons, incubated in a culture incubator and cultured for 12 weeks. Histological assessment and molecular evaluation were carried out at the end of the study. The results showed that the expression of Tekt1 as a mitotic gene in mouse pups decreased significantly (p ≤ 0.05) in comparison to adult mouse testis. Meanwhile, the expression of Tnp1 as a meiotic gene increased significantly (p ≤ 0.05) as compared to neonate mouse testis at the beginning of the culture. The expression of Plzf showed no significant difference during the 12 weeks of culture (p ≥ 0.05). Based on histological study, different types of spermatocytes and post-meiotic stages of germ cells could not be detected. This kind of three-dimensional culture can induce expression of post-meiotic gene, Tnp1, but only at the molecular level and not beyond meiosis.

Protective effect of Urtica dioica L against nicotine-induced damage on sperm parameters, testosterone and testis tissue in mice

PubMed Central

Jalili, Cyrus; Salahshoor, Mohammad Reza; Naseri, Ali

2014-01-01

Background: Nicotine consumption can decrease fertility drive in males by inducing oxidative stress and DNA damage. Urtica dioica L (U.dioica) is a multipurpose herb in traditional medicine for which some anti-oxidative and anti-inflammatory properties have been identified. Objective: The main goal is to investigate whether the U.dioica could inhibit nicotine adverse effects on sperm cells viability, count, motility, and testis histology and testosterone hormone. Materials and Methods: In this study, hydro-alcoholic extract of U.dioica was prepared and various doses of U.dioica (0, 10, 20, and 50 mg/kg) and U.dioica plus nicotine (0, 10, 20, and 50 mg/kg) were administered intraperitoneally to 56 male mice for 28 consequent days. These mice were randomly assigned to 8 groups (n=7) and sperm parameters (sperm cells viability, count, motility, and morphology), testis and prostate weight, testis histology and testosterone hormone were analyzed and compared. Results: The results indicated that nicotine administration (0.5 mg/kg) significantly decreased testosterone level, count and motility of sperm cells, and testis weight compared to control group (p=0.00). However, increasing the dose of U.dioica significantly boosted motility, count, normal morphology of sperm cells, seminiferous tubules diameter, and testosterone in all groups compared to control (p=0.00) and testis weight in 20 and 50 mg/kg doses in comparison with control group (p=0.00). Conclusion: It seems that U.dioica hydro-alcoholic extract administration could increase the quality of spermatozoa and inhibits nicotine-induced adverse effects on sperm parameters. PMID:25071848

Environmentally Induced Epigenetic Transgenerational Inheritance of Altered Sertoli Cell Transcriptome and Epigenome: Molecular Etiology of Male Infertility

PubMed Central

Guerrero-Bosagna, Carlos; Savenkova, Marina; Haque, Md. Muksitul; Nilsson, Eric; Skinner, Michael K.

2013-01-01

Environmental toxicants have been shown to induce the epigenetic transgenerational inheritance of adult onset disease, including testis disease and male infertility. The current study was designed to determine the impact of an altered sperm epigenome on the subsequent development of an adult somatic cell (Sertoli cell) that influences the onset of a specific disease (male infertility). A gestating female rat (F0 generation) was exposed to the agriculture fungicide vinclozolin during gonadal sex determination and then the subsequent F3 generation progeny used for the isolation of Sertoli cells and assessment of testis disease. As previously observed, enhanced spermatogenic cell apoptosis was observed. The Sertoli cells provide the physical and nutritional support for the spermatogenic cells. Over 400 genes were differentially expressed in the F3 generation control versus vinclozolin lineage Sertoli cells. A number of specific cellular pathways were identified to be transgenerationally altered. One of the key metabolic processes affected was pyruvate/lactate production that is directly linked to spermatogenic cell viability. The Sertoli cell epigenome was also altered with over 100 promoter differential DNA methylation regions (DMR) modified. The genomic features and overlap with the sperm DMR were investigated. Observations demonstrate that the transgenerational sperm epigenetic alterations subsequently alters the development of a specific somatic cell (Sertoli cell) epigenome and transcriptome that correlates with adult onset disease (male infertility). The environmentally induced epigenetic transgenerational inheritance of testis disease appears to be a component of the molecular etiology of male infertility. PMID:23555832

Activation of transcriptional activity of HSE by a novel mouse zinc finger protein ZNFD specifically expressed in testis.

PubMed

Xu, Fengqin; Wang, Weiping; Lei, Chen; Liu, Qingmei; Qiu, Hao; Muraleedharan, Vinaydhar; Zhou, Bin; Cheng, Hongxia; Huang, Zhongkai; Xu, Weian; Li, Bichun; Wang, Minghua

2012-04-01

Zinc finger proteins (ZFPs) that contain multiple cysteine and/or histidine residues perform important roles in various cellular functions, including transcriptional regulation, cell proliferation, differentiation, and apoptosis. The Cys-Cys-His-His (C(2)H(2)) type of ZFPs are the well-defined members of this super family and are the largest and most complex proteins in eukaryotic genomes. In this study, we identified a novel C(2)H(2) type of zinc finger gene ZNFD from mice which has a 1,002 bp open reading frame and encodes a protein with 333 amino acid residues. The predicted 37.4 kDa protein contains a C(2)H(2) zinc finger domain. ZNFD gene is located on chromosome 18qD1. RT-PCR analysis revealed that the ZNFD gene was specifically expressed in mouse testis but not in other tissues. Subcellular localization analysis demonstrated that ZNFD was localized in the nucleus. Reporter gene assays showed that overexpression of ZNFD in the COS7 cells activates the transcriptional activities of heat shock element (HSE). Overall, these results suggest that ZNFD is a member of the zinc finger transcription factor family and it participates in the transcriptional regulation of HSE. Many heat shock proteins regulated by HSE are involved in testicular development. Therefore, our results suggest that ZNFD may probably participate in the development of mouse testis and function as a transcription activator in HSE-mediated gene expression and signaling pathways.

Atypical chemokine receptor ACKR2 controls branching morphogenesis in the developing mammary gland

PubMed Central

Hewit, Kay D.; Pallas, Kenneth J.; Cairney, Claire J.; Lee, Kit M.; Hansell, Christopher A.; Stein, Torsten

2017-01-01

Macrophages are important regulators of branching morphogenesis during development and postnatally in the mammary gland. Regulation of macrophage dynamics during these processes can therefore have a profound impact on development. We demonstrate here that the developing mammary gland expresses high levels of inflammatory CC-chemokines, which are essential in vivo regulators of macrophage migration. We further demonstrate that the atypical chemokine receptor ACKR2, which scavenges inflammatory CC-chemokines, is differentially expressed during mammary gland development. We have previously shown that ACKR2 regulates macrophage dynamics during lymphatic vessel development. Here, we extend these observations to reveal a novel role for ACKR2 in regulating the postnatal development of the mammary gland. Specifically, we show that Ackr2−/− mice display precocious mammary gland development. This is associated with increased macrophage recruitment to the developing gland and increased density of the ductal epithelial network. These data demonstrate that ACKR2 is an important regulator of branching morphogenesis in diverse biological contexts and provide the first evidence of a role for chemokines and their receptors in postnatal development processes. PMID:27888192

Stress during a Critical Postnatal Period Induces Region-Specific Structural Abnormalities and Dysfunction of the Prefrontal Cortex via CRF1

PubMed Central

Yang, Xiao-Dun; Liao, Xue-Mei; Uribe-Mariño, Andrés; Liu, Rui; Xie, Xiao-Meng; Jia, Jiao; Su, Yun-Ai; Li, Ji-Tao; Schmidt, Mathias V; Wang, Xiao-Dong; Si, Tian-Mei

2015-01-01

During the early postnatal period, environmental influences play a pivotal role in shaping the development of the neocortex, including the prefrontal cortex (PFC) that is crucial for working memory and goal-directed actions. Exposure to stressful experiences during this critical period may disrupt the development of PFC pyramidal neurons and impair the wiring and function of related neural circuits. However, the molecular mechanisms of the impact of early-life stress on PFC development and function are not well understood. In this study, we found that repeated stress exposure during the first postnatal week hampered dendritic development in layers II/III and V pyramidal neurons in the dorsal agranular cingulate cortex (ACd) and prelimbic cortex (PL) of neonatal mice. The deleterious effects of early postnatal stress on structural plasticity persisted to adulthood only in ACd layer V pyramidal neurons. Most importantly, concurrent blockade of corticotropin-releasing factor receptor 1 (CRF1) by systemic antalarmin administration (20 μg/g of body weight) during early-life stress exposure prevented stress-induced apical dendritic retraction and spine loss in ACd layer V neurons and impairments in PFC-dependent cognitive tasks. Moreover, the magnitude of dendritic regression, especially the shrinkage of apical branches, of ACd layer V neurons predicted the degree of cognitive deficits in stressed mice. Our data highlight the region-specific effects of early postnatal stress on the structural plasticity of prefrontal pyramidal neurons, and suggest a critical role of CRF1 in modulating early-life stress-induced prefrontal abnormalities. PMID:25403725

Understanding exercise self-efficacy and barriers to leisure-time physical activity among postnatal women.

PubMed

Cramp, Anita G; Bray, Steven R

2011-07-01

Studies have demonstrated that postnatal women are at high risk for physical inactivity and generally show lower levels of leisure-time physical activity (LTPA) compared to prepregnancy. The overall purpose of the current study was to investigate social cognitive correlates of LTPA among postnatal women during a 6-month period following childbirth. A total of 230 women (mean age = 30.9) provided descriptive data regarding barriers to LTPA and completed measures of LTPA and self-efficacy (exercise and barrier) for at least one of the study data collection periods. A total of 1,520 barriers were content analyzed. Both exercise and barrier self-efficacy were positively associated with subsequent LTPA. Exercise self-efficacy at postnatal week 12 predicted LTPA from postnatal weeks 12 to 18 (β = .40, R (2) = .18) and exercise self-efficacy at postnatal week 24 predicted LTPA during weeks 24-30 (β = .49, R (2) = .30). Barrier self-efficacy at week 18 predicted LTPA from weeks 18 to 24 (β = .33, R (2) = .13). The results of the study identify a number of barriers to LTPA at multiple time points closely following childbirth which may hinder initiation, resumption or maintenance of LTPA. The results also suggest that higher levels of exercise and barrier self-efficacy are prospectively associated with higher levels of LTPA in the early postnatal period. Future interventions should be designed to investigate causal effects of developing participants' exercise and barrier self-efficacy for promoting and maintaining LTPA during the postnatal period.

The Effect of Congenital and Postnatal Hypothyroidism on Depression-Like Behaviors in Juvenile Rats.

PubMed

Özgür, Erdoğan; Gürbüz Özgür, Börte; Aksu, Hatice; Cesur, Gökhan

2016-12-01

The aim of this study was to investigate depression-like behaviors of juvenile rats with congenital and postnatal hypothyroidism. Twenty-seven newborn rat pups were used. First, 6-month-old Wistar Albino female rats were impregnated. Methimazole (0.025% wt/vol) was given to dam rats from the first day of pregnancy until postnatal 21 days (P21) to generate pups with congenital hypothyroidism (n=8), whereas in the postnatal hypothyroidism group (n=10), methimazole was given from P0 to P21. In the control group (n=9), dam rats were fed ad libitum and normal tap water. Offspring were fed with breast milk from their mothers. The behavioral parameters were measured with the juvenile forced swimming test (JFST). The procedure of JFST consisted of two sessions in two consecutive days: the 15-minute pre-test on day 1 and the 5-minute test on day 2. Increased immobility and decreased climbing duration were observed in both congenital and postnatal hypothyroidism groups. Decreased swimming duration was detected in the postnatal hypothyroidism group. Both hypothyroidism groups had a lower body weight gain compared with the control group, while the congenital hypothyroidism group had the lowest body weight. Our results showed that hypothyroidism had negative effects on depression-like behavior as well as on growth and development. Both congenital and postnatal hypothyroidism caused an increase in immobility time in JFST. New studies are required to understand the differing results on depression-like behavior between congenital and postnatal hypothyroidism.

The Non-Peptide Vasopressin V1b Receptor Antagonist, SSR149415, Ameliorates Spermatogenesis Function in a Mouse Model of Chronic Social Defeat Stress.

PubMed

Wang, Bin; Zhou, Jian; Zhuang, Yan-Yan; Wang, Liang-Liang; Pu, Jin-Xian; Huang, Yu-Hua; Xia, Fei; Lv, Jin-Xing

2017-11-01

To determine the effects of SSR149415 on testis and spermatogenesis in male mice subjected to chronic social defeat stress, C57BL/6 male mice were divided into two groups: Control and Stress. Then Stress group was subdivided into four subgroups administered water, SSR149415 (1 mg/kg/day), SSR149415 (10 mg/kg/day), SSR149415 (30 mg/kg/day), respectively. The behavioral alterations revealed by social interaction test and open field test were measured. The physical indices, including body weight and gonad weight (testis and epididymis) as well as testis/body weight and cauda epididymis/body weight were detected. Serum hormones, including testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were determined. Sperm count and abnormality as well as testicular histology structure were assessed. The germ cells apoptosis were also evaluated. Chronic social defeat stress-induced behavioral abnormality, as well as gonad atrophy (testis and epididymis) was significantly alleviated in stressed male mice exposed to SSR149415. Regressed serum testosterone levels and elevated serum FSH and LH levels exhibited by stressed male mice were observably reversed following SSR149415 administration. Chronic social defeat stress-induced damage in testicular histology structure and semen quality were also improved after SSR149415 administration. In addition, SSR149415 significantly reversed chronic social defeat stress-induced germ cells apoptosis. Overall, we provide clear evidence indicating the amelioration of chronic social defeat stress-induced behavioral abnormality and testicular dysfunction via SSR149415, promoting the development of drug-directed therapy against this disease. J. Cell. Biochem. 118: 3891-3898, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Prepubertal mouse testis growth and maturation and androgen production are acutely sensitive to di-n-butyl phthalate.

PubMed

Moody, Sarah; Goh, Hoey; Bielanowicz, Amanda; Rippon, Paul; Loveland, Kate L; Itman, Catherine

2013-09-01

Phthalates are plasticizers with widespread industrial, domestic, and medical applications. Epidemiological data indicating increased incidence of testicular dysgenesis in boys exposed to phthalates in utero are reinforced by studies demonstrating that phthalates impair fetal rodent testis development. Because humans are exposed to phthalates continuously from gestation through adulthood, it is imperative to understand what threat phthalates pose at other life stages. To determine the impact during prepuberty, we assessed the consequences of oral administration of 1 to 500 mg di-n-butyl phthalate (DBP)/kg/d in corn oil to wild-type (C57BL/6J) male mice from 4 to 14 days of age. Dose-dependent effects on testis growth correlated with reduced Sertoli cell proliferation. Histological and immunohistochemical analyses identified delayed spermatogenesis and impaired Sertoli cell maturation after exposure to 10 to 500 mg DBP/kg/d. Interference with the hypothalamic-pituitary-gonadal axis was indicated in mice fed 500 mg DBP/kg/d, which had elevated circulating inhibin but no change in serum FSH. Increased immunohistochemical staining for inhibin-α was apparent at doses of 10 to 500 mg DBP/kg/d. Serum testosterone and testicular androgen activity were lower in the 500 mg DBP/kg/d group; however, reduced anogenital distance in all DBP-treated mice suggested impaired androgen action at earlier time points. Long-term effects were evident, with smaller anogenital distance and indications of disrupted spermatogenesis in adult mice exposed prepubertally to doses from 1 mg DBP/kg/d. These data demonstrate the acute sensitivity of the prepubertal mouse testis to DBP at doses 50- to 500-fold lower than those used in rat and identify the upregulation of inhibin as a potential mechanism of DBP action.

BmTGIF, a Bombyx mori Homolog of Drosophila DmTGIF, Regulates Progression of Spermatogenesis

PubMed Central

Sheng, Jie; Xue, Renyu; Gong, Chengliang

2012-01-01

TG-interacting factor (TGIF) in Drosophila consists of two tandemly-repeated genes, achintya (Dmachi) and vismay (Dmvis), which act as transcriptional activators in Drosophila spermatogenesis. In contrast, TGIF in humans is a transcriptional repressor that binds directly to DNA or interacts with corepressors to repress the transcription of target genes. In this study, we investigated the characteristics and functions of BmTGIF, a Bombyx mori homolog of DmTGIF. Like DmTGIF, BmTGIF is predominantly expressed in the testes and ovaries. Four alternatively spliced isoforms could be isolated from testes, and two isoforms from ovaries. Quantitative polymerase chain reaction indicated BmTGIF was abundantly expressed in the testis of 3rd instar larvae, when the testis is almost full of primary spermatocytes. The results of luciferase assays indicated that BmTGIF contains two adjacent acidic domains that activate the transcription of reporter genes. Immunofluorescence assay in BmN cells showed that the BmTGIF protein was located mainly in the nucleus, and paraffin sections of testis showed BmTGIF was grossly expressed in primary spermatocytes and mature sperms. Consistent with the role of DmVis in Drosophila development, BmTGIF significantly affected spermatid differentiation, as indicated by hematoxylin-eosin staining of paraffin sections of testis from BmTGIF-small interfering RNA (siRNA)-injected male silkworms. Co-immunoprecipitation experiments suggested that BmTGIF interacted with BmAly, and that they may recruit other factors to form a complex to regulate the genes required for meiotic divisions and spermatid differentiation. The results of this analysis of BmTGIF will improve our understanding of the mechanism of spermatid differentiation in B. mori, with potential applications for pest control. PMID:23152760

Very small embryonic-like stem cells: implications in reproductive biology.

PubMed

Bhartiya, Deepa; Unni, Sreepoorna; Parte, Seema; Anand, Sandhya

2013-01-01

The most primitive germ cells in adult mammalian testis are the spermatogonial stem cells (SSCs) whereas primordial follicles (PFs) are considered the fundamental functional unit in ovary. However, this central dogma has recently been modified with the identification of a novel population of very small embryonic-like stem cells (VSELs) in the adult mammalian gonads. These stem cells are more primitive to SSCs and are also implicated during postnatal ovarian neo-oogenesis and primordial follicle assembly. VSELs are pluripotent in nature and characterized by nuclear Oct-4A, cell surface SSEA-4, and other pluripotent markers like Nanog, Sox2, and TERT. VSELs are considered to be the descendants of epiblast stem cells and possibly the primordial germ cells that persist into adulthood and undergo asymmetric cell division to replenish the gonadal germ cells throughout life. Elucidation of their role during infertility, endometrial repair, superovulation, and pathogenesis of various reproductive diseases like PCOS, endometriosis, cancer, and so on needs to be addressed. Hence, a detailed review of current understanding of VSEL biology is pertinent, which will hopefully open up new avenues for research to better understand various reproductive processes and cancers. It will also be relevant for future regenerative medicine, translational research, and clinical applications in human reproduction.

Non-School Influences and Educational Disadvantage: Pre and Post-natal Nutritional Deprivation

ERIC Educational Resources Information Center

Doll, Russell C.

1973-01-01

Deals with pre and post-natal malnutrition and its possible influence on the child, focusing on these points: How wide-spread and severe is the malnutrition? What might be the effects of the malnutrition at certain critical points in development? (Author/JM)

Metabolic perturbations of postnatal growth restriction and hyperoxia-induced pulmonary hypertension in a bronchopulmonary dysplasia model

USDA-ARS?s Scientific Manuscript database

Introduction: Neonatal pulmonary hypertension (PH) is a common manifestation of bronchopulmonary dysplasia (BPD) and contributes to increased morbidity and mortality of preterm birth. Postnatal growth restriction and hyperoxia are independent contributors to PH development, as indicated by our previ...

Modified prenatal sensory stimulation influences postnatal behavioral and perceptual responsiveness in bobwhite quail chicks (Colinus virginianus).

PubMed

Reynolds, Greg D; Lickliter, Robert

2004-06-01

Asynchronous bimodal stimulation during prenatal development elicits higher levels of behavioral and physiological arousal in precocial avian embryos than does unimodal sensory stimulation. To investigate whether the increased arousal associated with prenatal bimodal stimulation has enduring effects into postnatal development, bobwhite quail (Colinus virginianus) embryos received no supplemental stimulation, unimodal auditory stimulation, or bimodal (audiovisual) stimulation prior to hatching. Embryos exposed to concurrent bimodal stimulation demonstrated greater levels of behavioral activity and failed to use maternal visual cues to successfully direct species-specific perceptual preferences following hatching. These results provide initial evidence that asynchronous bimodal sensory stimulation during prenatal development can have enduring effects on early postnatal behavioral arousal and perceptual responsiveness and suggest that developmental limitations on prenatal sensory stimulation play an important role in the emergence of species-typical behavior.

The impact of early postnatal environmental enrichment on maternal care and offspring behaviour following weaning.

PubMed

Li, Ki Angel; Lund, Emilie Torp; Voigt, Jörg-Peter W

2016-01-01

The early postnatal period is a sensitive period in rodents as behavioural systems are developing and maturing during this time. However, relatively little information is available about the impact of environmental enrichment on offspring behaviour if enrichment is implemented only during this period. Here, environmental enrichment was provided from postnatal day 1 until weaning. On post-natal day 9, maternal behaviour and nonmaternal behaviour of the dam was observed. Nursing time in the enriched group was reduced but dams showed more non-maternal appetitive behaviours. Offspring were exposed to either the open field or the elevated plus maze (EPM) after weaning. In the open field, rats from the enriched group approached the more aversive inner zone of the open field later than control rats. Offspring from the enriched group made fewer entries into the inner zone and spent less time in this part of the arena. Enrichment had no impact on behaviour in the EPM. The present study provides evidence that postnatal enrichment can interfere with maternal behaviour in rats and can possibly lead to increased anxiety in the offspring. The findings suggest that enrichment procedures can have potentially unintended effects, interfering with the development of emotional behaviours in rats. Copyright © 2015 Elsevier B.V. All rights reserved.

Risk for Neurobehavioral Disinhibition in Prenatal Methamphetamine-Exposed Young Children with Positive Hair Toxicology Results

PubMed Central

Himes, Sarah K.; LaGasse, Linda L.; Derauf, Chris; Newman, Elana; Smith, Lynne M.; Arria, Amelia M.; Grotta, Sheri A. Della; Dansereau, Lynne M.; Abar, Beau; Neal, Charles R.; Lester, Barry M.; Huestis, Marilyn A.

2014-01-01

Background The objective was to evaluate effects of prenatal methamphetamine exposure (PME) and postnatal drug exposures identified by child hair analysis on neurobehavioral disinhibition at 6.5 years of age. Methods Mother-infant pairs were enrolled in the Infant Development, Environment, and Lifestyle (IDEAL) Study in Los Angeles, Honolulu, Tulsa and Des Moines. PME was determined by maternal self-report and/or positive meconium results. At the 6.5-year follow-up visit, hair was collected and analyzed for methamphetamine, tobacco, cocaine, and cannabinoid markers. Child behavioral and executive function test scores were aggregated to evaluate child neurobehavioral disinhibition. Hierarchical linear regression models assessed the impact of PME, postnatal substances, and combined PME with postnatal drug exposures on the child’s neurobehavioral disinhibition aggregate score. Past year caregiver substance use was compared to child hair results. Results A total of 264 children were evaluated. Significantly more PME children (n=133) had hair positive for methamphetamine/amphetamine (27.1% versus 8.4%) and nicotine/cotinine (38.3% versus 25.2%) than children without PME (n=131). Overall, no significant differences in analyte hair concentrations were noted between groups. Significant differences in behavioral and executive function were observed between children with and without PME. No independent effects of postnatal methamphetamine or tobacco exposure, identified by positive hair test, were noted and no additional neurobehavioral disinhibition was observed in PME children with postnatal drug exposures, as compared to PME children without postnatal exposure. Conclusions Child hair testing offered a non-invasive means to evaluate postnatal environmental drug exposure, although no effects from postnatal drug exposure alone were seen. PME, alone and in combination with postnatal drug exposures, was associated with behavioral and executive function deficits at 6.5 years. PMID:24518561

Risk of neurobehavioral disinhibition in prenatal methamphetamine-exposed young children with positive hair toxicology results.

PubMed

Himes, Sarah K; LaGasse, Linda L; Derauf, Chris; Newman, Elana; Smith, Lynne M; Arria, Amelia M; Della Grotta, Sheri A; Dansereau, Lynne M; Abar, Beau; Neal, Charles R; Lester, Barry M; Huestis, Marilyn A

2014-08-01

The objective was to evaluate the effects of prenatal methamphetamine exposure (PME) and postnatal drug exposures identified by child hair analysis on neurobehavioral disinhibition at 6.5 years of age. Mother-infant pairs were enrolled in the Infant Development, Environment, and Lifestyle (IDEAL) Study in Los Angeles, Honolulu, Tulsa, and Des Moines. PME was determined by maternal self-report and/or positive meconium results. At the 6.5-year follow-up visit, hair was collected and analyzed for methamphetamine, tobacco, cocaine, and cannabinoid markers. Child behavioral and executive function test scores were aggregated to evaluate child neurobehavioral disinhibition. Hierarchical linear regression models assessed the impact of PME, postnatal substances, and combined PME with postnatal drug exposures on the child's neurobehavioral disinhibition aggregate score. Past year caregiver substance use was compared with child hair results. A total of 264 children were evaluated. Significantly more PME children (n = 133) had hair positive for methamphetamine/amphetamine (27.1% versus 8.4%) and nicotine/cotinine (38.3% versus 25.2%) than children without PME (n = 131). Overall, no significant differences in analyte hair concentrations were noted between groups. Significant differences in behavioral and executive function were observed between children with and without PME. No independent effects of postnatal methamphetamine or tobacco exposure, identified by positive hair test, were noted and no additional neurobehavioral disinhibition was observed in PME children with postnatal drug exposures, as compared with PME children without postnatal exposure. Child hair testing offered a noninvasive means to evaluate postnatal environmental drug exposure, although no effects from postnatal drug exposure alone were seen. PME, alone and in combination with postnatal drug exposures, was associated with behavioral and executive function deficits at 6.5 years.

Localization of S-100 proteins in the testis and epididymis of poultry and rabbits

PubMed Central

Abd-Elmaksoud, Ahmed; Marei, Hany E. S.

2014-01-01

The present investigation was conducted to demonstrate S-100 protein in the testis and epididymis of adult chickens, Sudani ducks, pigeons, and rabbits. This study may represent the first indication for the presence of S-100 in the male reproductive organs of these species and might therefore serve as a milestone for further reports. In the testis of chickens, pigeons and rabbits, intense S-100 was seen in Sertoli cells. S-100 was also seen in the endothelial lining of blood vessels in rabbit testis. On the contrary, no S-100 reaction was detected in the Sertoli cells of Sudani ducks. In epididymis, the localization of S-100 had varied according to species studied; it was seen in the basal cells (BC) of epididymal duct in duck, non-ciliated cells of the distal efferent ductules in pigeons and ciliated cells of the efferent ductules and BC of rabbit epididymis. Conversely, S-100 specific staining was not detected in the epithelial lining of the rooster and pigeon epididymal duct as well as the principal cells of the rabbit epididymis. In conclusion, the distribution of the S-100 proteins in the testis and epididymis might point out to its roles in the male reproduction. PMID:25276477

Leptin Level and Oxidative Stress Contribute to Obesity-Induced Low Testosterone in Murine Testicular Tissue

PubMed Central

Zhao, Jian; Zhai, Lingling; Liu, Zheng; Wu, Shuang; Xu, Liping

2014-01-01

Objective. This study evaluated the effects of obesity on the function of reproductive organs in male mice and the possible mechanism of male secondary hypogonadism (SH) in obesity. Methods. Ninety-six mice were randomly assigned to three groups: the control group, diet-induced obesity group, and diet-induced obesity resistant group for 8 weeks and 19 weeks. The effects of short- and long-term high-fat diet on the reproductive organs were determined by measuring sperm count and motility, relative testis weight, testosterone level, pathological changes and apoptosis of Leydig cells. Oxidative stress was evaluated by determining malondialdehyde, H2O2, NO levels, and GSH in testis tissues. CAT, SOD, GSH-Px and Nrf2 mRNA were measured by real-time PCR. Results. Short- and long-term high-fat diet decreased sperm count and motility, relative testis weight, testosterone level; decreased CAT, SOD, GSH-Px and Nrf2 mRNA expression; increased MDA, H2O2, NO and leptin levels; inhibited the activity of CAT and GSH-Px enzymes. Pathological injury and apoptosis of Leydig cells were found in testis tissue. Conclusions. Pathological damage of Leydig cells, oxidative stress in testis tissue, and high level of leptin may provide some evidence to clarify the mechanisms of male SH in obesity. PMID:24829619

Insulin Rescues Impaired Spermatogenesis via the Hypothalamic-Pituitary-Gonadal Axis in Akita Diabetic Mice and Restores Male Fertility

PubMed Central

Schoeller, Erica L.; Albanna, Gabriella; Frolova, Antonina I.; Moley, Kelle H.

2012-01-01

The mechanism responsible for poor reproductive outcomes in type 1 diabetic males is not well understood. In light of new evidence that the Sertoli cells of the testis secrete insulin, it is currently unclear whether diabetic subfertility is the result of deficiency of pancreatic insulin, testicular insulin, or both. In this study, the Akita mouse diabetic model, which expresses a mutant, nonfunctional form of ins2 in testes and pancreas, was used to distinguish between systemic and local effects of insulin deficiency on the process of spermatogenesis and fertility. We determined that Akita homozygous male mice are infertile and have reduced testis size and abnormal morphology. Spermatogonial germ cells are still present but are unable to mature into spermatocytes and spermatids. Exogenous insulin treatment regenerates testes and restores fertility, but this plasma insulin cannot pass through the blood-testis barrier. We conclude that insulin does not rescue fertility through direct interaction with the testis; instead, it restores function of the hypothalamic-pituitary-gonadal axis and, thus, normalizes hormone levels of luteinizing hormone and testosterone. Although we show that the Sertoli cells of the testis secrete insulin protein, this insulin does not appear to be critical for fertility. PMID:22522616

Postnatal development of echolocation abilities in a bottlenose dolphin (Tursiops truncatus): temporal organization.

PubMed

Favaro, Livio; Gnone, Guido; Pessani, Daniela

2013-03-01

In spite of all the information available on adult bottlenose dolphin (Tursiops truncatus) biosonar, the ontogeny of its echolocation abilities has been investigated very little. Earlier studies have reported that neonatal dolphins can produce both whistles and burst-pulsed sounds just after birth and that early-pulsed sounds are probably a precursor of echolocation click trains. The aim of this research is to investigate the development of echolocation signals in a captive calf, born in the facilities of the Acquario di Genova. A set of 81 impulsive sounds were collected from birth to the seventh postnatal week and six additional echolocation click trains were recorded when the dolphin was 1 year old. Moreover, behavioral observations, concurring with sound production, were carried out by means of a video camera. For each sound we measured five acoustic parameters: click train duration (CTD), number of clicks per train, minimum, maximum, and mean click repetition rate (CRR). CTD and number of clicks per train were found to increase with age. Maximum and mean CRR followed a decreasing trend with dolphin growth starting from the second postnatal week. The calf's first head scanning movement was recorded 21 days after birth. Our data suggest that in the bottlenose dolphin the early postnatal weeks are essential for the development of echolocation abilities and that the temporal features of the echolocation click trains remain relatively stable from the seventh postnatal week up to the first year of life. © 2013 Wiley Periodicals, Inc.

Postnatal Loss of Mef2c Results in Dissociation of Effects on Synapse Number and Learning and Memory.

PubMed

Adachi, Megumi; Lin, Pei-Yi; Pranav, Heena; Monteggia, Lisa M

2016-07-15

Myocyte enhancer factor 2 (MEF2) transcription factors play critical roles in diverse cellular processes during central nervous system development. Studies attempting to address the role of MEF2 in brain have largely relied on overexpression of a constitutive MEF2 construct that impairs memory formation or knockdown of MEF2 function that increases spine numbers and enhances memory formation. Genetic deletion of individual MEF2 isoforms in brain during embryogenesis demonstrated that Mef2c loss negatively regulates spine numbers resulting in learning and memory deficits, possibly as a result of its essential role in development. To investigate MEF2C function in brain further, we genetically deleted Mef2c during postnatal development in mice. We characterized these conditional Mef2c knockout mice in an array of behavioral paradigms and examined the impact of postnatal loss of Mef2c on long-term potentiation. We observed increased spine numbers in hippocampus of the conditional Mef2c knockout mice. However, the postnatal loss of Mef2c did not impact learning and memory, long-term potentiation, or social and repetitive behaviors. Our findings demonstrate a critical role for MEF2C in the regulation of spine numbers with a dissociation of learning and memory, synaptic plasticity, and measures of autism-related behaviors in postnatal brain. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

The expression of Per1 and Aa-nat genes in the pineal gland of postnatal rats.

PubMed

Wongchitrat, Prapimpun; Govitrapong, Piyarat; Phansuwan-Pujito, Pansiri

2012-12-01

The circadian rhythm of melatonin synthesis is controlled by the master clock, suprachiasmatic nucleus (SCN). The level of melatonin changes throughout the aging process. The SCN's rhythm is driven by autoregulatory feedback loop composed of a set of clock genes families and their corresponding proteins. The Period (Per1), one of clock gene develops gradually during postnatal ontogenesis in the rat SCN and is also expressed in the pineal gland. It is of interest to study the relationship between the postnatal development of Per1 and Aa-nat, genes that produce the rate-limiting enzyme in melatonin synthesis, in the pineal. Daily profiles of mRNA expression of Per1 and Aa-nat were analyzed in the pineal gland of pups at postnatal ages 4 (P4), P8, P16 and P32, at puberty age of 6 weeks; and in 8 week-old adult rats by real-time PCR. As early as P4, Per1 and Aa-nat mRNAs were expressed and existed at relatively high levels during the nighttime. They gradually increased until puberty and decreased at 8 weeks of age. Additionally, the nocturnal changes of Per1 and Aa-nat mRNA levels in the rat pineal gland from P4 to adults were strongly correlated at r = 0.97 (p < 0.01). The present data indicate that there is a close relationship between the expression pattern of Per1 and that of melatonin synthesis during the development of postnatal rats.

Recurrent Moderate Hypoglycemia Suppresses Brain-Derived Neurotrophic Factor Expression in the Prefrontal Cortex and Impairs Sensorimotor Gating in the Post-Hypoglycemia Period in Young Rats

PubMed Central

Rao, Raghavendra; Ennis, Kathleen; Mitchell, Eugena P.; Tran, Phu V.; Gewirtz, Jonathan C.

2016-01-01

Recurrent hypoglycemia is common in infants and children. In developing rat models, recurrent moderate hypoglycemia leads to neuronal injury in the medial prefrontal cortex. To understand the effects beyond neuronal injury, three-week-old male rats were subjected to five episodes of moderate hypoglycemia (blood glucose concentration, approximately 30 mg/dl for 90 min) once daily from postnatal day 24 to 28. Neuronal injury was determined using Fluoro-jade B histochemistry on postnatal day 29. The effects on brain-derived neurotrophic factor (BDNF) and its cognate receptor, tyrosine kinase B (TrkB) expression, which is critical for prefrontal cortex development, were determined on postnatal day 29 and at adulthood. The effects on prefrontal cortex-mediated function were determined by assessing prepulse inhibition of the acoustic startle reflex on postnatal day 29 and two weeks later, and by testing for fear-potentiated startle at adulthood. Recurrent hypoglycemia led to neuronal injury confined primarily to the medial prefrontal cortex. BDNF and TrkB expression in the prefrontal cortex was suppressed on postnatal day 29 and was accompanied by lower prepulse inhibition, suggesting impaired sensorimotor gating. Following the cessation of recurrent hypoglycemia, prepulse inhibition had recovered at two weeks. BDNF/TrkB expression in the prefrontal cortex had normalized and fear-potentiated startle was intact at adulthood. Recurrent moderate hypoglycemia during development has significant adverse effects on the prefrontal cortex in the post-hypoglycemia period. PMID:26820887

Postnatal airway growth in cystic fibrosis piglets.

PubMed

Adam, Ryan J; Abou Alaiwa, Mahmoud H; Bouzek, Drake C; Cook, Daniel P; Gansemer, Nicholas D; Taft, Peter J; Powers, Linda S; Stroik, Mallory R; Hoegger, Mark J; McMenimen, James D; Hoffman, Eric A; Zabner, Joseph; Welsh, Michael J; Meyerholz, David K; Stoltz, David A

2017-09-01

Mutations in the gene encoding the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) anion channel cause CF. The leading cause of death in the CF population is lung disease. Increasing evidence suggests that in utero airway development is CFTR-dependent and that developmental abnormalities may contribute to CF lung disease. However, relatively little is known about postnatal CF airway growth, largely because such studies are limited in humans. Therefore, we examined airway growth and lung volume in a porcine model of CF. We hypothesized that CF pigs would have abnormal postnatal airway growth. To test this hypothesis, we performed CT-based airway and lung volume measurements in 3-wk-old non-CF and CF pigs. We found that 3-wk-old CF pigs had tracheas of reduced caliber and irregular shape. Their bronchial lumens were reduced in size proximally but not distally, were irregularly shaped, and had reduced distensibility. Our data suggest that lack of CFTR results in aberrant postnatal airway growth and development, which could contribute to CF lung disease pathogenesis. NEW & NOTEWORTHY This CT scan-based study of airway morphometry in the cystic fibrosis (CF) postnatal period is unique, as analogous studies in humans are greatly limited for ethical and technical reasons. Findings such as reduced airway lumen area and irregular caliber suggest that airway growth and development are CF transmembrane conductance regulator-dependent and that airway growth defects may contribute to CF lung disease pathogenesis. Copyright © 2017 the American Physiological Society.

Rax Homeoprotein Regulates Photoreceptor Cell Maturation and Survival in Association with Crx in the Postnatal Mouse Retina

PubMed Central

Irie, Shoichi; Sanuki, Rikako; Muranishi, Yuki; Kato, Kimiko; Chaya, Taro

2015-01-01

The Rax homeobox gene plays essential roles in multiple processes of vertebrate retina development. Many vertebrate species possess Rax and Rax2 genes, and different functions have been suggested. In contrast, mice contain a single Rax gene, and its functional roles in late retinal development are still unclear. To clarify mouse Rax function in postnatal photoreceptor development and maintenance, we generated conditional knockout mice in which Rax in maturing or mature photoreceptor cells was inactivated by tamoxifen treatment (Rax iCKO mice). When Rax was inactivated in postnatal Rax iCKO mice, developing photoreceptor cells showed a significant decrease in the level of the expression of rod and cone photoreceptor genes and mature adult photoreceptors exhibited a specific decrease in cone cell numbers. In luciferase assays, we found that Rax and Crx cooperatively transactivate Rhodopsin and cone opsin promoters and that an optimum Rax expression level to transactivate photoreceptor gene expression exists. Furthermore, Rax and Crx colocalized in maturing photoreceptor cells, and their coimmunoprecipitation was observed in cultured cells. Taken together, these results suggest that Rax plays essential roles in the maturation of both cones and rods and in the survival of cones by regulating photoreceptor gene expression with Crx in the postnatal mouse retina. PMID:25986607

Expression of klotho mRNA and protein in rat brain parenchyma from early postnatal development into adulthood

PubMed Central

Clinton, Sarah M.; Glover, Matthew E.; Maltare, Astha; Laszczyk, Ann M.; Mehi, Stephen J.; Simmons, Rebecca K.; King, Gwendalyn D.

2013-01-01

Without the age-regulating protein klotho, mouse lifespan is shortened and the rapid onset of age-related disorders occurs. Conversely, overexpression of klotho extends mouse lifespan. Klotho is most abundant in kidney and expressed in a limited number of other organs, including the brain, where klotho levels are highest in choroid plexus. Reports vary on where klotho is expressed within the brain parenchyma, and no data is available as to whether klotho levels change across postnatal development. We used in situ hybridization to map klotho mRNA expression in the developing and adult rat brain and report moderate, widespread expression across grey matter regions. mRNA expression levels in cortex, hippocampus, caudate putamen, and amygdala decreased during the second week of life and then gradually rose to adult levels by postnatal day 21. Immunohistochemistry revealed a protein expression pattern similar to the mRNA results, with klotho protein expressed widely throughout the brain. Klotho protein co-localized with both the neuronal marker NeuN, as well as, oligodendrocyte marker olig2. These results provide the first anatomical localization of klotho mRNA and protein in rat brain parenchyma and demonstrate that klotho levels vary during early postnatal development. PMID:23838326

Effect of methamphetamine exposure and cross-fostering on sensorimotor development of male and female rat pups.

PubMed

Hrubá, Lenka; Schutová, Barbora; Slamberová, Romana; Pometlová, Marie; Rokyta, Richard

2009-01-01

The present study tested the hypothesis that cross-fostering influences the development of rat pups. Mothers were exposed daily to injection of methamphetamine (M) (5 mg/kg) or saline for 9 weeks: 3 weeks prior to impregnation, throughout gestation and lactation periods. Control females animals without any injections were used. On postnatal day (PD) 1, pups were cross-fostered so that each mother received four pups of her own and eight pups from the mothers with the other two treatments. Offspring were tested for sensorimotor development in preweaning period by using tests of: negative geotaxis, tail pull, righting reflexes, rotarod and bar-holding. Further, the pups were weighed daily. Our results showed that birth weight in prenatally M-exposed pups was lower than in control or saline-exposed pups. Prenatally M-exposed pups gained less weight than control or saline-exposed pups regardless of postnatal treatment and sex. Further, our data demonstrated that prenatal and postnatal M exposure impairs sensorimotor functions in most of the tests. On the other hand, the negative effect of prenatal M exposure was partially suppressed in prenatally M-exposed pups by cross-fostering to control dams. Our hypothesis that cross-fostering may affect postnatal development of pups was confirmed.

Postnatal development of the myenteric plexus in cat stomach.

PubMed

Lolova, I; Itsev, D

1983-01-01

The postnatal development of the myenteric plexus in cat stomach has been studied at birth, on the 14th, 30th, 45th and 180th postnatal days, using light- and electronmicroscopic methods. In newborn kittens the main network of the Auerbach plexus is well formed, but the myenteric ganglia are composed of nerve cells with different maturity and a scarce neuropile. During the first two postnatal weeks the dimensions of the ganglia increase owing to the increase of the nerve bodies and the rising number of glials cells and intercellular fibres. This is accompanied by a potentiation of the AChE-activity, mainly in the nerve cell bodies and to a lesser extent in the neuropile. Impregnation reveals different in calibre and form nerve fibres and terminals. Different ultrastructural types of neurones are identified on the 14th day. Later development is expressed in the formation of large compact ganglia and thick connecting strands. The number of AChE-positive fibres in the neuropile increases. Owing to the increase in the cell organelles and their more advanced maturity, it is possible to define the ultrastructural type of an ever increasing number of neurones.

Expression patterns of DLK1 and INSL3 identify stages of Leydig cell differentiation during normal development and in testicular pathologies, including testicular cancer and Klinefelter syndrome.

PubMed

Lottrup, G; Nielsen, J E; Maroun, L L; Møller, L M A; Yassin, M; Leffers, H; Skakkebæk, N E; Rajpert-De Meyts, E

2014-08-01

What is the differentiation stage of human testicular interstitial cells, in particular Leydig cells (LC), within micronodules found in patients with infertility, testicular cancer and Klinefelter syndrome? The Leydig- and peritubular-cell populations in testes with dysgenesis contain an increased proportion of undifferentiated cells when compared with control samples, as demonstrated by increased delta-like homolog 1 (DLK1) and decreased insulin-like peptide 3 (INSL3) expression. Normal LC function is essential for male development and reproduction. Signs of LC failure, including LC micronodules, are often observed in patients with reproductive disorders. In this retrospective study, a panel of markers and factors linked to the differentiation of LCs was investigated in 33 fetal and prepubertal human specimens and in 58 adult testis samples from patients with testicular germ cell tumours, including precursor carcinoma in situ (CIS), infertility or Klinefelter syndrome. The expression patterns of DLK1, INSL3, chicken ovalbumin upstream promoter transcription factor 2 (COUP-TFII), cytochrome P450, family 11, subfamily A, polypeptide 1 (CYP11A1) and smooth muscle actin (SMA) were investigated by immunohistochemistry and quantitative RT-PCR. The percentage of positive LCs was estimated and correlated to total LC numbers and serum levels of reproductive hormones. DLK1, INSL3 and COUP-TFII expression changed during normal development and was linked to different stages of LC differentiation: DLK1 was expressed in all fetal LCs, but only in spindle-shaped progenitor cells and in a small subset of polygonal LCs in the normal adult testis; INSL3 was expressed in a subset of fetal LCs, but in the majority of adult LCs; and COUP-TFII was expressed in peritubular and mesenchymal stroma cells at all ages, in fetal LCs early in gestation and in a subset of adult LCs. CYP11A1 was expressed in the majority of LCs regardless of age and pathology and was the best general LC marker examined here. SMA was weakly expressed in peritubular cells in the fetal and infantile testis, but strongly expressed in the adult testis. In pathological testes, the numbers of DLK1-positive interstitial cells were increased. The proportion of DLK1-positive LCs correlated with total LC numbers (R = 0.53; P < 0.001) and was higher in testis with enlargement of the peritubular layers (P < 0.01), which was also highly associated with DLK1 expression in the peritubular compartment (P < 0.001). INSL3 expression was absent in some, but not all LC micronodules, and in the majority of LCs, it was mutually exclusive of DLK1. The number of samples was relatively small and no true normal adult controls were available. True stereology was not used for LC counting, instead LCs were counted in three fields of 0.5 µm(2) surface for each sample. The population of LCs, especially those clustered in large nodules, are heterogeneous and comprise cells at different stages of differentiation. The study demonstrated that the differentiation and function of LCs, and possibly also peritubular cells, are impaired in adult men with testicular pathologies including testis cancer and Klinefelter syndrome. This work was funded by Rigshospitalet's research funds, the Danish Cancer Society and Kirsten and Freddy Johansen's foundation. The authors have no conflicts of interest. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Neurobiology and Neurodevelopmental Impact of Childhood Traumatic Stress and Prenatal Alcohol Exposure

ERIC Educational Resources Information Center

Henry, Jim; Sloane, Mark; Black-Pond, Connie

2007-01-01

Purpose: Research reveals that prenatal alcohol exposure and child trauma (i.e., abuse, neglect, sexual abuse) can have deleterious effects on child development across multiple domains. This study analyzed the impact on childhood neurodevelopment of prenatal alcohol exposure and postnatal traumatic experience compared to postnatal traumatic…

The Development of Parenting Efficacy among New Mothers and Fathers

ERIC Educational Resources Information Center

Leerkes, Esther M.; Burney, Regan V.

2007-01-01

Predictors of prenatal and postnatal parenting efficacy were examined in a sample of 115 primiparous mothers and 73 fathers in an effort to examine the association between preexisting parental characteristics and prenatal efficacy and the association between prenatal characteristics and postnatal efficacy when aspects of the current parenting…

Implications of Post-Natal Cortical Development for Creativity Research.

ERIC Educational Resources Information Center

Gordon, Marjory; Dacey, John

Man's long period of cerebral growth has important implications for education. The brain goes through major developmental changes after birth, and researchers have suggested that this growth process presents an opportunity for fostering the plasticity of genetically determined connections. Animal studies show that postnatal growth of the brain is…

Report of the NASA Mammalian Developmental Biology Working Group

NASA Technical Reports Server (NTRS)

Keefe, J. R.

1985-01-01

Development is considered to encompass all aspects of the mammalian life span from initial initial germ cell production through the complete life cycle to death of the organism. Thus, gamete production, fertilization, embryogenesis, implantation, fetogenesis, birth, peri- and postnatal maturation, and aging were all considered as stages of a development continuum relevant to problems of Space Biology. Deliberations thus far have been limited to stages of the development cycle from fertilization to early postnatal life. The deliberations are detailed.

The development of diving in marine endotherms: preparing the skeletal muscles of dolphins, penguins, and seals for activity during submergence.

PubMed

Noren, S R; Williams, T M; Pabst, D A; McLellan, W A; Dearolf, J L

2001-03-01

Myoglobin is an important oxygen store for supporting aerobic diving in endotherms, yet little is known about its role during postnatal development. Therefore, we compared the postnatal development of myoglobin in marine endotherms that develop at sea (cetaceans) to those that develop on land (penguins and pinnipeds). We measured myoglobin concentrations in the major locomotor muscles of mature and immature bottlenose dolphins (Tursiops truncatus) and king penguins (Aptenodytes patagonicus) and compared the data to previously reported values for northern elephant seals (Mirounga angustirostris). Neonatal dolphins, penguins, and seals lack the myoglobin concentrations required for prolonged dive durations, having 10%, 9%, and 31% of adult values, respectively. Myoglobin contents increased significantly during subsequent development. The increases in myoglobin content with age may correspond to increases in activity levels, thermal demands, and time spent in apnea during swimming and diving. Across these phylogenetically diverse taxa (cetaceans, penguins, and pinnipeds), the final stage of postnatal development of myoglobin occurs during the initiation of independent foraging, regardless of whether development takes place at sea or on land.

Expression pattern of Anosmin-1 during pre- and postnatal rat brain development.

PubMed

Clemente, Diego; Esteban, Pedro F; Del Valle, Ignacio; Bribián, Ana; Soussi-Yanicostas, Nadia; Silva, Augusto; De Castro, Fernando

2008-09-01

Anosmin-1 participates in the development of the olfactory and GnRH systems. Defects in this protein are responsible for both the anosmia and the hypogonadotrophic hypogonadism found in Kallmann's syndrome patients. Sporadically, these patients also manifest some neurological symptoms that are not explained in terms of the developmental defects in the olfactory system. We describe the pattern of Anosmin-1 expression in the central nervous system during rat development using a novel antibody raised against Anosmin-1 (Anos1). The areas with Anos1-stained neurons and glial cells were classified into three groups: (1) areas with immunoreactivity from embryonic day 16 to postnatal day (P) 15; (2) areas with Anosmin-1 expression only at postnatal development; (3) nuclei with immunoreactivity only at P15. Our data show that Anos1 immunoreactivity is detected in projecting neurons and interneurons within areas of the brain that may be affected in patients with Kallmann's syndrome that develop both the principal as well as sporadic symptoms.

A post-weaning fish oil dietary intervention reverses adverse metabolic outcomes and 11β-hydroxysteroid dehydrogenase type 1 expression in postnatal overfed rats.

PubMed

Dai, Yanyan; Yang, Fan; Zhou, Nan; Sha, Lijun; Zhou, Shanshan; Wang, Junle; Li, Xiaonan

2016-11-01

Early life is considered a critical period for determining long-term metabolic health. Postnatal over-nutrition may alter glucocorticoid (GC) metabolism and increase the risk of developing obesity and metabolic disorders in adulthood. Our aim was to assess the effects of the dose and timing of a fish oil diet on obesity and the expression of GC-activated enzyme 11β-hydroxysteroid dehydrogenase type 1 (HSD1) in postnatal overfed rats. Litter sizes were adjusted to three (small litter (SL)) or ten (normal litter) rats on postnatal day 3 to induce overfeeding or normal feeding. The SL rats were divided into three groups after weaning: high-dose fish oil (HFO), low-dose fish oil (LFO) and standard-diet groups. After 10 weeks, the HFO diet reduced body weight gain (16 %, P0·05). In conclusion, the post-weaning HFO diet could reverse adverse outcomes and decrease tissue GC activity in postnatal overfed rats.

Identification and characterization of a non-satellite cell muscle resident progenitor during postnatal development.

PubMed

Mitchell, Kathryn J; Pannérec, Alice; Cadot, Bruno; Parlakian, Ara; Besson, Vanessa; Gomes, Edgar R; Marazzi, Giovanna; Sassoon, David A

2010-03-01

Satellite cells are resident myogenic progenitors in postnatal skeletal muscle involved in muscle postnatal growth and adult regenerative capacity. Here, we identify and describe a population of muscle-resident stem cells, which are located in the interstitium, that express the cell stress mediator PW1 but do not express other markers of muscle stem cells such as Pax7. PW1(+)/Pax7(-) interstitial cells (PICs) are myogenic in vitro and efficiently contribute to skeletal muscle regeneration in vivo as well as generating satellite cells and PICs. Whereas Pax7 mutant satellite cells show robust myogenic potential, Pax7 mutant PICs are unable to participate in myogenesis and accumulate during postnatal growth. Furthermore, we found that PICs are not derived from a satellite cell lineage. Taken together, our findings uncover a new and anatomically identifiable population of muscle progenitors and define a key role for Pax7 in a non-satellite cell population during postnatal muscle growth.

Experimental evidence showing that no mitotically active female germline progenitors exist in postnatal mouse ovaries.

PubMed

Zhang, Hua; Zheng, Wenjing; Shen, Yan; Adhikari, Deepak; Ueno, Hiroo; Liu, Kui

2012-07-31

It has been generally accepted for more than half a century that, in most mammalian species, oocytes cannot renew themselves in postnatal or adult life, and that the number of oocytes is already fixed in fetal or neonatal ovaries. This assumption, however, has been challenged over the past decade. In this study, we have taken an endogenous genetic approach to this question and generated a multiple fluorescent Rosa26(rbw/+);Ddx4-Cre germline reporter mouse model for in vivo and in vitro tracing of the development of female germline cell lineage. Through live cell imaging and de novo folliculogenesis experiments, we show that the Ddx4-expressing cells from postnatal mouse ovaries did not enter mitosis, nor did they contribute to oocytes during de novo folliculogenesis. Our results provide evidence that supports the traditional view that no postnatal follicular renewal occurs in mammals, and no mitotically active Ddx4-expressing female germline progenitors exist in postnatal mouse ovaries.

Risk profiles associated with postnatal depressive symptoms among women in a public sector hospital in Mexico: the role of sociodemographic and psychosocial factors.

PubMed

de Castro, Filipa; Place, Jean Marie S; Billings, Deborah L; Rivera, Leonor; Frongillo, Edward A

2015-06-01

This study examined the association between postnatal depressive symptoms and a set of demographic and psychosocial factors among 604 women attending a public hospital for postnatal care in Mexico City. Specific profiles of women that would indicate an increased probability for developing postnatal depression (PND) based on discrete combinations of risk and protective factors were generated. In a logistic model, followed by the estimation of predicted probabilities, we examined the association between depressive symptomatology and psychosocial factors: low social support, unplanned pregnancies, history of depression, and exposure to moderate or severe intimate partner violence (IPV) during pregnancy. Postnatal depressive symptomatology was reported by 10.6 % of the women, as measured by scores at 12 or above on the Edinburgh Postnatal Depression Scale. The cumulative probability of presenting PND in the simultaneous presence of the psychosocial factors was 67.0 %; however, this could be reduced to 5.5 % through preventive measures that work to eliminate low social support, unplanned pregnancy, and exposure to severe IPV during pregnancy. Early identification of psychosocial risk factors, specifically low social support, unplanned pregnancies, history of depression, and exposure to violence during pregnancy, is recommended.

Influences of different dietary energy level on sheep testicular development associated with AMPK/ULK1/autophagy pathway.

PubMed

Pang, Jing; Li, Fengzhe; Feng, Xu; Yang, Hua; Han, Le; Fan, Yixuan; Nie, Haitao; Wang, Zhen; Wang, Feng; Zhang, Yanli

2018-03-01

Energy balance is an important feature for spermatozoa production in the testis. The 5'-AMP-activated protein kinase (AMPK) is a sensor of cell energy, has been implicated as a mediator between gonadal function and energy balance. Herein, we intended to determine the physiological effects of AMPK on testicular development in feed energy restricted and compensated pre-pubertal rams. Lambs had restricted feeding for 2 months and then provided compensatory feeding for another 3 months. Feed levels were 100%(control), 15% and 30% of energy restriction (ER) diets, respectively. The results showed that lambs fed the 30% ER diet had significantly lower testicular weight (P < .05) and spermatids number in the seminiferous tubules, but there were no differences between control and 15% ER groups. Meanwhile, 15% ER and 30% ER diets induced testis autophagy and apoptosis through activating AMPK-ULK1(ULK1, Unc-51 like autophagy activating kinase) signal pathway with characterization of increased Beclin-1 and Light chain 3-Ⅱ/Light chain 3-Ⅰ (LC3-II/LC3-I) ratio, up-regulated the ratio of pro-apoptotic Bcl-2-associated X protein (BAX) and anti-apoptotic B-cell lymphoma 2 (Bcl-2), as well as activated AMPK, phosphorylated AMPK(p-AMPK) and ULK1. Furthermore, a compensation of these parameters occurred when the lambs were re-fed with normal energy requirement after restriction. Taken together, dietary energy levels influence testicular development through autophagy and apoptosis interplay mediated by AMPK-ULK1 signal pathway, which also indicates the important role of the actions of AMPK in the testis homeostasis. Copyright © 2017 Elsevier Inc. All rights reserved.

An Equine Intersex with Unilateral Gonadal Agenesis

PubMed Central

Basrur, P. K.; Kanagawa, H.; Gilman, J. P. W.

1969-01-01

Cytogenetic and histological studies have been carried out on an intersex horse which was clinically diagnosed as a cryptorchid. The horse had the general conformation of a stallion but the external genitalia included a well developed vulva and a penis. The right testis which was descended was devoid of germ cells and the left “gonad” located in the cavum vaginale contained neither testicular nor ovarian tissue. The male duct system on both sides were relatively well developed despite the absence of a testis on the left side. Chromosome analysis on cultured cells from the descended testis revealed the presence of four chromosomally-distinct cell types with XX, XY, XXY and XO sex complements indicating a quadruple mosaicism. The presence of polymorphonuclear neutrophils exhibiting a drumstick, in the hemopoietic tissues and a sex chromatin body in the nucleated cells of buccal mucosa suggest that mosaicism prevails in other somatic tissues of the horse. On the basis of information derived from similar conditions in humans and some domestic animals it would appear that this horse resulted from an XXY zygote. The four cell types noted in the horse probably resulted through mitotic mechanisms favouring the loss of an X and a Y at different stages during embryonic development. The absence of gonad on the left side of this horse might be causally related to the preponderance of XO cell types in the somatic blastema during early gonadal differentiation. ImagesFig. 1.Fig. 2.Fig. 3.Fig. 4.Fig. 5.Fig. 6.Fig. 7.Fig. 8.Fig. 9.Fig. 10.Fig. 11.Fig. 12.Fig. 13.Fig. 14.Fig. 15.Fig. 16.Fig. 17.Fig. 18.Fig. 19. PMID:4391028

Obif, a Transmembrane Protein, Is Required for Bone Mineralization and Spermatogenesis in Mice

PubMed Central

Mizuhashi, Koji; Chaya, Taro; Kanamoto, Takashi; Omori, Yoshihiro; Furukawa, Takahisa

2015-01-01

Background Various kinds of transmembrane and secreted proteins play pivotal roles in development through cell-cell communication. We previously reported that Obif (Osteoblast induction factor, Tmem119), encoding a single transmembrane protein, is expressed in differentiating osteoblasts, and that Obif−/− mice exhibit significantly reduced bone volume in the femur. In the current study, we characterized the Obif protein and further investigated the biological phenotypes of a variety of tissues in Obif−/− mice. Results First, we found that O-glycosylation of the Obif protein occurs at serine residue 36 in the Obif extracellular domain. Next, we observed that Obif−/− mice exhibit bone dysplasia in association with significantly increased osteoid volume per osteoid surface (OV/OS) and osteoid maturation time (Omt), and significantly decreased mineral apposition rate (MAR) and bone formation rate per bone surface (BFR/BS). In addition, we observed that Obif−/− mice show a significant decrease in testis weight as well as in sperm number. By histological analysis, we found that Obif is expressed in spermatocytes and spermatids in the developing testis and that spermatogenesis is halted at the round spermatid stage in the Obif−/− testis that lacks sperm. However, the number of litters fathered by male mice was slightly reduced in Obif−/− mice compared with wild-type mice, although this was not statistically significant. Conclusions Our results, taken together with previous observations, indicate that Obif is a type Ia transmembrane protein whose N-terminal region is O-glycosylated. In addition, we found that Obif is required for normal bone mineralization and late testicular differentiation in vivo. These findings suggest that Obif plays essential roles in the development of multiple tissues. PMID:26207632

Obif, a Transmembrane Protein, Is Required for Bone Mineralization and Spermatogenesis in Mice.

PubMed

Mizuhashi, Koji; Chaya, Taro; Kanamoto, Takashi; Omori, Yoshihiro; Furukawa, Takahisa

2015-01-01

Various kinds of transmembrane and secreted proteins play pivotal roles in development through cell-cell communication. We previously reported that Obif (Osteoblast induction factor, Tmem119), encoding a single transmembrane protein, is expressed in differentiating osteoblasts, and that Obif-/- mice exhibit significantly reduced bone volume in the femur. In the current study, we characterized the Obif protein and further investigated the biological phenotypes of a variety of tissues in Obif-/- mice. First, we found that O-glycosylation of the Obif protein occurs at serine residue 36 in the Obif extracellular domain. Next, we observed that Obif-/- mice exhibit bone dysplasia in association with significantly increased osteoid volume per osteoid surface (OV/OS) and osteoid maturation time (Omt), and significantly decreased mineral apposition rate (MAR) and bone formation rate per bone surface (BFR/BS). In addition, we observed that Obif-/- mice show a significant decrease in testis weight as well as in sperm number. By histological analysis, we found that Obif is expressed in spermatocytes and spermatids in the developing testis and that spermatogenesis is halted at the round spermatid stage in the Obif-/- testis that lacks sperm. However, the number of litters fathered by male mice was slightly reduced in Obif-/- mice compared with wild-type mice, although this was not statistically significant. Our results, taken together with previous observations, indicate that Obif is a type Ia transmembrane protein whose N-terminal region is O-glycosylated. In addition, we found that Obif is required for normal bone mineralization and late testicular differentiation in vivo. These findings suggest that Obif plays essential roles in the development of multiple tissues.

Cell adhesion molecules expression pattern indicates that somatic cells arbitrate gonadal sex of differentiating bipotential fetal mouse gonad.

PubMed

Piprek, Rafal P; Kolasa, Michal; Podkowa, Dagmara; Kloc, Malgorzata; Kubiak, Jacek Z

2017-10-01

Unlike other organ anlagens, the primordial gonad is sexually bipotential in all animals. In mouse, the bipotential gonad differentiates into testis or ovary depending on the genetic sex (XY or XX) of the fetus. During gonad development cells segregate, depending on genetic sex, into distinct compartments: testis cords and interstitium form in XY gonad, and germ cell cysts and stroma in XX gonad. However, our knowledge of mechanisms governing gonadal sex differentiation remains very vague. Because it is known that adhesion molecules (CAMs) play a key role in organogenesis, we suspected that diversified expression of CAMs should also play a crucial role in gonad development. Using microarray analysis we identified 129 CAMs and factors regulating cell adhesion during sexual differentiation of mouse gonad. To identify genes expressed differentially in three cell lines in XY and XX gonads: i) supporting (Sertoli or follicular cells), ii) interstitial or stromal cells, and iii) germ cells, we used transgenic mice expressing EGFP reporter gene and FACS cell sorting. Although a large number of CAMs expressed ubiquitously, expression of certain genes was cell line- and genetic sex-specific. The sets of CAMs differentially expressed in supporting versus interstitial/stromal cells may be responsible for segregation of these two cell lines during gonadal development. There was also a significant difference in CAMs expression pattern between XY supporting (Sertoli) and XX supporting (follicular) cells but not between XY and XX germ cells. This indicates that differential CAMs expression pattern in the somatic cells but not in the germ line arbitrates structural organization of gonadal anlagen into testis or ovary. Copyright © 2017 Elsevier B.V. All rights reserved.

Interleukin 6 inhibits the differentiation of rat stem Leydig cells.

PubMed

Wang, Yiyan; Chen, Lanlan; Xie, Lubin; Li, Linchao; Li, Xiaoheng; Li, Huitao; Liu, Jianpeng; Chen, Xianwu; Mao, Baiping; Song, Tiantian; Lian, Qingquan; Ge, Ren-Shan

2018-09-05

Inflammation causes male hypogonadism. Several inflammatory cytokines, including interleukin 6 (IL-6), are released into the blood and may suppress Leydig cell development. The objective of the present study was to investigate whether IL-6 affected the proliferation and differentiation of rat stem Leydig cells. Leydig cell-depleted rat testis (in vivo) and seminiferous tubules (in vitro) with ethane dimethane sulfonate (EDS) were used to explore the effects of IL-6 on stem Leydig cell development. Intratesticular injection of IL-6 (10 and 100 ng/testis) from post-EDS day 14 to 28 blocked the regeneration of Leydig cells, as shown by the lower serum testosterone levels (21.6% of the control at 100 ng/testis dose), the down-regulated Leydig cell gene (Lhcgr, Star, Cyp11a1, Cyp17a1, and Hsd17b3) expressions, and the reduced Leydig cell number. Stem Leydig cells on the surface of the seminiferous tubules were induced to enter the Leydig cell lineage in vitro in the medium containing luteinizing hormone and lithium. IL-6 (1, 10, and 100 ng/ml) concentration-dependently decreased testosterone production and Lhcgr, Cyp11a1, Cyp17a1, Hsd17b3 and Insl3 mRNA levels. The IL-6 mediated effects were antagonized by Janus kinase 1 (JAK) inhibitor (filgotinib) and Signal Transducers and Activators of Transcription 3 (STAT3) inhibitor (S3I-201), indicating that a JAK-STAT3 signaling pathway is involved. In conclusion, our results demonstrated that IL-6 was an inhibitory factor of stem Leydig cell development. Copyright © 2017. Published by Elsevier B.V.

The Scaffolding Protein, Grb2-associated Binder-1, in Skeletal Muscles and Terminal Schwann Cells Regulates Postnatal Neuromuscular Synapse Maturation

PubMed Central

Park, So Young; Jang, So Young; Shin, Yoon Kyoung; Jung, Dong Keun; Yoon, Byeol A; Kim, Jong Kook; Jo, Young Rae; Lee, Hye Jeong

2017-01-01

The vertebrate neuromuscular junction (NMJ) is considered as a “tripartite synapse” consisting of a motor axon terminal, a muscle endplate, and terminal Schwann cells that envelope the motor axon terminal. The neuregulin 1 (NRG1)-ErbB2 signaling pathway plays an important role in the development of the NMJ. We previously showed that Grb2-associated binder 1 (Gab1), a scaffolding mediator of receptor tyrosine kinase signaling, is required for NRG1-induced peripheral nerve myelination. Here, we determined the role of Gab1 in the development of the NMJ using muscle-specific conditional Gab1 knockout mice. The mutant mice showed delayed postnatal maturation of the NMJ. Furthermore, the selective loss of the gab1 gene in terminal Schwann cells produced delayed synaptic elimination with abnormal morphology of the motor endplate, suggesting that Gab1 in both muscles and terminal Schwann cells is required for proper NMJ development. Gab1 in terminal Schwann cells appeared to regulate the number and process elongation of terminal Schwann cells during synaptic elimination. However, Gab2 knockout mice did not show any defects in the development of the NMJ. Considering the role of Gab1 in postnatal peripheral nerve myelination, our findings suggest that Gab1 is a pleiotropic and important component of NRG1 signals during postnatal development of the peripheral neuromuscular system. PMID:28680299

Oligodendrocytes as Regulators of Neuronal Networks during Early Postnatal Development

PubMed Central

Ramos, Maria; Ikrar, Taruna; Kinoshita, Chisato; De Mei, Claudia; Tirotta, Emanuele; Xu, Xiangmin; Borrelli, Emiliana

2011-01-01

Oligodendrocytes are the glial cells responsible for myelin formation. Myelination occurs during the first postnatal weeks and, in rodents, is completed during the third week after birth. Myelin ensures the fast conduction of the nerve impulse; in the adult, myelin proteins have an inhibitory role on axon growth and regeneration after injury. During brain development, oligodendrocytes precursors originating in multiple locations along the antero-posterior axis actively proliferate and migrate to colonize the whole brain. Whether the initial interactions between oligodendrocytes and neurons might play a functional role before the onset of myelination is still not completely elucidated. In this article, we addressed this question by transgenically targeted ablation of proliferating oligodendrocytes during cerebellum development. Interestingly, we show that depletion of oligodendrocytes at postnatal day 1 (P1) profoundly affects the establishment of cerebellar circuitries. We observed an impressive deregulation in the expression of molecules involved in axon growth, guidance and synaptic plasticity. These effects were accompanied by an outstanding increase of neurofilament staining observed 4 hours after the beginning of the ablation protocol, likely dependent from sprouting of cerebellar fibers. Oligodendrocyte ablation modifies localization and function of ionotropic glutamate receptors in Purkinje neurons. These results show a novel oligodendrocyte function expressed during early postnatal brain development, where these cells participate in the formation of cerebellar circuitries, and influence its development. PMID:21589880

The Scaffolding Protein, Grb2-associated Binder-1, in Skeletal Muscles and Terminal Schwann Cells Regulates Postnatal Neuromuscular Synapse Maturation.

PubMed

Park, So Young; Jang, So Young; Shin, Yoon Kyoung; Jung, Dong Keun; Yoon, Byeol A; Kim, Jong Kook; Jo, Young Rae; Lee, Hye Jeong; Park, Hwan Tae

2017-06-01

The vertebrate neuromuscular junction (NMJ) is considered as a "tripartite synapse" consisting of a motor axon terminal, a muscle endplate, and terminal Schwann cells that envelope the motor axon terminal. The neuregulin 1 (NRG1)-ErbB2 signaling pathway plays an important role in the development of the NMJ. We previously showed that Grb2-associated binder 1 (Gab1), a scaffolding mediator of receptor tyrosine kinase signaling, is required for NRG1-induced peripheral nerve myelination. Here, we determined the role of Gab1 in the development of the NMJ using muscle-specific conditional Gab1 knockout mice. The mutant mice showed delayed postnatal maturation of the NMJ. Furthermore, the selective loss of the gab1 gene in terminal Schwann cells produced delayed synaptic elimination with abnormal morphology of the motor endplate, suggesting that Gab1 in both muscles and terminal Schwann cells is required for proper NMJ development. Gab1 in terminal Schwann cells appeared to regulate the number and process elongation of terminal Schwann cells during synaptic elimination. However, Gab2 knockout mice did not show any defects in the development of the NMJ. Considering the role of Gab1 in postnatal peripheral nerve myelination, our findings suggest that Gab1 is a pleiotropic and important component of NRG1 signals during postnatal development of the peripheral neuromuscular system.

Virtual voices: social support and stigma in postnatal mental illness Internet forums.

PubMed

Moore, Donna; Ayers, Susan

2017-06-01

Many women with postnatal mental illness do not get the treatment they need and this is often because stigma prevents disclosure. The purpose of this study was to explore online social support for postnatal mental illness, how women experience stigma and potential disadvantages of using Internet forums. Interviews were conducted with fifteen participants who had suffered postnatal mental illness and had used forums. Systematic thematic analysis identified common themes in relation to social support, stigma and disadvantages of using forums. Most women felt they benefited from visiting forums by developing a shared understanding and discourse about their illness. Findings suggest future research should investigate if women benefit from using online social support provided by forums, if use challenges stigma and further explore potential concerns about using forums.