Normal pelvic ultrasound or MRI does not rule out neoplasm in patients with gonadal dysgenesis and Y chromosome material.

PubMed

Ebert, Kristin M; Hewitt, Geri D; Indyk, Justin A; McCracken, Katherine A; Nahata, Leena; Jayanthi, Venkata R

2018-04-01

Patients with gonadal dysgenesis (GD) with a Y chromosome have an increased risk of gonadal neoplasm. Few data exist on the ability of imaging to detect malignancy in intra-abdominal gonads in these patients. We aimed to determine the correlation between preoperative imaging findings and gonadal pathology in GD patients with Y chromosome material. A retrospective review was performed of patients with XY or XO/XY GD who underwent gonadectomy at our institution from 2003 to 2017. Patients were assessed preoperatively with ultrasonography; some additionally underwent MRI. The series consisted of 10 patients, all with female gender and non-palpable gonads. Median age was 13.1 years (range 2.4-18.3 years). Overall, four of the ten patients (40%) had a tumor (gonadoblastoma or dysgerminoma) on final pathology. Four patients had a gonad or gonads that were definitively seen on ultrasonography. All visualized gonads were described as "normal" or "small" with the exception of one patient, who had a normal MRI. Three of the four patients in this group had a tumor on final pathology. The remaining six patients had a gonad or gonads that were not definitively visualized on ultrasound; one patient in this group had a tumor on final pathology. Overall, five of seven gonads (71%) definitively visualized on ultrasound had tumor on final pathology, and two of thirteen gonads (15%) not visualized on ultrasound had tumor on final pathology; this difference was statistically significant (p = 0.012). Three patients were imaged with MRI. Of the gonads that could be visualized on MRI, no definitive abnormalities were seen. All patients imaged with MRI had tumors on final pathology. Both ultrasound and MRI are relatively poor at identifying and characterizing intra-abdominal gonads in GD patients. The majority of patients who had a neoplasm had normal imaging findings. Gonads that were definitively visualized on ultrasound were more likely to contain neoplasms that could not be

Gender identity and gender of rearing in 46 XY disorders of sexual development

PubMed Central

Gangaher, Arushi; Chauhan, Vasundhera; Jyotsna, Viveka P.; Mehta, Manju

2016-01-01

Background: Disorders of sexual development (DSD) may pose a challenge to live as a fully-functioning male or female. In this study, we prospectively assessed eleven 46 XY DSD patients who were being treated at our center over the last 8 months for gender dysphoria. Materials and Methods: To determine gender dysphoria, age-appropriate gender identity (GI) questionnaires were used. For patients, 12 years and below, parent report GI questionnaire for children was used and for those above 12 years of age, GI/gender dysphoria questionnaire for adolescents and adults was administered. Results: Of 11 patients with 46 XY DSD, three were diagnosed with 5 alpha reductase deficiency (5aRD), two with partial gonadal dysgenesis, three with partial androgen insensitivity syndrome, one each with ovotesticular, complete gonadal dysgenesis, and complete androgen insensitivity. Gender assigned at birth was female in eight and male in three patients. Among the eight reared as female, gender had been reassigned as male in three patients well before the present study was conducted. None of the eleven patients had gender dysphoria at the time of this study. Conclusion: Early gender of rearing was seen to be a critical indicator of present GI in our patients except in cases of 5aRD. PMID:27366722

FGFR2 mutation in 46,XY sex reversal with craniosynostosis

PubMed Central

Bagheri-Fam, Stefan; Ono, Makoto; Li, Li; Zhao, Liang; Ryan, Janelle; Lai, Raymond; Katsura, Yukako; Rossello, Fernando J.; Koopman, Peter; Scherer, Gerd; Bartsch, Oliver; Eswarakumar, Jacob V.P.; Harley, Vincent R.

2015-01-01

Patients with 46,XY gonadal dysgenesis (GD) exhibit genital anomalies, which range from hypospadias to complete male-to-female sex reversal. However, a molecular diagnosis is made in only 30% of cases. Heterozygous mutations in the human FGFR2 gene cause various craniosynostosis syndromes including Crouzon and Pfeiffer, but testicular defects were not reported. Here, we describe a patient whose features we would suggest represent a new FGFR2-related syndrome, craniosynostosis with XY male-to-female sex reversal or CSR. The craniosynostosis patient was chromosomally XY, but presented as a phenotypic female due to complete GD. DNA sequencing identified the FGFR2c heterozygous missense mutation, c.1025G>C (p.Cys342Ser). Substitution of Cys342 by Ser or other amino acids (Arg/Phe/Try/Tyr) has been previously reported in Crouzon and Pfeiffer syndrome. We show that the ‘knock-in’ Crouzon mouse model Fgfr2cC342Y/C342Y carrying a Cys342Tyr substitution displays XY gonadal sex reversal with variable expressivity. We also show that despite FGFR2c-Cys342Tyr being widely considered a gain-of-function mutation, Cys342Tyr substitution in the gonad leads to loss of function, as demonstrated by sex reversal in Fgfr2cC342Y/− mice carrying the knock-in allele on a null background. The rarity of our patient suggests the influence of modifier genes which exacerbated the testicular phenotype. Indeed, patient whole exome analysis revealed several potential modifiers expressed in Sertoli cells at the time of testis determination in mice. In summary, this study identifies the first FGFR2 mutation in a 46,XY GD patient. We conclude that, in certain rare genetic contexts, maintaining normal levels of FGFR2 signaling is important for human testis determination. PMID:26362256

Clinical features and management of 33 patients with 46,XX pure gonadal dysgenesis.

PubMed

Huang, He; Wang, Chun-Qing; Tian, Qin-Jie

2016-12-01

The objective of the study is to summarize the clinical characteristics of 33 patients' cohort (46,XX pure gonadal dysgenesis, 46,XX PGD), discuss the management, and propose treatment suggestions. Patients' information, medical history, and medical records were obtained. All patients were closely followed up. At the time of diagnosis, the patients presented 19.53 ± 3.60 years old, 165 ± 6.49 cm height, breast development of Tanner stage I, and infantile female genitalia. High level of follicle-stimulating hormone (87.41 ± 21.50 mIU/mL) and LH (27.10 ± 8.47 mIU/mL) and low level of E2 (8.85 ± 6.13 pg/mL) were observed. Individualized hormone replacement therapy (HRT) was initiated after diagnosis. After 2 years of treatment, all patients had obvious breast development; the uterus showed (2.38 ± 0.60) × (1.38 ± 0.70) × (1.38 ± 0.55) cm growth. The incidence of osteopenia changed from 69.70% to 22.22% and that of osteoporosis changed from 18.18% to 0. Dysgeminoma was found in one patient. We concluded that gonadal dysgenesis in 46,XX PGD causes secondary sexual characteristic absence, tendency of taller, osteoporosis, infertility, and sexual health problems. There is minor chance of tumor occurrence for the patients. Optimal care including HRT and close follow-up are required.

The genetics of XX gonadal dysgenesis

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

Aittomaeki, K.

1994-05-01

In a nationwide population-based study of women born between 1950 and 1976, 75 patients with XX gonadal dysgenesis (XXGD) were identified in Finland. Patients were ascertained through hospital records and the registers of chromosome laboratories. In one family 4 daughters were affected; in six families 2 daughters were affected; and 57 cases were isolated. In one additional family the two affected females were in successive generations. Population records were utilized to trace ancestors of patients back to the beginning of the 19th century, in most cases. Consanguinity was detected in 8 (12%) of 66 families. When females only are considered,more » the segregation analyses yield a proportion of .23 affected. The relatively large number of affected individuals identified (incidence 1 in 8,300 live-born girls) implies a high gene frequency in the Finnish population. The geographic distribution was highly uneven, with most families originating in the sparsely populated north-central part of Finland. These findings support the existence of an autosomal recessive (XXGD) gene (locus designation [open quotes]ODG1[close quotes]) that is highly enriched in Finland. The multiplex families already identified will make it possible to map the ODG1 gene by a random search for linkage by using polymorphic markers. Linkage-disequilibrium analysis in the sporadic patients will then be used to test for genetic homogeneity versus heterogeneity. 27 refs., 3 figs.« less

A mutation in the nucleoporin-107 gene causes XX gonadal dysgenesis.

PubMed

Weinberg-Shukron, Ariella; Renbaum, Paul; Kalifa, Rachel; Zeligson, Sharon; Ben-Neriah, Ziva; Dreifuss, Amatzia; Abu-Rayyan, Amal; Maatuk, Noa; Fardian, Nilly; Rekler, Dina; Kanaan, Moien; Samson, Abraham O; Levy-Lahad, Ephrat; Gerlitz, Offer; Zangen, David

2015-11-02

Ovarian development and maintenance are poorly understood; however, diseases that affect these processes can offer insights into the underlying mechanisms. XX female gonadal dysgenesis (XX-GD) is a rare, genetically heterogeneous disorder that is characterized by underdeveloped, dysfunctional ovaries, with subsequent lack of spontaneous pubertal development, primary amenorrhea, uterine hypoplasia, and hypergonadotropic hypogonadism. Here, we report an extended consanguineous family of Palestinian origin, in which 4 females exhibited XX-GD. Using homozygosity mapping and whole-exome sequencing, we identified a recessive missense mutation in nucleoporin-107 (NUP107, c.1339G>A, p.D447N). This mutation segregated with the XX-GD phenotype and was not present in available databases or in 150 healthy ethnically matched controls. NUP107 is a component of the nuclear pore complex, and the NUP107-associated protein SEH1 is required for oogenesis in Drosophila. In Drosophila, Nup107 knockdown in somatic gonadal cells resulted in female sterility, whereas males were fully fertile. Transgenic rescue of Drosophila females bearing the Nup107D364N mutation, which corresponds to the human NUP107 (p.D447N), resulted in almost complete sterility, with a marked reduction in progeny, morphologically aberrant eggshells, and disintegrating egg chambers, indicating defective oogenesis. These results indicate a pivotal role for NUP107 in ovarian development and suggest that nucleoporin defects may play a role in milder and more common conditions such as premature ovarian failure.

Unexpected diagnosis of stage IIA dysgerminoma in streak gonad in a patient with Swyer syndrome: a case report.

PubMed

Yada-Hashimoto, Namiko; Komura, Hiroko; Nagata, Shigenori; Kubo, Chiaki; Fujita, Masami; Kamiura, Shoji

2018-06-01

Patients with Swyer syndrome, which is also known as 46,XY pure gonadal dysgenesis, are at an increased risk of gonadoblastoma and germ cell tumor. Prophylactic gonadectomy is recommended for these patients. We report a case of stage IIA dysgerminoma arising in a streak gonad in a patient with Swyer syndrome, which was not diagnosable preoperatively and intraoperatively. The patient was primarily amenorrheic and identified as female phenotypically. She underwent gonadectomy at 27 years of age. Preoperative image analysis showed a relatively small uterus without adnexal masses. Laparoscopic findings showed bilateral streak gonads. Postoperatively, histopathological examination revealed that the patient had dysgerminoma in her left streak gonad. Preoperative and intraoperative diagnosis of dysgerminoma in normal size ovaries is thought to be difficult. Although it is rare, considering the occurrence of dysgerminoma in streak gonad with extension to the mesosalpinx, prompt prophylactic gonadectomy is strongly recommended for these patients regardless of the size of the ovaries.

Rare successful pregnancy in a patient with Swyer Syndrome.

PubMed

Taneja, Jyoti; Ogutu, David; Ah-Moye, Michael

2016-10-01

To report a rare successful pregnancy after fertility treatment in a patient with Swyer syndrome. Case report. Herts & Essex Fertility Centre, Cheshunt, UK. A 36-year-old patient with 46, XY gonadal dysgenesis. 31 year old husband with normal sperm analysis. Chromosomal analysis, Saline infusion sonography, Pipelle endometrial scratch, ICSI using donor eggs, Embryo Transfer, and Caesarean delivery. Successful pregnancy and live birth. Successful treatment with donor eggs, pregnancy, and delivery. A patient with 46, XY gonadal dysgenesis in a specially tailored fertility program, can maintain a normal pregnancy and delivery.

The Distribution and Cellular Lineages of XX and XY Cells in Gonads Associated with Ovotesticular Disorder of Sexual Development.

PubMed

Nishina-Uchida, Noriko; Fukuzawa, Ryuji; Ishii, Tomohiro; Anaka, Matthew R; Hasegawa, Tomonobu; Hasegawa, Yukihiro

2016-01-01

Individuals with a 46,XX/46,XY karyotype are categorized as ovotesticular disorder of sexual development (ODSD) and have gonads with either an ovary on one side and a testis on the other side or a mixed ovotestis. To examine the distribution of 46,XX and 46,XY cells in gonads of 3 patients with ODSD, FISH for X and Y chromosomes and immunohistochemistry for SOX9 and FOXL2 were carried out. FISH analysis showed that XX signals were present in Sertoli cells in the seminiferous tubules, while cells containing Y signals were seen in epithelia of ovarian follicles. The immunolabeling of SOX9 and FOXL2 in the seminiferous tubules and ovarian follicles was mutually exclusive, irrespective of the presence of reversed sex chromosomes. We therefore suggest that the fate of individual gonadal epithelial cells is determined not only by the sex chromosomes but also by local environmental factors. © 2016 S. Karger AG, Basel.

Insulin and IGF1 Receptors Are Essential for XX and XY Gonadal Differentiation and Adrenal Development in Mice

PubMed Central

Romero, Yannick; Conne, Béatrice; Truong, Vy; Papaioannou, Marilena D.; Schaad, Olivier; Docquier, Mylène; Herrera, Pedro Luis; Wilhelm, Dagmar; Nef, Serge

2013-01-01

Mouse sex determination provides an attractive model to study how regulatory genetic networks and signaling pathways control cell specification and cell fate decisions. This study characterizes in detail the essential role played by the insulin receptor (INSR) and the IGF type I receptor (IGF1R) in adrenogenital development and primary sex determination. Constitutive ablation of insulin/IGF signaling pathway led to reduced proliferation rate of somatic progenitor cells in both XX and XY gonads prior to sex determination together with the downregulation of hundreds of genes associated with the adrenal, testicular, and ovarian genetic programs. These findings indicate that prior to sex determination somatic progenitors in Insr;Igf1r mutant gonads are not lineage primed and thus incapable of upregulating/repressing the male and female genetic programs required for cell fate restriction. In consequence, embryos lacking functional insulin/IGF signaling exhibit (i) complete agenesis of the adrenal cortex, (ii) embryonic XY gonadal sex reversal, with a delay of Sry upregulation and the subsequent failure of the testicular genetic program, and (iii) a delay in ovarian differentiation so that Insr;Igf1r mutant gonads, irrespective of genetic sex, remained in an extended undifferentiated state, before the ovarian differentiation program ultimately is initiated at around E16.5. PMID:23300479

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

Deletions of 9p and the quest for a conserved mechanism of sex determination.

PubMed

Ottolenghi, C; McElreavey, K

2000-01-01

Distal chromosome 9p contains a locus that, when deleted, is a cause of 46,XY gonadal dysgenesis in the absence of extragenital anomalies. This locus might account for the frequently observed cases of 46,XY pure gonadal dysgenesis who do not harbor mutations in SRY, the sex master regulator gene found in mammalian species. The genomic organization of 9p positional candidate genes is currently being studied and mutational screens are ongoing. Among other positional candidates, including two additional doublesex-related genes, the evidence to support a role for the gene DMRT1 in vertebrate male sexual development is accumulating. Although formal proof of the requirement of DMRT1 in gonadal sex fate choice has not been obtained so far, the particular interest in this gene and perhaps other doublesex-related genes identified in vertebrates lies in that they may provide an entry point to a conserved mechanism of sex determination across animal phyla. We discuss recent results and emerging views on the genetics of sex determination, while stressing that the majority of cases of 46,XY gonadal dysgenesis remain unexplained. The latter is likely to be efficiently addressed by positional cloning efforts, particularly by considering the wealth of sequence data provided by the Human Genome Project. Copyright 2000 Academic Press.

Repression of P Element-Mediated Hybrid Dysgenesis in Drosophila Melanogaster

PubMed Central

Simmons, M. J.; Raymond, J. D.; Rasmusson, K. E.; Miller, L. M.; McLarnon, C. F.; Zunt, J. R.

1990-01-01

Inbred lines derived from a strain called Sexi were analyzed for their abilities to repress P element-mediated gonadal dysgenesis. One line had high repression ability, four had intermediate ability and two had very low ability. The four intermediate lines also exhibited considerable within-line variation for this trait; furthermore, in at least two cases, this variation could not be attributed to recurring P element movement. Repression of gonadal dysgenesis in the hybrid offspring of all seven lines was due primarily to a maternal effect; there was no evidence for repression arising de novo in the hybrids themselves. In one of the lines, repression ability was inherited maternally, indicating the involvement of cytoplasmic factors. In three other lines, repression ability appeared to be determined by partially dominant or additive chromosomal factors; however, there was also evidence for a maternal effect that reduced the expression of these factors in at least two of the lines. In another line, repression ability seemed to be due to recessive chromosomal factors. All seven lines possessed numerous copies of a particular P element, called KP, which has been hypothesized to produce a polypeptide repressor of gonadal dysgenesis. This hypothesis, however, does not explain why the inbred Sexi lines varied so much in their repression abilities. It is suggested that some of this variation may be due to differences in the chromosomal position of the KP elements, or that other nonautonomous P elements are involved in the repression of hybrid dysgenesis in these lines. PMID:2155854

Human Sex Determination at the Edge of Ambiguity: INHERITED XY SEX REVERSAL DUE TO ENHANCED UBIQUITINATION AND PROTEASOMAL DEGRADATION OF A MASTER TRANSCRIPTION FACTOR.

PubMed

Racca, Joseph D; Chen, Yen-Shan; Yang, Yanwu; Phillips, Nelson B; Weiss, Michael A

2016-10-14

A general problem is posed by analysis of transcriptional thresholds governing cell fate decisions in metazoan development. A model is provided by testis determination in therian mammals. Its key step, Sertoli cell differentiation in the embryonic gonadal ridge, is initiated by SRY, a Y-encoded architectural transcription factor. Mutations in human SRY cause gonadal dysgenesis leading to XY female development (Swyer syndrome). Here, we have characterized an inherited mutation compatible with either male or female somatic phenotypes as observed in an XY father and XY daughter, respectively. The mutation (a crevice-forming substitution at a conserved back surface of the SRY high mobility group box) markedly destabilizes the domain but preserves specific DNA affinity and induced DNA bend angle. On transient transfection of diverse human and rodent cell lines, the variant SRY exhibited accelerated proteasomal degradation (relative to wild type) associated with increased ubiquitination; in vitro susceptibility to ubiquitin-independent ("default") cleavage by the 20S core proteasome was unchanged. The variant's gene regulatory activity (as assessed in a cellular model of the rat embryonic XY gonadal ridge) was reduced by 2-fold relative to wild-type SRY at similar levels of mRNA expression. Chemical proteasome inhibition restored native-like SRY expression and transcriptional activity in association with restored occupancy of a sex-specific enhancer element in principal downstream gene Sox9, demonstrating that the variant SRY exhibits essentially native activity on a per molecule basis. Our findings define a novel mechanism of impaired organogenesis, accelerated ubiquitin-directed proteasomal degradation of a master transcription factor leading to a developmental decision poised at the edge of ambiguity. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

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.

Screening and Familial Characterization of Copy-Number Variations in NR5A1 in 46,XY Disorders of Sex Development and Premature Ovarian Failure

PubMed Central

Harrison, Steven M.; Campbell, Ian M.; Keays, Melise; Granberg, Candace F.; Villanueva, Carlos; Tannin, Grace; Zinn, Andrew R.; Castrillon, Diego H.; Shaw, Chad A.; Stankiewicz, Paweł; Baker, Linda A.

2013-01-01

The NR5A1 gene encodes for steroidogenic factor 1, a nuclear receptor that regulates proper adrenal and gonadal development and function. Mutations identified by NR5A1 sequencing have been associated with disorders of sex development (DSD), ranging from sex reversal to severe hypospadias in 46,XY patients and premature ovarian failure (POF) in 46,XX patients. Previous reports have identified four families with a history of both 46,XY DSD and 46,XX POF carrying segregating NR5A1 sequence mutations. Recently, three 46,XY DSD sporadic cases with NR5A1 microdeletions have been reported. Here, we identify the first NR5A1 microdeletion transmitted in a pedigree with both 46,XY DSD and 46,XX POF. A 46,XY individual with DSD due to gonadal dysgenesis was born to a young mother who developed POF. Array CGH analysis revealed a maternally inherited 0.23 Mb microdeletion of chromosome 9q33.3, including the NR5A1 gene. Based on this finding, we screened patients with unexplained 46,XY DSD (n=11), proximal hypospadias (n=21) and 46,XX POF (n=36) for possible NR5A1 copy-number variations (CNVs) via multiplex ligation-dependent probe amplification (MLPA), but did not identify any additional CNVs involving NR5A1. These data suggest that NR5A1 CNVs are an infrequent cause of these disorders but that array CGH and MLPA are useful genomic screening tools to uncover the genetic basis of such unexplained cases. This case is the first report of a familial NR5A1 CNV transmitting in a pedigree, causing both the male and female phenotypes associated with NR5A1 mutations, and the first report of a NR5A1 CNV associated with POF. PMID:23918653

Characterization of Gonadal Transcriptomes from Nile Tilapia (Oreochromis niloticus) Reveals Differentially Expressed Genes

PubMed Central

Sun, Yunlv; Yang, Shijie; Li, Minghui; Zeng, Sheng; Huang, Baofeng; Wang, Deshou

2013-01-01

Four pairs of XX and XY gonads from Nile tilapia were sequenced at four developmental stages, 5, 30, 90, and 180 days after hatching (dah) using Illumina HiseqTM technology. This produced 28 Gb sequences, which were mapped to 21,334 genes. Of these, 259 genes were found to be specifically expressed in XY gonads, and 69 were found to be specific to XX gonads. Totally, 187 XX- and 1,358 XY-enhanced genes were identified, and 2,978 genes were found to be co-expressed in XX and XY gonads. Almost all steroidogenic enzymes, including cyp19a1a, were up-regulated in XX gonads at 5 dah; but in XY gonads these enzymes, including cyp11b2, were significantly up-regulated at 90 dah, indicating that, at a time critical to sex determination, the XX fish produced estrogen and the XY fish did not produce androgens. The most pronounced expression of steroidogenic enzyme genes was observed at 30 and 90 dah for XX and XY gonads, corresponding to the initiation of germ cell meiosis in the female and male gonads, respectively. Both estrogen and androgen receptors were found to be expressed in XX gonads, but only estrogen receptors were expressed in XY gonads at 5 dah. This could explain why exogenous steroid treatment induced XX and XY sex reversal. The XX-enhanced expression of cyp19a1a and cyp19a1b at all stages suggests an important role for estrogen in female sex determination and maintenance of phenotypic sex. This work is the largest collection of gonadal transcriptome data in tilapia and lays the foundation for future studies into the molecular mechanisms of sex determination and maintenance of phenotypic sex in non-model teleosts. PMID:23658843

Increased HDL cholesterol levels in mice with XX versus XY sex chromosomes

PubMed Central

Link, Jenny C.; Chen, Xuqi; Prien, Christopher; Borja, Mark S.; Hammerson, Bradley; Oda, Michael N.; Arnold, Arthur P.; Reue, Karen

2015-01-01

Objective The molecular mechanisms underlying sex differences in dyslipidemia are poorly understood. We aimed to distinguish genetic and hormonal regulators of sex differences in plasma lipid levels. Approach and Results We assessed the role of gonadal hormones and sex chromosome complement on lipid levels using the Four Core Genotypes mouse model (XX females, XX males, XY females, and XY males). In gonadally intact mice fed a chow diet, lipid levels were influenced by both male–female gonadal sex and XX–XY chromosome complement. Gonadectomy of adult mice revealed that the male–female differences are dependent on acute effects of gonadal hormones. In both intact and gonadectomized animals, XX mice had higher HDL cholesterol (HDL-C) levels than XY mice, regardless of male–female sex. Feeding a cholesterol-enriched diet produced distinct patterns of sex differences in lipid levels compared to a chow diet, revealing the interaction of gonadal and chromosomal sex with diet. Notably, under all dietary and gonadal conditions, HDL-C levels were higher in mice with two X chromosomes compared to mice with an X and Y chromosome. By generating mice with XX, XY and XXY chromosome complements, we determined that the presence of two X chromosomes, and not the absence of the Y chromosome, influences HDL-C concentration. Conclusions We demonstrate that having two X chromosomes versus an X and Y chromosome complement drives sex differences in HDL-C. It is conceivable that increased expression of genes escaping X-inactivation in XX mice regulates downstream processes to establish sexual dimorphism in plasma lipid levels. PMID:26112012

Sterility and hypermutability in the P-M system of hybrid dysgenesis in Drosophila melanogaster.

PubMed

Kocur, G J; Drier, E A; Simmons, M J

1986-12-01

Inbred wild strains of Drosophila melanogaster derived from the central and eastern United States were used to make dysgenic hybrids in the P-M system. These strains possessed P elements and the P cytotype, the condition that represses P element transposition. Their hybrids were studied for the mutability of the P element insertion mutation, snw, and for the incidence of gonadal dysgenesis (GD) sterility. All the strains tested were able to induce hybrid dysgenesis by one or both of these assays; however, high levels of dysgenesis were rare. Sets of X chromosomes and autosomes from the inbred wild strains were more effective at inducing GD sterility than were sets of Y chromosomes and autosomes. In two separate analyses, GD sterility was positively correlated with snw mutability, suggesting a linear relationship. However, one strain appeared to induce too much GD sterility for its level of snw destabilization, indicating an uncoupling of these two manifestations of hybrid dysgenesis.

Sterility and Hypermutability in the P-M System of Hybrid Dysgenesis in DROSOPHILA MELANOGASTER

PubMed Central

Kocur, Gordon J.; Drier, Eric A.; Simmons, Michael J.

1986-01-01

Inbred wild strains of Drosophila melanogaster derived from the central and eastern United States were used to make dysgenic hybrids in the P-M system. These strains possessed P elements and the P cytotype, the condition that represses P element transposition. Their hybrids were studied for the mutability of the P element insertion mutation, snw, and for the incidence of gonadal dysgenesis (GD) sterility. All the strains tested were able to induce hybrid dysgenesis by one or both of these assays; however, high levels of dysgenesis were rare. Sets of X chromosomes and autosomes from the inbred wild strains were more effective at inducing GD sterility than were sets of Y chromosomes and autosomes. In two separate analyses, GD sterility was positively correlated with snw mutability, suggesting a linear relationship. However, one strain appeared to induce too much GD sterility for its level of snw destabilization, indicating an uncoupling of these two manifestations of hybrid dysgenesis. PMID:3100389

Increased high-density lipoprotein cholesterol levels in mice with XX versus XY sex chromosomes.

PubMed

Link, Jenny C; Chen, Xuqi; Prien, Christopher; Borja, Mark S; Hammerson, Bradley; Oda, Michael N; Arnold, Arthur P; Reue, Karen

2015-08-01

The molecular mechanisms underlying sex differences in dyslipidemia are poorly understood. We aimed to distinguish genetic and hormonal regulators of sex differences in plasma lipid levels. We assessed the role of gonadal hormones and sex chromosome complement on lipid levels using the four core genotypes mouse model (XX females, XX males, XY females, and XY males). In gonadally intact mice fed a chow diet, lipid levels were influenced by both male-female gonadal sex and XX-XY chromosome complement. Gonadectomy of adult mice revealed that the male-female differences are dependent on acute effects of gonadal hormones. In both intact and gonadectomized animals, XX mice had higher HDL cholesterol (HDL-C) levels than XY mice, regardless of male-female sex. Feeding a cholesterol-enriched diet produced distinct patterns of sex differences in lipid levels compared with a chow diet, revealing the interaction of gonadal and chromosomal sex with diet. Notably, under all dietary and gonadal conditions, HDL-C levels were higher in mice with 2 X chromosomes compared with mice with an X and Y chromosome. By generating mice with XX, XY, and XXY chromosome complements, we determined that the presence of 2 X chromosomes, and not the absence of the Y chromosome, influences HDL-C concentration. We demonstrate that having 2 X chromosomes versus an X and Y chromosome complement drives sex differences in HDL-C. It is conceivable that increased expression of genes escaping X-inactivation in XX mice regulates downstream processes to establish sexual dimorphism in plasma lipid levels. © 2015 American Heart Association, Inc.

GATA4 Variants in Individuals With a 46,XY Disorder of Sex Development (DSD) May or May Not Be Associated With Cardiac Defects Depending on Second Hits in Other DSD Genes.

PubMed

Martinez de LaPiscina, Idoia; de Mingo, Carmen; Riedl, Stefan; Rodriguez, Amaia; Pandey, Amit V; Fernández-Cancio, Mónica; Camats, Nuria; Sinclair, Andrew; Castaño, Luis; Audi, Laura; Flück, Christa E

2018-01-01

Disorders of sex development (DSD) consist of a wide range of conditions involving numerous genes. Nevertheless, about half of 46,XY individuals remain genetically unsolved. GATA4 gene variants, mainly related to congenital heart defects (CHD), have also been recently associated with 46,XY DSD. In this study, we characterized three individuals presenting with 46,XY DSD with or without CHD and GATA4 variants in order to understand the phenotypical variability. We studied one patient presenting CHD and 46,XY gonadal dysgenesis, and two patients with a history of genetically unsolved 46,XY DSD, also known as male primary hypogonadism. Mutation analysis was carried out by candidate gene approach or targeted gene panel sequencing. Functional activity of GATA4 variants was tested in vitro on the CYP17 promoter involved in sex development using JEG3 cells. We found two novel and one previously described GATA4 variants located in the N-terminal zinc finger domain of the protein. Cys238Arg variant lost transcriptional activity on the CYP17 promoter reporter, while Trp228Cys and Pro226Leu behaved similar to wild type. These results were in line with bioinformatics simulation studies. Additional DSD variations, in the LRP4 and LHCGR genes, respectively, were identified in the two 46,XY individuals without CHD. Overall, our study shows that human GATA4 mutations identified in patients with 46,XY DSD may or may not be associated with CHD. Possible explanations for phenotypical variability may comprise incomplete penetrance, variable sensitivity of partner genes, and oligogenic mechanisms.

GATA4 Variants in Individuals With a 46,XY Disorder of Sex Development (DSD) May or May Not Be Associated With Cardiac Defects Depending on Second Hits in Other DSD Genes

PubMed Central

Martinez de LaPiscina, Idoia; de Mingo, Carmen; Riedl, Stefan; Rodriguez, Amaia; Pandey, Amit V.; Fernández-Cancio, Mónica; Camats, Nuria; Sinclair, Andrew; Castaño, Luis; Audi, Laura; Flück, Christa E.

2018-01-01

Disorders of sex development (DSD) consist of a wide range of conditions involving numerous genes. Nevertheless, about half of 46,XY individuals remain genetically unsolved. GATA4 gene variants, mainly related to congenital heart defects (CHD), have also been recently associated with 46,XY DSD. In this study, we characterized three individuals presenting with 46,XY DSD with or without CHD and GATA4 variants in order to understand the phenotypical variability. We studied one patient presenting CHD and 46,XY gonadal dysgenesis, and two patients with a history of genetically unsolved 46,XY DSD, also known as male primary hypogonadism. Mutation analysis was carried out by candidate gene approach or targeted gene panel sequencing. Functional activity of GATA4 variants was tested in vitro on the CYP17 promoter involved in sex development using JEG3 cells. We found two novel and one previously described GATA4 variants located in the N-terminal zinc finger domain of the protein. Cys238Arg variant lost transcriptional activity on the CYP17 promoter reporter, while Trp228Cys and Pro226Leu behaved similar to wild type. These results were in line with bioinformatics simulation studies. Additional DSD variations, in the LRP4 and LHCGR genes, respectively, were identified in the two 46,XY individuals without CHD. Overall, our study shows that human GATA4 mutations identified in patients with 46,XY DSD may or may not be associated with CHD. Possible explanations for phenotypical variability may comprise incomplete penetrance, variable sensitivity of partner genes, and oligogenic mechanisms. PMID:29670578

A novel morphological approach to gonads in disorders of sex development.

PubMed

Lepais, Laureline; Morel, Yves; Mouriquand, Pierre; Gorduza, Daniela; Plotton, Ingrid; Collardeau-Frachon, Sophie; Dijoud, Frédérique

2016-11-01

Disorders of sex development are defined as congenital conditions with discordance between the phenotype, the genotype, the karyotype, and the hormonal profile. The disorders of sex development consensus classification established in 2005 are mainly based on chromosomal and biological data. However, histological anomalies are not considered. The aims of this study were to define the specific pathological features of gonads in various groups of disorders of sex development in order to clarify the nosology of histological findings and to evaluate the tumor risk in case of a conservative approach. One hundred and seventy-five samples from 86 patients with disorders of sex development were analyzed following a strict histological reading protocol. The term 'gonadal dysgenesis' for the histological analysis was found confusing and therefore excluded. The concept of 'dysplasia' was subsequently introduced in order to describe the architectural disorganization of the gonad (various degrees of irregular seminiferous tubules, thin albuginea, fibrous interstitium). Five histological types were identified: normal gonad, hypoplastic testis, dysplastic testis, streak gonad, and ovotestis. The analysis showed an association between undifferentiated gonadal tissue, a potential precursor of gonadoblastoma, and dysplasia. Dysplasia and undifferentiated gonadal tissue were only encountered in cases of genetic or chromosomal abnormality ('dysgenesis' groups in the disorders of sex development consensus classification). 'Dysgenetic testes', related to an embryonic malformation of the gonad, have variable histological presentations, from normal to streak. Conversely, gonads associated with hormonal deficiencies always display a normal architecture. A loss of expression of AMH and α-inhibin was identified in dysplastic areas. Foci of abnormal expression of the CD117 and OCT4 immature germ cells markers in dysplasia and undifferentiated gonadal tissue were associated with an increased

A practical guide for evaluating gonadal germ cell tumor predisposition in differences of sex development.

PubMed

Pyle, Louise C; Nathanson, Katherine L

2017-06-01

Differences of Sex Development (DSD) includes a wide spectrum of etiologies and phenotypes. A subset of individuals with DSDs are predisposed to gonadal germ cell tumor (GCT). In this setting, GCT risk varies widely, depending on the DSD molecular etiology and penetrance. Prognostication based on molecular diagnosis remains challenging, as natural history data specific to recently identified molecular causes of DSD is lacking. In this review, we provide a framework for the clinical geneticist to consider GCT tumor risk in the patient with DSD. We discuss germ cell development and etiology of GCT growth, along with parameters to consider when recommending prophylactic gonadectomy including fertility, hormonal output, and malignant GTC treatment outcomes. Shortly after the 2006 reorganization of DSD nomenclature, literature reviews of natural history publications stratified GCT risk by a chromosomal, pathological, and hormonal taxonomy. Our 2017 literature review reveals a larger body of publications. However, the broad DSD GCT risk stratification within the 2006 taxonomy remains stable. We discuss precise GCT risk assessment for specific diagnoses, including androgen insensitivity, Smith-Lemli-Opitz, and 46,XY with MAP3K1 mutations and gonadal dysgenesis, as examples. We also examine the GCT risk in non-DSD syndromes, in addition to the cancer risks in DSD patients with dimorphic gonads and genitalia. This review is intended to provide a nuanced assessment of relative germ cell tumor risk in the DSD patient, including modern precise molecular diagnosis, for use by the clinical geneticist. © 2017 Wiley Periodicals, Inc.

Cell-autonomous sex determination outside of the gonad

PubMed Central

Arnold, Arthur P.; Chen, Xuqi; Link, Jenny C.; Itoh, Yuichiro; Reue, Karen

2013-01-01

The classic model of sex determination in mammals states that the sex of the individual is determined by the type of gonad that develops, which in turn determines the gonadal hormonal milieu that creates sex differences outside of the gonads. However, XX and XY cells are intrinsically different because of the cell-autonomous sex-biasing action of X and Y genes. Recent studies of mice, in which sex chromosome complement is independent of gonadal sex, reveal that sex chromosome complement has strong effects contributing to sex differences in phenotypes such as metabolism. Adult mice with two X chromosomes (relative to mice with one X chromosome) show dramatically greater increases in body weight and adiposity after gonadectomy, irrespective of their gonadal sex. When fed a high fat diet, XX mice develop striking hyperinsulinemia and fatty liver, relative to XY mice. The sex chromosome effects are modulated by the presence of gonadal hormones, indicating an interaction of the sex-biasing effects of gonadal hormones and sex chromosome genes. Other cell-autonomous sex chromosome effects are detected in mice in many phenotypes. Birds (relative to eutherian mammals) are expected to show more widespread cell-autonomous sex determination in non-gonadal tissues, because of ineffective sex chromosome dosage compensation mechanisms. PMID:23361913

Quantitative Effects of P Elements on Hybrid Dysgenesis in Drosophila Melanogaster

PubMed Central

Rasmusson, K. E.; Simmons, M. J.; Raymond, J. D.; McLarnon, C. F.

1990-01-01

Genetic analyses involving chromosomes from seven inbred lines derived from a single M' strain were used to study the quantitative relationships between the incidence and severity of P-M hybrid dysgenesis and the number of genomic P elements. In four separate analyses, the mutability of sn(w), a P element-insertion mutation of the X-linked singed locus, was found to be inversely related to the number of autosomal P elements. Since sn(w) mutability is caused by the action of the P transposase, this finding supports the hypothesis that genomic P elements titrate the transposase present within a cell. Other analyses demonstrated that autosomal transmission ratios were distorted by P element action. In these analyses, the amount of distortion against an autosome increased more or less linearly with the number of P elements carried by the autosome. Additional analyses showed that the magnitude of this distortion was reduced when a second P element-containing autosome was present in the genome. This reduction could adequately be explained by transposase titration; there was no evidence that it was due to repressor molecules binding to P elements and inhibiting their movement. The influence of genomic P elements on the incidence of gonadal dysgenesis was also investigated. Although no simple relationship between the number of P elements and the incidence of the trait could be discerned, it was clear that even a small number of elements could increase the incidence markedly. The failure to find a quantitative relationship between P element number and the incidence of gonadal dysgenesis probably reflects the complex etiology of this trait. PMID:2155853

[The role of gonadal peptides in clinical investigation].

PubMed

Lahlou, N; Bouvattier, C; Linglart, A; Rodrigue, D; Teinturier, C

2009-01-01

Inhibins, activins, and anti-Mullerian hormone (AMH) are gonadal dimeric peptides produced in ovaries and testes by homologous cells, granulosa cells and Sertoli cells, respectively. The production of inhibins is driven by FSH, that of AMH may indirectly depends on FSH, while it is down regulated, at least in the male, by testosterone. In the past decade, measurements of serum inhibin and AMH have provided useful tools for clinical investigation in gonadal disorders: pseudohermaphroditism, androgen insensitivity, anorchidism, gonadal dysgenesis, disorders of pubertal developpement. Inhibins, activins, and AMH are also reliable markers of gonadal tumors. They are extensively used as indexes of fertility: in the male the production of inhibin B reflects the spermatogenetic activity, in women both inhibin B and AMH levels are correlated with the number of preantral and early antral follicles and reflect the ovarian reserve of follicles available for recruitment.

A case of 46,XX dysgenesis and marked tall stature; the need for caution in interpreting array comparative genomic hybridization (CGH).

PubMed

Narayanan, Vidya Kanamkote; Kharbanda, Mira; Donaldson, Malcolm

2016-12-01

Gonadal dysgenesis with an apparently normal 46,XX karyotype is a rare cause of hypergonadotrophic hypogonadism. Tall stature is not a widely recognized association. A 15-year-old girl presented with primary amenorrhoea. Examination showed a non-dysmorphic girl of normal intellect with no breast development (Tanner stage B1P4A1) who was tall compared with her parents: height standard deviation score (SDS) +1.56 vs. midparental height of +0.23 SDS, and slim build (weight -0.13 SDS). Investigations showed a 46,XX karyotype, elevated gonadotropins (FSH 119 and LH 33.7 IU/L), serum estradiol <5 pmol/L, uterine length 3.75 cm with cylindrical shape, and absent ovaries on ultrasound. Initially, a 364055-bp deletion on Xp21.2 was reported on array CGH. However, repeat analysis using BlueGnome CytoChip ISCA 4x180k v2.0 array was normal. With oral ethinyl estradiol induction puberty progressed to B4P4A2 but aged 18.4 years, the patient was remarkably tall with height SDS +2.88, weight SDS +0.97. Caution is needed in interpreting small changes with array CGH, particularly with the older assays. We postulate that the genetic change causing 46,XX gonadal dysgenesis in our patient may have also resulted in unsuppressed somatic growth. More critical height assessment, including parental height measurement, of future patients with 46,XX gonadal dysgenesis is recommended in order to determine whether or not a true association with tall stature may be present in certain cases.

Sex differences in diurnal rhythms of food intake in mice caused by gonadal hormones and complement of sex chromosomes.

PubMed

Chen, Xuqi; Wang, Lixin; Loh, Dawn H; Colwell, Christopher S; Taché, Yvette; Reue, Karen; Arnold, Arthur P

2015-09-01

We measured diurnal rhythms of food intake, as well as body weight and composition, while varying three major classes of sex-biasing factors: activational and organizational effects of gonadal hormones, and sex chromosome complement (SCC). Four Core Genotypes (FCG) mice, comprising XX and XY gonadal males and XX and XY gonadal females, were either gonad-intact or gonadectomized (GDX) as adults (2.5months); food intake was measured second-by-second for 7days starting 5weeks later, and body weight and composition were measured for 22weeks thereafter. Gonadal males weighed more than females. GDX increased body weight/fat of gonadal females, but increased body fat and reduced body weight of males. After GDX, XX mice had greater body weight and more fat than XY mice. In gonad-intact mice, males had greater total food intake and more meals than females during the dark phase, but females had more food intake and meals and larger meals than males during the light phase. GDX reduced overall food intake irrespective of gonad type or SCC, and eliminated differences in feeding between groups with different gonads. Diurnal phase of feeding was influenced by all three sex-biasing variables. Gonad-intact females had earlier onset and acrophase (peak) of feeding relative to males. GDX caused a phase-advance of feeding, especially in XX mice, leading to an earlier onset of feeding in GDX XX vs. XY mice, but earlier acrophase in GDX males relative to females. Gonadal hormones and SCC interact in the control of diurnal rhythms of food intake. Copyright © 2015 Elsevier Inc. All rights reserved.

Loss of DMRT1 gene in a Mos 45,XY,-9[8]/46,XY,r(9)[29]/47,XY,+idic r(9)× 2[1]/46,XY,idic r(9)[1]/46,XY[1] female presenting with short stature.

PubMed

Marsudi, Bagas A; Kartapradja, Hannie; Paramayuda, Chrysantine; Batubara, Jose R L; Harahap, Alida R; Marzuki, Nanis S

2018-01-01

A 46,XY sex reversal syndrome is characterized by discordant genetic and phenotypic sex, leading to normal external female genitalia, undeveloped gonads and presence of Müllerian structures in an otherwise 46,XY individual. Chromosome 9pter aberrations, such as ring chromosome have been reported to cause 46,XY disorders of sex development (DSD), due to involvement of DMRT1 gene located at the 9p24.3 region. This study presents a unique case of a 12-year-old female with mos 46,XY, (r)9[31]/45,XY,-9[9] karyotype, presenting with intellectual disability and short stature, mimicking Turner syndrome. Re-karyotyping was performed using standard GTL-banding technique. Further cytogenetic study using standard metaphase fluorescent in situ hybridization (FISH) technique was applied to cultured lymphocytes from peripheral blood, hybridized using green control probe specific to 9q21 loci, and red DMRT1 probe specific to 9p24.3 loci. Cytogenetics and FISH analysis revealed mos 45,XY,-9[8]/46,XY,r(9)[29]/47,XY,+idic r(9)× 2[1]/46,XY,idic r(9)[1]/46,XY[1] and haploinsufficiency of DMRT1 gene in most cells. CGH array revealed a deletion around 1.25 Mb at 9p24.3 loci [arr 9p24.3(204,193-1,457,665)× 1] and three duplications around 13 Mb [9p24.3p22.3(1,477,660-14,506,754)× 3] near the breakage point that formed the ring chromosome 9. The clinical presentation of the subject that mimics Turner syndrome highlights the importance of cytogenetic analysis to detect the possibility of ring chromosome 9. Sex reversal due to haploinsufficiency of DMRT1 gene in ring chromosome 9 structures is exceedingly rare with only a handful of cases ever reported. This finding further highlights the importance of DMRT1 gene in sex determination and differentiation in males. More research is required to pinpoint the exact mechanism that underlies sex reversal caused by DMRT1 haploinsufficiency.

[Intersexuality in domestic mammals].

PubMed

Cribiu, E P; Chaffaux, S

1990-01-01

With the exception of bovine freemartinism, intersexuality is rarely reported in domestic animals. The few cases of intersexuality reported here in dogs, cattle, goats, sheep and horses were classified according to the karyotype. The XX intersexes described here included goats which were either polled male pseudohermaphrodites or true hermaphrodites and dogs which were female pseudohermaphrodites. Among the XY intersexes studied, one dog was a true hermaphrodite, whereas the others were male pseudohermaphrodites, all mares showed gonadal dysgenesis and one cow was a female pseudohermaphrodite. XX/XY intersexes were detected in ovine cases of freemartinism.

Recovery of gonadal development in tiger puffer Takifugu rubripes after exposure to 17β-estradiol during early life stages

NASA Astrophysics Data System (ADS)

Hu, Peng; Liu, Bin; Meng, Zhen; Liu, Xinfu; Jia, Yudong; Yang, Zhi; Lei, Jilin

2017-05-01

The aim of the present study was to investigate the long-term effects of 17β-estradiol (E2) exposure on gonadal development in the tiger puff er ( Takifugu rubripes), which has a genetic sex determination system of male homogametic XY-XX. Tiger puff er larvae were exposed to 1, 10 and 100 μg/L E2 from 15 to 100 days post-hatch (dph) and then maintained in clean seawater until 400 dph. Changes in sex ratio, gonadal structure and gonadosomatic index (GSI) were monitored at 100, 160, 270 and 400 dph. Sex-associated single nucleotide polymorphism (SNP) markers were used to analyze the genetic sex of samples, except those at 100 dph. Exposure had a positive effect on the conversion of genetically male gonads into phenotypically female gonads at 100 dph. However, gonads from 60% of genetic XY males in the 1-μg/L E2 group and 100% in the 10-μg/L E2 group developed intersexual gonads at 160 dph; gonads of all genetic XY males in the two treatment groups reverted to testis by 270 dph. While 38%, 57% and 44% of gonads of XY fish in the 100-μg/L E2 group reverted to intersexual gonads at 160, 270 and 400 dph, respectively, none reverted to testis after E2 treatment. In addition, E2 exposure inhibited gonadal growth of both genetic sexes, as indicated by the clear dose-dependent decrease in GSI at 270 and 400 dph. The results showed that exposure to E2 during the early life stages of tiger puff er disrupted gonadal development, but that fish recovered after migration to clean seawater. The study suggests the potential use of tiger puff er as a valuable indicator species to evaluate the effects of environmental estrogens on marine fish, thereby protecting valuable fishery resources.

Disorders of sexual development and associated changes in the pituitary-gonadal axis in dogs.

PubMed

Buijtels, J J C W M; de Gier, J; Kooistra, H S; Grinwis, G C M; Naan, E C; Zijlstra, C; Okkens, A C

2012-10-15

Normal sexual differentiation depends on completion of chromosomal sex determination, gonadal differentiation, and development of the phenotypic sex. An irregularity in any of these three steps can lead to a disorder in sexual development (DSD). We examined nine dogs with DSD by abdominal ultrasonography, laparotomy, histologic examination of the gonads, and reproductive tract, cytogenetic analysis, and mRNA expression of the SRY gene. We also determined the plasma concentrations of luteinizing hormone (LH), estradiol-17β, and testosterone before and after administration of gonadotropin-releasing hormone (GnRH) and compared these results with those obtained in anestrous bitches and male control dogs. The gonads of three dogs with DSD contained both testicular and ovarian tissue, while in the other six only testicular tissue was found. Each of the dogs had a uterus. Based on gynecologic examination, cytogenetic analysis, and the histology of the gonads, seven of the nine dogs appeared to be XX sex reversals. Three of these were XX true hermaphrodites and four were XX males; the other two dogs had incomplete XY gonadal dysgenesis. All seven XX sex-reversed dogs were found to be negative for the SRY gene by polymerase chain reaction. The basal plasma luteinizing hormone (LH) concentration was significantly higher in dogs with DSD than in anestrous bitches but not significantly different from that in male dogs. The basal plasma LH concentration increased significantly after GnRH administration in all dogs with DSD. The basal plasma estradiol concentration was significantly higher in dogs with DSD than in anestrous bitches but not significantly different from that in male dogs. The basal plasma testosterone concentration was lower in dogs with DSD than in male dogs. In all dogs with DSD both the basal and GnRH-induced plasma testosterone concentrations were above the upper limit of their respective ranges in the anestrous bitches. In conclusion, the secretion of LH and

Steroidogenic Factor-1 and Human Disease

PubMed Central

El-Khairi, Ranna; Achermann, John C.

2016-01-01

Steroidogenic factor-1 (SF-1) (Ad4BP, NR5A1) is a nuclear receptor that plays a key role in adrenal and reproductive development and function. Deletion of the gene encoding Sf-1 (Nr5a1) in mice results in severe developmental defects of the adrenal gland and gonad. Consequently, initial work on the potential effects of SF-1 disruption in humans focused on individuals with primary adrenal failure, a 46,XY karyotype, complete gonadal dysgenesis, and Müllerian structures. This is a rare phenotype, but has been reported on two occasions, because of alterations that affect key DNA-binding domains of SF-1. Attention then turned to a potential wider role of SF-1 in human adrenal and reproductive disorders. Although changes in SF-1 only very rarely cause isolated adrenal failure, it is emerging that variations in SF-1 are a surprisingly frequent cause of reproductive dysfunction in humans. In 46,XY disorders of sex development, a spectrum of phenotypes has been reported including severe and partial forms of gonadal (testicular) dysgenesis, hypospadias, anorchia with microphallus, and even male factor infertility. In 46,XX females, alterations in SF-1 are associated with primary ovarian insufficiency. Thus, SF-1 seems be a more significant factor in human reproductive health than was first envisioned, with implications for adults as well as children. PMID:23044873

46,XY female sex reversal syndrome with bilateral gonadoblastoma and dysgerminoma.

PubMed

DU, Xue; Zhang, Xuhong; Li, Yongmei; Han, Yukun

2014-10-01

Sex reversal syndrome is a rare congenital condition of complete or disordered gonadal development leading to discordance between the genetic, gonadal and phenotypic sexes, including 46,XX and 46,XY. The gonadoblastoma on the Y-chromosome (GBY) region is associated with an increased risk of developing type II germ cell tumors/cancer. The present study reports a unique case of a phenotypically normal female (age 17 years), presenting with primary amenorrhea and later diagnosed with 46,XY female sex reversal syndrome. Following bilateral gonadectomy, bilateral gonadoblastoma and dysgerminoma were diagnosed. Thus, estrogen replacement therapy was administered periodically to promote the development of secondary sexual characteristics and menstruation, and to prevent osteoporosis. A four year follow-up showed no tumor recurrence and a regular menstrual cycle in this patient.

Laparoscopic Removal of Streak Gonads in Turner Syndrome.

PubMed

Mandelberger, Adrienne; Mathews, Shyama; Andikyan, Vaagn; Chuang, Linus

To demonstrate the skills necessary for complete resection of bilateral streak gonads in Turner syndrome. Video case presentation with narration highlighting the key techniques used. The video was deemed exempt from formal review by our institutional review board. Turner syndrome is a form of gonadal dysgenesis that affects 1 in 2500 live births. Patients often have streak gonads and may present with primary amenorrhea or premature ovarian failure. Patients with a mosaic karyotype that includes a Y chromosome are at increased risk for gonadoblastoma and subsequent transformation into malignancy. Gonadectomy is recommended for these patients, typically at adolescence. Streak gonads can be difficult to identify, and tissue margins are often in close proximity to critical retroperitoneal structures. Resection can be technically challenging and requires a thorough understanding of retroperitoneal anatomy and precise dissection techniques to ensure complete removal. Laparoscopic approach to bilateral salpingo-oophorectomy of streak gonads. Retroperitoneal dissection and ureterolysis are performed, with the aid of the Ethicon Harmonic Ace, to ensure complete gonadectomy. Careful and complete resection of gonadal tissue in the hands of a skilled laparoscopic surgeon is key for effective cancer risk reduction surgery in Turner syndrome mosaics. Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.

Gender role across development in adults with 46,XY disorders of sex development including perineoscrotal hypospadias and small phallus raised male or female.

PubMed

Pappas, Kara B; Wisniewski, Amy B; Migeon, Claude J

2008-07-01

Self-rated degree of femininity and masculinity across development were evaluated for 40 adults affected by 46,XY disorders of sex development (DSDs) who presented at birth with a small phallus and perineoscrotal hypospadias, raised either male (n = 22) or female (n = 18). Most participants were confirmed or presumed to be affected by partial androgen insensitivity syndrome (n = 14), partial gonadal dysgenesis (n = 11), or were considered to have a poorly defined case of 46,XY DSD including ambiguous external genitalia (n = 15). Participants retrospectively evaluated their degree of masculinity and femininity during their childhood, adolescence, adulthood, and in the past 12 months of filling out a questionnaire pertaining to their psychosexual development. Participants raised male reported more masculinity than those raised female due to an increase in masculinization during adolescence and adulthood. Participants raised male also reported less femininity than those raised female throughout development. Participants raised female reported more femininity than those raised male due to an increase in feminization during adolescence and adulthood. Participants raised female also reported less masculinity than those raised male throughout development. These data support the proposition that some aspects of gender role (GR), such as masculinity and femininity, are capable of proceeding along female- or male-typic patterns depending on sex of rearing among individuals affected by specific types of 46,XY DSD. Furthermore, regardless of male or female rearing, GR increasingly corresponds with assigned sex as individuals proceed through sexual maturity and into adulthood. These results are consistent with the idea that socialization/learning contributes to GR development in humans in addition to data from others demonstrating endocrine influences.

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

The complete coding region sequence of river buffalo (Bubalus bubalis) SRY gene.

PubMed

Parma, Pietro; Feligini, Maria; Greppi, Gianfranco; Enne, Giuseppe

2004-02-01

The Y-linked SRY gene is responsible for testis determination in mammals. Mutations in this gene can lead to XY Gonadal Dysgenesis, an abnormal sexual phenotype described in humans, cattle, horses and river buffalo. We report here the complete river buffalo SRY sequence in order to enable the genetic diagnosis of this disease. The SRY sequence was also used to confirm the evolutionary divergence time between cattle and river buffalo 10 million years ago.

Testicular dysgenesis syndrome and the origin of carcinoma in situ testis.

PubMed

Sonne, Si Brask; Kristensen, David Møbjerg; Novotny, Guy W; Olesen, Inge Ahlmann; Nielsen, John E; Skakkebaek, Niels E; Rajpert-De Meyts, Ewa; Leffers, Henrik

2008-04-01

Recent increases in male reproductive disorders have been linked to exposure to environmental factors leading to the testicular dysgenesis syndrome (TDS). Testicular cancer is the most severe condition in TDS and studies have shown a clear correlation between risk of testicular cancer and other components of TDS and that the geographical location of the mother during pregnancy can be a risk factor. This suggests that the dysgenesis has its origin in utero and that TDS is initiated by environmental factors, including possibly hormone-disrupting compounds that act on the mother and the developing foetus, but the genetic background may also play a role. The morphological similarity of carcinoma in situ (CIS) cells (the precursor of the majority of invasive testicular cancers) with primordial germ cells and gonocytes, and overlap in expression of protein markers suggests an origin of CIS from primordial germ cells or gonocytes. CIS cells and germ cell-derived cancers of the human type have so far not been described in any animal model of TDS, which could be caused by species differences in the development of the male gonad. Regardless of this, it is plausible that the dysgenesis, and hence the development of CIS cells, is a result of disturbed signalling between nurse cells and germ cells that allow embryonic germ cells to survive in the pre-pubertal and adult testis. The post-pubertal proliferation of CIS cells combined with aberrant signalling then leads to an accumulation of genetic changes in the CIS cells, which eventually results in the development of invasive testicular cancer in the adult.

Loss of function mutation in the palmitoyl-transferase HHAT leads to syndromic 46,XY disorder of sex development by impeding Hedgehog protein palmitoylation and signaling.

PubMed

Callier, Patrick; Calvel, Pierre; Matevossian, Armine; Makrythanasis, Periklis; Bernard, Pascal; Kurosaka, Hiroshi; Vannier, Anne; Thauvin-Robinet, Christel; Borel, Christelle; Mazaud-Guittot, Séverine; Rolland, Antoine; Desdoits-Lethimonier, Christèle; Guipponi, Michel; Zimmermann, Céline; Stévant, Isabelle; Kuhne, Françoise; Conne, Béatrice; Santoni, Federico; Lambert, Sandy; Huet, Frederic; Mugneret, Francine; Jaruzelska, Jadwiga; Faivre, Laurence; Wilhelm, Dagmar; Jégou, Bernard; Trainor, Paul A; Resh, Marilyn D; Antonarakis, Stylianos E; Nef, Serge

2014-05-01

The Hedgehog (Hh) family of secreted proteins act as morphogens to control embryonic patterning and development in a variety of organ systems. Post-translational covalent attachment of cholesterol and palmitate to Hh proteins are critical for multimerization and long range signaling potency. However, the biological impact of lipid modifications on Hh ligand distribution and signal reception in humans remains unclear. In the present study, we report a unique case of autosomal recessive syndromic 46,XY Disorder of Sex Development (DSD) with testicular dysgenesis and chondrodysplasia resulting from a homozygous G287V missense mutation in the hedgehog acyl-transferase (HHAT) gene. This mutation occurred in the conserved membrane bound O-acyltransferase (MBOAT) domain and experimentally disrupted the ability of HHAT to palmitoylate Hh proteins such as DHH and SHH. Consistent with the patient phenotype, HHAT was found to be expressed in the somatic cells of both XX and XY gonads at the time of sex determination, and Hhat loss of function in mice recapitulates most of the testicular, skeletal, neuronal and growth defects observed in humans. In the developing testis, HHAT is not required for Sertoli cell commitment but plays a role in proper testis cord formation and the differentiation of fetal Leydig cells. Altogether, these results shed new light on the mechanisms of action of Hh proteins. Furthermore, they provide the first clinical evidence of the essential role played by lipid modification of Hh proteins in human testicular organogenesis and embryonic development.

Loss of Function Mutation in the Palmitoyl-Transferase HHAT Leads to Syndromic 46,XY Disorder of Sex Development by Impeding Hedgehog Protein Palmitoylation and Signaling

PubMed Central

Makrythanasis, Periklis; Bernard, Pascal; Kurosaka, Hiroshi; Vannier, Anne; Thauvin-Robinet, Christel; Borel, Christelle; Mazaud-Guittot, Séverine; Rolland, Antoine; Desdoits-Lethimonier, Christèle; Guipponi, Michel; Zimmermann, Céline; Stévant, Isabelle; Kuhne, Françoise; Conne, Béatrice; Santoni, Federico; Lambert, Sandy; Huet, Frederic; Mugneret, Francine; Jaruzelska, Jadwiga; Faivre, Laurence; Wilhelm, Dagmar; Jégou, Bernard; Trainor, Paul A.; Resh, Marilyn D.; Antonarakis, Stylianos E.; Nef, Serge

2014-01-01

The Hedgehog (Hh) family of secreted proteins act as morphogens to control embryonic patterning and development in a variety of organ systems. Post-translational covalent attachment of cholesterol and palmitate to Hh proteins are critical for multimerization and long range signaling potency. However, the biological impact of lipid modifications on Hh ligand distribution and signal reception in humans remains unclear. In the present study, we report a unique case of autosomal recessive syndromic 46,XY Disorder of Sex Development (DSD) with testicular dysgenesis and chondrodysplasia resulting from a homozygous G287V missense mutation in the hedgehog acyl-transferase (HHAT) gene. This mutation occurred in the conserved membrane bound O-acyltransferase (MBOAT) domain and experimentally disrupted the ability of HHAT to palmitoylate Hh proteins such as DHH and SHH. Consistent with the patient phenotype, HHAT was found to be expressed in the somatic cells of both XX and XY gonads at the time of sex determination, and Hhat loss of function in mice recapitulates most of the testicular, skeletal, neuronal and growth defects observed in humans. In the developing testis, HHAT is not required for Sertoli cell commitment but plays a role in proper testis cord formation and the differentiation of fetal Leydig cells. Altogether, these results shed new light on the mechanisms of action of Hh proteins. Furthermore, they provide the first clinical evidence of the essential role played by lipid modification of Hh proteins in human testicular organogenesis and embryonic development. PMID:24784881

Aetiological diagnosis of male sex ambiguity: a collaborative study.

PubMed

Morel, Yves; Rey, Rodolfo; Teinturier, Cécile; Nicolino, Marc; Michel-Calemard, Laurence; Mowszowicz, Irène; Jaubert, Francis; Fellous, Marc; Chaussain, Jean-Louis; Chatelain, Pierre; David, Michel; Nihoul-Fékété, Claire; Forest, Maguelone G; Josso, Nathalie

2002-01-01

A collaborative study, supported by the Biomed2 Programme of the European Community, was initiated to optimise the aetiological diagnosis in genetic or gonadal males with intersex disorders, a total of 67 patients with external sexual ambiguity, testicular tissue and/or a XY karyotype. In patients with gonadal dysgenesis or true hermaphroditism, the incidence of vaginal development was 100%, a uterus was present in 60%; uni or bilateral cryptorchidism was seen in nearly all cases of testicular dysgenesis (99%) but in only 57% of true hermaphrodites. Mean serum levels of anti-mullerian hormone and of serum testosterone response to chorionic gonadotropin stimulation were significantly decreased in both conditions, by comparison with patients with unexplained male pseudohermaphroditism or partial androgen insensitivity (PAIS). Mutations in the androgen receptor, 90% within exons 2-8, were detected in patients with PAIS. Clinically, a vaginal pouch was present in 90%, cryptorchidism in 36%. In 52% of cases, no diagnosis could be reached, despite an exhaustive clinical and laboratory work-up, including routine sequencing of exons 2-8 of the androgen receptor. By comparison with PAIS, unexplained male pseudohermaphroditism was characterised by a lower incidence of vaginal pouch (55%) and cryptorchidism (22%) but a high incidence of prematurity/intrauterine growth retardation (30%) or mild malformations (14%). reaching an aetiological diagnosis in cases of male intersex is difficult because of the variability of individual cases. Hormonal tests may help to discriminate between partial androgen insensitivity and gonadal dysgenesis/true hermaphroditism but are of less use for differentiating from unexplained male pseudohermaphroditism. Sequencing of exons 2-8 of the androgen receptor after study of testosterone precursors following human chorionic gonadotrophin stimulation is recommended when gonadal dysgenesis and true hermaphroditism can be excluded.

XY (SRY-positive) Ovarian Disorder of Sex Development in Cattle.

PubMed

De Lorenzi, Lisa; Arrighi, Silvana; Rossi, Elena; Grignani, Pierangela; Previderè, Carlo; Bonacina, Stefania; Cremonesi, Fausto; Parma, Pietro

2018-06-13

In mammals, the sex of the embryo depends on the SRY gene. In the presence of at least one intact and functional copy of this genetic factor (XY embryo) undifferentiated gonads will develop as testicles that subsequently determine the male phenotype. When this factor is not present, i.e., in subjects with 2 X chromosomes, an alternative pathway induces the development of ovaries, hence a female phenotype. In this case study, we describe a female cattle affected by a disorder of sex development (DSD). The subject, despite having a chromosomal XY constitution, did not develop testicles but ovaries, although they were underdeveloped. Moreover, genetic analysis highlighted the presence of the SRY gene with a normal coding region in both blood- and tissue-derived DNA. A chimeric condition was excluded in blood by sexing more than 350 cells and by allele profile investigation of 18 microsatellite markers. Array CGH analysis showed the presence of a not yet described 99-kb duplication (BTA18), but its relationship with the phenotype remains to be demonstrated. Gonadal histology demonstrated paired ovaries: the left one containing a large corpus luteum and the right one showing an underdeveloped aspect and very few early follicles. To our knowledge, we describe the first case of XY (SRY+) DSD in cattle with a normal SRY gene coding sequence. © 2018 S. Karger AG, Basel.

Wide spectrum of NR5A1-related phenotypes in 46,XY and 46,XX individuals.

PubMed

Domenice, Sorahia; Machado, Aline Zamboni; Ferreira, Frederico Moraes; Ferraz-de-Souza, Bruno; Lerario, Antonio Marcondes; Lin, Lin; Nishi, Mirian Yumie; Gomes, Nathalia Lisboa; da Silva, Thatiana Evelin; Silva, Rosana Barbosa; Correa, Rafaela Vieira; Montenegro, Luciana Ribeiro; Narciso, Amanda; Costa, Elaine Maria Frade; Achermann, John C; Mendonca, Berenice Bilharinho

2016-12-01

Steroidogenic factor 1 (NR5A1, SF-1, Ad4BP) is a transcriptional regulator of genes involved in adrenal and gonadal development and function. Mutations in NR5A1 have been among the most frequently identified genetic causes of gonadal development disorders and are associated with a wide phenotypic spectrum. In 46,XY individuals, NR5A1-related phenotypes may range from disorders of sex development (DSD) to oligo/azoospermia, and in 46,XX individuals, from 46,XX ovotesticular and testicular DSD to primary ovarian insufficiency (POI). The most common 46,XY phenotype is atypical or female external genitalia with clitoromegaly, palpable gonads, and absence of Müllerian derivatives. Notably, an undervirilized external genitalia is frequently seen at birth, while spontaneous virilization may occur later, at puberty. In 46,XX individuals, NR5A1 mutations are a rare genetic cause of POI, manifesting as primary or secondary amenorrhea, infertility, hypoestrogenism, and elevated gonadotropin levels. Mothers and sisters of 46,XY DSD patients carrying heterozygous NR5A1 mutations may develop POI, and therefore require appropriate counseling. Moreover, the recurrent heterozygous p.Arg92Trp NR5A1 mutation is associated with variable degrees of testis development in 46,XX patients. A clear genotype-phenotype correlation is not seen in patients bearing NR5A1 mutations, suggesting that genetic modifiers, such as pathogenic variants in other testis/ovarian-determining genes, may contribute to the phenotypic expression. Here, we review the published literature on NR5A1-related disease, and discuss our findings at a single tertiary center in Brazil, including ten novel NR5A1 mutations identified in 46,XY DSD patients. The ever-expanding phenotypic range associated with NR5A1 variants in XY and XX individuals confirms its pivotal role in reproductive biology, and should alert clinicians to the possibility of NR5A1 defects in a variety of phenotypes presenting with gonadal dysfunction

Wide spectrum of NR5A1‐related phenotypes in 46,XY and 46,XX individuals

PubMed Central

Domenice, Sorahia; Machado, Aline Zamboni; Ferreira, Frederico Moraes; Ferraz‐de‐Souza, Bruno; Lerario, Antonio Marcondes; Lin, Lin; Nishi, Mirian Yumie; Gomes, Nathalia Lisboa; da Silva, Thatiana Evelin; Silva, Rosana Barbosa; Correa, Rafaela Vieira; Montenegro, Luciana Ribeiro; Narciso, Amanda; Costa, Elaine Maria Frade; Achermann, John C

2016-01-01

Steroidogenic factor 1 (NR5A1, SF‐1, Ad4BP) is a transcriptional regulator of genes involved in adrenal and gonadal development and function. Mutations in NR5A1 have been among the most frequently identified genetic causes of gonadal development disorders and are associated with a wide phenotypic spectrum. In 46,XY individuals, NR5A1‐related phenotypes may range from disorders of sex development (DSD) to oligo/azoospermia, and in 46,XX individuals, from 46,XX ovotesticular and testicular DSD to primary ovarian insufficiency (POI). The most common 46,XY phenotype is atypical or female external genitalia with clitoromegaly, palpable gonads, and absence of Müllerian derivatives. Notably, an undervirilized external genitalia is frequently seen at birth, while spontaneous virilization may occur later, at puberty. In 46,XX individuals, NR5A1 mutations are a rare genetic cause of POI, manifesting as primary or secondary amenorrhea, infertility, hypoestrogenism, and elevated gonadotropin levels. Mothers and sisters of 46,XY DSD patients carrying heterozygous NR5A1 mutations may develop POI, and therefore require appropriate counseling. Moreover, the recurrent heterozygous p.Arg92Trp NR5A1 mutation is associated with variable degrees of testis development in 46,XX patients. A clear genotype‐phenotype correlation is not seen in patients bearing NR5A1 mutations, suggesting that genetic modifiers, such as pathogenic variants in other testis/ovarian‐determining genes, may contribute to the phenotypic expression. Here, we review the published literature on NR5A1‐related disease, and discuss our findings at a single tertiary center in Brazil, including ten novel NR5A1 mutations identified in 46,XY DSD patients. The ever‐expanding phenotypic range associated with NR5A1 variants in XY and XX individuals confirms its pivotal role in reproductive biology, and should alert clinicians to the possibility of NR5A1 defects in a variety of phenotypes presenting with gonadal

[Pure gonad dysgenesia or Swyer sindrome. A case report having tumoral development: melanoma].

PubMed

Russo, D; Blanco, M; Falke, G; Rocca Rivarola, M; Séller, R; Puigdevall, J C; Bergada, C

2006-10-01

A 14 year old girl having 10-days lumbar pain, polaquiuria and moderate pain to palpation is reported. Blood and urine analysis were normal. Abdominal ultrasound scan showed cavity free and solid, rounded, heterogeneous, intrapelvic mass compressing bladder and uterus. Magnetic resonance image was performed showing right gonad compromise with extensive liver and sacro-lumbar spine invasion. Tumoral markers were ruled out. During surgery, primary tumor mass localizad in the right gonad was completely excised. Melanotic peritoneal and hepatic disemination were observed. The patient had left streak gonad and infantile uterus (2 x 3 cm). As gonad dysgenesia was suspected, high resolution cromosomic study was performed and resulted in cariotype 46 XY. Microscopy of the resected gonad showed primary gonad melanoma. Chemotherapy was instituted with no tumor response and the patient died two month later.

True hermaphroditism in a 46, XY individual, caused by a postzygotic somatic point mutation in the male gonadal sex-determining locus (SRY): Molecular genetics and histological findings in a sporadic case

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

Braun, A.; Kammerer, S.; Cleve, H.

1993-03-01

Recently, the gene for the determination of maleness has been identified in the sex-determining region on the short arm of the Y chromosome (SRY) between the Y-chromosomal pseudoautosomal boundary (PABY) and the ZFY gene locus. Experiments with transgenic mice confirmed that SRY is a part of the testis-determining factor (TDF). The authors describe a sporadic case of a patient with intersexual genitalia and the histological finding of ovotestes in the gonad, which resembles the mixed type of gonadal tissue without primordial follicle structures. The karyotype of the patient was 46,XY. By PCR amplification, they tested for the presence of SRYmore » by using DNA obtained from histological gonadal slices. The SRY products of both DNA preparations were further analyzed by direct sequencing. All three parts of the sex-determining region of the Y chromosome could be amplified from leukocytic DNA. The patient's and the father's SRY sequences were identical with the published sequence. In the SRY PCR product of gonadal DNA, the wild-type and two point mutations were present in the patient's sequence, simulating a heterozygous state of a Y-chromosomal gene: one of the mutations was silent, while the other encoded for a nonconservative amino acid substitution from leucine to histidine. Subcloning procedures showed that the two point mutations always occurred together. The origin of the patient's intersexuality is a postzygotic mutation of the SRY occurring in part of the gonadal tissue. This event caused the loss of the testis-determining function in affected cells. 37 refs., 6 figs.« less

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.

The XX sex chromosome complement in mice is associated with increased spontaneous lupus compared with XY.

PubMed

Sasidhar, Manda V; Itoh, Noriko; Gold, Stefan M; Lawson, Gregory W; Voskuhl, Rhonda R

2012-08-01

Many autoimmune diseases are characterised by a female predominance. This may be caused by sex hormones, sex chromosomes or both. This report uses a transgenic mouse model to investigate how sex chromosome complement, not confounded by differences in gonadal type, might contribute to lupus pathogenesis. Transgenic NZM2328 mice were created by deletion of the Sry gene from the Y chromosome, thereby separating genetic from gonadal sex. Survival, renal histopathology and markers of immune activation were compared in mice carrying the XX versus the XY(-) sex chromosome complement, with each genotype being ovary bearing. Mice with XX sex chromosome complement compared with XY(-) exhibited poorer survival rates and increased kidney pathology. Splenic T lymphocytes from XX mice demonstrated upregulated X-linked CD40 ligand expression and higher levels of activation markers ex vivo. Increased MMP, TGF and IL-13 production was found, while IL-2 was lower in XX mice. An accumulation of splenic follicular B cells and peritoneal marginal zone B cells was observed, coupled with upregulated costimulatory marker expression on B cells in XX mice. These data show that the XX sex chromosome complement, compared with XY(-), is associated with accelerated spontaneous lupus.

Radiological Evaluation of Ambiguous Genitalia with Various Imaging Modalities

NASA Astrophysics Data System (ADS)

Ravi, N.; Bindushree, Kadakola

2012-07-01

Disorders of sex development (DSDs) are congenital conditions in which the development of chromosomal, gonadal, or anatomic sex is atypical. These can be classified broadly into four categories on the basis of gonadal histologic features: female pseudohermaphroditism (46,XX with two ovaries); male pseudohermaphroditism (46,XY with two testes); true hermaphroditism (ovotesticular DSD) (both ovarian and testicular tissues); and gonadal dysgenesis, either mixed (a testis and a streak gonad) or pure (bilateral streak gonads). Imaging plays an important role in demonstrating the anatomy and associated anomalies. Ultrasonography is the primary modality for demonstrating internal organs and magnetic resonance imaging is used as an adjunct modality to assess for internal gonads and genitalia. Early and appropriate gender assignment is necessary for healthy physical and psychologic development of children with ambiguous genitalia. Gender assignment can be facilitated with a team approach that involves a pediatric endocrinologist, geneticist, urologist, psychiatrist, social worker, neonatologist, nurse, and radiologist, allowing timely diagnosis and proper management. We describe case series on ambiguous genitalia presented to our department who were evaluated with multiple imaging modalities.

Sex steroid levels in XY males and sex-reversed XX males, of rainbow trout (Oncorhynchus mykiss), during the reproductive cycle.

PubMed

Espinosa, E; Josa, A; Gil, L; González, N

2011-02-01

In this study, the annual cycle of the gonadal steroids testosterone (T), 11-ketotestosterone (11-KT), 17β-oestradiol (E2) and 17α, 20β-dihydroxy-4-pregnen-3-one (DHP) was determined using radioimmunoassay and then compared, for XY males (n=35) and sex-reversed XX males (n=27) rainbow trout, to establish possible endocrinology differences. Both in XY males and sex-reversed XX males, significant correlation was shown between body weight and T (r=0.5046 and 0.34078, respectively; p<0.0001) or KT (r=0.52494 and 0.43545, respectively; p<0.0001) concentrations. Plasma androgen levels in XY and sex-reversed XX males were similar and showed an intense seasonal variation. The highest levels for T and 11-KT were detected from December to April with a peak in January (51.67 ± 5.11 and 61.95 ± 4.25 ng/ml, for XY males and 57.1 ± 5.82 and 59.27 ± 4.84 ng/ml, respectively, for XX males). In addition, there was a positive correlation (p<0.0001) between T and 11-KT levels for XY males (r=0.7533) and sex-reversed XX males (r=0.6019). Concentrations of DHP in XY males also showed seasonal variation with a peak in February (25.18 ± 12.99 ng/ml). However, DHP levels in sex-reversed XX males were undetectable (<0.1 ng/ml) over the year. Levels of E2 were undetectable through the year in both groups of trout. In conclusion, the androgenic and oestrogenic profiles of sex-reversed XX males were similar to those observed in XY males. The only difference in the annual gonadal steroid cycle between XY and sex-reversed XX males was in the DHP profile. © 2009 Blackwell Verlag GmbH.

Diversity of P-element piRNA production among M' and Q strains and its association with P-M hybrid dysgenesis in Drosophila melanogaster.

PubMed

Wakisaka, Keiko Tsuji; Ichiyanagi, Kenji; Ohno, Seiko; Itoh, Masanobu

2017-01-01

Transposition of P elements in the genome causes P-M hybrid dysgenesis in Drosophila melanogaster . For the P strain, the P-M phenotypes are associated with the ability to express a class of small RNAs, called piwi-interacting small RNAs (piRNAs), that suppress the P elements in female gonads. However, little is known about the extent to which piRNAs are involved in the P-M hybrid dysgenesis in M' and Q strains, which show different abilities to regulate the P elements from P strains. To elucidate the molecular basis of the suppression of paternally inherited P elements, we analyzed the mRNA and piRNA levels of P elements in the F1 progeny between males of a P strain and nine-line females of M' or Q strains (M' or Q progenies). M' progenies showed the hybrid dysgenesis phenotype, while Q progenies did not. Consistently, the levels of P -element mRNA in both the ovaries and F1 embryos were higher in M' progenies than in Q progenies, indicating that the M' progenies have a weaker ability to suppress P -element expression. The level of P -element mRNA was inversely correlated to the level of piRNAs in F1 embryos. Importantly, the M' progenies were characterized by a lower abundance of P -element piRNAs in both young ovaries and F1 embryonic bodies. The Q progenies showed various levels of piRNAs in both young ovaries and F1 embryonic bodies despite all of the Q progenies suppressing P -element transposition in their gonad. Our results are consistent with an idea that the level of P -element piRNAs is a determinant for dividing strain types between M' and Q and that the suppression mechanisms of transposable elements, including piRNAs, are varied between natural populations.

Clinical aspects of 49 infertile males with 45,X/46,XY mosaicism karyotype: A case series.

PubMed

Mohammadpour Lashkari, F; Sadighi Gilani, M A; Ghaheri, A; Zamanian, M R; Borjian Boroujeni, P; Mohseni Meybodi, A; Sabbaghian, M

2018-06-01

Disorders of sex development (DSD) are congenital abnormalities as an atypical development process in either gonadal or chromosomal structure. It is the cause of the abnormality in phenotype and characteristics. Chromosomal analysis plays an important role in the DSD determination. 45,X/46,XY mosaicism is a rare karyotype, and its prevalence is about 1.5 in 10,000 newborns. It affects the growth, hormonal balance, gonad development and histology. All data such as height, male general appearance, testis size and volume, external genitalia, spermogram and hormonal levels, testis pathology, Y chromosome microdeletion and karyotype, and assisted reproductive technology (ART) outcome were recorded based on patients profile and history. We investigated 64 infertile males with 45,X/46,XY mosaicism. Fifteen cases who had structural abnormalities in Y chromosome were excluded. From 49 available spermogram, 21 cases reported as azoospermic men, while 28 of them classified as nonazoospermic patients in which four of them displayed normal spermogram. According to hormonal evaluation, there were no significant differences between azoospermic and nonazoospermic groups. In azoospermia, only three couples underwent an ART cycle in which all of them failed. From 14 nonazoospermic cases who entered into the ART cycle, three cases experienced a successful pregnancy that one of the prosperous outcomes was twins. In 45,X/46,XY cases, both 45,X and 46,XY cell lines are seen. Various distributions of both cell lines can reflect a wide range of phenotypes that may be the most comprehensive evaluation in infertile males with 45,X/46,XY karyotype. It assumes that karyotyping as a main diagnostic test can enable us to find these rare cases. © 2018 Blackwell Verlag GmbH.

A 46,XX Ovotesticular Disorder of Sex Development Likely Caused by a Steroidogenic Factor-1 (NR5A1) Variant.

PubMed

Swartz, Jonathan M; Ciarlo, Ryan; Guo, Michael H; Abrha, Aser; Weaver, Benjamin; Diamond, David A; Chan, Yee-Ming; Hirschhorn, Joel N

2017-01-01

A variant in steroidogenic factor-1 (SF-1, encoded by the gene NR5A1), p.Arg92Trp, has recently been reported in multiple families with 46,XX ovotesticular or testicular disorders of sex development (DSD). This amino acid change impacts the DNA-binding domain and perturbs gonadal differentiation pathways. Whole-exome sequencing was performed on a 46,XX subject with ovotesticular DSD. Exome results identified a heterozygous NR5A1 variant, p.Arg92Gln, in the 46,XX ovotesticular DSD proband. This arginine-to-glutamine change has been previously reported in the homozygous state in a 46,XY patient with gonadal and adrenal dysgenesis, though 46,XY and 46,XX heterozygous carriers of this variant have not been previously reported to have any clinical phenotype. The NR5A1 p.Arg92Gln variant, which has thus far only been seen in a family with 46,XY DSD, most likely contributes to the ovotesticular DSD in this case. In light of the recent reports of unrelated 46,XX subjects with testicular or ovotesticular DSD with the NR5A1 variant p.Arg92Trp, it appears that other mutations in the DNA binding domain have the potential to impact the factors determining testicular and ovarian differentiation. This case demonstrates the variability of phenotypes with the same genotype and broadens our understanding of the role of SF-1 in gonadal differentiation. © 2016 S. Karger AG, Basel.

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

Human Sex Determination at the Edge of Ambiguity

PubMed Central

Racca, Joseph D.; Chen, Yen-Shan; Yang, Yanwu; Phillips, Nelson B.; Weiss, Michael A.

2016-01-01

A general problem is posed by analysis of transcriptional thresholds governing cell fate decisions in metazoan development. A model is provided by testis determination in therian mammals. Its key step, Sertoli cell differentiation in the embryonic gonadal ridge, is initiated by SRY, a Y-encoded architectural transcription factor. Mutations in human SRY cause gonadal dysgenesis leading to XY female development (Swyer syndrome). Here, we have characterized an inherited mutation compatible with either male or female somatic phenotypes as observed in an XY father and XY daughter, respectively. The mutation (a crevice-forming substitution at a conserved back surface of the SRY high mobility group box) markedly destabilizes the domain but preserves specific DNA affinity and induced DNA bend angle. On transient transfection of diverse human and rodent cell lines, the variant SRY exhibited accelerated proteasomal degradation (relative to wild type) associated with increased ubiquitination; in vitro susceptibility to ubiquitin-independent (“default”) cleavage by the 20S core proteasome was unchanged. The variant's gene regulatory activity (as assessed in a cellular model of the rat embryonic XY gonadal ridge) was reduced by 2-fold relative to wild-type SRY at similar levels of mRNA expression. Chemical proteasome inhibition restored native-like SRY expression and transcriptional activity in association with restored occupancy of a sex-specific enhancer element in principal downstream gene Sox9, demonstrating that the variant SRY exhibits essentially native activity on a per molecule basis. Our findings define a novel mechanism of impaired organogenesis, accelerated ubiquitin-directed proteasomal degradation of a master transcription factor leading to a developmental decision poised at the edge of ambiguity. PMID:27576690

Non-mosaic monosomy 59,X in cattle: a case report.

PubMed

Romano, Juan E; Raussdepp, Terje; Mulon, Pierre Y; Villadóniga, Graciela B

2015-05-01

A 3-year-old Longhorn heifer was referred to the Veterinary Medical Teaching Hospital of Texas A&M University for inability to get pregnant. Physical examination revealed a small-sized female for age and breed with a normal vulva, vaginal length, and external cervical os. Further assessment by per rectum palpation and trans-rectal ultrasonography revealed a small uterine cervix and cord-like uterine horns with no identifiable ovaries. Additional evaluation including laparoscopy, hormonal evaluation, and genetic analysis allowed ruling out conditions commonly associated with a phenotypic female with infantile or underdeveloped reproductive organs such as freemartin, XY gonadal dysgenesis, testicular feminization, and bilateral ovarian agenesis. Laparoscopy confirmed the presence of a small cervix with small uterine horns and absence of ovaries. Testosterone, progesterone, and 17-β estradiol concentrations were 200.0pg/mL, 1.48ng/mL, and undetectable, respectively. Genetic evaluation determined that the karyotype was 59,X non-mosaic. Evaluation of phenotypically female cattle with infertility and infantile genital organs and absence of ovaries should include cytogenetic analysis to test for possible X monosomy. The 59,X condition should be considered in the differential diagnoses together with freemartin, dysgenesis XY, testicular feminization, and bilateral ovarian agenesis. Copyright © 2015 Elsevier B.V. All rights reserved.

Equine disorders of sexual development in 17 mares including XX, SRY-negative, XY, SRY-negative and XY, SRY-positive genotypes.

PubMed

Villagómez, D A F; Lear, T L; Chenier, T; Lee, S; McGee, R B; Cahill, J; Foster, R A; Reyes, E; St John, E; King, W A

2011-01-01

We described the clinical, cytogenetic and molecular findings of 17 clinical equine cases presented for abnormal sexual development and infertility. Six horses with an enlarged clitoris had an XX, SRY-negative genotype, which displayed male-like behavior (adult individuals). Bilateral ovotestes were noted in 2 of those cases, while another case showed increased levels of circulating testosterone. Six horses with a female phenotype, including normal external genitalia, had an XY, SRY-negative genotype. These individuals had small gonads and an underdeveloped internal reproductive tract. Four horses with normal appearing external genitalia had an XY, SRY-positive genotype, 3 of them had hypoplastic testes and male-like behavior. In addition, one young filly with enlarged clitoris and hypoplastic testes had the same genotype but did not show male-like behavior due to her age. Three of these horses were related with 2 being siblings. These findings demonstrate the diversity of disorders of sexual development seen in the horse. Furthermore, they emphasize the need for further research to identify genes involved in abnormal sex determination and differentiation in the horse. Copyright © 2010 S. Karger AG, Basel.

Genetics Home Reference: sudden infant death with dysgenesis of the testes syndrome

MedlinePlus

... Facebook Twitter Home Health Conditions SIDDT Sudden infant death with dysgenesis of the testes syndrome Printable PDF ... view the expand/collapse boxes. Description Sudden infant death with dysgenesis of the testes syndrome ( SIDDT ) is ...

Temporal Transcriptional Profiling of Somatic and Germ Cells Reveals Biased Lineage Priming of Sexual Fate in the Fetal Mouse Gonad

PubMed Central

Jameson, Samantha A.; Natarajan, Anirudh; Cool, Jonah; DeFalco, Tony; Maatouk, Danielle M.; Mork, Lindsey; Munger, Steven C.; Capel, Blanche

2012-01-01

The divergence of distinct cell populations from multipotent progenitors is poorly understood, particularly in vivo. The gonad is an ideal place to study this process, because it originates as a bipotential primordium where multiple distinct lineages acquire sex-specific fates as the organ differentiates as a testis or an ovary. To gain a more detailed understanding of the process of gonadal differentiation at the level of the individual cell populations, we conducted microarrays on sorted cells from XX and XY mouse gonads at three time points spanning the period when the gonadal cells transition from sexually undifferentiated progenitors to their respective sex-specific fates. We analyzed supporting cells, interstitial/stromal cells, germ cells, and endothelial cells. This work identified genes specifically depleted and enriched in each lineage as it underwent sex-specific differentiation. We determined that the sexually undifferentiated germ cell and supporting cell progenitors showed lineage priming. We found that germ cell progenitors were primed with a bias toward the male fate. In contrast, supporting cells were primed with a female bias, indicative of the robust repression program involved in the commitment to XY supporting cell fate. This study provides a molecular explanation reconciling the female default and balanced models of sex determination and represents a rich resource for the field. More importantly, it yields new insights into the mechanisms by which different cell types in a single organ adopt their respective fates. PMID:22438826

Case of 46,XX/47,XY, +21 chimerism in a newborn infant with ambiguous genitalia

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

Sawai, Tomoko; Yoshimoto, Masaaki; Kinoshita, Ei-ichi

The authors describe the whole-body chimerism in a newborn infant with small phallus, pseudo-vaginal perineal hypospadias, and a bifid scrotum containing gonads. The human testis determining factor gene (SRY) was detected by PCR amplification. GTG-banding chromosome analysis in peripheral blood lymphocytes and cultured fibroblasts derived from right cubital skin showed a 46,XX/47,XY, +21 karyotype. Their ratios in each cell line were 294:5 and 178:7, respectively. QFQ-banding chromosome analysis documented 3 heteromorphic satellites on trisomic chromsomes 21 in the 47,XY,+21 cell line and a homozygous satellite pattern in the 46,XX cell line. Heteromorphic patterns of chromsomes 4, 13, 14, and 22more » were also different between the two cell lines. To our knowledge, such disomy/trisomy chimeras have not been described previously. 10 refs., 3 figs.« less

Genetics Home Reference: renal tubular dysgenesis

MedlinePlus

... genetic condition? Genetic and Rare Diseases Information Center Frequency Renal tubular dysgenesis is a rare disorder, but ... of Medicine Lister Hill National Center for Biomedical Communications 8600 Rockville Pike, Bethesda, MD 20894, USA HONCode ...

Gender Development in 46,XY DSD: Influences of Chromosomes, Hormones, and Interactions with Parents and Healthcare Professionals

PubMed Central

Wisniewski, Amy B.

2012-01-01

Variables that impact gender development in humans are difficult to evaluate. This difficulty exists because it is not usually possible to tease apart biological influences on gender from social variables. People with disorders of sex development, or DSD, provide important opportunities to study gender within individuals for whom biologic components of sex can be discordant with social components of gender. While most studies of gender development in people with 46,XY DSD have historically emphasized the importance of genes and hormones on gender identity and gender role, more recent evidence for a significant role for socialization exists and is considered here. For example, the influence of parents' perceptions of, and reactions to, DSD are considered. Additionally, the impact of treatments for DSD such as receiving gonadal surgeries or genitoplasty to reduce genital ambiguity on the psychological development of people with 46,XY DSD is presented. Finally, the role of multi-disciplinary care including access to peer support for advancing medical, surgical and psychosexual outcomes of children and adults with 46,XY DSD, regardless of sex of rearing, is discussed. PMID:24278745

XX ovarian dysgenesis is caused by a PSMC3IP/HOP2 mutation that abolishes coactivation of estrogen-driven transcription.

PubMed

Zangen, David; Kaufman, Yotam; Zeligson, Sharon; Perlberg, Shira; Fridman, Hila; Kanaan, Moein; Abdulhadi-Atwan, Maha; Abu Libdeh, Abdulsalam; Gussow, Ayal; Kisslov, Irit; Carmel, Liran; Renbaum, Paul; Levy-Lahad, Ephrat

2011-10-07

XX female gonadal dysgenesis (XX-GD) is a rare, genetically heterogeneous disorder characterized by lack of spontaneous pubertal development, primary amenorrhea, uterine hypoplasia, and hypergonadotropic hypogonadism as a result of streak gonads. Most cases are unexplained but thought to be autosomal recessive. We elucidated the genetic basis of XX-GD in a highly consanguineous Palestinian family by using homozygosity mapping and candidate-gene and whole-exome sequencing. Affected females were homozygous for a 3 bp deletion (NM_016556.2, c.600_602del) in the PSMC3IP gene, leading to deletion of a glutamic acid residue (p.Glu201del) in the highly conserved C-terminal acidic domain. Proteasome 26S subunit, ATPase, 3-Interacting Protein (PSMC3IP)/Tat Binding Protein Interacting Protein (TBPIP) is a nuclear, tissue-specific protein with multiple functions. It is critical for meiotic recombination as indicated by the known role of its yeast ortholog, Hop2. Through the C terminus (not present in yeast), PSMC3IP also coactivates ligand-driven transcription mediated by estrogen, androgen, glucocorticoid, progesterone, and thyroid nuclear receptors. In cell lines, the p.Glu201del mutation abolished PSMC3IP activation of estrogen-driven transcription. Impaired estrogenic signaling can lead to ovarian dysgenesis both by affecting the size of the follicular pool created during fetal development and by failing to counteract follicular atresia during puberty. PSMC3IP joins previous genes known to be mutated in XX-GD, the FSH receptor, and BMP15, highlighting the importance of hormonal signaling in ovarian development and maintenance and suggesting a common pathway perturbed in isolated XX-GD. By analogy to other XX-GD genes, PSMC3IP is also a candidate gene for premature ovarian failure, and its role in folliculogenesis should be further investigated. Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

InXy and SeXy, compact heterologous reporter proteins for mammalian cells.

PubMed

Fluri, David A; Kelm, Jens M; Lesage, Guillaume; Baba, Marie Daoud-El; Fussenegger, Martin

2007-10-15

Mammalian reporter proteins are essential for gene-function analysis, drugscreening initiatives and as model product proteins for biopharmaceutical manufacturing. Bacillus subtilis can maintain its metabolism by secreting Xylanase A (XynA), which converts xylan into shorter xylose oligosaccharides. XynA is a family 11 xylanase monospecific for D-xylose containing substrates. Mammalian cells transgenic for constitutive expression of wild-type xynA showed substantial secretion of this prokaryotic enzyme. Deletion analysis confirmed that a prokaryotic signal sequence encoded within the first 81 nucleotides was compatible with the secretory pathway of mammalian cells. Codon optimization combined with elimination of the prokaryotic signal sequence resulted in an exclusively intracellular mammalian Xylanase A variant (InXy) while replacement by an immunoglobulin-derived secretion signal created an optimal secreted Xylanase A derivative (SeXy). A variety of chromogenic and fluorescence-based assays adapted for use with mammalian cells detected InXy and SeXy with high sensitivity and showed that both reporter proteins resisted repeated freeze/thaw cycles, remained active over wide temperature and pH ranges, were extremely stable in human serum stored at room temperature and could independently be quantified in samples also containing other prominent reporter proteins such as the human placental alkaline phosphatase (SEAP) and the Bacillus stearothermophilus-derived secreted alpha-amylase (SAMY). Glycoprofiling revealed that SeXy produced in mammalian cells was N- glycosylated at four different sites, mutation of which resulted in impaired secretion. SeXy was successfully expressed in a variety of mammalian cell lines and primary cells following transient transfection and transduction with adeno-associated virus particles (AAV) engineered for constitutive SeXy expression. Intramuscular injection of transgenic AAVs into mice showed significant SeXy levels in the bloodstream

An assessment of sex chromosome copy number in a phenotypic female patient with hypergonadtropic hypogonadism, primary amenorrhea and growth retardation by GTG-banding and FISH in peripheral blood and skin tissues

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

Jackson, I.M.D.; DeMoranville, B.; Grollino, M.G.

The present report describes studies performed on an 18-year-old phenotypic female referred because of primary amenorrhea, hypergonadotropic hypoganadism and growth retardation. The clinical features raised the possibility of a gonadal dysgenesis. The ovaries were not identified on either side. Her testosterone was significantly elevated, with serum level at 48 ng/dl, and her free testosterone at 7 pg/ml. A GTG-banding analysis of 33 peripheral blood leukocytes revealed the modal number of chromosomes to be 46 per cell with a male sex constitution and normal appearing banding patterns (46,XY). In view of the clinical findings, additional cells were scored to rule outmore » low percentage mosaicism. Out of 35 additional GTG-banded cells scored for the sex chromosomes, 4 cells (11.5%) were found to contain only one copy of the X chromosome. Fluorescent in situ hybridization (FISH) using dual color biotinylated X and Y probes (Imagenetics) was subsequently performed. Out of approximately 500 cells scored, 87% were found to be XY and 9% were found to be positive for the X signal only, versus 7% and 3% X signal only for 2 XY controls, aged 61 and 46, respectively. As loss of the Y chromosome has been reported in elderly males as well as certain males with leukemia, the age of the controls was important to note. To unequivocally establish the presence of mosaicism, a skin biopsy was obtained for fibroblast culture. Out of 388 total cells scored, 286 (74%) were found to be XY and 46 (12%) were found to be X, versus 99% XY and <1% X in controls. GTG-banding analysis of the same fibroblast culture is currently in progress. Preliminary data on this specimen thus far corroborate results of the FISH study. The presence of XY cells, along with an increased testosterone level, raises the distinct possibility of a gonadoblastoma. In view of this increased risk, arrangements are being made for the patient to have a laparoscopy and surgical removal of her presumptive streak

Dendritic spine dysgenesis in Autism Related Disorders

PubMed Central

Phillips, Mary; Pozzo-Miller, Lucas

2015-01-01

The activity-dependent structural and functional plasticity of dendritic spines has led to the long-standing belief that these neuronal compartments are the subcellular sites of learning and memory. Of relevance to human health, central neurons in several neuropsychiatric illnesses, including autism related disorders, have atypical numbers and morphologies of dendritic spines. These so-called dendritic spine dysgeneses found in individuals with autism related disorders are consistently replicated in experimental mouse models. Dendritic spine dysgenesis reflects the underlying synaptopathology that drives clinically relevant behavioral deficits in experimental mouse models, providing a platform for testing new therapeutic approaches. By examining molecular signaling pathways, synaptic deficits, and spine dysgenesis in experimental mouse models of autism related disorders we find strong evidence for mTOR to be a critical point of convergence and promising therapeutic target. PMID:25578949

Dendritic spine dysgenesis in autism related disorders.

PubMed

Phillips, Mary; Pozzo-Miller, Lucas

2015-08-05

The activity-dependent structural and functional plasticity of dendritic spines has led to the long-standing belief that these neuronal compartments are the subcellular sites of learning and memory. Of relevance to human health, central neurons in several neuropsychiatric illnesses, including autism related disorders, have atypical numbers and morphologies of dendritic spines. These so-called dendritic spine dysgeneses found in individuals with autism related disorders are consistently replicated in experimental mouse models. Dendritic spine dysgenesis reflects the underlying synaptopathology that drives clinically relevant behavioral deficits in experimental mouse models, providing a platform for testing new therapeutic approaches. By examining molecular signaling pathways, synaptic deficits, and spine dysgenesis in experimental mouse models of autism related disorders we find strong evidence for mTOR to be a critical point of convergence and promising therapeutic target. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Sexual dimorphic expression of DMRT1 and Sox9a during gonadal differentiation and hormone-induced sex reversal in the teleost fish Nile tilapia (Oreochromis niloticus).

PubMed

Kobayashi, Tohru; Kajiura-Kobayashi, Hiroko; Guan, Guijun; Nagahama, Yoshitaka

2008-01-01

We examined the expression profiles of tDMRT1 and Sox9a during gonadal sex differentiation and hormone-induced sex reversal. tDMRT1 was detected in the gonial germ-cell-surrounding cells in XY fry specifically before the appearance of any signs of morphological sex differentiation, that is, sex differences in germ cell number and histogenesis, such as differentiation into intratesticular efferent duct or ovarian cavity. The signals became localized in the Sertoli and epithelial cells comprising the efferent duct during gonadal differentiation. After the induction of XY sex reversal with estrogen, tDMRT1 decreased and then disappeared completely. In contrast, tDMRT1 was expressed in the germ-cell-surrounding cells in XX sex reversal with androgen. On the other hand, Sox9a did not show sexual dimorphism before the appearance of sex differences in histogenesis and was not expressed in the efferent duct in the testis. These results suggest that tDMRT1 is a superior testicular differentiation marker in tilapia.

Steroidogenic factor-1 (SF-1, NR5A1) and human disease

PubMed Central

Ferraz-de-Souza, Bruno; Lin, Lin; Achermann, John C.

2011-01-01

Steroidogenic factor-1 (SF-1, Ad4BP, encoded by NR5A1) is a key regulator of adrenal and reproductive development and function. Based upon the features found in Nr5a1 null mice, initial attempts to identify SF-1 changes in humans focused on those rare individuals with primary adrenal failure, a 46,XY karyotype, complete gonadal dysgenesis and Müllerian structures. Although alterations affecting DNA-binding of SF-1 were found in two such cases, disruption of SF-1 is not commonly found in patients with adrenal failure. In contrast, it is emerging that variations in SF-1 can be found in association with a range of human reproductive phenotypes such as 46,XY disorders of sex development (DSD), hypospadias, anorchia, male factor infertility, or primary ovarian insufficiency in women. Overexpression or overactivity of SF-1 is also reported in some adrenal tumors or endometriosis. Therefore, the clinical spectrum of phenotypes associated with variations in SF-1 is expanding and the importance of this nuclear receptor in human endocrine disease is now firmly established. PMID:21078366

Androgen induces gonadal soma-derived factor, Gsdf, in XX gonads correlated to sex-reversal but not Dmrt1 directly, in the teleost fish, northern medaka (Oryzias sakaizumii).

PubMed

Horie, Yoshifumi; Myosho, Taijun; Sato, Tadashi; Sakaizumi, Mitsuru; Hamaguchi, Satoshi; Kobayashi, Tohru

2016-11-15

In the inbred HNI-II strain of Oryzias sakaizumii, Dmy and Gsdf are expressed in XY gonads from Stages 35 and 36, respectively, similarly to the inbred Hd-rR strain of Oryzias latipes. However, Dmrt1 respectively becomes detectable at Stage 36 and 5 days post hatching (dph) in the two strains. In XX HNI-II embryos, 17α-methyltestosterone (MT) induces Gsdf mRNA from Stage 36, accompanied by complete sex-reversal in all treated individuals (MT, 10 ng/mL), while Dmrt1 mRNA was first detectable at 5 dph. In XX d-rR, MT induced Gsdf mRNA expression and sex-reversal in only some of the treated individuals. Together, these results suggest the testis differentiation cascade in XY individuals differs between the HNI-II and Hd-rR strains. In addition, it is suggested that androgen-induced XX sex-reversal proceeds via an androgen-Gsdf-Dmrt1 cascade and that Gsdf plays an important role in sex-reversal in medaka. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Identical NR5A1 Missense Mutations in Two Unrelated 46,XX Individuals with Testicular Tissues.

PubMed

Igarashi, Maki; Takasawa, Kei; Hakoda, Akiko; Kanno, Junko; Takada, Shuji; Miyado, Mami; Baba, Takashi; Morohashi, Ken-Ichirou; Tajima, Toshihiro; Hata, Kenichiro; Nakabayashi, Kazuhiko; Matsubara, Yoichi; Sekido, Ryohei; Ogata, Tsutomu; Kashimada, Kenichi; Fukami, Maki

2017-01-01

The role of monogenic mutations in the development of 46,XX testicular/ovotesticular disorders of sex development (DSD) remains speculative. Although mutations in NR5A1 are known to cause 46,XY gonadal dysgenesis and 46,XX ovarian insufficiency, such mutations have not been implicated in testicular development of 46,XX gonads. Here, we identified identical NR5A1 mutations in two unrelated Japanese patients with 46,XX testicular/ovotesticular DSD. The p.Arg92Trp mutation was absent from the clinically normal mothers and from 200 unaffected Japanese individuals. In silico analyses scored p.Arg92Trp as probably pathogenic. In vitro assays demonstrated that compared with wild-type NR5A1, the mutant protein was less sensitive to NR0B1-induced suppression on the SOX9 enhancer element. Other sequence variants found in the patients were unlikely to be associated with the phenotype. The results raise the possibility that specific mutations in NR5A1 underlie testicular development in genetic females. © 2016 WILEY PERIODICALS, INC.

Wnt signaling in caudal dysgenesis and diabetic embryopathy

PubMed Central

Pavlinkova, Gabriela; Salbaum, J. Michael; Kappen, Claudia

2010-01-01

Congenital defects are a major complication of diabetic pregnancy, and the leading cause of infant death in the first year of life. Caudal dysgenesis, occurring up to 200-fold more frequently in children born to diabetic mothers, is a hallmark of diabetic pregnancy. Given that there is also an at least 3-fold higher risk for heart defects and neural tube defects, it is important to identify the underlying molecular mechanisms for aberrant embryonic development. We have investigated gene expression in a transgenic mouse model of caudal dysgenesis, and in a pharmacological model using situ hybridization and quantitative real-time PCR. We identify altered expression of several molecules that control developmental processes and embryonic growth. The results from our models point towards major implication of altered Wnt signaling in the pathogenesis of developmental anomalies associated with embryonic exposure to maternal diabetes. PMID:18937363

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.

Surgery in disorders of sex development (DSD) with a gender issue: If (why), when, and how?

PubMed

Mouriquand, Pierre D E; Gorduza, Daniela Brindusa; Gay, Claire-Lise; Meyer-Bahlburg, Heino F L; Baker, Linda; Baskin, Laurence S; Bouvattier, Claire; Braga, Luis H; Caldamone, Anthony C; Duranteau, Lise; El Ghoneimi, Alaa; Hensle, Terry W; Hoebeke, Piet; Kaefer, Martin; Kalfa, Nicolas; Kolon, Thomas F; Manzoni, Gianantonio; Mure, Pierre-Yves; Nordenskjöld, Agneta; Pippi Salle, J L; Poppas, Dix Phillip; Ransley, Philip G; Rink, Richard C; Rodrigo, Romao; Sann, Léon; Schober, Justine; Sibai, Hisham; Wisniewski, Amy; Wolffenbuttel, Katja P; Lee, Peter

2016-06-01

Ten years after the consensus meeting on disorders of sex development (DSD), genital surgery continues to raise questions and criticisms concerning its indications, its technical aspects, timing and evaluation. This standpoint details each distinct situation and its possible management in 5 main groups of DSD patients with atypical genitalia: the 46,XX DSD group (congenital adrenal hyperplasia); the heterogeneous 46,XY DSD group (gonadal dysgenesis, disorders of steroidogenesis, target tissues impairments …); gonosomic mosaicisms (45,X/46,XY patients); ovo-testicular DSD; and "non-hormonal/non chromosomal" DSD. Questions are summarized for each DSD group with the support of literature and the feed-back of several world experts. Given the complexity and heterogeneity of presentation there is no consensus regarding the indications, the timing, the procedure nor the evaluation of outcome of DSD surgery. There are, however, some issues on which most experts would agree: 1) The need for identifying centres of expertise with a multidisciplinary approach; 2) A conservative management of the gonads in complete androgen insensitivity syndrome at least until puberty although some studies expressed concerns about the heightened tumour risk in this group; 3) To avoid vaginal dilatation in children after surgical reconstruction; 4) To keep asymptomatic mullerian remnants during childhood; 5) To remove confirmed streak gonads when Y material is present; 6) It is likely that 46,XY cloacal exstrophy, aphallia and severe micropenis would do best raised as male although this is based on limited outcome data. There is general acknowledgement among experts that timing, the choice of the individual and irreversibility of surgical procedures are sources of concerns. There is, however, little evidence provided regarding the impact of non-treated DSD during childhood for the individual development, the parents, society and the risk of stigmatization. The low level of evidence should

Ovarian Gonadoblastoma with Dysgerminoma in a Young Girl with 46, XX Karyotype: A Case Report

PubMed Central

Kanagal, Deepa V; Prasad, Kishan; Rajesh, Aparna; Kumar, Rohan G; Cherian, Sara; Shetty, Harish; Shetty, Prasanna Kumar

2013-01-01

Gonadoblastoma is a rare gonadal tumour consisting of a mixture of germ cells and sex cord stromal derivatives resembling immature granulosa and Sertoli cells. It usually arises in various types of gonadal dysgenesis containing Y chromosome like pure or mixed gonadal dysgenesis. Occurrence in phenotypically and chromosomally normal women is very rare. We report here a case of gonadoblastoma with dysgerminoma in a 14–years–old girl who presented with a huge tumour, virilisation and normal 46XX karyotype. Association of dysgerminoma is seen in 50% cases of gonadoblastomas. Elevated tumour markers like hCG and alpha Fetoprotein may make the diagnosis challenging. PMID:24179931

Inter-relationship between testicular dysgenesis and Leydig cell function in the masculinization programming window in the rat.

PubMed

van den Driesche, Sander; Kolovos, Petros; Platts, Sophie; Drake, Amanda J; Sharpe, Richard M

2012-01-01

The testicular dysgenesis syndrome (TDS) hypothesis proposes that maldevelopment of the testis, irrespective of cause, leads to malfunction of the somatic (Leydig, Sertoli) cells and consequent downstream TDS disorders. Studies in rats exposed in utero to di(n-butyl) phthalate (DBP) have strongly supported the TDS concept, but so far no direct evidence has been produced that links dysgenesis per se to somatic cell dysfunction, in particular to androgen production/action during the 'masculinization programming window' (MPW; e15.5-e18.5). Normal reproductive tract development and anogenital distance (AGD) are programmed within the MPW, and TDS disorders arise because of deficiencies in this programming. However, DBP-induced focal testicular dysgenesis (Leydig cell aggregation, ectopic Sertoli cells, malformed seminiferous cords) is not evident until after the MPW. Therefore, we used AGD as a read-out of androgen exposure in the MPW, and investigated if this measure was related to objectively quantified dysgenesis (Leydig cell aggregation) at e21.5 in male fetuses exposed to vehicle, DBP (500 or 750 mg/kg/day) or the synthetic glucocorticoid dexamethasone (Dex; alone or plus DBP-500) from e15.5-e18.5 (MPW), e13.5-e20.5 or e19.5-e20.5 (late window). Dysgenesis was found only in animals exposed to DBP during the MPW, and was negatively correlated (R² = -0.5) with AGD at e21.5 and at postnatal day 8, irrespective of treatment period. Dysgenesis was also negatively correlated (R² = -0.5) with intratesticular testosterone (ITT) at e21.5, but only when treatments in short windows (MPW, late window) were excluded; the same was true for correlation between AGD and ITT. We conclude that AGD, reflecting Leydig cell function solely within the MPW, is strongly related to focal dysgenesis. Our results point to this occurring because of a common early mechanism, targeted by DBP that determines both dysgenesis and early (during the MPW) fetal Leydig cell dysfunction. The

A Biallelic Mutation in the Homologous Recombination Repair Gene SPIDR Is Associated With Human Gonadal Dysgenesis.

PubMed

Smirin-Yosef, Pola; Zuckerman-Levin, Nehama; Tzur, Shay; Granot, Yaron; Cohen, Lior; Sachsenweger, Juliane; Borck, Guntram; Lagovsky, Irina; Salmon-Divon, Mali; Wiesmüller, Lisa; Basel-Vanagaite, Lina

2017-02-01

Primary ovarian insufficiency (POI) is caused by ovarian follicle depletion or follicle dysfunction, characterized by amenorrhea with elevated gonadotropin levels. The disorder presents as absence of normal progression of puberty. To elucidate the cause of ovarian dysfunction in a family with POI. We performed whole-exome sequencing in 2 affected individuals. To evaluate whether DNA double-strand break (DSB) repair activities are altered in biallelic mutation carriers, we applied an enhanced green fluorescent protein-based assay for the detection of specific DSB repair pathways in blood-derived cells. Diagnoses were made at the Pediatric Endocrine Clinic, Clalit Health Services, Sharon-Shomron District, Israel. Genetic counseling and sample collection were performed at the Pediatric Genetics Unit, Schneider Children's Medical Center Israel, Petah Tikva, Israel. Two sisters born to consanguineous parents of Israeli Muslim Arab ancestry presented with a lack of normal progression of puberty, high gonadotropin levels, and hypoplastic or absent ovaries on ultrasound. Blood samples for DNA extraction were obtained from all family members. Exome analysis to elucidate the cause of POI in 2 affected sisters. Analysis revealed a stop-gain homozygous mutation in the SPIDR gene (KIAA0146) c.839G>A, p.W280*. This mutation altered SPIDR activity in homologous recombination, resulting in the accumulation of 53BP1-labeled DSBs postionizing radiation and γH2AX-labeled damage during unperturbed growth. SPIDR is important for ovarian function in humans. A biallelic mutation in this gene may be associated with ovarian dysgenesis in cases of autosomal recessive inheritance. Copyright © 2017 by the Endocrine Society

Variants in congenital hypogonadotrophic hypogonadism genes identified in an Indonesian cohort of 46,XY under-virilised boys.

PubMed

Ayers, Katie L; Bouty, Aurore; Robevska, Gorjana; van den Bergen, Jocelyn A; Juniarto, Achmad Zulfa; Listyasari, Nurin Aisyiyah; Sinclair, Andrew H; Faradz, Sultana M H

2017-02-16

Congenital hypogonadotrophic hypogonadism (CHH) and Kallmann syndrome (KS) are caused by disruption to the hypothalamic-pituitary-gonadal (H-P-G) axis. In particular, reduced production, secretion or action of gonadotrophin-releasing hormone (GnRH) is often responsible. Various genes, many of which play a role in the development and function of the GnRH neurons, have been implicated in these disorders. Clinically, CHH and KS are heterogeneous; however, in 46,XY patients, they can be characterised by under-virilisation phenotypes such as cryptorchidism and micropenis or delayed puberty. In rare cases, hypospadias may also be present. Here, we describe genetic mutational analysis of CHH genes in Indonesian 46,XY disorder of sex development patients with under-virilisation. We present 11 male patients with varying degrees of under-virilisation who have rare variants in known CHH genes. Interestingly, many of these patients had hypospadias. We postulate that variants in CHH genes, in particular PROKR2, PROK2, WDR11 and FGFR1 with CHD7, may contribute to under-virilisation phenotypes including hypospadias in Indonesia.

AB020. Chromosome rearrangement in patients with 46,XY disorders of sex development

PubMed Central

Vu, Dung Chi; Nguyen, Khanh Ngoc; Can, Ngoc Bich; Bui, Thao Phuong; Fukami, Maki

2017-01-01

Background Disorders of sex development (DSD) is defined by congenital conditions in which development of chromosomal, gonadal, or anatomical sex is atypical. Causative mutations have not been identified in more than 50% 46,XY DSD cases. We aimed to identify chromosomal rearrangement in the development of 46,XY DSD in Vietnamese patients. Methods Case series report including clinical presentations and data from array-based comparative genomic hybridization analysis for six genetic males with genital abnormalities combines with mental disability and other congenital anomalies. Results Heterozygous submicroscopic deletions and/or duplications were identified in six cases. A 7.2 Mb terminal deletion at chromosome 9 including deletion of DMRT1 gene and a 2.7 Mb terminal duplication at chromosome 17 were detected in case 1 that presented with prematurity, dysmorphism and ambiguous genitalia. A terminal deletion affects DMRT1-3 at 9p22-23 was identified in case 2 with ambiguous genitalia, mental disability and dysmorphism. An 18 Mb terminal duplication at chromosome 5 was detected in case 3 with DSD, growth retardation, microcephaly and dysmorphism, ptosis, ventricular septal defect and craniosynostosis. An interstitial deletion including deletions of WT1, PAX6, and PRRG4 genes at chromosome 11 was detected in case 4 with WAGR syndrome. A terminal duplication at chromosome 7 was detected in case 5 with DSD, severe hypospadias, small phallus size (1 cm at 3 years of age), and no testis found clinically. A 5 Mb terminal deletion at chromosome 4 and a 6 Mb terminal duplication of chromosome 16 were detected in case 6 with severe motor-mental retardation, microcephaly (head circumference −3.5 SD), micrognathia, and DSD. Conclusions The results indicate that chromosomal rearrangements constitute an important part of the molecular bases of 46,XY DSD and that submicroscopic deletions and/or duplication can lead to various types of 46,XY DSD combined with other congenital

Genome-wide identification, phylogeny, and gonadal expression of fox genes in Nile tilapia, Oreochromis niloticus.

PubMed

Yuan, Jing; Tao, Wenjing; Cheng, Yunying; Huang, Baofeng; Wang, Deshou

2014-08-01

The fox genes play important roles in various biological processes, including sexual development. In the present study, we isolated 65 fox genes, belonging to 18 subfamilies named A-R, from Nile tilapia through genome-wide screening. Twenty-four of them have two or three (foxm1) copies. Furthermore, 16, 25, 68, and 45 fox members were isolated from nematodes, protochordates, teleosts, and tetrapods, respectively. Phylogenetic analyses indicated fox gene family had undergone three expansions parallel to the three rounds of genome duplication during evolution. We also analyzed the clustered fox genes and found that apparent linkage duplication existed in teleosts, which further supported fish-specific genome duplication hypothesis. In addition, species- and lineage-specific duplication is another reason for fox gene family expansion. Based on the four pairs of XX and XY gonadal transcriptome data from four critical developmental stages, we analyzed the expression profile of all fox genes and identified sexually dimorphic fox genes at each stage. All fox genes were detected in gonads, with 15 of them at the background expression level (total read per kb per million reads, RPKM < 10), 29 at moderate expression level (10 < total RPKM < 100), and 21 at high expression level (total RPKM > 100). There are 27, 24, 28, and 9 sexually dimorphic fox genes at 5, 30, 90, and 180 days after hatching (dah), respectively. foxq1a, foxf1, foxr1, and foxr1 were identified as the most differentially expressed genes at each stage. foxl2 was characterized as XX-dominant gene, while foxd5, foxi3, foxn3, foxj1a, foxj3b, and foxo6b were characterized as XY-dominant genes. qPCR and in situ hybridization of foxh1 and foxj1a were performed to confirm the expression profiles and to validate the transcriptome data. Our results suggest that fox genes might play important roles in sex determination and gonadal development in teleosts.

Integrated analysis of miRNA and mRNA expression profiles in tilapia gonads at an early stage of sex differentiation.

PubMed

Tao, Wenjing; Sun, Lina; Shi, Hongjuan; Cheng, Yunying; Jiang, Dongneng; Fu, Beide; Conte, Matthew A; Gammerdinger, William J; Kocher, Thomas D; Wang, Deshou

2016-05-04

MicroRNAs (miRNAs) represent a second regulatory network that has important effects on gene expression and protein translation during biological process. However, the possible role of miRNAs in the early stages of fish sex differentiation is not well understood. In this study, we carried an integrated analysis of miRNA and mRNA expression profiles to explore their possibly regulatory patterns at the critical stage of sex differentiation in tilapia. We identified 279 pre-miRNA genes in tilapia genome, which were highly conserved in other fish species. Based on small RNA library sequencing, we identified 635 mature miRNAs in tilapia gonads, in which 62 and 49 miRNAs showed higher expression in XX and XY gonads, respectively. The predicted targets of these sex-biased miRNAs (e.g., miR-9, miR-21, miR-30a, miR-96, miR-200b, miR-212 and miR-7977) included genes encoding key enzymes in steroidogenic pathways (Cyp11a1, Hsd3b, Cyp19a1a, Hsd11b) and key molecules involved in vertebrate sex differentiation (Foxl2, Amh, Star1, Sf1, Dmrt1, and Gsdf). These genes also showed sex-biased expression in tilapia gonads at 5 dah. Some miRNAs (e.g., miR-96 and miR-737) targeted multiple genes involved in steroid synthesis, suggesting a complex miRNA regulatory network during early sex differentiation in this fish. The sequence and expression patterns of most miRNAs in tilapia are conserved in fishes, indicating the basic functions of vertebrate miRNAs might share a common evolutionary origin. This comprehensive analysis of miRNA and mRNA at the early stage of molecular sex differentiation in tilapia XX and XY gonads lead to the discovery of differentially expressed miRNAs and their putative targets, which will facilitate studies of the regulatory network of molecular sex determination and differentiation in fishes.

Controversies of Sex Re-assignment in Genetic Males with Congenital Inadequacy of the Penis.

PubMed

Raveenthiran, Venkatachalam

2017-09-01

Sex assignment in 46XY genetic male children with congenital inadequacy of the penis (CIP) is controversial. Traditionally, children with penile length less than 2 cm at birth are considered unsuitable to be raised as males. They are typically re-assigned to female-sex and feminizing genitoplasty is usually done in infancy. However, the concept of cerebral androgen imprinting has caused paradigm shift in the philosophy of sex re-assignment. Masculinization of the brain, rather than length of the penis, is the modern criterion of sex re-assignment in CIP. This review summarizes the current understanding of the complex issue. In 46XY children with CIP, male-sex assignment appears appropriate in non-hormonal conditions such as idiopathic micropenis, aphallia and exstrophy. Female-sex re-assignment appears acceptable in complete androgen insensitivity (CAIS), while partial androgen insensitivity syndrome (PAIS) patients are highly dissatisfied with the assignment of either sex. Children with 5-alpha reductase deficiency are likely to have spontaneous penile lengthening at puberty. Hence, they are better raised as males. Although female assignment is common in pure gonadal dysgenesis, long-term results are not known to justify the decision.

Gonadotrophic cells and gonadal sex differentiation in medaka: Characterization of several northern and southern strains.

PubMed

Horie, Yoshifumi; Kobayashi, Tohru

2015-07-01

Gonadotropins play an important role in gametogenesis and reproduction in vertebrates. Their localization in the pituitary during gonadal sex differentiation has been studied mainly in southern (Oryzias latipes) strains of medaka fish, with that in northern medaka (O. sakaizumii) remaining poorly understood. Hence, in this study, we characterized gonadal differentiation and gonadotrophic cells during sex differentiation in two northern strains (HNI and Kaga) and two southern strains (Hd-rR and d-rR/Tokyo). All strains exhibited similar sex differentiation at hatching, such as (1) sex difference in germ cell number (XX > XY), and (2) the transition of XX germ cells into meiosis, and (3) presence of glycoprotein-α (Gpa)-positive cells. However, follicle-stimulating hormone-β (Fshb)-positive cells were first detected in the pituitary 1 day post-hatching in HNI. Exposure to high-temperature conditions and to cortisol in a dose dependent manner resulted in the localization of Fshb cells in the pituitary at hatching. This study demonstrates differences in gonadotropin subunit expression between northern and southern strains of medaka, and suggests that Fsh is not involved in early gonadal sex differentiation, such as the sex difference in germ cell number, and that high-temperature induce Fshb expression via cortisol production in medaka. © 2015 Wiley Periodicals, Inc.

Clinical review of 95 patients with 46,XX disorders of sex development based on the new Chicago classification.

PubMed

Öcal, Gönül; Berberoğlu, Merih; Sıklar, Zeynep; Aycan, Zehra; Hacıhamdioglu, Bülent; Savas Erdeve, Şenay; Çamtosun, Emine; Kocaay, Pınar; Ruhi, Hatice I; Kılıç, Birim G; Tukun, Ajlan

2015-02-01

The aim of our study was to determine the etiologic distribution of 46,XX disorder of sexual development (DSD) according to the new DSD classification system and to evaluate the clinical features of this DSD subgroup in our patient cohort. The evaluation criteria and clinical findings of 95 46,XX patients were described by clinical presentation, gonadal morphology, genital anatomy, associated dysmorphic features, presence during prenatal period with/without postnatal virilization, hormonal characteristics, and presence or absence of steroidogenic defects among 319 patients with DSD. Types and ratios of each presentation of our 95 patients with 46,XX DSD were as follows: 82 had androgen excess (86.3%): (74 had classical congenital adrenal hyperplasia, 2 had CAH variant possibility of P450-oxidoreductase gene defect), 6 had disorders of ovarian development (6.3%): (1 patient had gonadal dysgenesis with virilization at birth with bilateral streak gonad, 4 patients had complete gonadal dysgenesis, and 1 patient had ovotesticular DSD) and 7 had other 46,XX DSD. Two sisters, who had 46,XX complete gonadal dysgenesis,were diagnosed with Perrault Syndrome with ovarian failure due to streak gonads and associated with sensorineural deafness. 46,XX DSD are usually derived from intrauterine virilization and CAH is the most common cause of 46,XX DSD due to fetal androgen exposure. Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Experimentally induced testicular dysgenesis syndrome originates in the masculinization programming window

PubMed Central

van den Driesche, Sander; Kilcoyne, Karen R.; Wagner, Ida; Rebourcet, Diane; Mitchell, Rod; McKinnell, Chris; Macpherson, Sheila; Donat, Roland; Shukla, Chitranjan J.; Jorgensen, Anne; Skakkebaek, Niels E.; Sharpe, Richard M.

2017-01-01

The testicular dysgenesis syndrome (TDS) hypothesis, which proposes that common reproductive disorders of newborn and adult human males may have a common fetal origin, is largely untested. We tested this hypothesis using a rat model involving gestational exposure to dibutyl phthalate (DBP), which suppresses testosterone production by the fetal testis. We evaluated if induction of TDS via testosterone suppression is restricted to the “masculinization programming window” (MPW), as indicated by reduction in anogenital distance (AGD). We show that DBP suppresses fetal testosterone equally during and after the MPW, but only DBP exposure in the MPW causes reduced AGD, focal testicular dysgenesis, and TDS disorders (cryptorchidism, hypospadias, reduced adult testis size, and compensated adult Leydig cell failure). Focal testicular dysgenesis, reduced size of adult male reproductive organs, and TDS disorders and their severity were all strongly associated with reduced AGD. We related our findings to human TDS cases by demonstrating similar focal dysgenetic changes in testes of men with preinvasive germ cell neoplasia (GCNIS) and in testes of DBP-MPW animals. If our results are translatable to humans, they suggest that identification of potential causes of human TDS disorders should focus on exposures during a human MPW equivalent, especially if negatively associated with offspring AGD. PMID:28352662

The molecular and cellular basis of gonadal sex reversal in mice and humans

PubMed Central

Warr, Nick; Greenfield, Andy

2012-01-01

The mammalian gonad is adapted for the production of germ cells and is an endocrine gland that controls sexual maturation and fertility. Gonadal sex reversal, namely, the development of ovaries in an XY individual or testes in an XX, has fascinated biologists for decades. The phenomenon suggests the existence of genetic suppressors of the male and female developmental pathways and molecular genetic studies, particularly in the mouse, have revealed controlled antagonism at the core of mammalian sex determination. Both testis and ovary determination represent design solutions to a number of problems: how to generate cells with the right properties to populate the organ primordium; how to produce distinct organs from an initially bipotential primordium; how to pattern an organ when the expression of key cell fate determinants is initiated only in a discrete region of the primordium and extends to other regions asynchronously; how to coordinate the interaction between distinct cell types in time and space and stabilize the resulting morphology; and how to maintain the differentiated state of the organ throughout the adult period. Some of these, and related problems, are common to organogenesis in general; some are distinctive to gonad development. In this review, we discuss recent studies of the molecular and cellular events underlying testis and ovary development, with an emphasis on the phenomenon of gonadal sex reversal and its causes in mice and humans. Finally, we discuss sex-determining loci and disorders of sex development in humans and the future of research in this important area. WIREs Dev Biol 2012, 1:559–577. doi: 10.1002/wdev.42 PMID:23801533

Impact of X/Y genes and sex hormones on mouse neuroanatomy.

PubMed

Vousden, Dulcie A; Corre, Christina; Spring, Shoshana; Qiu, Lily R; Metcalf, Ariane; Cox, Elizabeth; Lerch, Jason P; Palmert, Mark R

2018-06-01

Biological sex influences brain anatomy across many species. Sex differences in brain anatomy have classically been attributed to differences in sex chromosome complement (XX versus XY) and/or in levels of gonadal sex steroids released from ovaries and testes. Using the four core genotype (4CG) mouse model in which gonadal sex and sex chromosome complement are decoupled, we previously found that sex hormones and chromosomes influence the volume of distinct brain regions. However, recent studies suggest there may be more complex interactions between hormones and chromosomes, and that circulating steroids can compensate for and/or mask underlying chromosomal effects. Moreover, the impact of pre vs post-pubertal sex hormone exposure on this sex hormone/sex chromosome interplay is not well understood. Thus, we used whole brain high-resolution ex-vivo MRI of intact and pre-pubertally gonadectomized 4CG mice to investigate two questions: 1) Do circulating steroids mask sex differences in brain anatomy driven by sex chromosome complement? And 2) What is the contribution of pre- versus post-pubertal hormones to sex-hormone-dependent differences in brain anatomy? We found evidence of both cooperative and compensatory interactions between sex chromosomes and sex hormones in several brain regions, but the interaction effects were of low magnitude. Additionally, most brain regions affected by sex hormones were sensitive to both pre- and post-pubertal hormones. This data provides further insight into the biological origins of sex differences in brain anatomy. Copyright © 2018 Elsevier Inc. All rights reserved.

Hormonal evaluation in relation to phenotype and genotype in 286 patients with a disorder of sex development from Indonesia.

PubMed

Juniarto, A Zulfa; van der Zwan, Yvonne G; Santosa, Ardy; Ariani, Mahayu Dewi; Eggers, Stefanie; Hersmus, Remko; Themmen, Axel P N; Bruggenwirth, Hennie T; Wolffenbuttel, Katja P; Sinclair, Andrew; White, Stefan J; Looijenga, Leendert H J; de Jong, Frank H; Faradz, Sultana M H; Drop, Stenvert L S

2016-08-01

The objective of this study was to determine the aetiological spectrum of disorders of sex development (DSD) in a large cohort of underprivileged and undiagnosed patients from Indonesia. A total of 286 patients with atypical external and/or internal genitalia were evaluated using clinical, hormonal, molecular genetic and histological parameters. The age (years) at presentation was 0-0·5 in 41 (14·3%), >0·5-12 in 181 (63·3%) and >12 in 64 cases (22·4%). 46,XY DSD was most common (68·2%, n = 195), 46,XX DSD was found in 23·4% (n = 67) and sex chromosomal DSD in 8·4% (n = 24). In 61·2% of 46,XX DSD patients, 17·9% of 46,XY DSD patients and all sex chromosome DSD patients (29·4% in total), a final diagnosis was reached based on genetic or histological gonadal tissue evaluation. 17-hydroxyprogesterone and androstenedione levels were the most distinctive parameters in 46,XX DSD patients. In 46,XY DSD, diagnostic groups were identified based on the external masculinization score: androgen action disorder (AAD), unknown male undermasculinization (UMU), and gonadal dysgenesis (GD). LH, FSH and testosterone levels were most informative especially in the older age group. HCG tests were of no additional value as no patients with androgen synthesis disorders were found. Hormonal profiles of patients with sex chromosome DSD and a Y-chromosome sequence containing karyotype showed high levels of LH and FSH, and low levels of AMH, inhibin B and testosterone compared with the normal male range. Gene mutations were found in all patients with CAH, but in only 24·5% and 1·8% of patients with AAD and UMU. In 32% of 46,XY GD patients, copy number variants of different genes were found. A stepwise diagnostic approach led to a molecularly or histologically proven final diagnosis in 29·4% of the patients. The most informative parameters were serum levels of 17-hydroxyprogesterone and androstenedione in 46,XX DSD patients, and serum LH, FSH and testosterone levels in 46,XY DSD

Multiparameter Investigation of a 46,XX/46,XY Tetragametic Chimeric Phenotypical Male Patient with Bilateral Scrotal Ovotestes and Ovulatory Activity.

PubMed

van Bever, Yolande; Wolffenbuttel, Katja P; Brüggenwirth, Hennie T; Blom, Eric; de Klein, Annelies; Eussen, Bert H J; van der Windt, Florijn; Hannema, Sabine E; Dessens, Arianne B; Dorssers, Lambert C J; Biermann, Katharina; Hersmus, Remko; de Rijke, Yolanda B; Looijenga, Leendert H J

2018-01-01

We report on an adult male initially presenting with gynecomastia and a painless scrotal mass without additional genital anomalies. Hyperpigmentation of the skin following the Blaschko's lines was identified. He underwent gonadectomy because of suspected cancer. Histological analyses revealed an ovotestis with ovulatory activity confirmed by immunohistochemistry with multiple markers. Karyotyping of cultured peripheral blood lymphocytes and a buccal smear revealed a 46,XX/46,XY chimeric constitution with different percentages. Multiple molecular analyses as well as blood typing implied a tetragametic origin. After the unilateral gonadectomy, the patient developed recurrent painful cystic swellings of the remaining gonad. Because of the wish to preserve hormonal activity as well as future fertility, the patient underwent surgical resection of a cystic gonadal area. The removed tissue showed ovulation-related features in addition to both testicular and ovarian tissue, diagnosed as an ovotestis. Testosterone therapy was initiated to suppress the persistently elevated gonadotropins and thereby suppress ovarian activity. During treatment, the recurrent pain complaints and cystic swellings ceased, although gonadotropin levels were not fully suppressed. Based on these observations, the importance of a detailed genetic and pathological diagnosis and the clinical dilemmas including the pros and cons of personalized treatment with gonadal preservative surgery are discussed. © 2017 S. Karger AG, Basel.

Testicular Dysgenesis Syndrome and the Estrogen Hypothesis: A Quantitative Meta-Analysis

PubMed Central

Martin, Olwenn V.; Shialis, Tassos; Lester, John N.; Scrimshaw, Mark D.; Boobis, Alan R.; Voulvoulis, Nikolaos

2008-01-01

Background Male reproductive tract abnormalities such as hypospadias and cryptorchidism, and testicular cancer have been proposed to comprise a common syndrome together with impaired spermatogenesis with a common etiology resulting from the disruption of gonadal development during fetal life, the testicular dysgenesis syndrome (TDS). The hypothesis that in utero exposure to estrogenic agents could induce these disorders was first proposed in 1993. The only quantitative summary estimate of the association between prenatal exposure to estrogenic agents and testicular cancer was published over 10 years ago, and other systematic reviews of the association between estrogenic compounds, other than the potent pharmaceutical estrogen diethylstilbestrol (DES), and TDS end points have remained inconclusive. Objectives We conducted a quantitative meta-analysis of the association between the end points related to TDS and prenatal exposure to estrogenic agents. Inclusion in this analysis was based on mechanistic criteria, and the plausibility of an estrogen receptor (ER)-α–mediated mode of action was specifically explored. Results We included in this meta-analysis eight studies investigating the etiology of hypospadias and/or cryptorchidism that had not been identified in previous systematic reviews. Four additional studies of pharmaceutical estrogens yielded a statistically significant updated summary estimate for testicular cancer. Conclusions The doubling of the risk ratios for all three end points investigated after DES exposure is consistent with a shared etiology and the TDS hypothesis but does not constitute evidence of an estrogenic mode of action. Results of the subset analyses point to the existence of unidentified sources of heterogeneity between studies or within the study population. PMID:18288311

Testicular dysgenesis syndrome and the estrogen hypothesis: a quantitative meta-analysis.

PubMed

Martin, Olwenn V; Shialis, Tassos; Lester, John N; Scrimshaw, Mark D; Boobis, Alan R; Voulvoulis, Nikolaos

2008-02-01

Male reproductive tract abnormalities such as hypospadias and cryptorchidism, and testicular cancer have been proposed to comprise a common syndrome together with impaired spermatogenesis with a common etiology resulting from the disruption of gonadal development during fetal life, the testicular dysgenesis syndrome (TDS). The hypothesis that in utero exposure to estrogenic agents could induce these disorders was first proposed in 1993. The only quantitative summary estimate of the association between prenatal exposure to estrogenic agents and testicular cancer was published over 10 years ago, and other systematic reviews of the association between estrogenic compounds, other than the potent pharmaceutical estrogen diethylstilbestrol (DES), and TDS end points have remained inconclusive. We conducted a quantitative meta-analysis of the association between the end points related to TDS and prenatal exposure to estrogenic agents. Inclusion in this analysis was based on mechanistic criteria, and the plausibility of an estrogen receptor (ER)-alpha-mediated mode of action was specifically explored. We included in this meta-analysis eight studies investigating the etiology of hypospadias and/or cryptorchidism that had not been identified in previous systematic reviews. Four additional studies of pharmaceutical estrogens yielded a statistically significant updated summary estimate for testicular cancer. The doubling of the risk ratios for all three end points investigated after DES exposure is consistent with a shared etiology and the TDS hypothesis but does not constitute evidence of an estrogenic mode of action. Results of the subset analyses point to the existence of unidentified sources of heterogeneity between studies or within the study population.

X and Y Chromosome Complement Influence Adiposity and Metabolism in Mice

PubMed Central

Chen, Xuqi; McClusky, Rebecca; Itoh, Yuichiro; Reue, Karen

2013-01-01

Three different models of MF1 strain mice were studied to measure the effects of gonadal secretions and sex chromosome type and number on body weight and composition, and on related metabolic variables such as glucose homeostasis, feeding, and activity. The 3 genetic models varied sex chromosome complement in different ways, as follows: 1) “four core genotypes” mice, comprising XX and XY gonadal males, and XX and XY gonadal females; 2) the XY* model comprising groups similar to XO, XX, XY, and XXY; and 3) a novel model comprising 6 groups having XO, XX, and XY chromosomes with either testes or ovaries. In gonadally intact mice, gonadal males were heavier than gonadal females, but sex chromosome complement also influenced weight. The male/female difference was abolished by adult gonadectomy, after which mice with 2 sex chromosomes (XX or XY) had greater body weight and percentage of body fat than mice with 1 X chromosome. A second sex chromosome of either type, X or Y, had similar effects, indicating that the 2 sex chromosomes each possess factors that influence body weight and composition in the MF1 genetic background. Sex chromosome complement also influenced metabolic variables such as food intake and glucose tolerance. The results reveal a role for the Y chromosome in metabolism independent of testes and gonadal hormones and point to a small number of X–Y gene pairs with similar coding sequences as candidates for causing these effects. PMID:23397033

Bilateral anterior segment dysgenesis with the presumed Peters' anomaly in a cat.

PubMed

Park, Sangwan; Kim, Kiwoong; Kim, Youngbeum; Seo, Kangmoon

2018-02-20

A seven-month-old female domestic shorthaired cat was presented for buphthalmos in the right eye and corneal cloudiness in the left eye. Full ophthalmic examinations were performed for both eyes and enucleation was done for the right nonvisual eye. Congenital glaucoma caused by anterior segment dysgenesis was confirmed for the right eye. In the left eye, slit-lamp examination revealed focal corneal edema with several iris strands from iris collarette to the affected posterior corneal surfaces. Circular posterior corneal defect was suggested to be the cause of edema. Goniodysgenesis, additionally, was identified. Taken together, the diagnosis of Peters' anomaly which is a subtype of anterior segment dysgenesis was suggested in the left eye.

Chromosomal Effects on Mutability in the P-M System of Hybrid Dysgenesis in DROSOPHILA MELANOGASTER

PubMed Central

Simmons, Michael J.; Raymond, John D.; Laverty, Todd R.; Doll, Rhonda F.; Raymond, Nancy C.; Kocur, Gordon J.; Drier, Eric A.

1985-01-01

Two manifestations of hybrid dysgenesis were studied in flies with chromosomes derived from two different P strains. In one set of experiments, the occurrence of recessive X-linked lethal mutations in the germ cells of dysgenic males was monitored. In the other, the behavior of an X-linked P-element insertion mutation, sn w, was studied in dysgenic males and also in dysgenic females. The chromosomes of one P strain were more proficient at causing dysgenesis in both sets of experiments. However, there was variation among the chromosomes of each strain in regard to the ability to induce lethals or to destabilize snw. The X chromosome, especially when it came from the stronger P strain, had a pronounced effect on both measures of dysgenesis, but in combination with the major autosomes, these effects were reduced. For the stronger P strain, the autosomes by themselves contributed significantly to the production of X-linked lethals and also had large effects on the behavior of snw, but they did not act additively on these two characters. For this strain, the effects of the autosomes on the X-linked lethal mutation rate suggest that only 1/100 P element transpositions causes a recessive lethal mutation. For the weaker P strain, the autosomes had only slight effects on the behavior of snw and appeared to have negligible effects on the X-linked lethal mutation rate. Combinations of chromosomes from either the strong or the weak P strain affected both aspects of dysgenesis in a nonadditive fashion, suggesting that the P elements on these chromosomes competed with each other for transposase, the P-encoded function that triggers P element activity. Age and sex also influenced the ability of chromosomes and combinations of chromosomes to cause dysgenesis. PMID:3934034

Epileptic phenotype of FGFR3-related bilateral medial temporal lobe dysgenesis.

PubMed

Okazaki, Tetsuya; Saito, Yoshiaki; Ueda, Riyo; Awashima, Takeya; Nishimura, Yoko; Yuasa, Isao; Shinohara, Yuki; Adachi, Kaori; Sasaki, Masayuki; Nanba, Eiji; Maegaki, Yoshihiro

2017-01-01

Hypochondroplasia (HCH) is a skeletal dysplasia, characterized by short stature and macrocephaly. Clinical symptoms and radiological and histopathological features of HCH are similar, but milder than those seen in achondroplasia. Particularly, HCH patients with Asn540Lys mutation in the FGFR3 gene are reported to have medial temporal lobe dysgenesis and epilepsy. We report a 3-year-old girl who developed recurrent epileptic apnea, which started immediately after birth. The apneic seizures were refractory to antiepileptic medications; ictal electroencephalography showed rhythmic activity originating from the left or right temporal areas and rarely from the right frontal area. Macrocephaly was noted since birth. Neuroimaging revealed bilateral dysgenesis and hypometabolism of the medial temporal structures as well as perfusion changes in the left lateral temporofrontal areas during the ictal period. Clonazepam was initiated and acetazolamide dosage was increased at 6months, resulting in complete seizure control after 8months of age. Genetic analysis identified an Asn540Lys (c.1620 C>A) mutation in the FGFR3 gene. Characteristic bone findings on the lumbar spine, iliac bone, and femur were retrospectively confirmed on X-rays during infancy. This was the first report that delineated the epilepsy phenotype in FGFR3-related bilateral medial temporal lobe dysgenesis; such findings would lead to an early diagnosis and better epilepsy management. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Pituitary origin of persistently elevated human chorionic gonadotropin in a patient with gonadal failure.

PubMed

Merhi, Zaher; Pollack, Staci E

2013-01-01

To report a case of persistently elevated low levels of hCG to increase awareness of pituitary origin of persistently elevated hCG in patients with gonadal failure. Case report and literature review. Large university-affiliated infertility practice. A 16-year-old patient with primary amenorrhea, normal secondary sex characteristics, ovarian failure, and a 46,XY karyotype. Her past medical history was significant for focal segmental glomerulosclerosis, leading to a diagnosis of Frasier syndrome. At age 31 years, she desired pregnancy by oocyte donation and was found to have persistently elevated low levels of hCG (>35 mIU/mL). Pituitary hCG. Both serum free β-hCG and hyperglycosylated hCG were undetectable. Total serum hCG diluted appropriately was not blocked by blocking agent and was detected in the urine. Subsequent treatment with exogenous E(2), in preparation of a donor oocyte cycle, suppressed her hCG levels (down to 8 mIU/mL). These results indicated a pituitary source of the serum hCG. This report reinforces the need to consider pituitary hCG as the origin of persistently elevated hCG levels in patients with gonadal failure. Although levels of hCG <14 mIU/mL have been considered normal in postmenopausal women, our case suggests that patients with gonadal failure at younger ages might have a higher pituitary output of hCG. Copyright © 2013 American Society for Reproductive Medicine. Published by 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

Coordinated X-Y stage apparatus

DOEpatents

Morimoto, Alan K.; Kozlowski, David M.; Charles, Steven T.; Spalding, James A.

2000-01-01

An apparatus based on precision X-Y stages that are stacked. Attached to arms projecting from each X-Y stage are a set of two axis gimbals. Attached to the gimbals is a rod, which provides motion along the axis of the rod and rotation around its axis. A dual-planar apparatus that provides six degrees of freedom of motion precise to within microns of motion.

Broad phenotypes in heterozygous NR5A1 46,XY patients with a disorder of sex development: an oligogenic origin?

PubMed

Camats, Núria; Fernández-Cancio, Mónica; Audí, Laura; Schaller, André; Flück, Christa E

2018-06-11

SF-1/NR5A1 is a transcriptional regulator of adrenal and gonadal development. NR5A1 disease-causing variants cause disorders of sex development (DSD) and adrenal failure, but most affected individuals show a broad DSD/reproductive phenotype only. Most NR5A1 variants show in vitro pathogenic effects, but not when tested in heterozygote state together with wild-type NR5A1 as usually seen in patients. Thus, the genotype-phenotype correlation for NR5A1 variants remains an unsolved question. We analyzed heterozygous 46,XY SF-1/NR5A1 patients by whole exome sequencing and used an algorithm for data analysis based on selected project-specific DSD- and SF-1-related genes. The variants detected were evaluated for their significance in literature, databases and checked in silico using webtools. We identified 19 potentially deleterious variants (one to seven per patient) in 18 genes in four 46,XY DSD subjects carrying heterozygous NR5A1 disease-causing variants. We constructed a scheme of all these hits within the landscape of currently known genes involved in male sex determination and differentiation. Our results suggest that the broad phenotype in these heterozygous NR5A1 46,XY DSD subjects may well be explained by an oligogenic mode of inheritance, in which multiple hits, individually non-deleterious, may contribute to a DSD phenotype unique to each heterozygous SF-1/NR5A1 individual.

Integrated optical XY coupler

DOEpatents

Vawter, G. Allen; Hadley, G. Ronald

1997-01-01

An integrated optical XY coupler having two converging input waveguide arms meeting in a central section and a central output waveguide arm and two diverging flanking output waveguide arms emanating from the central section. In-phase light from the input arms constructively interfers in the central section to produce a single mode output in the central output arm with the rest of the light being collected in the flanking output arms. Crosstalk between devices on a substrate is minimized by this collection of the out-of-phase light by the flanking output arms of the XY coupler.

Integrated optical XY coupler

DOEpatents

Vawter, G.A.; Hadley, G.R.

1997-05-06

An integrated optical XY coupler having two converging input waveguide arms meeting in a central section and a central output waveguide arm and two diverging flanking output waveguide arms emanating from the central section. In-phase light from the input arms constructively interferes in the central section to produce a single mode output in the central output arm with the rest of the light being collected in the flanking output arms. Crosstalk between devices on a substrate is minimized by this collection of the out-of-phase light by the flanking output arms of the XY coupler. 9 figs.

Hypogonadism and Sex Steroid Replacement Therapy in Girls with Turner Syndrome.

PubMed

Gawlik, Aneta; Hankus, Magdalena; Such, Kamila; Drosdzol-Cop, Agnieszka; Madej, Paweł; Borkowska, Marzena; Zachurzok, Agnieszka; Malecka-Tendera, Ewa

2016-12-01

Turner syndrome is the most common example of hypergonadotropic hypogonadism resulting from gonadal dysgenesis. Most patients present delayed, or even absent, puberty. Premature ovarian failure can be expected even if spontaneous menarche occurs. Laboratory markers of gonadal dysgenesis are well known. The choice of optimal hormone replacement therapy in children and adolescents remains controversial, particularly regarding the age at which therapy should be initiated, and the dose and route of estrogen administration. On the basis of a review of the literature, we present the most acceptable schedule of sex steroid replacement therapy in younger patients with Turner syndrome. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Effects of 17α-Methyltestosterone and Aromatase Inhibitor Letrozole on Sex Reversal, Gonadal Structure, and Growth in Yellow Catfish Pelteobagrus fulvidraco.

PubMed

Shen, Zhi-Gang; Fan, Qi-Xue; Yang, Wei; Zhang, Yun-Long; Wang, Han-Ping

2015-04-01

Monosex populations are in demand in many fish species with sexual dimorphism, e.g., better growth performance, higher gonad value, superior ornamental value. From the point of view of research, a monosex population is one of the best materials for investigating sex-determining mechanisms, sex differentiation, and sex-linked markers. Sex reversal of females (phenotypic reversal from XX female to XX male) is the first step in all-female production in species with an XX/XY system for sex determination. In the present study, masculinization of yellow catfish, a species with XX/XY sex determination, was investigated by oral administration of various doses of 17α-methyltestosterone (MT) or an aromatase inhibitor (AI) letrozole (LZ); effects on survival, growth performance, sex ratio, and changes in gonadal structure were evaluated. Three doses (20, 50, and 100 mg kg(-1) diet) of oral MT or LZ were administered to fry from 10 days post-hatching (DPH) to 59 DPH. Oral administration of MT at all doses did not significantly change the ratio of males (45.8%, 33.3%, and 50.0% respectively) compared to the control group (37.5%), while yielding intersex fish at all doses (4.2% to 8.3%). Oral administration of LZ produced a significantly higher proportion of males in all doses (75.5%, 83.3%, and 75.0%, respectively). Additionally, the lowest dose of LZ improved the growth of treated fish compared to the control, and all doses of LZ enhanced spermatogenesis in treated males. © 2015 Marine Biological Laboratory.

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

An extreme bias in the germ line of XY C57BL/6<->XY FVB/N chimaeric mice

PubMed Central

MacGregor, G. R.

2011-01-01

Chimaeric analysis is a powerful method to address questions about the cell-autonomous nature of defects in spermatogenesis. Symplastic spermatids (sys) mice have a recessive mutation that causes male sterility due to an arrest in germ-cell development during spermiogenesis. Chimaeric mice were generated by aggregation of eight-cell embryos from sys (FVB/N genetic background) and wild-type C57BL/6 (B6) mice to determine whether the male germ-cell defect is cell-autonomous. The resulting FVB/N<->B6 chimaeras (<-> denotes fusion of embryos) were mated with FVB/N mice and coat colour of offspring was used to identify transmission of FVB/N or B6 gametes. Regardless of the relative contribution of B6 to somatic tissues of the chimaeras, almost all (282 of 284; 99.3%) offspring of B6 XY<->XY FVB/N (+/+ or sys/+) males (n = 9) received a FVB/N-derived paternal gamete. After mating of female B6<->FVB/N chimaeras, 51 of 73 (69.9%) offspring received an FVB-derived maternal gamete. Southern blot analysis of different tissues from chimaeric males indicated that, despite the presence of balanced chimaerism in somatic tissues, the germ line in B6 XY<->XY FVB/N mice was essentially FVB/N in composition. Thus there is a strong selective advantage for FVB/N male germ cells over B6 male germ cells in B6<->FVB/N-aggregation chimaeras at some stage during development of the male germ line. Each of three male chimaeras that were either B6 XY<->XY FVB/N (sys/sys) or B6 XX<->XY FVB/N (sys/sys) in composition was sterile, and testis histology was essentially sys mutant. This finding indicates that the function of the gene(s) affected in the sys mutation may be required in the testis, although whether expression is required in germ cells, somatic cells or both remains unknown. The extreme bias in transmission of male gametes has implications for experimental design in studies that use chimaeric analysis to address questions regarding the cell-autonomous nature of germ-cell defects in mice

Automated edge finishing using an active XY table

DOEpatents

Loucks, Clifford S.; Starr, Gregory P.

1993-01-01

The disclosure is directed to an apparatus and method for automated edge finishing using hybrid position/force control of an XY table. The disclosure is particularly directed to learning the trajectory of the edge of a workpiece by "guarded moves". Machining is done by controllably moving the XY table, with the workpiece mounted thereon, along the learned trajectory with feedback from a force sensor. Other similar workpieces can be mounted, without a fixture on the XY table, located and the learned trajectory adjusted

Helicity moduli of three-dimensional dilute XY models

NASA Astrophysics Data System (ADS)

Garg, Anupam; Pandit, Rahul; Solla, Sara A.; Ebner, C.

1984-07-01

The helicity moduli of various dilute, classical XY models on three-dimensional lattices are studied with a view to understanding some aspects of the superfluidity of 4He in Vycor glass. A spinwave calculation is used to obtain the low-temperature helicity modulus of a regularly-diluted XY model. A similar calculation is performed for the randomly bond-diluted and site-diluted XY models in the limit of low dilution. A Monte Carlo simulation is used to obtain the helicity modulus of the randomly bond-diluted XY model over a wide range of temperature and dilution. It is found that the randomly diluted models do agree and the regularly diluted model does not agree with certain experimentally found features of the variation in superfluid fraction with coverage of 4He in Vycor glass.

Aetiological bases of 46,XY disorders of sex development in the Hong Kong Chinese population.

PubMed

Chan, Angel O K; But, W M; Lee, C Y; Lam, Y Y; Ng, K L; Loung, P Y; Lam, Aimen; Cheng, C W; Shek, C C; Wong, W S; Wong, K F; Wong, M Y; Tse, W Y

2015-12-01

Disorders of sex development are due to congenital defects in chromosomal, gonadal, or anatomical sex development. The objective of this study was to determine the aetiology of this group of disorders in the Hong Kong Chinese population. Five public hospitals in Hong Kong. Patients with 46,XY disorders of sex development under the care of paediatric endocrinologists between July 2009 and June 2011. Measurement of serum gonadotropins, adrenal and testicular hormones, and urinary steroid profiling. Mutational analysis of genes involved in sexual differentiation by direct DNA sequencing and multiplex ligation-dependent probe amplification. Overall, 64 patients were recruited for the study. Their age at presentation ranged from birth to 17 years. The majority presented with ambiguous external genitalia including micropenis and severe hypospadias. A few presented with delayed puberty and primary amenorrhea. Baseline and post-human chorionic gonadotropin-stimulated testosterone and dihydrotestosterone levels were not discriminatory in patients with or without AR gene mutations. Of the patients, 22 had a confirmed genetic disease, with 11 having 5α-reductase 2 deficiency, seven with androgen insensitivity syndrome, one each with cholesterol side-chain cleavage enzyme deficiency, Frasier syndrome, NR5A1-related sex reversal, and persistent Müllerian duct syndrome. Our findings suggest that 5α-reductase 2 deficiency and androgen insensitivity syndrome are possibly the two most common causes of 46,XY disorders of sex development in the Hong Kong Chinese population. Since hormonal findings can be unreliable, mutational analysis of the SRD5A2 and AR genes should be considered the first-line tests for these patients.

[Relationship between phthalates and testicular dysgenesis syndrome].

PubMed

Chen, Guo-Rong; Dong, Lei; Ge, Ren-Shan; Hardy, Matthew P

2007-03-01

Recent epidemiological evidence demonstrates that boys born to women exposed to phthalates during pregnancy have an increased incidence of cryptorchidism, hypospadias, testicular cancer and spermatogenic dysfunction, which are collectively referred to as testicular dysgenesis syndrome (TDS). TDS may be attributed to the dysfunction of Leydig cells and Sertoli cells during their differentiation after exposure to phthalates in utero. Fox example, Leydig cell functions are significantly affected by phthalates, leading to the decrease of two Leydig cell products--insulin-like growth factor 3 (INSL3) and testosterone, which are critical factors for testis descent. The disorientation of Leydig cells and Sertoli cells in the adult testis may be the cause of spermatogenic dysfunction.

Detection of Y chromosome sequences in a 45,X/46,XXq - patient by Southern blot analysis of PCR-amplified DNA and fluorescent in situ hybridization (FISH)

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

Kocova, M.; Siegel, S.F.; Wenger, S.L.

1995-02-13

In some cases of gonadal dysgenesis, cytogenetic analysis seems to be discordant with the phenotype of the patients. We have applied techniques such as Southern blot analysis and fluorescent in situ hybridization (FISH) to resolve the phenotype/genotype discrepancy in a patient with ambiguous genitalia in whom the peripheral blood karotype was 45,X. Gonadectomy at age 7 months showed the gonadal tissue to be prepubertal testis on the left side and a streak gonad on the right. The karyotype obtained from the left gonad was 45,X/46,XXq- and that from the right gonad was 45,X. Three different techniques, PCR amplification, FISH, andmore » chromosome painting for X and Y chromosomes, confirmed the presence of Y chromosome sequences. Five different tissues were evaluated. The highest percentage of Y chromosome positive cells were detected in the left gonad, followed by the peripheral blood lymphocytes, skin fibroblasts, and buccal mucosa. No Y chromosomal material could be identified in the right gonad. Since the Xq- chromosome is present in the left gonad (testis), it is likely that the Xq- contains Y chromosomal material. Sophisticated analysis in this patient showed that she has at least 2 cell lines, one of which contains Y chromosomal material. These techniques elucidated the molecular basis of the genital ambiguity for this patient. When Y chromosome sequences are present in patients with Ullrich-Turner syndrome or gonadal dysgenesis, the risk for gonadal malignancy is significantly increased. Hence, molecular diagnostic methods to ascertain for the presence of Y chromosome sequences may expedite the evaluation of patients with the ambiguous genitalia. 21 refs., 4 figs., 2 tabs.« less

The protocadherin 11X/Y (PCDH11X/Y) gene pair as determinant of cerebral asymmetry in modern Homo sapiens.

PubMed

Priddle, Thomas H; Crow, Timothy J

2013-06-01

Annett's right-shift theory proposes that human cerebral dominance (the functional and anatomical asymmetry or torque along the antero-posterior axis) and handedness are determined by a single "right-shift" gene. Familial transmission of handedness and specific deviations of cerebral dominance in sex chromosome aneuploidies implicate a locus within an X-Y homologous region of the sex chromosomes. The Xq21.3/Yp11.2 human-specific region of homology includes the protocadherin 11X/Y (PCDH11X/Y) gene pair, which encode cell adhesion molecules subject to accelerated evolution following the separation of the human and chimpanzee lineages six million years ago. PCDH11X and PCDH11Y, differentially regulated by retinoic acid, are highly expressed in the ventricular zone, subplate, and cortical plate of the developing cerebral cortex. Both proteins interact with β-catenin, a protein that plays a role in determining axis formation and regulating cortical size. In this way, the PCDH11X/Y gene pair determines cerebral asymmetry by initiating the right shift in Homo sapiens. © 2013 New York Academy of Sciences.

Dissociable Effects of Sry and Sex Chromosome Complement on Activity, Feeding and Anxiety-Related Behaviours in Mice

PubMed Central

Kopsida, Eleni; Lynn, Phoebe M.; Humby, Trevor; Wilkinson, Lawrence S.; Davies, William

2013-01-01

Whilst gonadal hormones can substantially influence sexual differentiation of the brain, recent findings have suggested that sex-linked genes may also directly influence neurodevelopment. Here we used the well-established murine ‘four core genotype’ (FCG) model on a gonadally-intact, outbred genetic background to characterise the contribution of Sry-dependent effects (i.e. those arising from the expression of the Y-linked Sry gene in the brain, or from hormonal sequelae of gonadal Sry expression) and direct effects of sex-linked genes other than Sry (‘sex chromosome complement’ effects) to sexually dimorphic mouse behavioural phenotypes. Over a 24 hour period, XX and XY gonadally female mice (lacking Sry) exhibited greater horizontal locomotor activity and reduced food consumption per unit bodyweight than XX and XY gonadally male mice (possessing Sry); in two behavioural tests (the elevated plus and zero mazes) XX and XY gonadally female mice showed evidence for increased anxiety-related behaviours relative to XX and XY gonadally male mice. Exploratory correlational analyses indicated that these Sry-dependent effects could not be simply explained by brain expression of the gene, nor by circulating testosterone levels. We also noted a sex chromosome complement effect on food (but not water) consumption whereby XY mice consumed more over a 24hr period than XX mice, and a sex chromosome complement effect in a third test of anxiety-related behaviour, the light-dark box. The present data suggest that: i) the male-specific factor Sry may influence activity and feeding behaviours in mice, and ii) dissociable feeding and anxiety-related murine phenotypes may be differentially modulated by Sry and by other sex-linked genes. Our results may have relevance for understanding the molecular underpinnings of sexually dimorphic behavioural phenotypes in healthy men and women, and in individuals with abnormal sex chromosome constitutions. PMID:24009762

NOVEL MOLECULAR TARGETS IMPLICATED IN TESTICULAR DYSGENESIS INDUCED BY GESTATIONAL EXPOSURE TO DIETHYLHEXYL PHTHALATE (DEHP)

EPA Science Inventory

Phthalate-induced Testicular Dysgenesis Syndrome describes reproductive alterations in human males such as: hypospadias, cryptorchism, low sperm counts, and testicular cancer. This work is the first comprehensive evaluation of the rat fetal testis proteome following phthalate exp...

Simultaneous development of ulcerative colitis in the colon and sigmoid neovagina.

PubMed

Webster, Toni; Appelbaum, Heather; Weinstein, Toba A; Rosen, Nelson; Mitchell, Ian; Levine, Jeremiah J

2013-03-01

Vaginoplasty using sigmoid colon is a common technique for creation of a neovagina. However, special consideration must be given to potential long term consequences of using a colonic conduit for vaginal replacement. We report on the youngest described case in which a patient developed ulcerative colitis refractory to medical therapy with simultaneous involvement of a sigmoid neovagina requiring total proctocolectomy and neovaginectomy. A 17 year old XY female with a history of gonadal dysgenesis and sigmoid graft vaginoplasty presented with a history of bloody, mucoid vaginal discharge, abdominal pain, bloody diarrhea and weight loss. Colonic and neovaginal biopsies demonstrated active colitis with diffuse ulcerations, consistent with ulcerative colitis. Despite aggressive immunosuppressive treatment she had persistent neovaginal and colonic bleeding requiring multiple transfusions, subtotal colectomy and ultimately completion proctectomy and neovaginectomy. It is imperative to recognize that colectomy alone may be an inadequate surgical intervention in patients with ulcerative colitis and a colonic neovaginal graft and that a concomitant neovaginectomy may be integral in providing appropriate treatment. Copyright © 2013 Elsevier Inc. All rights reserved.

Caudal dysgenesis in islet-1 transgenic mice

PubMed Central

Muller, Yunhua Li; Yueh, Yir Gloria; Yaworsky, Paul J.; Salbaum, J. Michael; Kappen, Claudia

2014-01-01

Maternal diabetes during pregnancy is responsible for the occurrence of diabetic embryopathy, a spectrum of birth defects that includes heart abnormalities, neural tube defects, and caudal dysgenesis syndromes. Here, we report that mice transgenic for the homeodomain transcription factor Isl-1 develop profound caudal growth defects that resemble human sacral/caudal agenesis. Isl-1 is normally expressed in the pancreas and is required for pancreas development and endocrine cell differentiation. Aberrant regulation of this pancreatic transcription factor causes increased mesodermal cell death, and the severity of defects is dependent on transgene dosage. Together with the finding that mutation of the pancreatic transcription factor HLXB9 causes sacral agenesis, our results implicate pancreatic transcription factors in the pathogenesis of birth defects associated with diabetes. PMID:12738808

Eddy current X-Y scanner system

NASA Technical Reports Server (NTRS)

Kurtz, G. W.

1983-01-01

The Nondestructive Evaluation Branch of the Materials and Processes Laboratory became aware of a need for a miniature, portable X-Y scanner capable of performing eddy current or other nondestructive testing scanning operations such as ultrasonic, or small areas of flat plate. The technical description and operational theory of the X-Y scanner system designed and built to fulfill this need are covered. The scanner was given limited testing and performs according to its design intent, which is to scan flat plate areas of approximately 412 sq cm (64 sq in) during each complete cycle of scanning.

Neuropeptides in the Gonads: From Evolution to Pharmacology

PubMed Central

McGuire, Nicolette L.; Bentley, George E.

2010-01-01

Vertebrate gonads are the sites of synthesis and binding of many peptides that were initially classified as neuropeptides. These gonadal neuropeptide systems are neither well understood in isolation, nor in their interactions with other neuropeptide systems. Further, our knowledge of the control of these gonadal neuropeptides by peripheral hormones that bind to the gonads, and which themselves are under regulation by true neuropeptide systems from the hypothalamus, is relatively meager. This review discusses the existence of a variety of neuropeptides and their receptors which have been discovered in vertebrate gonads, and the possible way in which such systems could have evolved. We then focus on two key neuropeptides for regulation of the hypothalamo-pituitary-gonadal axis: gonadotropin-releasing hormone (GnRH) and gonadotropin-inhibitory hormone (GnIH). Comparative studies have provided us with a degree of understanding as to how a gonadal GnRH system might have evolved, and they have been responsible for the discovery of GnIH and its gonadal counterpart. We attempt to highlight what is known about these two key gonadal neuropeptides, how their actions differ from their hypothalamic counterparts, and how we might learn from comparative studies of them and other gonadal neuropeptides in terms of pharmacology, reproductive physiology and evolutionary biology. PMID:21607065

Neonatal Thymulin Gene Therapy Prevents Ovarian Dysgenesis and Attenuates Reproductive Derangements in Nude Female Mice

PubMed Central

Reggiani, Paula C.; Barbeito, Claudio G.; Zuccolilli, Gustavo O.; Cónsole, Gloria M.; Flamini, Alicia M.; Dardenne, Mireille

2012-01-01

Congenitally athymic (nude) female mice show severe ovarian dysgenesis after puberty, which seems to be consequential to a number of neuroendocrine derangements described in these mutants. Thus, considerable evidence suggests that thymulin, a thymic peptide, may be involved in thymus-pituitary communication. In order to clarify the relevance of thymulin for the maturation of the female reproductive system, we assessed at hypothalamic, pituitary, ovarian, and uterine level the preventive action of neonatal thymulin gene therapy (NTGT) on the changes that typically occur after puberty in congenitally athymic female mice. We injected (im) an adenoviral vector harboring a synthetic DNA sequence encoding a biologically active analog of thymulin, methionine-serum thymic factor, in newborn nude mice (which are thymulin deficient) and killed the animals at 70–71 d of age. NTGT in the athymic mice restored the serum thymulin levels. Morphometric analysis revealed that athymic nudes have reduced numbers of brain GnRH neurons and pituitary gonadotropic cells as compared with heterozygous controls. NTGT prevented these changes and also rescued the premature ovarian failure phenotype typically observed in athymic nude mice (marked reduction in the number of antral follicles and corpora lutea, increase in atretic follicles). Serum estrogen, but not progesterone, levels were low in athymic nudes, a reduction that was partially prevented by NTGT. Little to no morphological changes were observed in the endometrium of female nudes. The delay in the age of vaginal opening that occurs in athymic nudes was significantly prevented by NTGT. Our results suggest that thymulin plays a relevant physiologic role in the thymus-hypothalamo-pituitary-gonadal axis. PMID:22700775

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.

Transcriptional regulation of Drosophila gonad formation.

PubMed

Tripathy, Ratna; Kunwar, Prabhat S; Sano, Hiroko; Renault, Andrew D

2014-08-15

The formation of the Drosophila embryonic gonad, involving the fusion of clusters of somatic gonadal precursor cells (SGPs) and their ensheathment of germ cells, provides a simple and genetically tractable model for the interplay between cells during organ formation. In a screen for mutants affecting gonad formation we identified a SGP cell autonomous role for Midline (Mid) and Longitudinals lacking (Lola). These transcriptional factors are required for multiple aspects of SGP behaviour including SGP cluster fusion, germ cell ensheathment and gonad compaction. The lola locus encodes more than 25 differentially spliced isoforms and we have identified an isoform specific requirement for lola in the gonad which is distinct from that in nervous system development. Mid and Lola work in parallel in gonad formation and surprisingly Mid overexpression in a lola background leads to additional SGPs at the expense of fat body cells. Our findings support the idea that although the transcription factors required by SGPs can ostensibly be assigned to those being required for either SGP specification or behaviour, they can also interact to impinge on both processes. Copyright © 2014 Elsevier Inc. All rights reserved.

Gonadal transcriptome analysis of wild contaminated female European eels during artificial gonad maturation.

PubMed

Baillon, Lucie; Oses, Jennifer; Pierron, Fabien; Bureau du Colombier, Sarah; Caron, Antoine; Normandeau, Eric; Lambert, Patrick; Couture, Patrice; Labadie, Pierre; Budzinski, Hélène; Dufour, Sylvie; Bernatchez, Louis; Baudrimont, Magalie

2015-11-01

Since the early 1980s, the population of European eels (Anguilla anguilla) has dramatically declined. Nowadays, the European eel is listed on the red list of threatened species (IUCN Red List) and is considered as critically endangered of extinction. Pollution is one of the putative causes for the collapse of this species. Among their possible effects, contaminants gradually accumulated in eels during their somatic growth phase (yellow eel stage) would be remobilized during their reproductive migration leading to potential toxic events in gonads. The aim of this study was to investigate the effects of organic and inorganic contaminants on the gonad development of wild female silver eels. Female silver eels from two sites with differing contamination levels were artificially matured. Transcriptomic analyses by means of a 1000 candidate gene cDNA microarray were performed on gonads after 11weeks of maturation to get insight into the mechanisms of toxicity of contaminants. The transcription levels of several genes, that were associated to the gonadosomatic index (GSI), were involved in mitotic cell division but also in gametogenesis. Genes associated to contaminants were mainly involved in the mechanisms of protection against oxidative stress, in DNA repair, in the purinergic signaling pathway and in steroidogenesis, suggesting an impairment of gonad development in eels from the polluted site. This was in agreement with the fact that eels from the reference site showed a higher gonad growth in comparison to contaminated fish. Copyright © 2015 Elsevier Ltd. All rights reserved.

Equine fetal adrenal, gonadal and placental steroidogenesis.

PubMed

Legacki, Erin L; Ball, Barry A; Corbin, C Jo; Loux, Shavahn C; Scoggin, Kirsten E; Stanley, Scott D; Conley, Alan J

2017-10-01

Equine fetuses have substantial circulating pregnenolone concentrations and thus have been postulated to provide significant substrate for placental 5α-reduced pregnane production, but the fetal site of pregnenolone synthesis remains unclear. The current studies investigated steroid concentrations in blood, adrenal glands, gonads and placenta from fetuses (4, 6, 9 and 10 months of gestational age (GA)), as well as tissue steroidogenic enzyme transcript levels. Pregnenolone and dehydroepiandrosterone (DHEA) were the most abundant steroids in fetal blood, pregnenolone was consistently higher but decreased progressively with GA. Tissue steroid concentrations generally paralleled those in serum with time. Adrenal and gonadal tissue pregnenolone concentrations were similar and 100-fold higher than those in allantochorion. DHEA was far higher in gonads than adrenals and progesterone was higher in adrenals than gonads. Androstenedione decreased with GA in adrenals but not in gonads. Transcript analysis generally supported these data. CYP17A1 was higher in fetal gonads than adrenals or allantochorion, and HSD3B1 was higher in fetal adrenals and allantochorion than gonads. CYP11A1 transcript was also significantly higher in adrenals and gonads than allantochorion and CYP19 and SRD5A1 transcripts were higher in allantochorion than either fetal adrenals or gonads. Given these data, and their much greater size, the fetal gonads are the source of DHEA and likely contribute more than fetal adrenal glands to circulating fetal pregnenolone concentrations. Low CYP11A1 but high HSD3B1 and SRD5A1 transcript abundance in allantochorion, and low tissue pregnenolone, suggests that endogenous placental pregnenolone synthesis is low and likely contributes little to equine placental 5α-reduced pregnane secretion. © 2017 Society for Reproduction and Fertility.

1. VIEW OF THE CONTROL ROOM FOR THE XY RETRIEVER. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. VIEW OF THE CONTROL ROOM FOR THE X-Y RETRIEVER. USING THE X-Y RETRIEVER, OPERATORS RETRIEVED PLUTONIUM METAL FROM THE PLUTONIUM STORAGE VAULTS (IN MODULE K) AND CONVEYED IT TO THE X-Y SHUTTLE AREA WHERE IT WAS CUT AND WEIGHED. FROM THE SHUTTLE AREA THE PLUTONIUM WAS CONVEYED TO MODULES A, J OR K FOR CASTING, OR MODULE B FOR ROLLING AND FORMING. (5/17/71) - Rocky Flats Plant, Plutonium Manufacturing Facility, North-central section of Plant, just south of Building 776/777, Golden, Jefferson County, CO

The Number of X Chromosomes Causes Sex Differences in Adiposity in Mice

PubMed Central

Chen, Xuqi; McClusky, Rebecca; Chen, Jenny; Beaven, Simon W.; Tontonoz, Peter

2012-01-01

Sexual dimorphism in body weight, fat distribution, and metabolic disease has been attributed largely to differential effects of male and female gonadal hormones. Here, we report that the number of X chromosomes within cells also contributes to these sex differences. We employed a unique mouse model, known as the “four core genotypes,” to distinguish between effects of gonadal sex (testes or ovaries) and sex chromosomes (XX or XY). With this model, we produced gonadal male and female mice carrying XX or XY sex chromosome complements. Mice were gonadectomized to remove the acute effects of gonadal hormones and to uncover effects of sex chromosome complement on obesity. Mice with XX sex chromosomes (relative to XY), regardless of their type of gonad, had up to 2-fold increased adiposity and greater food intake during daylight hours, when mice are normally inactive. Mice with two X chromosomes also had accelerated weight gain on a high fat diet and developed fatty liver and elevated lipid and insulin levels. Further genetic studies with mice carrying XO and XXY chromosome complements revealed that the differences between XX and XY mice are attributable to dosage of the X chromosome, rather than effects of the Y chromosome. A subset of genes that escape X chromosome inactivation exhibited higher expression levels in adipose tissue and liver of XX compared to XY mice, and may contribute to the sex differences in obesity. Overall, our study is the first to identify sex chromosome complement, a factor distinguishing all male and female cells, as a cause of sex differences in obesity and metabolism. PMID:22589744

Experimental Insights into Ground-State Selection of Quantum XY Pyrochlores

NASA Astrophysics Data System (ADS)

Hallas, Alannah M.; Gaudet, Jonathan; Gaulin, Bruce D.

2018-03-01

Extensive experimental investigations of the magnetic structures and excitations in the XY pyrochlores have been carried out over the past decade. Three families of XY pyrochlores have emerged: Yb2B2O7, Er2B2O7, and, most recently, [Formula: see text]Co2F7. In each case, the magnetic cation (either Yb, Er, or Co) exhibits XY anisotropy within the local pyrochlore coordinates, a consequence of crystal field effects. Materials in these families display rich phase behavior and are candidates for exotic ground states, such as quantum spin ice, and exotic ground-state selection via order-by-disorder mechanisms. In this review, we present an experimental summary of the ground-state properties of the XY pyrochlores, including evidence that they are strongly influenced by phase competition. We empirically demonstrate the signatures for phase competition in a frustrated magnet: multiple heat capacity anomalies, suppressed TN or TC, sample- and pressure-dependent ground states, and unconventional spin dynamics.

A Simple X-Y Scanner.

ERIC Educational Resources Information Center

Halse, M. R.; Hudson, W. J.

1986-01-01

Describes an X-Y scanner used to create acoustic holograms. Scanner is computer controlled and can be adapted to digitize pictures. Scanner geometry is discussed. An appendix gives equipment details. The control program in ATOM BASIC and 6502 machine code is available from the authors. (JM)

Methods for the Study of Gonadal Development.

PubMed

Piprek, Rafal P

2016-01-01

Current knowledge on gonadal development and sex determination is the product of many decades of research involving a variety of scientific methods from different biological disciplines such as histology, genetics, biochemistry, and molecular biology. The earliest embryological investigations, followed by the invention of microscopy and staining methods, were based on histological examinations. The most robust development of histological staining techniques occurred in the second half of the nineteenth century and resulted in structural descriptions of gonadogenesis. These first studies on gonadal development were conducted on domesticated animals; however, currently the mouse is the most extensively studied species. The next key point in the study of gonadogenesis was the advancement of methods allowing for the in vitro culture of fetal gonads. For instance, this led to the description of the origin of cell lines forming the gonads. Protein detection using antibodies and immunolabeling methods and the use of reporter genes were also invaluable for developmental studies, enabling the visualization of the formation of gonadal structure. Recently, genetic and molecular biology techniques, especially gene expression analysis, have revolutionized studies on gonadogenesis and have provided insight into the molecular mechanisms that govern this process. The successive invention of new methods is reflected in the progress of research on gonadal development.

Participation of OCT3/4 and beta-catenin during dysgenetic gonadal malignant transformation.

PubMed

Palma, Icela; Peña, Rocio-Yolanda; Contreras, Alejandra; Ceballos-Reyes, Guillermo; Coyote, Ninel; Eraña, Luis; Kofman-Alfaro, Susana; Queipo, Gloria

2008-05-18

Gonadoblastoma (GB) is an in situ tumor consisting of a heterogeneous population of mature and immature germ cells, other cells resembling immature Sertoli/granulosa cells, and Leydig/lutein-like cells, may also be present. GB almost exclusively affects a subset of patients with intersex disorders and in 30% of them overgrowth of the germinal component of the tumor is observed and the lesion is term dysgerminoma/seminoma. Several pathways have been proposed to explain the malignant process, and abnormal OCT3/4 expression is the most robust risk factor for malignant transformation. Some authors have suggested that OCT3/4 and beta-catenin might both be involved in the same oncogenic pathway, as both genes are master regulators of cell differentiation and, overexpression of either gene may result in cancer development. The mechanism by which beta-catenin participates in GB transformation is not completely clear and exploration of the E-cadherin pathway did not conclusively show that this pathway participated in the molecular pathogenesis of GB. Here we analyze seven patients with mixed gonadal dysgenesis and GB, in an effort to elucidate the participation of beta-catenin and E-cadherin, as well as OCT3/4, in the oncogenic pathways involved in the transformation of GB into seminoma/dysgerminoma. We conclude that the proliferation of immature germ cells in GB may be due to an interaction between OCT3/4 and accumulated beta-catenin in the nuclei of the immature germ cells.

Boltzmann sampling for an XY model using a non-degenerate optical parametric oscillator network

NASA Astrophysics Data System (ADS)

Takeda, Y.; Tamate, S.; Yamamoto, Y.; Takesue, H.; Inagaki, T.; Utsunomiya, S.

2018-01-01

We present an experimental scheme of implementing multiple spins in a classical XY model using a non-degenerate optical parametric oscillator (NOPO) network. We built an NOPO network to simulate a one-dimensional XY Hamiltonian with 5000 spins and externally controllable effective temperatures. The XY spin variables in our scheme are mapped onto the phases of multiple NOPO pulses in a single ring cavity and interactions between XY spins are implemented by mutual injections between NOPOs. We show the steady-state distribution of optical phases of such NOPO pulses is equivalent to the Boltzmann distribution of the corresponding XY model. Estimated effective temperatures converged to the setting values, and the estimated temperatures and the mean energy exhibited good agreement with the numerical simulations of the Langevin dynamics of NOPO phases.

Anti-Ma-associated encephalitis due to dysgerminoma in a woman with Swyer syndrome.

PubMed

Al-Thubaiti, Ibtisam; Al-Hayek, Kefah; Binfalah, Mohammed

2013-04-09

Paraneoplastic limbic encephalitis (PLE)/diencephalitis associated with anti-Ma2 antibodies was linked to testicular cancer and non-small-cell lung cancer (non-SCLC).(1,2) We report a case of anti-Ma-associated PLE/diencephalitis due to dysgerminoma in a woman with gonadal dysgenesis, or Swyer syndrome.

Steroidogenic Factor-1 (SF-1, Ad4BP, NR5A1) and Disorders of Testis Development

PubMed Central

Lin, L.; Achermann, J.C.

2009-01-01

Steroidogenic factor-1 (SF-1) (Ad4BP, NR5A1) is a nuclear receptor that regulates many aspects of adrenal and reproductive development and function. Consequently, deletion of the gene (Nr5a1) encoding Sf-1 in XY mice results in impaired adrenal development, complete testicular dysgenesis with Müllerian structures, and female external genitalia. Initial efforts to identify NR5A1 changes in humans focused on 46,XY individuals with combined adrenogonadal failure and Müllerian structures. Although this combination of clinical features is rare, 2 such patients harboring NR5A1 mutations have been described within the past decade. More recently, however, it has emerged that heterozygous loss of function mutations in NR5A1 can be found relatively frequently in children and adults with 46,XY disorders of sex development (DSD) but with apparently normal adrenal function. The phenotypic spectrum associated with these changes ranges from complete testicular dysgenesis with Müllerian structures, through individuals with mild clitoromegaly or genital ambiguity, to severe penoscrotal hypospadias or even anorchia. Furthermore, a non-synonymous polymorphism in NR5A1 may be associated with micropenis or undescended testes within the population. Taken together, these reports suggest that variable loss of SF-1 function can be associated with a wide range of reproductive phenotypes in humans. PMID:18987494

The Islamic Perspectives of Gender-Related Issues in the Management of Patients With Disorders of Sex Development.

PubMed

Zainuddin, Ani Amelia; Mahdy, Zaleha Abdullah

2017-02-01

In Islam, the person with somatic sex ambiguity due to a disorder of sex development (DSD), such as 46,XX congenital adrenal hyperplasia or 46,XY androgen insensitivity, is recognized as khunsa. Two types of khunsa are distinguished: wadhih (discernible) and musykil (intractable). A recent fatwa (religious edict) in Malaysia decreed that it is permissible for male-assigned patients from these two groups to have gender reassignment surgery to female following diagnosis; however, the religious authority has yet to rule on the reassignment from female to male, if requested. The different schools of law in Islam agree on some aspects of gender-related issues like the position of khunsa in prayer congregations, but differ in their opinions on others such as property inheritance and bathing rituals. For purposes of illustration, this article includes three case reports on Muslim patients with DSD in Malaysia, focusing on issues of gender assignment: (1) a patient with 46,XX CAH, assigned as female, requesting reassignment to male; (2) a patient with 46,XX CAH, assigned female, and gender dysphoric, but undecided on the gender to be; and (3) a patient with 46,XY complete gonadal dysgenesis, raised female due to her phenotype at birth, diagnosed late, at age 18 years, and content to remain female. Gender-related issues from the perspective of Islamic jurisprudence are highlighted and discussed. To ensure holistic care, health-service providers involved in the care of Muslim patients with DSDs need to be aware of the Islamic perspectives on gender-related issues and involve expert religious authorities.

Characterization of early gonadal development in smallmouth bass (Micropterus dolomieu) and effects of ethinyl estradiol on gonadal differentiation

EPA Science Inventory

Teleosts vary widely in patterns of gonadal sex differentiation, which might lead to differences in how gonadal development is affected by the presence of estrogenic compounds. This makes it difficult to apply our knowledge of model species such as medaka and fathead minnow to o...

Adrenal-kidney-gonad complex measurements may not predict gonad-specific changes in gene expression patterns during temperature-dependent sex determination in the red-eared slider turtle (Trachemys scripta elegans).

PubMed

Ramsey, Mary; Crews, David

2007-08-01

Many turtles, including the red-eared slider turtle (Trachemys scripta elegans) have temperature-dependent sex determination in which gonadal sex is determined by temperature during the middle third of incubation. The gonad develops as part of a heterogenous tissue complex that comprises the developing adrenal, kidney, and gonad (AKG complex). Owing to the difficulty in excising the gonad from the adjacent tissues, the AKG complex is often used as tissue source in assays examining gene expression in the developing gonad. However, the gonad is a relatively small component of the AKG, and gene expression in the adrenal-kidney (AK) compartment may interfere with the detection of gonad-specific changes in gene expression, particularly during early key phases of gonadal development and sex determination. In this study, we examine transcript levels as measured by quantitative real-time polymerase chain reaction for five genes important in slider turtle sex determination and differentiation (AR, ERalpha, ERbeta, aromatase, and Sf1) in AKG, AK, and isolated gonad tissues. In all cases, gonad-specific gene expression patterns were attenuated in AKG versus gonad tissue. All five genes were expressed in the AK in addition to the gonad at all stages/temperatures. Inclusion of the AK compartment masked important changes in gonadal gene expression. In addition, AK and gonad expression patterns are not additive, and gonadal gene expression cannot be predicted from intact AKG measurements. (c) 2007 Wiley-Liss, Inc.

Loss of Mitogen-Activated Protein Kinase Kinase Kinase 4 (MAP3K4) Reveals a Requirement for MAPK Signalling in Mouse Sex Determination

PubMed Central

Bogani, Debora; Siggers, Pam; Brixey, Rachel; Warr, Nick; Beddow, Sarah; Edwards, Jessica; Williams, Debbie; Wilhelm, Dagmar; Koopman, Peter; Flavell, Richard A.; Chi, Hongbo; Ostrer, Harry; Wells, Sara; Cheeseman, Michael; Greenfield, Andy

2009-01-01

Sex determination in mammals is controlled by the presence or absence of the Y-linked gene SRY. In the developing male (XY) gonad, sex-determining region of the Y (SRY) protein acts to up-regulate expression of the related gene, SOX9, a transcriptional regulator that in turn initiates a downstream pathway of testis development, whilst also suppressing ovary development. Despite the requirement for a number of transcription factors and secreted signalling molecules in sex determination, intracellular signalling components functioning in this process have not been defined. Here we report a role for the phylogenetically ancient mitogen-activated protein kinase (MAPK) signalling pathway in mouse sex determination. Using a forward genetic screen, we identified the recessive boygirl (byg) mutation. On the C57BL/6J background, embryos homozygous for byg exhibit consistent XY gonadal sex reversal. The byg mutation is an A to T transversion causing a premature stop codon in the gene encoding MAP3K4 (also known as MEKK4), a mitogen-activated protein kinase kinase kinase. Analysis of XY byg/byg gonads at 11.5 d post coitum reveals a growth deficit and a failure to support mesonephric cell migration, both early cellular processes normally associated with testis development. Expression analysis of mutant XY gonads at the same stage also reveals a dramatic reduction in Sox9 and, crucially, Sry at the transcript and protein levels. Moreover, we describe experiments showing the presence of activated MKK4, a direct target of MAP3K4, and activated p38 in the coelomic region of the XY gonad at 11.5 d post coitum, establishing a link between MAPK signalling in proliferating gonadal somatic cells and regulation of Sry expression. Finally, we provide evidence that haploinsufficiency for Map3k4 accounts for T-associated sex reversal (Tas). These data demonstrate that MAP3K4-dependent signalling events are required for normal expression of Sry during testis development, and create a novel

Female gonadal shielding with automatic exposure control increases radiation risks.

PubMed

Kaplan, Summer L; Magill, Dennise; Felice, Marc A; Xiao, Rui; Ali, Sayed; Zhu, Xiaowei

2018-02-01

Gonadal shielding remains common, but current estimates of gonadal radiation risk are lower than estimated risks to colon and stomach. A female gonadal shield may attenuate active automatic exposure control (AEC) sensors, resulting in increased dose to colon and stomach as well as to ovaries outside the shielded area. We assess changes in dose-area product (DAP) and absorbed organ dose when female gonadal shielding is used with AEC for pelvis radiography. We imaged adult and 5-year-old equivalent dosimetry phantoms using pelvis radiograph technique with AEC in the presence and absence of a female gonadal shield. We recorded DAP and mAs and measured organ absorbed dose at six internal sites using film dosimetry. Female gonadal shielding with AEC increased DAP 63% for the 5-year-old phantom and 147% for the adult phantom. Absorbed organ dose at unshielded locations of colon, stomach and ovaries increased 21-51% in the 5-year-old phantom and 17-100% in the adult phantom. Absorbed organ dose sampled under the shield decreased 67% in the 5-year-old phantom and 16% in the adult phantom. Female gonadal shielding combined with AEC during pelvic radiography increases absorbed dose to organs with greater radiation sensitivity and to unshielded ovaries. Difficulty in proper use of gonadal shields has been well described, and use of female gonadal shielding may be inadvisable given the risks of increasing radiation.

seXY: a tool for sex inference from genotype arrays.

PubMed

Qian, David C; Busam, Jonathan A; Xiao, Xiangjun; O'Mara, Tracy A; Eeles, Rosalind A; Schumacher, Frederick R; Phelan, Catherine M; Amos, Christopher I

2017-02-15

Checking concordance between reported sex and genotype-inferred sex is a crucial quality control measure in genome-wide association studies (GWAS). However, limited insights exist regarding the true accuracy of software that infer sex from genotype array data. We present seXY, a logistic regression model trained on both X chromosome heterozygosity and Y chromosome missingness, that consistently demonstrated >99.5% sex inference accuracy in cross-validation for 889 males and 5,361 females enrolled in prostate cancer and ovarian cancer GWAS. Compared to PLINK, one of the most popular tools for sex inference in GWAS that assesses only X chromosome heterozygosity, seXY achieved marginally better male classification and 3% more accurate female classification. https://github.com/Christopher-Amos-Lab/seXY. Christopher.I.Amos@dartmouth.edu. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Maturity Gonad Sea Cucumber Holothuria scabra Under The Month Cycle

NASA Astrophysics Data System (ADS)

Penina Tua Rahantoknam, Santi

2017-10-01

Gonad maturity level of the sea cucumber Holothuria scabra is important to note for selection of parent ready spawn. Sea cucumbers are giving a reaction to the treatment of excitatory spawn mature individuals only. For the determination of the level of maturity of gonads of sea cucumbers, the necessary observation of the gonads are microscopic, macroscopic and gonad maturity gonado somatic indeks (GSI). GSI value is important to know the changes that occur in the gonads quantitatively, so that time can be presumed spawning (Effendie, 1997). Reproductive cycle can be determined by observing the evolution of GSI. The study of sea cucumbers Holothuria scabra gonad maturity conducted in Langgur, Southeast Maluku. Observations were made at every cycle of the moon is the full moon phase (BP) and new moon (BB) in the period January 29, 2017 until July 23, 2017. Observations H. scabra gonad maturity level is done with surgery, observation and calculation GSI gonad histology. GSI highest value obtained in May that full moon cycle at 90% of individuals that are in the spawning stage (phase 5), then 70% of the individuals that are in the spawning stage (phase 5) in March that the full moon cycle. The results obtained show that the peak spawning H. scabra period January 2017 to July 2017 occurred on the full moon cycle in May.

High-precision control of LSRM based X-Y table for industrial applications.

PubMed

Pan, J F; Cheung, Norbert C; Zou, Yu

2013-01-01

The design of an X-Y table applying direct-drive linear switched reluctance motor (LSRM) principle is proposed in this paper. The proposed X-Y table has the characteristics of low cost, simple and stable mechanical structure. After the design procedure is introduced, an adaptive position control method based on online parameter identification and pole-placement regulation scheme is developed for the X-Y table. Experimental results prove the feasibility and its priority over a traditional PID controller with better dynamic response, static performance and robustness to disturbances. It is expected that the novel two-dimensional direct-drive system find its applications in high-precision manufacture area. Copyright © 2012 ISA. Published by Elsevier Ltd. All rights reserved.

An infant with mos45,X/46,XY/47,XYY/48,XYYY: Genetic and clinical findings

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

Fox, J.; Blumenthal, D.; Brock, W.

1994-09-01

We report on an infant with mos45,X/46,XY/47,XYY/48,XYYY who presented with ambiguous genitalia. The patient was the 2,637 gram product of a 38 week gestation and elective repeat C-section born to a 35 year old G3P2 mother. The pregnancy was complicated by placenta previa. There was no history of maternal health problems or drug or steroid use. At birth bilateral epicanthal folds and overfolded helices were noted without webbing of the neck or lymphedema. There was a phallic structure measuring 1.5 cm with dorsal hood and midline cleft with a normal female introitus, urethra, and vagina. Congenital adrenal hyperplaxia was excluded.more » Renal ultrasound was normal. Periperal blood chromosomes revealed a mos45,X(38%)/47,XYY(29%)/48,XYYY(33%) karyotype. Echocardiography revealed coarctation of the aorta and a bicuspid aortic valve. An additional cell line, 46,XY, was identified in aortic tissue obtained at the time of surgery. At age 15 months she was 25% in height and weight and had bilateral ptosis. Her development was within normal limits, but no words except {open_quotes}Mama{close_quotes} or {open_quotes}Dada{close_quotes} were spoken. A left intraabdominal testis with epididymis and dilated tubules and bilateral Fallopian tubes were removed at laparoscopy/reconstruction. Cell cultures were initiated from gonadal tissue, and karyotypes are pending. Patients with mosaic Y chromosome aneuploidy involving 2 Y chromosomes are rare. Eighteen patients with 45,X/47,XYY have been described; prenatally diagnosed cases appeared to be normal male whereas cases diagnosed postnally presented with ambiguous genitalia and/or other anomalies. The phenotype of Y chromosome aneuploidy with 3 Y chromosomes is even more unpredictable due to the paucity of reported cases. To our knowledge this is the first patient described with this unusual karyotype, thus adding to the limited information of patients with rare mosaic Y chromosome aneuploidy.« less

The end of gonad-centric sex determination in mammals

PubMed Central

Arnold, Arthur P.

2011-01-01

The 20th century theory of mammalian sex determination states that the embryo is sexually indifferent until the differentiation of gonads, after which sex differences in phenotype are caused by differential effects of gonadal hormones. That theory is inadequate because some sex differences precede differentiation of the gonads and/or are determined by non-gonadal effects of the sexual inequality in number and type of sex chromosomes. A general theory of sex determination is proposed, which recognizes multiple parallel primary sex-determining pathways initiated by genes or factors encoded by the sex chromosomes. The separate sex-specific pathways interact to synergize with or antagonize each other, enhancing or reducing sex differences in phenotype. PMID:22078126

Seventeen Alpha-Hydroxylase Deficiency Associated with Absent Gonads and Myelolipoma: A Case Report and Review of Literature.

PubMed

Soveid, Mahmood; Rais-Jalali, Ghanbar Ali

2016-11-01

Congenital adrenal hyperplasia comprises a group of disorders resulting from defects in enzymes required for the synthesis of cortisol. The clinical presentation depends on the specific enzyme defect. We report a rare case of congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency. A 26-year-old female patient referred with hypertension and hypokalemia. She also had primary amenorrhea and lack of sexual development. The karyotype was 46, XY. Hormonal evaluation showed low serum levels of all steroid hormones, requiring alpha-hydroxylation, which included cortisol, 17 alpha-hydroxy progesterone, dehydroepiandrosterone sulfate, estradiol, and testosterone. The levels of adrenocorticotropic, follicle-stimulating, and luteinizing hormones were high. Radiological and surgical investigations failed to show a gonad. She also had a large myelolipoma. Treatment was commenced with low-dose dexamethasone and conjugated estrogen. Her hypertension and hypokalemia were resolved. The myelolipoma was removed by laparoscopy due to pain and sensation of heaviness. Our review of literature revealed that a combination of this disorder with either agonadism or myelolipoma is very rare and that only 2 previous cases have been reported for each entity.

Morbidity, Mortality, and Socioeconomics in Females With 46,XY Disorders of Sex Development: A Nationwide Study.

PubMed

Berglund, Agnethe; Johannsen, Trine H; Stochholm, Kirstine; Viuff, Mette H; Fedder, Jens; Main, Katharina M; Gravholt, Claus H

2018-04-01

Little is known about long-term health outcomes in phenotypic females with 46,XY disorders of sex development (XY females), and the socioeconomic profile has not been described in detail. To describe morbidity, mortality, and socioeconomic status in XY females in a comparison to the general population. Nationwide registry study with complete follow-up. Uniform public health care system. A total of 123 XY females karyotyped in Denmark during 1960 to 2012 and a randomly selected age-matched control cohort of 12,300 females and 12,300 males from the general population. Overall mortality and morbidity as well as cause-specific morbidity; medicine use and socioeconomics (education, income, cohabitation, motherhood, and retirement). Compared with female controls, overall morbidity was increased in XY females [hazard ratio (HR), 1.72; 95% confidence interval (CI), 1.43 to 2.08] but not when excluding diagnoses associated with the specific disorder of sex development (DSD) diagnosis or pregnancy and birth (HR, 1.13; CI, 0.93 to 1.37). Mortality was similar to controls (HR, 0.79; CI, 0.35 to 1.77). Cohabitation (HR, 0.44; CI, 0.33 to 0.58) and motherhood (HR, 0.10; CI, 0.05 to 0.18) were reduced in XY females but education (HR, 0.92; CI, 0.61 to 1.37) was similar to controls. Income was higher than among controls in the older years. Morbidity was not increased in XY females when excluding diagnoses associated to the DSD condition per se. Judged on education and income, XY females perform well in the labor market. However, DSD seems to impact on the prospects of family life.

Stem Cells in Mammalian Gonads.

PubMed

Wu, Ji; Ding, Xinbao; Wang, Jian

Stem cells have great value in clinical application because of their ability to self-renew and their potential to differentiate into many different cell types. Mammalian gonads, including testes for males and ovaries for females, are composed of germline and somatic cells. In male mammals, spermatogonial stem cells maintain spermatogenesis which occurs continuously in adult testis. Likewise, a growing body of evidence demonstrated that female germline stem cells could be found in mammalian ovaries. Meanwhile, prior studies have shown that somatic stem cells exist in both testes and ovaries. In this chapter, we focus on mammalian gonad stem cells and discuss their characteristics as well as differentiation potentials.

Graphical Representation of Complex Solutions of the Quadratic Equation in the "xy" Plane

ERIC Educational Resources Information Center

McDonald, Todd

2006-01-01

This paper presents a visual representation of complex solutions of quadratic equations in the xy plane. Rather than moving to the complex plane, students are able to experience a geometric interpretation of the solutions in the xy plane. I am also working on these types of representations with higher order polynomials with some success.

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

Ion, A.; Telvi, L.; Galacteros, F.

We describe a pedigree presenting X-linked severe mental retardation associated with multiple congenital abnormalities and 46,XY gonadal dysgenesis, leading in one family member to female gender assignment. Female carriers are unaffected. The dysmorphic features are similar to those described in the {alpha}-thalassemia and mental retardation (ATR-X) syndrome, although there is no clinical evidence of {alpha}-thalassemia in this family. In addition, the family had other clinical features not previously observed in the ATR-X syndrome, including partial optic-nerve atrophy and partial ocular albinism. Mutations in a putative DNA helicase, termed XH2, have been reported to give rise to the ATR-X syndrome. Wemore » screened the YCH2 gene for mutations in affected members of the family and identified a 4-bp deletion at an intron/exon boundary that removes an invariant 3{prime} splice-acceptor site. The mutation cosegregates with the syndrome. The genomic deletion causes missplicing of the pre-mRNA, which results in the loss of 8 bp of coding sequence, thereby generating a frameshift and a downstream premature stop codon. Our finding increases the range of clinical features associated with mutations in the XH2 gene. 17 refs., 4 figs., 2 tabs.« less

Transgenic expression of Map3k4 rescues T-associated sex reversal (Tas) in mice

PubMed Central

Warr, Nick; Siggers, Pam; Carré, Gwenn-Aël; Bogani, Debora; Brixey, Rachel; Akiyoshi, Mika; Tachibana, Makoto; Teboul, Lydia; Wells, Sara; Sanderson, Jeremy; Greenfield, Andy

2014-01-01

Disorders of sex development in the human population range in severity from mild genital defects to gonadal sex reversal. XY female development has been associated with heterozygous mutations in several genes, including SOX9, WT1 and MAP3K1. In contrast, XY sex reversal in mice usually requires complete absence of testis-determining gene products. One exception to this involves T-associated sex reversal (Tas), a phenomenon characterized by the formation of ovotestes or ovaries in XY mice hemizygous for the hairpin-tail (Thp) or T-Orleans (TOrl) deletions on proximal mouse chromosome 17. We recently reported that mice heterozygous for a null allele of Map3k4, which resides in the Thp deletion, exhibit XY ovotestis development and occasional gonadal sex reversal on the sensitized C57BL/6J-YAKR (B6-YAKR) genetic background, reminiscent of the Tas phenotype. However, these experiments did not exclude the possibility that loss of other loci in the Thp deletion, or other effects of the deletion itself, might contribute to Tas. Here, we show that disruption to Sry expression underlies XY gonadal defects in B6-YAKR embryos harbouring the Thp deletion and that a functional Map3k4 bacterial artificial chromosome rescues these abnormalities by re-establishing a normal Sry expression profile. These data demonstrate that Map3k4 haploinsufficiency is the cause of T-associated sex reversal and that levels of this signalling molecule are a major determinant of the expression profile of Sry. PMID:24452333

Fibroblast growth factor signaling is required for early somatic gonad development in zebrafish.

PubMed

Leerberg, Dena M; Sano, Kaori; Draper, Bruce W

2017-09-01

The vertebrate ovary and testis develop from a sexually indifferent gonad. During early development of the organism, primordial germ cells (the gamete lineage) and somatic gonad cells coalesce and begin to undergo growth and morphogenesis to form this bipotential gonad. Although this aspect of development is requisite for a fertile adult, little is known about the genetic regulation of early gonadogenesis in any vertebrate. Here, we provide evidence that fibroblast growth factor (Fgf) signaling is required for the early growth phase of a vertebrate bipotential gonad. Based on mutational analysis in zebrafish, we show that the Fgf ligand 24 (Fgf24) is required for proliferation, differentiation, and morphogenesis of the early somatic gonad, and as a result, most fgf24 mutants are sterile as adults. Additionally, we describe the ultrastructural elements of the early zebrafish gonad and show that distinct somatic cell populations can be identified soon after the gonad forms. Specifically, we show that fgf24 is expressed in an epithelial population of early somatic gonad cells that surrounds an inner population of mesenchymal somatic gonad cells that are in direct contact with the germ cells, and that fgf24 is required for stratification of the somatic tissue. Furthermore, based on gene expression analysis, we find that differentiation of the inner mesenchymal somatic gonad cells into functional cell types in the larval and early juvenile-stage gonad is dependent on Fgf24 signaling. Finally, we argue that the role of Fgf24 in zebrafish is functionally analogous to the role of tetrapod FGF9 in early gonad development.

45,X/46,XY Mosaicism and Possible Association With Hypothyroidism in Males.

PubMed

Hojat, Leila; Schweiger, Michelle

2016-06-01

Mosaicism has a wide phenotypic spectrum but frequently manifests as the normal male phenotype. Its association with short stature has been well recognized and appears to respond effectively to growth hormone therapy. We present 2 phenotypically normal males who both initially presented with short stature and were found to have hypothyroidism. They were treated for hypothyroidism but their growth did not improve as expected. Further testing revealed 45,X/46,XY mosaicism in both males. We propose that a potential link exists between 45,X/46,XY mosaicism and hypothyroidism, which has not been previously described in the literature. Furthermore, it may be beneficial to evaluate for other disorders such as 45,X/46,XY mosaicism in young males with short stature and hypothyroidism if their growth does not improve once they become euthyroid. © The Author(s) 2015.

A Recurrent De Novo PACS2 Heterozygous Missense Variant Causes Neonatal-Onset Developmental Epileptic Encephalopathy, Facial Dysmorphism, and Cerebellar Dysgenesis.

PubMed

Olson, Heather E; Jean-Marçais, Nolwenn; Yang, Edward; Heron, Delphine; Tatton-Brown, Katrina; van der Zwaag, Paul A; Bijlsma, Emilia K; Krock, Bryan L; Backer, E; Kamsteeg, Erik-Jan; Sinnema, Margje; Reijnders, Margot R F; Bearden, David; Begtrup, Amber; Telegrafi, Aida; Lunsing, Roelineke J; Burglen, Lydie; Lesca, Gaetan; Cho, Megan T; Smith, Lacey A; Sheidley, Beth R; Moufawad El Achkar, Christelle; Pearl, Phillip L; Poduri, Annapurna; Skraban, Cara M; Tarpinian, Jennifer; Nesbitt, Addie I; Fransen van de Putte, Dietje E; Ruivenkamp, Claudia A L; Rump, Patrick; Chatron, Nicolas; Sabatier, Isabelle; De Bellescize, Julitta; Guibaud, Laurent; Sweetser, David A; Waxler, Jessica L; Wierenga, Klaas J; Donadieu, Jean; Narayanan, Vinodh; Ramsey, Keri M; Nava, Caroline; Rivière, Jean-Baptiste; Vitobello, Antonio; Tran Mau-Them, Frédéric; Philippe, Christophe; Bruel, Ange-Line; Duffourd, Yannis; Thomas, Laurel; Lelieveld, Stefan H; Schuurs-Hoeijmakers, Janneke; Brunner, Han G; Keren, Boris; Thevenon, Julien; Faivre, Laurence; Thomas, Gary; Thauvin-Robinet, Christel

2018-05-03

Developmental and epileptic encephalopathies (DEEs) represent a large clinical and genetic heterogeneous group of neurodevelopmental diseases. The identification of pathogenic genetic variants in DEEs remains crucial for deciphering this complex group and for accurately caring for affected individuals (clinical diagnosis, genetic counseling, impacting medical, precision therapy, clinical trials, etc.). Whole-exome sequencing and intensive data sharing identified a recurrent de novo PACS2 heterozygous missense variant in 14 unrelated individuals. Their phenotype was characterized by epilepsy, global developmental delay with or without autism, common cerebellar dysgenesis, and facial dysmorphism. Mixed focal and generalized epilepsy occurred in the neonatal period, controlled with difficulty in the first year, but many improved in early childhood. PACS2 is an important PACS1 paralog and encodes a multifunctional sorting protein involved in nuclear gene expression and pathway traffic regulation. Both proteins harbor cargo(furin)-binding regions (FBRs) that bind cargo proteins, sorting adaptors, and cellular kinase. Compared to the defined PACS1 recurrent variant series, individuals with PACS2 variant have more consistently neonatal/early-infantile-onset epilepsy that can be challenging to control. Cerebellar abnormalities may be similar but PACS2 individuals exhibit a pattern of clear dysgenesis ranging from mild to severe. Functional studies demonstrated that the PACS2 recurrent variant reduces the ability of the predicted autoregulatory domain to modulate the interaction between the PACS2 FBR and client proteins, which may disturb cellular function. These findings support the causality of this recurrent de novo PACS2 heterozygous missense in DEEs with facial dysmorphim and cerebellar dysgenesis. Copyright © 2018 American Society of Human Genetics. All rights reserved.

Phase diagram and quench dynamics of the cluster-XY spin chain

NASA Astrophysics Data System (ADS)

Montes, Sebastián; Hamma, Alioscia

2012-08-01

We study the complete phase space and the quench dynamics of an exactly solvable spin chain, the cluster-XY model. In this chain, the cluster term and the XY couplings compete to give a rich phase diagram. The phase diagram is studied by means of the quantum geometric tensor. We study the time evolution of the system after a critical quantum quench using the Loschmidt echo. The structure of the revivals after critical quantum quenches presents a nontrivial behavior depending on the phase of the initial state and the critical point.

Phase diagram and quench dynamics of the cluster-XY spin chain.

PubMed

Montes, Sebastián; Hamma, Alioscia

2012-08-01

We study the complete phase space and the quench dynamics of an exactly solvable spin chain, the cluster-XY model. In this chain, the cluster term and the XY couplings compete to give a rich phase diagram. The phase diagram is studied by means of the quantum geometric tensor. We study the time evolution of the system after a critical quantum quench using the Loschmidt echo. The structure of the revivals after critical quantum quenches presents a nontrivial behavior depending on the phase of the initial state and the critical point.

Effects of centrifugation on gonadal and adrenocortical steroids in rats

NASA Technical Reports Server (NTRS)

Kakihana, R.; Butte, J. C.

1980-01-01

Many endocrine systems are sensitive to external changes in the environment. Both the pituitary adrenal and pituitary gonadal systems are affected by stress including centrifugation stress. The effect of centrifugation on the pituitary gonadal and pituitary adrenocortical systems was examined by measuring the gonadal and adrenal steroids in the plasma and brain following different duration and intensity of centrifugation stress in rats. Two studies were completed and the results are presented. The second study was carried out to describe the developmental changes of brain, plasma and testicular testosterone and dihydrotestosterone in Sprague Dawley rats so that the effect of centrifugation stress on the pituitary gonadal syatem could be better evaluated in future studies.

Gender identity and recalled gender related childhood play-behaviour in adult individuals with different forms of intersexuality.

PubMed

Richter-Appelt, Hertha; Discher, Christine; Gedrose, Benjamin

2005-09-01

The concept of intersexuality subsumes a wide variety of phenomena with very specific underlying causes. In all these cases, an untypical development takes place during the prenatal sex differentiation process becoming clinically manifest, either at, or soon after birth or at the time of puberty. It subsumes conditions in which biological sexual characteristics (e.g. chromosomal sex, gonadal sex, hormonal sex, morphological sex) differ from each other and one person cannot easily be assigned to one sex. One of the main goals of medical treatment of persons with intersex-syndroms is the development of a stable gender identity. Over the last few years, sex (and gender) assignment of persons with different forms of intersexuality has become a much discussed topic. An interesting--and very obviously observable--variable that was brought in connection with sex assignment is gender related childhood play behaviour. The purpose of the presented study is to examine 37 persons with different forms of intersexuality (disturbances of androgen biosynthesis, partial and complete androgen insensitivity, gonadal dysgenesis with 46,XY and congenital adrenal hyperplasia with 46,XX) with regard to gender identity and gender role behaviour in childhood. Not all subjects in the study group had developed a clear female or male gender identity. In contrast to previous studies, some persons with CAIS did not recall distinguished female childhood play behaviour and these persons did not show a clear female gender identity. In contrast to results from other studies, the CAH-affected girls in this study did not seem to recall masculinized behaviour. Further research is needed to guarantee better psychosexual development with good quality of life in individuals with intersexuality.

XY females do better than the XX in the African pygmy mouse, Mus minutoides.

PubMed

Saunders, Paul A; Perez, Julie; Rahmoun, Massilva; Ronce, Ophélie; Crochet, Pierre-André; Veyrunes, Frédéric

2014-07-01

All therian mammals have a similar XY/XX sex-determination system except for a dozen species. The African pygmy mouse, Mus minutoides, harbors an unconventional system in which all males are XY, and there are three types of females: the usual XX but also XX* and X*Y ones (the asterisk designates a sex-reversal mutation on the X chromosome). The long-term evolution of such a system is a paradox, because X*Y females are expected to face high reproductive costs (e.g., meiotic disruption and loss of unviable YY embryos), which should prevent invasion and maintenance of a sex-reversal mutation. Hence, mechanisms for compensating for the costs could have evolved in M. minutoides. Data gathered from our laboratory colony revealed that X*Y females do compensate and even show enhanced reproductive performance in comparison to the XX and XX*; they produce significantly more offspring due to (i) a higher probability of breeding, (ii) an earlier first litter, and (iii) a larger litter size, linked to (iv) a greater ovulation rate. These findings confirm that rare conditions are needed for an atypical sex-determination mechanism to evolve in mammals, and provide valuable insight into understanding modifications of systems with highly heteromorphic sex chromosomes. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

Ex vivo culture of human fetal gonads: manipulation of meiosis signalling by retinoic acid treatment disrupts testis development.

PubMed

Jørgensen, A; Nielsen, J E; Perlman, S; Lundvall, L; Mitchell, R T; Juul, A; Rajpert-De Meyts, E

2015-10-01

'-deoxyuridine (BrdU) incorporation assay. A novel ex vivo 'hanging-drop' culture model for human fetal gonads was successfully established. Continued proliferation of cells without signs of increased apoptosis was observed after 2 weeks of culture. In cultured fetal ovaries treated with RA, an increased number of meiotic germ cells (P < 0.05) and DMRT1-positive oogonia initiating meiosis (P < 0.05) was observed, which is in agreement with a previous study. In fetal testes, RA-treatment resulted in a decreased number of gonocytes (P < 0.05), a reduced percentage of proliferating gonocytes (P < 0.05), altered expression pattern of the somatic cell markers AMH and COUP-TFII, as well as disrupted seminiferous cord structure and testis morphology. The number of samples included in this study was relatively small due to the limited availability of human fetal tissue. The hanging-drop culture, similarly to other organ culture approaches, allows studies of germ cell-somatic niche interactions and determination of effects after manipulating specific signalling pathways. Our novel finding of disrupted fetal testis development after treatment with RA indicates that abnormal meiosis regulation can potentially cause gonadal dysgenesis. Further studies will elucidate the exact mechanisms and timing of observed effects. This work was supported in part by an ESPE Research Fellowship, sponsored by Novo Nordisk A/S to A.Jø. Additional funding for this project was obtained from The Research Council of the Capital Region of Denmark (E.R.-D.M.), The Research Fund at Rigshospitalet (A.Ju. and J.E.N.), Familien Erichssens Fund (A.Jø.), Dagmar Marshalls Fund (A.Jø.) and Aase & Ejnar Danielsens Fund (A.Jø.). The authors have no conflicts of interest. © The Author 2015. 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.

Unilateral congenital corneal keloid with anterior segment mesenchymal dysgenesis and subluxated lens: case report and review of literature.

PubMed

Vanathi, M; Sen, Seema; Panda, Anita; Dada, Tanuj; Behera, Geeta; Khokhar, Sudharshan

2007-01-01

To report the unusual association of unilateral congenital corneal keloid with anterior-segment mesenchymal dysgenesis and bilateral subluxated lens. A 20-year old man presented with a mass lesion involving the left cornea. The corneal lesion had been present since birth. On biomicroscopic examination, a well-defined vascularized, grayish-white mass occupying the whole of the left cornea was seen. The right eye showed multiple peripheral corneal opacities with iridocorneal adhesions, a poorly defined supranasal limbus, and a subluxated lens. Excision biopsy of the mass was done for histopathologic examination. Histopathologic examination of the excised corneal mass showed features consistent with that of a corneal keloid: thickened keratinized epithelium, absent Bowman membrane layer, and fibrovascular hyperplasia composed of hyalinized collagen fibers with irregular orientation of the collagen lamellae. During penetrating keratoplasty of the left eye, an anomalous iris pattern with poorly defined angle and a supranasal subluxated lens was also observed. Extraction of the subluxated lens was also done. The graft failed subsequent to a nonhealing persistent epithelial defect. Our case report highlights the rare association of a unilateral congenital corneal keloid with anterior-segment mesenchymal dysgenesis and bilateral subluxated lens.

AmgRS-mediated envelope stress-inducible expression of the mexXY multidrug efflux operon of Pseudomonas aeruginosa

PubMed Central

Lau, Calvin Ho-Fung; Krahn, Thomas; Gilmour, Christie; Mullen, Erin; Poole, Keith

2015-01-01

AmgRS is an envelope stress-responsive two-component system and aminoglycoside resistance determinant in Pseudomonas aeruginosa that is proposed to protect cells from membrane damage caused by aminoglycoside-generated mistranslated polypeptides. Consistent with this, a ΔamgR strain showed increased aminoglycoside-promoted membrane damage, damage that was largely absent in AmgRS-activated amgS-mutant strains. Intriguingly, one such mutation, V121G, while providing for enhanced resistance to aminoglycosides, rendered P. aeruginosa susceptible to several ribosome-targeting nonaminoglycoside antimicrobials that are inducers and presumed substrates of the MexXY-OprM multidrug efflux system. Surprisingly, the amgSV121G mutation increased mexXY expression threefold, suggesting that export of these nonaminoglycosides was compromised in the amgSV121G mutant. Nonetheless, a link was established between AmgRS activation and mexXY expression and this was confirmed in studies showing that aminoglycoside-promoted mexXY expression is dependent on AmgRS. While nonaminoglycosides also induced mexXY expression, this was not AmgRS-dependent, consistent with these agents not generating mistranslated polypeptides and not activating AmgRS. The aminoglycoside inducibility of mexXY was abrogated in a mutant lacking the AmgRS target genes htpX and PA5528, encoding a presumed cytoplasmic membrane-associated protease and a membrane protein of unknown function, respectively. Thus, aminoglycoside induction of mexXY is a response to membrane damage and activation of the AmgRS two-component system. PMID:25450797

A High Rigidity and Precision Scanning Tunneling Microscope with Decoupled XY and Z Scans

PubMed Central

Chen, Xu; Guo, Tengfei; Hou, Yubin; Zhang, Jing

2017-01-01

A new scan-head structure for the scanning tunneling microscope (STM) is proposed, featuring high scan precision and rigidity. The core structure consists of a piezoelectric tube scanner of quadrant type (for XY scans) coaxially housed in a piezoelectric tube with single inner and outer electrodes (for Z scan). They are fixed at one end (called common end). A hollow tantalum shaft is coaxially housed in the XY-scan tube and they are mutually fixed at both ends. When the XY scanner scans, its free end will bring the shaft to scan and the tip which is coaxially inserted in the shaft at the common end will scan a smaller area if the tip protrudes short enough from the common end. The decoupled XY and Z scans are desired for less image distortion and the mechanically reduced scan range has the superiority of reducing the impact of the background electronic noise on the scanner and enhancing the tip positioning precision. High quality atomic resolution images are also shown. PMID:29270242

A High Rigidity and Precision Scanning Tunneling Microscope with Decoupled XY and Z Scans.

PubMed

Chen, Xu; Guo, Tengfei; Hou, Yubin; Zhang, Jing; Meng, Wenjie; Lu, Qingyou

2017-01-01

A new scan-head structure for the scanning tunneling microscope (STM) is proposed, featuring high scan precision and rigidity. The core structure consists of a piezoelectric tube scanner of quadrant type (for XY scans) coaxially housed in a piezoelectric tube with single inner and outer electrodes (for Z scan). They are fixed at one end (called common end). A hollow tantalum shaft is coaxially housed in the XY -scan tube and they are mutually fixed at both ends. When the XY scanner scans, its free end will bring the shaft to scan and the tip which is coaxially inserted in the shaft at the common end will scan a smaller area if the tip protrudes short enough from the common end. The decoupled XY and Z scans are desired for less image distortion and the mechanically reduced scan range has the superiority of reducing the impact of the background electronic noise on the scanner and enhancing the tip positioning precision. High quality atomic resolution images are also shown.

Anterior segment dysgenesis associated with Williams-Beuren syndrome: a case report and review of the literature.

PubMed

Todorova, Margarita G; Grieshaber, Matthias C; Cámara, Rafael J A; Miny, Peter; Palmowski-Wolfe, Anja M

2014-05-21

Williams-Beuren syndrome is characterized by mild mental retardation, specific neurocognitive profile, hypercalcemia during infancy, distinctive facial features and cardiovascular diseases. We report on complete ophthalmologic, sonographic and genetic evaluation of a girl with a clinical phenotype of Williams-Beuren syndrome, associated with unilateral anterior segment dysgenesis and bilateral cleft of the soft and hard palate. These phenotypic features have not been linked to the haploinsufficiency of genes involved in the microdeletion. A term born girl presented at the initial examination with clouding of the right cornea. On ultrasound biomicroscopy the anterior chamber structures were difficult to differentiate, showing severe adhesions from the opacified cornea to the iris with a kerato-irido-lenticular contact to the remnant lens, a finding consistent with Peters' anomaly. Genetic analyses including FISH confirmed a loss of the critical region 7q11.23, usually associated with the typical Williams-Beuren syndrome. Microsatellite analysis showed a loss of about 2.36 Mb. A diagnosis of Williams-Beuren syndrome was made based on the microdeletion of 7q11.23. The unique features, including unilateral microphthalmia and anterior segment dysgenesis, were unlikely to be caused by the microdeletion. Arguments in favor of the latter are unilateral manifestation, as well as the fact that numerous patients with deletions of comparable or microscopically visible size have not shown similar manifestations.

Global quantum discord and quantum phase transition in XY model

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

Liu, Si-Yuan; Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190; Zhang, Yu-Ran, E-mail: yrzhang@iphy.ac.cn

We study the relationship between the behavior of global quantum correlations and quantum phase transitions in XY model. We find that the two kinds of phase transitions in the studied model can be characterized by the features of global quantum discord (GQD) and the corresponding quantum correlations. We demonstrate that the maximum of the sum of all the nearest neighbor bipartite GQDs is effective and accurate for signaling the Ising quantum phase transition, in contrast, the sudden change of GQD is very suitable for characterizing another phase transition in the XY model. This may shed lights on the study ofmore » properties of quantum correlations in different quantum phases.« less

Gonadal status in long-term male survivors of childhood cancer.

PubMed

Brignardello, E; Felicetti, F; Castiglione, A; Nervo, A; Biasin, E; Ciccone, G; Fagioli, F; Corrias, A

2016-05-01

To evaluate the prevalence of gonadal dysfunction and the associated risk factors in a cohort of male childhood cancer survivors (CCS). Gonadal function was evaluated measuring FSH, LH, inhibin B and total testosterone levels. Patients with total testosterone <3 ng/dl were considered to have hypogonadism. Patients with FSH >10 UI/l and inhibin B <100 pg/ml were considered to have spermatogenesis damage (SD). To assess the impact of risk factors, we estimated crude and adjusted OR performing logistic regression models. One hundred and ninety-nine male CCS were enrolled; the median follow-up time was 14.01 years. SD was diagnosed in 68 patients, 16 CCS had primary hypogonadism, and 13 had central hypogonadism. The prevalence of gonadal dysfunction (SD or primary hypogonadism) was 45 %, similar in the three considered periods of pediatric cancer diagnosis (1985-1989, 1990-1999, >2000). The adjusted risk of gonadal dysfunction was higher in patients treated with radiotherapy (OR = 8.72; 95 % CI 3.94-19.30) and in those exposed to both alkylating and platinum-derived agents (OR = 9.22; 95 % CI 2.17-39.23). Sarcomas were the cancer diagnosis associated with the higher risk of gonadal dysfunction (OR = 3.69; 95 % CI 1.11-12.22). An extremely high rate of gonadal dysfunction was detected in patients who underwent hematopoietic stem cell transplantation and/or total body irradiation. Gonadal dysfunction still remains a significant late effect of anticancer therapies; thus, it is mandatory to inform patients (and parents) about this risk, and semen cryopreservation should be offered to all boys who are able to produce semen.

Histological and transcriptomic effects of 17α-methyltestosterone on zebrafish gonad development.

PubMed

Lee, Stephanie Ling Jie; Horsfield, Julia A; Black, Michael A; Rutherford, Kim; Fisher, Amanda; Gemmell, Neil J

2017-07-24

Sex hormones play important roles in teleost ovarian and testicular development. In zebrafish, ovarian differentiation appears to be dictated by an oocyte-derived signal via Cyp19a1a aromatase-mediated estrogen production. Androgens and aromatase inhibitors can induce female-to-male sex reversal, however, the mechanisms underlying gonadal masculinisation are poorly understood. We used histological analyses together with RNA sequencing to characterise zebrafish gonadal transcriptomes and investigate the effects of 17α-methyltestosterone on gonadal differentiation. At a morphological level, 17α-methyltestosterone (MT) masculinised gonads and accelerated spermatogenesis, and these changes were paralleled in masculinisation and de-feminisation of gonadal transcriptomes. MT treatment upregulated expression of genes involved in male sex determination and differentiation (amh, dmrt1, gsdf and wt1a) and those involved in 11-oxygenated androgen production (cyp11c1 and hsd11b2). It also repressed expression of ovarian development and folliculogenesis genes (bmp15, gdf9, figla, zp2.1 and zp3b). Furthermore, MT treatment altered epigenetic modification of histones in zebrafish gonads. Contrary to expectations, higher levels of cyp19a1a or foxl2 expression in control ovaries compared to MT-treated testes and control testes were not statistically significant during early gonad development (40 dpf). Our study suggests that both androgen production and aromatase inhibition are important for androgen-induced gonadal masculinisation and natural testicular differentiation in zebrafish.

Developmental staging of male murine embryonic gonad by SAGE analysis

PubMed Central

Lee, Tin-Lap; Li, Yunmin; Alba, Diana; Vong, Queenie P.; Wu, Shao-Ming; Baxendale, Vanessa; Rennert, Owen M.; Lau, Yun-Fai Chris; Chan, Wai-Yee

2012-01-01

Despite the identification of key genes such as Sry integral to embryonic gonadal development, the genomic classification and identification of chromosomal activation of this process is still poorly understood. To better understand the genetic regulation of gonadal development, we performed Serial Analysis of Gene Expression (SAGE) to profile the genes and novel transcripts, and an average of 152,000 tags from male embryonic gonads at E10.5 (embryonic day 10.5), E11.5, E12.5, E13.5, E15.5 and E17.5 were analyzed. A total of 275,583 non-singleton tags that do not map to any annotated sequence were identified in the six gonad libraries, and 47,255 tags were mapped to 24,975 annotated sequences, among which 987 sequences were uncharacterized. Utilizing an unsupervised pattern identification technique, we established molecular staging of male gonadal development. Rather than providing a static descriptive analysis, we developed algorithms to cluster the SAGE data and assign SAGE tags to a corresponding chromosomal position; these data are displayed in chromosome graphic format. A prominent increase in global genomic activity from E10.5 to E17.5 was observed. Important chromosomal regions related to the developmental processes were identified and validated based on established mouse models with developmental disorders. These regions may represent markers for early diagnosis for disorders of male gonad development as well as potential treatment targets. PMID:19376482

The Discovery of XY Sex Chromosomes in a Boa and Python.

PubMed

Gamble, Tony; Castoe, Todd A; Nielsen, Stuart V; Banks, Jaison L; Card, Daren C; Schield, Drew R; Schuett, Gordon W; Booth, Warren

2017-07-24

For over 50 years, biologists have accepted that all extant snakes share the same ZW sex chromosomes derived from a common ancestor [1-3], with different species exhibiting sex chromosomes at varying stages of differentiation. Accordingly, snakes have been a well-studied model for sex chromosome evolution in animals [1, 4]. A review of the literature, however, reveals no compelling support that boas and pythons possess ZW sex chromosomes [2, 5]. Furthermore, phylogenetic patterns of facultative parthenogenesis in snakes and a sex-linked color mutation in the ball python (Python regius) are best explained by boas and pythons possessing an XY sex chromosome system [6, 7]. Here we demonstrate that a boa (Boa imperator) and python (Python bivittatus) indeed possess XY sex chromosomes, based on the discovery of male-specific genetic markers in both species. We use these markers, along with transcriptomic and genomic data, to identify distinct sex chromosomes in boas and pythons, demonstrating that XY systems evolved independently in each lineage. This discovery highlights the dynamic evolution of vertebrate sex chromosomes and further enhances the value of snakes as a model for studying sex chromosome evolution. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ovarian dysgenesis in an alpaca with a minute chromosome 36.

PubMed

Fellows, Elizabeth; Kutzler, Michelle; Avila, Felipe; Das, Pranab J; Raudsepp, Terje

2014-01-01

A 4-year-old female alpaca (Lama pacos [LPA]) was presented to the Oregon State Veterinary Teaching Hospital for failure to display receptive behavior to males. Although no abnormalities were found on physical examination, transrectal ultrasonographic examination of the reproductive tract revealed uterine hypoplasia and ovarian dysgenesis. Cytogenetic analysis demonstrated a normal female 74,XX karyotype with 1 exceptionally small (minute) homologue of autosome LPA36. Chromosome analysis by Giemsa staining and DAPI- and C-banding revealed that the minute LPA36 was submetacentric, AT-rich, and largely heterochromatic. Because of the small size and lack of molecular markers, it was not possible to identify the origin of the minute. There is a need to improve molecular cytogenetic tools to further study the phenomenon of this minute chromosome and its relation to female reproduction in alpacas and llamas. © The American Genetic Association. 2012. All rights reserved. For permissions, please email: journals.permissions@oup.com.

xyZET: A Simulation Program for Physics Teaching.

ERIC Educational Resources Information Center

Hartel, Hermann

2000-01-01

Discusses xyZET, a simulation program that allows 3D-space in numerous experiments in basic mechanics and electricity and was developed to support physics teaching. Tests course material for 11th grade at German high schools under classroom conditions and reports on their stability and effectiveness. (Contains 15 references.) (Author/YDS)

Body size and symbiotic status influence gonad development in Aiptasia pallida anemones.

PubMed

Carlisle, Judith F; Murphy, Grant K; Roark, Alison M

2017-01-01

Pale anemones ( Aiptasia pallida ) coexist with dinoflagellates (primarily Symbiodinium minutum ) in a mutualistic relationship. The purpose of this study was to investigate the role of these symbionts in gonad development of anemone hosts. Symbiotic and aposymbiotic anemones were subjected to light cycles that induced gametogenesis. These anemones were then sampled weekly for nine weeks, and gonad development was analyzed histologically. Anemone size was measured as mean body column diameter, and oocytes or sperm follicles were counted for each anemone. Generalized linear models were used to evaluate the influence of body size and symbiotic status on whether gonads were present and on the number of oocytes or sperm follicles produced. Body size predicted whether gonads were present, with larger anemones being more likely than smaller anemones to develop gonads. Both body size and symbiotic status predicted gonad size, such that larger and symbiotic anemones produced more oocytes and sperm follicles than smaller and aposymbiotic anemones. Overall, only 22 % of aposymbiotic females produced oocytes, whereas 63 % of symbiotic females produced oocytes. Similarly, 6 % of aposymbiotic males produced sperm follicles, whereas 60 % of symbiotic males produced sperm follicles. Thus, while gonads were present in 62 % of symbiotic anemones, they were present in only 11 % of aposymbiotic anemones. These results indicate that dinoflagellate symbionts influence gonad development and thus sexual maturation in both female and male Aiptasia pallida anemones. This finding substantiates and expands our current understanding of the importance of symbionts in the development and physiology of cnidarian hosts.

An X-Y Platform for Randsight-Type Instruments.

ERIC Educational Resources Information Center

Clewett, R. W.; And Others

A hand-operated mechanical device, called an X-Y Platform because of its ability to undergo orthogonal planar motions reminiscent of X and Y coordinates, permits design simplifications and lower costs when used with RANDSIGHT-type closed circuit television to enable the partially sighted to read and write. This paper presents a detailed discussion…

Differential lactate and cholesterol synthetic activities in XY and XX Sertoli cells.

PubMed

Shishido, Yurina; Baba, Takashi; Sato, Tetsuya; Shima, Yuichi; Miyabayashi, Kanako; Inoue, Miki; Akiyama, Haruhiko; Kimura, Hiroshi; Kanai, Yoshiakira; Ishihara, Yasuhiro; Haraguchi, Shogo; Miyazaki, Akira; Rozman, Damjana; Yamazaki, Takeshi; Choi, Man-Ho; Ohkawa, Yasuyuki; Suyama, Mikita; Morohashi, Ken-Ichirou

2017-02-02

SRY, a sex-determining gene, induces testis development in chromosomally female (XX) individuals. However, mouse XX Sertoli cells carrying Sry (XX/Sry Sertoli cells) are incapable of fully supporting germ cell development, even when the karyotype of the germ cells is XY. While it has therefore been assumed that XX/Sry Sertoli cells are not functionally equivalent to XY Sertoli cells, it has remained unclear which specific functions are affected. To elucidate the functional difference, we compared the gene expression of XY and XX/Sry Sertoli cells. Lactate and cholesterol metabolisms, essential for nursing the developing germ cells, were down-regulated in XX/Sry cells, which appears to be caused at least in part by the differential expression of histone modification enzymes SMCX/SMCY (H3K4me3 demethylase) and UTX/UTY (H3K27me3 demethylase) encoded by the sex chromosomes. We suggest that down-regulation of lactate and cholesterol metabolism that may be due to altered epigenetic modification affects the nursing functions of XX/Sry Sertoli cells.

Differential lactate and cholesterol synthetic activities in XY and XX Sertoli cells

PubMed Central

Shishido, Yurina; Baba, Takashi; Sato, Tetsuya; Shima, Yuichi; Miyabayashi, Kanako; Inoue, Miki; Akiyama, Haruhiko; Kimura, Hiroshi; Kanai, Yoshiakira; Ishihara, Yasuhiro; Haraguchi, Shogo; Miyazaki, Akira; Rozman, Damjana; Yamazaki, Takeshi; Choi, Man-Ho; Ohkawa, Yasuyuki; Suyama, Mikita; Morohashi, Ken-ichirou

2017-01-01

SRY, a sex-determining gene, induces testis development in chromosomally female (XX) individuals. However, mouse XX Sertoli cells carrying Sry (XX/Sry Sertoli cells) are incapable of fully supporting germ cell development, even when the karyotype of the germ cells is XY. While it has therefore been assumed that XX/Sry Sertoli cells are not functionally equivalent to XY Sertoli cells, it has remained unclear which specific functions are affected. To elucidate the functional difference, we compared the gene expression of XY and XX/Sry Sertoli cells. Lactate and cholesterol metabolisms, essential for nursing the developing germ cells, were down-regulated in XX/Sry cells, which appears to be caused at least in part by the differential expression of histone modification enzymes SMCX/SMCY (H3K4me3 demethylase) and UTX/UTY (H3K27me3 demethylase) encoded by the sex chromosomes. We suggest that down-regulation of lactate and cholesterol metabolism that may be due to altered epigenetic modification affects the nursing functions of XX/Sry Sertoli cells. PMID:28150810

Testicular Dysgenesis Syndrome and Long-Lasting Epigenetic Silencing of Mouse Sperm Genes Involved in the Reproductive System after Prenatal Exposure to DEHP.

PubMed

Stenz, Ludwig; Escoffier, Jessica; Rahban, Rita; Nef, Serge; Paoloni-Giacobino, Ariane

2017-01-01

The endocrine disruptor bis(2-ethylhexyl) phthalate (DEHP) has been shown to exert adverse effects on the male animal reproductive system. However, its mode of action is unclear and a systematic analysis of its molecular targets is needed. In the present study, we investigated the effects of prenatal exposure to 300 mg/kg/day DEHP during a critical period for gonads differentiation to testes on male mice offspring reproductive parameters, including the genome-wide RNA expression and associated promoter methylation status in the sperm of the first filial generation. It was observed that adult male offspring displayed symptoms similar to the human testicular dysgenesis syndrome. A combination of sperm transcriptome and methylome data analysis allowed to detect a long-lasting DEHP-induced and robust promoter methylation-associated silencing of almost the entire cluster of the seminal vesicle secretory proteins and antigen genes, which are known to play a fundamental role in sperm physiology. It also resulted in the detection of a DEHP-induced promoter demethylation associated with an up-regulation of three genes apparently not relevant for sperm physiology and partially related to the immune system. As previously reported, DEHP induced an increase in mir-615 microRNA expression and a genome-wide decrease in microRNA promoter methylation. A functional analysis revealed DEHP-induced enrichments in down-regulated gene transcripts coding for peroxisome proliferator-activated receptors and tumor necrosis factor signaling pathways, and in up-regulated gene transcripts coding for calcium binding and numerous myosin proteins. All these enriched pathways and networks have been described to be associated in some way with the reproductive system. This study identifies a large new array of genes dysregulated by DEHP that may play a role in the complex system controlling the development of the male reproductive system.

Cytogenetic analysis of somatic and germinal cells from 38,XX/38,XY phenotypically normal boars.

PubMed

Barasc, Harmonie; Ferchaud, Stéphane; Mary, Nicolas; Cucchi, Marie Adélaïde; Lucena, Amalia Naranjo; Letron, Isabelle Raymond; Calgaro, Anne; Bonnet, Nathalie; Dudez, Anne Marie; Yerle, Martine; Ducos, Alain; Pinton, Alain

2014-01-15

Many chromosomal abnormalities have been reported to date in pigs. Most of them have been balanced structural rearrangements, especially reciprocal translocations. A few cases of XY/XX chimerism have also been diagnosed within the national systematic chromosomal control program of young purebred boars carried out in France. Until now, this kind of chromosomal abnormality has been mainly reported in intersex individuals. We investigated 38,XY/38,XX boars presenting apparently normal phenotypes to evaluate the potential effects of this particular chromosomal constitution on their reproductive performance. To do this, we analyzed (1) the chromosomal constitution of cells from different organs in one boar; (2) the aneuploidy rates for chromosomes X, Y, and 13 in sperm nuclei sampled from seven XY/XX boars. 2n = 38,XX cells were identified in different nonhematopoietic tissues including testis (frequency, <8%). Similar aneuploidy rates were observed in the sperm nuclei of XY/XX and normal individuals (controls). Altogether, these results suggest that the presence of XX cells had no or only a very limited effect on the reproduction abilities of the analyzed boars. Copyright © 2014 Elsevier Inc. All rights reserved.

The organizing actions of adolescent gonadal steroid hormones on brain and behavioral development

PubMed Central

Schulz, Kalynn M.; Sisk, Cheryl L.

2016-01-01

Adolescence is a developmental period characterized by dramatic changes in cognition, risk-taking and social behavior. Although gonadal steroid hormones are well-known mediators of these behaviors in adulthood, the role gonadal steroid hormones play in shaping the adolescent brain and behavioral development has only come to light in recent years. Here we discuss the sex-specific impact of gonadal steroid hormones on the developing adolescent brain. Indeed, the effects of gonadal steroid hormones during adolescence on brain structure and behavioral outcomes differs markedly between the sexes. Research findings suggest that adolescence, like the perinatal period, is a sensitive period for the sex-specific effects of gonadal steroid hormones on brain and behavioral development. Furthermore, evidence from studies on male sexual behavior suggests that adolescence is part of a protracted postnatal sensitive period that begins perinatally and ends following adolescence. As such, the perinatal and peripubertal periods of brain and behavioral organization likely do not represent two discrete sensitive periods, but instead are the consequence of normative developmental timing of gonadal hormone secretions in males and females. PMID:27497718

Subjective need for psychological support (PsySupp) in parents of children and adolescents with disorders of sex development (dsd).

PubMed

Bennecke, Elena; Werner-Rosen, Knut; Thyen, Ute; Kleinemeier, Eva; Lux, Anke; Jürgensen, Martina; Grüters, Annette; Köhler, Birgit

2015-10-01

Disorders/diversity of sex development (dsd) is an umbrella term for congenital conditions often diagnosed within childhood. As most parents are unprepared for this situation, psychological support (PsySupp) is recommended. The aim of this study was to analyse the extent to which parents express a need for PsySupp. Three hundred twenty-nine parents of children with dsd were included; 40.4 % of the parents indicated to have a need for PsySupp, only 50 % of this group received it adequately. The diagnoses partial gonadal dysgenesis, partial androgen insensitivity syndrome (pAIS) and disorders of androgen synthesis are associated with a high need for PsySupp in parents (54, 65, and 50 %). Sex assignment surgery neither reduced nor increased the need for PsySupp. Taking a picture, radiography, laparoscopy, gonadal biopsy, gonadectomy and hormonal puberty induction are associated with a high need for PsySupp. There was no association between the need for PsySupp and the parents' perception of the appearance of the genitalia. Having a child with dsd is associated with a high need for PsySupp in parents. In particular, parents of children with XY-dsd with androgen effects other than hypospadias expressed a high need of PsySupp. PsySupp for parents should be an obligatory part of interdisciplinary care to reduce fears and concerns. What is known • In parents, having a child with dsd provokes insecurities and fears. Hence, psychological support is recommended as part of the interdisciplinary care. What is new • This is the first study investigating the subjective need for psychological support in a large sample of parents of children with dsd in Germany. We present data on the subjective need for psychological support of the parents, related diagnoses and factors, which should be considered in psychological counselling.

Extraction and analysis of carotenoids from the New Zealand sea urchin Evechinus chloroticus gonads.

PubMed

Garama, Daniel; Bremer, Phil; Carne, Alan

2012-01-01

Sea urchin gonad (roe) is a highly valued food in Japan and North America. Gonad price is strongly influenced by quality, with appearance, especially colour being a major determinant. Previous attempts to extract a carotenoid profile from the New Zealand sea urchin species Evechinus chloroticus have been challenging due to the large amount of lipid present in the gonad. A carotenoid extraction and high performance liquid chromatography (HPLC) analysis method was developed to reduce lipid contamination by incorporating a saponification and lipid cold precipitation in the extraction procedure. This method enabled greater carotenoid purity and enhanced analysis by HPLC. Echinenone was found to be the main carotenoid present in all E. chloroticus gonads. Dark coloured gonads contained higher levels of fucoxanthin/fucoxanthinol, β-carotene and xanthophylls such as astaxanthin and canthaxanthin. This information on the modification and deposition of carotenoids will help in the development of diets to enhance gonad colour.

TriXY-Homogeneous genetic sexing of highly degraded forensic samples including hair shafts.

PubMed

Madel, Maria-Bernadette; Niederstätter, Harald; Parson, Walther

2016-11-01

Sexing of biological evidence is an important aspect in forensic investigations. A routinely used molecular-genetic approach to this endeavour is the amelogenin sex test, which is integrated in most commercially available polymerase chain reaction (PCR) kits for human identification. However, this assay is not entirely effective in respect to highly degraded DNA samples. This study presents a homogeneous PCR assay for robust sex diagnosis, especially for the analysis of severely fragmented DNA. The introduced triplex for the X and Y chromosome (TriXY) is based on real-time PCR amplification of short intergenic sequences (<50bp) on both gonosomes. Subsequent PCR product examination and molecular-genetic sex-assignment rely on high-resolution melting (HRM) curve analysis. TriXY was optimized using commercially available multi-donor human DNA preparations of either male or female origin and successfully evaluated on challenging samples, including 46 ancient DNA specimens from archaeological excavations and a total of 16 DNA samples extracted from different segments of eight hair shafts of male and female donors. Additionally, sensitivity and cross-species amplification were examined to further test the assay's utility in forensic investigations. TriXY's closed-tube format avoids post-PCR sample manipulations and, therefore, distinctly reduces the risk of PCR product carry-over contamination and sample mix-up, while reducing labour and financial expenses at the same time. The method is sensitive down to the DNA content of approximately two diploid cells and has proven highly useful on severely fragmented and low quantity ancient DNA samples. Furthermore, it even allowed for sexing of proximal hair shafts with very good results. In summary, TriXY facilitates highly sensitive, rapid, and costeffective genetic sex-determination. It outperforms existing sexing methods both in terms of sensitivity and minimum required template molecule lengths. Therefore, we feel confident

Skew information in the XY model with staggered Dzyaloshinskii-Moriya interaction

NASA Astrophysics Data System (ADS)

Qiu, Liang; Quan, Dongxiao; Pan, Fei; Liu, Zhi

2017-06-01

We study the performance of the lower bound of skew information in the vicinity of transition point for the anisotropic spin-1/2 XY chain with staggered Dzyaloshinskii-Moriya interaction by use of quantum renormalization-group method. For a fixed value of the Dzyaloshinskii-Moriya interaction, there are two saturated values for the lower bound of skew information corresponding to the spin-fluid and Néel phases, respectively. The scaling exponent of the lower bound of skew information closely relates to the correlation length of the model and the Dzyaloshinskii-Moriya interaction shifts the factorization point. Our results show that the lower bound of skew information can be a good candidate to detect the critical point of XY spin chain with staggered Dzyaloshinskii-Moriya interaction.

Program Aids Creation Of X-Y Plots

NASA Technical Reports Server (NTRS)

Jeletic, James F.

1993-01-01

VEGAS computer program enables application programmers to create X-Y plots in various modes through high-level subroutine calls. Modes consist of passive, autoupdate, and interactive modes. In passive mode, VEGAS takes input data, produces plot, and returns control to application program. In autoupdate mode, forms plots and automatically updates them as more information received. In interactive mode, displays plot and provides popup menus for user to alter appearance of plot or to modify data. Written in FORTRAN 77.

Genetic effects of radiotherapy for childhood cancer: gonadal dose reconstruction.

PubMed

Stovall, Marilyn; Donaldson, Sarah S; Weathers, Rita E; Robison, Leslie L; Mertens, Ann C; Winther, Jeanette Falck; Olsen, Jorgen H; Boice, John D

2004-10-01

To estimate the doses of radiation to organs of interest during treatment of childhood cancer for use in an epidemiologic study of possible heritable diseases, including birth defects, chromosomal abnormalities, cancer, stillbirth, and neonatal and premature death. The study population was composed of more than 25,000 patients with cancer in Denmark and the United States who were survivors of childhood cancer and subsequently had nearly 6,500 children of their own. Radiation therapy records were sought for the survivors who parented offspring who had adverse pregnancy outcomes (>300 offspring), and for a sample of all survivors in a case-cohort design. The records were imaged and centrally abstracted. Water phantom measurements were made to estimate doses for a wide range of treatments. Mathematical phantoms were used to apply measured results to estimate doses to ovaries, uterus, testes, and pituitary for patients ranging in age from newborn to 25 years. Gonadal shielding, ovarian pinning (oophoropexy), and field blocking were taken into account. Testicular radiation doses ranged from <1 to 700 cGy (median, 7 cGy) and ovarian doses from <1 to >2,500 cGy (median, 13 cGy). Ten percent of the records were incomplete, but sufficient data were available for broad characterizations of gonadal dose. More than 49% of the gonadal doses were >10 cGy and 16% were >100 cGy. Sufficient radiation therapy data exist as far back as 1943 to enable computation of gonadal doses administered for curative therapy for childhood cancer. The range of gonadal doses is broad, and for many cancer survivors, is high and just below the threshold for infertility. Accordingly, the epidemiologic study has >90% power to detect a 1.3-fold risk of an adverse pregnancy outcome associated with radiation exposure to the gonads. This study should provide important information on the genetic consequences of radiation exposure to humans.

Dissecting the Role of Hedgehog Pathway in Murine Gonadal Development

ERIC Educational Resources Information Center

Barsoum, Ivraym Boshra

2009-01-01

Hedgehog (Hh) signaling pathway is one of the universal pathways involved in animal development. This dissertation focuses on Hh role in the mammalian gonad development, which is a central part of mammalian sexual development and identity. The central dogma of mammalian sex development is that genetic sex determines the gonadal sex, which in turn…

Decision Processes During Development of Molecular Biomarkers for Gonadal Phenotypic Sex

EPA Science Inventory

Molecular biomarkers for determination of gonadal phenotypic sex in the Japanese medaka (Oryzias latipes), will serve as a case study. The medaka has unique features that aid in the development of appropriate molecular biomarkers of gonad phenotype, a) genetic sex can be determin...

Inverting x,y grid coordinates to obtain latitude and longitude in the vanderGrinten projection

NASA Technical Reports Server (NTRS)

Rubincam, D. P.

1980-01-01

The latitude and longitude of a point on the Earth's surface are found from its x,y grid coordinates in the vanderGrinten projection. The latitude is a solution of a cubic equation and the longitude a solution of a quadratic equation. Also, the x,y grid coordinates of a point on the Earth's surface can be found if its latitude and longitude are known by solving two simultaneous quadratic equations.

Gonadal morphogenesis and gene expression in reptiles with temperature-dependent sex determination.

PubMed

Merchant-Larios, H; Díaz-Hernández, V; Marmolejo-Valencia, A

2010-01-01

In reptiles with temperature-dependent sexual determination, the thermosensitive period (TSP) is the interval in which the sex is defined during gonadal morphogenesis. One-shift experiments in a group of eggs define the onset and the end of the TSP as all and none responses, respectively. Timing for sex-undetermined (UG) and -determined gonads (DG) differs at male- (MPT) or female-producing temperatures (FPT). During the TSP a decreasing number of embryos respond to temperature shifts indicating that in this period embryos with both UG and DG exist. Although most UG correspond to undifferentiated gonads, some embryos extend UG after the onset of histological differentiation. Thus, temperature affects gonadal cells during the process of morphogenesis, but timing of commitment depends on individual embryos. A correlation between gonadal morphogenesis, TSP, and gene expression suggests that determination of the molecular pathways modulated by temperature in epithelial cells (surface epithelium and medullary cords) holds the key for a unifying hypothesis on temperature-dependent sex determination. (c) 2010 S. Karger AG, Basel.

Ranitidine does not affect gonadal function in man.

PubMed Central

Wang, C; Wong, K L; Lam, K C; Lai, C L

1983-01-01

We studied the effect of ranitidine on gonadal function in 20 male subjects with chronic duodenal ulcer. Eleven were treated with ranitidine 150 mg twice daily for 3 months and 150 mg at night for 9 months, nine with placebo for 3 months. Similar to placebo, treatment with ranitidine did not influence basal serum concentrations of testosterone (T), luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (PRL). No significant changes were found in sperm concentration, motility or morphology. Ranitidine does not affect gonadal function in man. PMID:6313029

The organizing actions of adolescent gonadal steroid hormones on brain and behavioral development.

PubMed

Schulz, Kalynn M; Sisk, Cheryl L

2016-11-01

Adolescence is a developmental period characterized by dramatic changes in cognition, risk-taking and social behavior. Although gonadal steroid hormones are well-known mediators of these behaviors in adulthood, the role gonadal steroid hormones play in shaping the adolescent brain and behavioral development has only come to light in recent years. Here we discuss the sex-specific impact of gonadal steroid hormones on the developing adolescent brain. Indeed, the effects of gonadal steroid hormones during adolescence on brain structure and behavioral outcomes differs markedly between the sexes. Research findings suggest that adolescence, like the perinatal period, is a sensitive period for the sex-specific effects of gonadal steroid hormones on brain and behavioral development. Furthermore, evidence from studies on male sexual behavior suggests that adolescence is part of a protracted postnatal sensitive period that begins perinatally and ends following adolescence. As such, the perinatal and peripubertal periods of brain and behavioral organization likely do not represent two discrete sensitive periods, but instead are the consequence of normative developmental timing of gonadal hormone secretions in males and females. Copyright © 2016 Elsevier Ltd. All rights reserved.

UV laser radiation alters the embryonic protein profile of adrenal-kidney-gonadal complex and gonadal differentiation in the lizard, Calotes Versicolor.

PubMed

Khodnapur, Bharati S; Inamdar, Laxmi S; Nindi, Robertraj S; Math, Shivkumar A; Mulimani, B G; Inamdar, Sanjeev R

2015-02-01

To examine the impact of ultraviolet (UV) laser radiation on the embryos of Calotes versicolor in terms of its effects on the protein profile of the adrenal-kidney-gonadal complex (AKG), sex determination and differentiation, embryonic development and hatching synchrony. The eggs of C. versicolor, during thermo-sensitive period (TSP), were exposed to third harmonic laser pulses at 355 nm from a Q-switched Nd:YAG laser for 180 sec. Subsequent to the exposure they were incubated at the male-producing temperature (MPT) of 25.5 ± 0.5°C. The AKG of hatchlings was subjected to protein analysis by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and to histology. The UV laser radiation altered the expression of the protein banding pattern in the AKG complex of hatchlings and it also affected the gonadal sex differentiation. SDS-PAGE of AKG of one-day-old hatchlings revealed a total of nine protein bands in the control group whereas UV laser irradiated hatchlings expressed a total of seven protein bands only one of which had the same Rf as a control band. The UV laser treated hatchlings have an ovotestes kind of gonad exhibiting a tendency towards femaleness instead of the typical testes. It is inferred that 355 nm UV laser radiation during TSP induces changes in the expression of proteins as well as their secretions. UV laser radiation had an impact on the gonadal differentiation pathway but no morphological anomalies were noticed.

[Gonad protective effect of radiation protective apron in chest radiography].

PubMed

Hashimoto, Masatoshi; Kato, Hideyuki; Fujibuchi, Toshiou; Ochi, Shigehiro; Morita, Fuminori

2004-12-01

Depending on the facility, a radiation protective apron (protector) is used to protect the gonad from radiation exposure in chest radiography. To determine the necessity of using a protector during chest radiography, we measured the effect of the protector on the gonad in this study. First, using a human body phantom, we measured the absorbed dose of the female gonad with and without the protector, using a thermoluminescence dosimeter (TLD), and confirmed its protective effect. Using the protector, the absorbed dose was reduced to 28+/-2% and 39+/-4% for field sizes of 14 x 17 inch and 14 x 14 inch, respectively. Next, we used Monte Carlo simulation and confirmed, not only the validity of the actual measurement values, but also the fact that the influence of radiation on the absorbed dose of the gonad was mostly from scattered radiation from inside the body for the 14 x 17 inch field size, and also from the X-ray tube for the 14 x 14 inch field size. Although a certain protective effect is achieved by using the protector, the radiation dose to the gonad is only a few microGy even without a protector. Thus, the risk of a genetic effect would be as small as 10(-8). Given that acceptable risk is below 10(-6), we conclude the use of a radiation protective apron is not necessary for diagnostic chest radiography.

Transcriptome analysis identifies genes involved in sex determination and development of Xenopus laevis gonads.

PubMed

Piprek, Rafal P; Damulewicz, Milena; Kloc, Malgorzata; Kubiak, Jacek Z

Development of the gonads is a complex process, which starts with a period of undifferentiated, bipotential gonads. During this period the expression of sex-determining genes is initiated. Sex determination is a process triggering differentiation of the gonads into the testis or ovary. Sex determination period is followed by sexual differentiation, i.e. appearance of the first testis- and ovary-specific features. In Xenopus laevis W-linked DM-domain gene (DM-W) had been described as a master determinant of the gonadal female sex. However, the data on the expression and function of other genes participating in gonad development in X. laevis, and in anurans, in general, are very limited. We applied microarray technique to analyze the expression pattern of a subset of X. laevis genes previously identified to be involved in gonad development in several vertebrate species. We also analyzed the localization and the expression level of proteins encoded by these genes in developing X. laevis gonads. These analyses pointed to the set of genes differentially expressed in developing testes and ovaries. Gata4, Sox9, Dmrt1, Amh, Fgf9, Ptgds, Pdgf, Fshr, and Cyp17a1 expression was upregulated in developing testes, while DM-W, Fst, Foxl2, and Cyp19a1 were upregulated in developing ovaries. We discuss the possible roles of these genes in development of X. laevis gonads. Copyright © 2018 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

Global Survey of Protein Expression during Gonadal Sex Determination in Mice*

PubMed Central

Ewen, Katherine; Baker, Mark; Wilhelm, Dagmar; Aitken, R. John; Koopman, Peter

2009-01-01

The development of an embryo as male or female depends on differentiation of the gonads as either testes or ovaries. A number of genes are known to be important for gonadal differentiation, but our understanding of the regulatory networks underpinning sex determination remains fragmentary. To advance our understanding of sexual development beyond the transcriptome level, we performed the first global survey of the mouse gonad proteome at the time of sex determination by using two-dimensional nanoflow LC-MS/MS. The resulting data set contains a total of 1037 gene products (154 non-redundant and 883 redundant proteins) identified from 620 peptides. Functional classification and biological network construction suggested that the identified proteins primarily serve in RNA post-transcriptional modification and trafficking, protein synthesis and folding, and post-translational modification. The data set contains potential novel regulators of gonad development and sex determination not revealed previously by transcriptomics and proteomics studies and more than 60 proteins with potential links to human disorders of sexual development. PMID:19617587

GONADAL AND BONE MARROW DOSE IN MEDICAL DIAGNOSTIC RADIOLOGY

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

Mahmoud, K.A.; Mahfouz, M.M.; Mahmoud, M.E.

1961-08-01

Measurements were made of the active mean bone marrow, integral bone marrow, gonadal, and maximum skin doses from diagnostic x-ray procedures used in Cairo University Hospitals. The active mean marrow dose in cervical, dorsal, and lumbar spine diagnostic exposures were: found to be somewhat smaller than those reported by some western couatries. One of the most striking results of the survey was the relatively high values of the urinary tract cases investigated diagnostically; owing to the high incidence of urinary tract Schistosomiasis. The gonadal dose delivered to males and females was found to be almosi negligible for all diagnostic investigationsmore » of the spine, except for the lumbo-dorsal region which was within the range 50 to 500 mrads. It was also found that the gonadal dose was significant in investigations of the lower gastrointestinal tract, gall bladder, and urinary tract. (P.C.H.)« less

Anterior segment dysgenesis (Peters' anomaly) in two snow leopard (Panthera uncia) cubs.

PubMed

Hamoudi, Hassan; Rudnick, Jens-Christian; Prause, Jan U; Tauscher, Kerstin; Breithaupt, Angele; Teifke, Jens P; Heegaard, Steffen

2013-07-01

Two sibling snow leopards, a male and a female, with bilateral anterior segment dysgenesis (ASD), are reported. Both snow leopards also had colobomas of both upper eyelids. All eyes exhibited a central corneal opacity associated with a defect in posterior corneal stroma, endothelium and Descemet's membrane. Iris strands were present attached to the termination of Descemet's membrane and to the periphery of the posterior corneal defect. The iris was hypoplastic, and cataract was present in all four eyes. The left eye of the female was microphthalmic, with no trabecular meshwork and with persistent remnant of the hyaloid artery. The male had hydrocephalus and thus some of the features of Peters' plus syndrome (Peters' anomaly in addition to systemic malformations). The histological findings in the eyes of these snow leopard siblings are identical with those described in humans with Peters' anomaly. © 2012 American College of Veterinary Ophthalmologists.

Intersexuality associated with XX/XY mosaicism in a horned goat.

PubMed

Bongso, T A; Thavalingam, M; Mukherjee, T K

1982-01-01

Anatomical, histological, and cytogenetic studies were undertaken on a horned intersex goat kid and three of its normal litter mates. The intersex had male type horns, male beard, vestigial mammary glands, female external genitalia, and an enlarged peniform clitoris, exuded a pungent male odor, had a male bleat, and came into estrus every 20 days. At laparotomy and subsequent slaughter, an ovotestes was observed on the right side and a testis and epididymal remnants on the left side. Uterine horn segments, cervix, vagina, and enlarged clitoris (2 cm) were also present. Histologically, spermatogenesis was not observed in either testis, but active Leydig cells were present. The ovary contained mature follicles. Chromosome analysis revealed 60XX/60XY cell populations in blood, bone marrow, and skin. Lymphocytic metaphases from the male and female cosibs showed single populations of 60XY and 60XX, respectively. Mosaicism associated with the horned condition in the intersex goat was established.

Determination of gonad doses during robotic stereotactic radiosurgery for various tumor sites

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

Zorlu, Faruk; Dugel, Gozde; Ozyigit, Gokhan

Purpose: The authors evaluated the absorbed dose received by the gonads during robotic stereotactic radiosurgery (SRS) for the treatment of different tumor localizations. Methods: The authors measured the gonad doses during the treatment of head and neck, thoracic, abdominal, or pelvic tumors in both RANDO phantom and actual patients. The computerized tomography images were transferred to the treatment planning system. The contours of tumor and critical organs were delineated on each slice, and treatment plans were generated. Measurements for gonad doses were taken from the geometric projection of the ovary onto the skin for female patients, and from the scrotalmore » skin for male patients by attaching films and Thermoluminescent dosimeters (TLDs). SRS was delivered with CyberKnife (Accuray Inc., Sunnyvale, CA). Results: The median gonadal doses with TLD and film dosimeter in actual patients were 0.19 Gy (range, 0.035-2.71 Gy) and 0.34 Gy (range, 0.066-3.18 Gy), respectively. In the RANDO phantom, the median ovarian doses with TLD and film dosimeter were 0.08 Gy (range, 0.03-0.159 Gy) and 0.05 Gy (range, 0.015-0.13 Gy), respectively. In the RANDO phantom, the median testicular doses with TLD and film dosimeter were 0.134 Gy (range 0.056-1.97 Gy) and 0.306 Gy (range, 0.065-2.25 Gy). Conclusions: Gonad doses are below sterility threshold in robotic SRS for different tumor localizations. However, particular attention should be given to gonads during robotic SRS for pelvic tumors.« less

Oscilloscope used as X-Y plotter or two-dimensional analyzer

NASA Technical Reports Server (NTRS)

Hansen, D.; Roy, N.

1967-01-01

Oscilloscope used as an X-Y plotter or two-dimensional analyzer tags each point with a yes or no, depending on a third parameter. The usual square-wave pulse is replaced on the scope by a single information-bearing dot which lengthens to a dash in response to a simultaneous event.

Terminology of Gonadal Anomalies in Fish and Amphibians Resulting from Chemical Exposures

EPA Science Inventory

This paper reviews the terms that have been used to describe various types of gonadal deformities and lesions in amphibians and fish, identifies the body of literature that has reported effects on gonad morphology/histology, and suggests a standardized set of terms and definition...

Gonad establishment during asexual reproduction in the annelid Pristina leidyi.

PubMed

Özpolat, B Duygu; Bely, Alexandra E

2015-09-01

Animals that can reproduce by both asexual agametic reproduction and sexual reproduction must transmit or re-establish their germ line post-embryonically. Although such a dual reproductive mode has evolved repeatedly among animals, how asexually produced individuals establish their germ line remains poorly understood in most groups. We investigated germ line development in the annelid Pristina leidyi, a species that typically reproduces asexually by paratomic fission, intercalating a new tail and head in the middle of the body followed by splitting. We found that in fissioning individuals, gonads occur in anterior segments in the anterior-most individual as well as in new heads forming within fission zones. Homologs of the germ line/multipotency genes piwi, vasa, and nanos are expressed in the gonads, as well as in proliferative tissues including the posterior growth zone, fission zone, and regeneration blastema. In fissioning animals, certain cells on the ventral nerve cord express a homolog of piwi, are abundant near fission zones, and sometimes make contact with gonads. Such cells are typically undetectable near the blastema and posterior growth zone. Time-lapse imaging provides direct evidence that cells on the ventral nerve cord migrate preferentially towards fission zones. Our findings indicate that gonads form routinely in fissioning individuals, that a population of piwi-positive cells on the ventral nerve cord is associated with fission and gonads, and that cells resembling these piwi-positive cells migrate along the ventral nerve cord. We suggest that the piwi-positive ventral cells are germ cells that transmit the germ line across asexually produced individuals via migration along the ventral nerve cord. Copyright © 2015 Elsevier Inc. All rights reserved.

Characterization of the Epigenetic Changes During Human Gonadal Primordial Germ Cells Reprogramming.

PubMed

Eguizabal, C; Herrera, L; De Oñate, L; Montserrat, N; Hajkova, P; Izpisua Belmonte, J C

2016-09-01

Epigenetic reprogramming is a central process during mammalian germline development. Genome-wide DNA demethylation in primordial germ cells (PGCs) is a prerequisite for the erasure of epigenetic memory, preventing the transmission of epimutations to the next generation. Apart from DNA demethylation, germline reprogramming has been shown to entail reprogramming of histone marks and chromatin remodelling. Contrary to other animal models, there is limited information about the epigenetic dynamics during early germ cell development in humans. Here, we provide further characterization of the epigenetic configuration of the early human gonadal PGCs. We show that early gonadal human PGCs are DNA hypomethylated and their chromatin is characterized by low H3K9me2 and high H3K27me3 marks. Similarly to previous observations in mice, human gonadal PGCs undergo dynamic chromatin changes concomitant with the erasure of genomic imprints. Interestingly, and contrary to mouse early germ cells, expression of BLIMP1/PRDM1 persists in through all gestational stages in human gonadal PGCs and is associated with nuclear lysine-specific demethylase-1. Our work provides important additional information regarding the chromatin changes associated with human PGCs development between 6 and 13 weeks of gestation in male and female gonads. Stem Cells 2016;34:2418-2428. © 2016 AlphaMed Press.

Comparison of growth-related traits and gene expression profiles between the offspring of neomale (XX) and normal male (XY) rainbow trout.

PubMed

Kocmarek, Andrea L; Ferguson, Moira M; Danzmann, Roy G

2015-04-01

All-female lines of fish are created by crossing sex reversed (XX genotype) males with normal females. All-female lines avoid the deleterious phenotypic effects that are typical of precocious maturation in males. To determine whether all-female and mixed sex populations of rainbow trout (Oncorhynchus mykiss) differ in performance, we compared the growth and gene expression profiles in progeny groups produced by crossing a XX male and a XY male to the same five females. Body weight and length were measured in the resulting all-female (XX) and mixed sex (XX/XY) offspring groups. Microarray experiments with liver and white muscle were used to determine if the gene expression profiles of large and small XX offspring differ from those in large and small XX/XY offspring. We detected no significant differences in body length and weight between offspring groups but XX offspring were significantly less variable in the value of these traits. A large number of upregulated genes were shared between the large XX and large XX/XY offspring; the small XX and small XX/XY offspring also shared similar expression profiles. No GO category differences were seen in the liver or between the large XX and large XX/XY offspring in the muscle. The greatest differences between the small XX and small XX/XY offspring were in the genes assigned to the "small molecule metabolic process" and "cellular metabolic process" GO level 3 categories. Similarly, genes within these categories as well as the category "macromolecule metabolic process" were more highly expressed in small compared to large XX fish.

What Does f[subscript xx]f[subscript yy] - f[superscript 2][subscript xy] Greater than 0 "Really" Mean?

ERIC Educational Resources Information Center

McCartin, Brian J.

2008-01-01

This note presents geometric and physical interpretations of the sufficient condition for a critical point to be a strict relative extremum: f[subscript xx]f[subscript yy] - f[superscript 2][subscript xy] greater than 0. The role of the double derivative f[subscript xy] in this inequality will be highlighted in these interpretations. (Contains 14…

GONAD DOSES IN THE X IRRADIATION OF SOME SO-CALLED MILD ILLNESSES (in German)

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

Glauner, R.; Messner, D.; Thelen, P.O.

1958-10-01

Measurements of gonad doses were carried out on men and women using ionization chambers. In women the measurements were made in the vagina. Gonad doses were measured in patients who received x-ray therapy for puerperal mastitis, sweat gland abscesses in the axilla, and furunculi of the face. The conditions of irradiation, as well as the single and total doses, are briefiy discussed. Various means of reducing gonad dose are discussed in detail. (auth)

Universality and robustness of revivals in the transverse field XY model

NASA Astrophysics Data System (ADS)

Häppölä, Juho; Halász, Gábor B.; Hamma, Alioscia

2012-03-01

We study the structure of the revivals in an integrable quantum many-body system, the transverse field XY spin chain, after a quantum quench. The time evolutions of the Loschmidt echo, the magnetization, and the single-spin entanglement entropy are calculated. We find that the revival times for all of these observables are given by integer multiples of Trev≃L/vmax, where L is the linear size of the system and vmax is the maximal group velocity of quasiparticles. This revival structure is universal in the sense that it does not depend on the initial state and the size of the quench. Applying nonintegrable perturbations to the XY model, we observe that the revivals are robust against such perturbations: they are still visible at time scales much larger than the quasiparticle lifetime. We therefore propose a generic connection between the revival structure and the locality of the dynamics, where the quasiparticle speed vmax generalizes into the Lieb-Robinson speed vLR.

Neural Activation During Mental Rotation in Complete Androgen Insensitivity Syndrome: The Influence of Sex Hormones and Sex Chromosomes.

PubMed

van Hemmen, Judy; Veltman, Dick J; Hoekzema, Elseline; Cohen-Kettenis, Peggy T; Dessens, Arianne B; Bakker, Julie

2016-03-01

Sex hormones, androgens in particular, are hypothesized to play a key role in the sexual differentiation of the human brain. However, possible direct effects of the sex chromosomes, that is, XX or XY, have not been well studied in humans. Individuals with complete androgen insensitivity syndrome (CAIS), who have a 46,XY karyotype but a female phenotype due to a complete androgen resistance, enable us to study the separate effects of gonadal hormones versus sex chromosomes on neural sex differences. Therefore, in the present study, we compared 46,XY men (n = 30) and 46,XX women (n = 29) to 46,XY individuals with CAIS (n = 21) on a mental rotation task using functional magnetic resonance imaging. Previously reported sex differences in neural activation during mental rotation were replicated in the control groups, with control men showing more activation in the inferior parietal lobe than control women. Individuals with CAIS showed a female-like neural activation pattern in the parietal lobe, indicating feminization of the brain in CAIS. Furthermore, this first neuroimaging study in individuals with CAIS provides evidence that sex differences in regional brain function during mental rotation are most likely not directly driven by genetic sex, but rather reflect gonadal hormone exposure. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Proteomic analysis of three gonad types of swamp eel reveals genes differentially expressed during sex reversal.

PubMed

Sheng, Yue; Zhao, Wei; Song, Ying; Li, Zhigang; Luo, Majing; Lei, Quan; Cheng, Hanhua; Zhou, Rongjia

2015-05-18

A variety of mechanisms are engaged in sex determination in vertebrates. The teleost fish swamp eel undergoes sex reversal naturally and is an ideal model for vertebrate sexual development. However, the importance of proteome-wide scanning for gonad reversal was not previously determined. We report a 2-D electrophoresis analysis of three gonad types of proteomes during sex reversal. MS/MS analysis revealed a group of differentially expressed proteins during ovary to ovotestis to testis transformation. Cbx3 is up-regulated during gonad reversal and is likely to have a role in spermatogenesis. Rab37 is down-regulated during the reversal and is mainly associated with oogenesis. Both Cbx3 and Rab37 are linked up in a protein network. These datasets in gonadal proteomes provide a new resource for further studies in gonadal development.

Drosophila I-R hybrid dysgenesis is associated with catastrophic meiosis and abnormal zygote formation.

PubMed

Orsi, Guillermo A; Joyce, Eric F; Couble, Pierre; McKim, Kim S; Loppin, Benjamin

2010-10-15

The Drosophila I-R type of hybrid dysgenesis is a sterility syndrome (SF sterility) associated with the mobilization of the I retrotransposon in female germ cells. SF sterility results from a maternal-effect embryonic lethality whose origin has remained unclear since its discovery about 40 years ago. Here, we show that meiotic divisions in SF oocytes are catastrophic and systematically fail to produce a functional female pronucleus at fertilization. As a consequence, most embryos from SF females rapidly arrest their development with aneuploid or damaged nuclei, whereas others develop as non-viable, androgenetic haploid embryos. Finally, we show that, in contrast to mutants affecting the biogenesis of piRNAs, SF egg chambers do not accumulate persistent DNA double-strand breaks, suggesting that I-element activity might perturb the functional organization of meiotic chromosomes without triggering an early DNA damage response.

The Drosophila actin regulator ENABLED regulates cell shape and orientation during gonad morphogenesis.

PubMed

Sano, Hiroko; Kunwar, Prabhat S; Renault, Andrew D; Barbosa, Vitor; Clark, Ivan B N; Ishihara, Shuji; Sugimura, Kaoru; Lehmann, Ruth

2012-01-01

Organs develop distinctive morphologies to fulfill their unique functions. We used Drosophila embryonic gonads as a model to study how two different cell lineages, primordial germ cells (PGCs) and somatic gonadal precursors (SGPs), combine to form one organ. We developed a membrane GFP marker to image SGP behaviors live. These studies show that a combination of SGP cell shape changes and inward movement of anterior and posterior SGPs leads to the compaction of the spherical gonad. This process is disrupted in mutants of the actin regulator, enabled (ena). We show that Ena coordinates these cell shape changes and the inward movement of the SGPs, and Ena affects the intracellular localization of DE-cadherin (DE-cad). Mathematical simulation based on these observations suggests that changes in DE-cad localization can generate the forces needed to compact an elongated structure into a sphere. We propose that Ena regulates force balance in the SGPs by sequestering DE-cad, leading to the morphogenetic movement required for gonad compaction.

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.

Molecular Identification of XY Sex-Reversed Female and YY Male Channel Catfish

USDA-ARS?s Scientific Manuscript database

Production of channel catfish leads U.S. aquaculture, and monosex culture may provide higher production efficiencies. Determination of phenotypic sex is labor intensive and not practical for large scale culture. Catfish have an X-Y sex determination system with monomorphic sex chromosomes. Hormonal...

The union of somatic gonad precursors and primordial germ cells during C. elegans embryogenesis

PubMed Central

Rohrschneider, Monica R.; Nance, Jeremy

2013-01-01

Somatic gonadal niche cells control the survival, differentiation, and proliferation of germline stem cells. The establishment of this niche-stem cell relationship is critical, and yet the precursors to these two cell types are often born at a distance from one another. The simple C. elegans gonadal primordium, which contains two somatic gonad precursors (SGPs) and two primordial germ cells (PGCs), provides an accessible model for determining how stem cell and niche cell precursors first assemble during development. To visualize the morphogenetic events that lead to formation of the gonadal primordium, we generated transgenic strains to label the cell membranes of the SGPs and PGCs and captured time-lapse movies as the gonadal primordium formed. We identify three distinct phases of SGP behavior: posterior migration along the endoderm towards the PGCs, extension of a single long projection around the adjacent PGC, and a dramatic wrapping over the PGC surfaces. We show that the endoderm and PGCs are dispensable for SGP posterior migration and initiation of projections. However, both tissues are required for the final positioning of the SGPs and the morphology of their projections, and PGCs are absolutely required for SGP wrapping behaviors. Finally, we demonstrate that the basement membrane component laminin, which localizes adjacent to the developing gonadal primordium, is required to prevent the SGPs from over-extending past the PGCs. Our findings provide a foundation for understanding the cellular and molecular regulation of the establishment of a niche-stem cell relationship. PMID:23562590

XX/XY Sex Chromosomes in the South American Dwarf Gecko (Gonatodes humeralis).

PubMed

Gamble, Tony; McKenna, Erin; Meyer, Wyatt; Nielsen, Stuart V; Pinto, Brendan J; Scantlebury, Daniel P; Higham, Timothy E

2018-05-11

Sex-specific genetic markers identified using restriction site-associated DNA sequencing, or RADseq, permits the recognition of a species' sex chromosome system in cases where standard cytogenetic methods fail. Thus, species with male-specific RAD markers have an XX/XY sex chromosome system (male heterogamety) while species with female-specific RAD markers have a ZZ/ZW sex chromosome (female heterogamety). Here, we use RADseq data from 5 male and 5 female South American dwarf geckos (Gonatodes humeralis) to identify an XX/XY sex chromosome system. This is the first confidently known sex chromosome system in a Gonatodes species. We used a low-coverage de novo G. humeralis genome assembly to design PCR primers to validate the male-specificity of a subset of the sex-specific RADseq markers and describe how even modest genome assemblies can facilitate the design of sex-specific PCR primers in species with diverse sex chromosome systems.

Sleep, rhythms, and the endocrine brain: influence of sex and gonadal hormones.

PubMed

Mong, Jessica A; Baker, Fiona C; Mahoney, Megan M; Paul, Ketema N; Schwartz, Michael D; Semba, Kazue; Silver, Rae

2011-11-09

While much is known about the mechanisms that underlie sleep and circadian rhythms, the investigation into sex differences and gonadal steroid modulation of sleep and biological rhythms is in its infancy. There is a growing recognition of sex disparities in sleep and rhythm disorders. Understanding how neuroendocrine mediators and sex differences influence sleep and biological rhythms is central to advancing our understanding of sleep-related disorders. While it is known that ovarian steroids affect circadian rhythms in rodents, the role of androgen is less understood. Surprising findings that androgens, acting via androgen receptors in the master "circadian clock" within the suprachiasmatic nucleus, modulate photic effects on activity in males point to novel mechanisms of circadian control. Work in aromatase-deficient mice suggests that some sex differences in photic responsiveness are independent of gonadal hormone effects during development. In parallel, aspects of sex differences in sleep are also reported to be independent of gonadal steroids and may involve sex chromosome complement. This a summary of recent work illustrating how sex differences and gonadal hormones influence sleep and circadian rhythms that was presented at a Mini-Symposium at the 2011 annual meeting of the Society for Neuroscience.

Familial 46,XY sex reversal without campomelic dysplasia caused by a deletion upstream of the SOX9 gene

PubMed Central

Layman, Lawrence C.; Ullmann, Reinhard; Shen, Yiping; Ha, Kyungsoo; Rehman, Khurram; Looney, Stephen; McDonough, Paul G.; Kim, Hyung-Goo; Carr, Bruce R.

2014-01-01

Background 46,XY sex reversal is a rare disorder and familial cases are even more rare. The purpose of the present study was to determine the molecular basis for a family with three affected siblings who had 46,XY sex reversal. Methods DNA was extracted from three females with 46,XY sex reversal, two normal sisters, and both unaffected parents. All protein coding exons of the SRY and NR5A1 genes were subjected to PCR-based DNA sequencing. In addition, array comparative genomic hybridization was performed on DNA from all seven family members. A deletion was confirmed using quantitative polymerase chain reaction. Expression of SOX9 gene was quantified using reverse transcriptase polymerase chain reaction. Results A 349kb heterozygous deletion located 353kb upstream of the SOX9 gene on the long arm of chromosome 17 was discovered in the father and three affected siblings, but not in the mother. The expression of SOX9 was significantly decreased in the affected siblings. Two of three affected sisters had gonadoblastomas. Conclusion This is the first report of 46,XY sex reversal in three siblings who have a paternally inherited deletion upstream of SOX9 associated with reduced SOX9 mRNA expression. PMID:24907458

Thermal quantum coherence and correlation in the extended XY spin chain

NASA Astrophysics Data System (ADS)

Sha, Ya-Ting; Wang, Yue; Sun, Zheng-Hang; Hou, Xi-Wen

2018-05-01

Quantum coherence and correlation of thermal states in the extended XY spin chain are studied in terms of the recently proposed l1 norm, skew information, and Bures distance of geometry discord (BGD), respectively. The entanglement measured via concurrence is calculated for reference. A two-dimensional susceptibility is introduced to explore their capability in highlighting the critical lines associated with quantum phase transitions in the model. It is shown that the susceptibility of the skew information and BGD is a genuine indicator of quantum phase transitions, and characterizes the factorization. However, the l1 norm is trivial for the factorization. An explicit scaling law of BGD is captured at low temperature in the XY model. In contrast to the entanglement, quantum coherence reveals a kind of long-range nonclassical correlation. Moreover, the obvious relation among model parameters is extracted for the factorized line in the extended model. Those are instructive for the understanding of quantum coherence and correlation in the theory of quantum information, and quantum phase transitions and factorization in condensed-matter physics.

Phase diagram for a two-dimensional, two-temperature, diffusive XY model.

PubMed

Reichl, Matthew D; Del Genio, Charo I; Bassler, Kevin E

2010-10-01

Using Monte Carlo simulations, we determine the phase diagram of a diffusive two-temperature conserved order parameter XY model. When the two temperatures are equal the system becomes the equilibrium XY model with the continuous Kosterlitz-Thouless (KT) vortex-antivortex unbinding phase transition. When the two temperatures are unequal the system is driven by an energy flow from the higher temperature heat-bath to the lower temperature one and reaches a far-from-equilibrium steady state. We show that the nonequilibrium phase diagram contains three phases: A homogenous disordered phase and two phases with long range, spin texture order. Two critical lines, representing continuous phase transitions from a homogenous disordered phase to two phases of long range order, meet at the equilibrium KT point. The shape of the nonequilibrium critical lines as they approach the KT point is described by a crossover exponent φ=2.52±0.05. Finally, we suggest that the transition between the two phases with long-range order is first-order, making the KT-point where all three phases meet a bicritical point.

miRNAome expression profiles in the gonads of adult Melopsittacus undulatus

PubMed Central

Jiang, Lan; Wang, Qingqing; Yu, Jue; Gowda, Vinita; Johnson, Gabriel; Yang, Jianke

2018-01-01

The budgerigar (Melopsittacus undulatus) is one of the most widely studied parrot species, serving as an excellent animal model for behavior and neuroscience research. Until recently, it was unknown how sexual differences in the behavior, physiology, and development of organisms are regulated by differential gene expression. MicroRNAs (miRNAs) are endogenous short non-coding RNA molecules that can post-transcriptionally regulate gene expression and play a critical role in gonadal differentiation as well as early development of animals. However, very little is known about the role gonadal miRNAs play in the early development of birds. Research on the sex-biased expression of miRNAs in avian gonads are limited, and little is known about M. undulatus. In the current study, we sequenced two small non-coding RNA libraries made from the gonads of adult male and female budgerigars using Illumina paired-end sequencing technology. We obtained 254 known and 141 novel miRNAs, and randomly validated five miRNAs. Of these, three miRNAs were differentially expressed miRNAs and 18 miRNAs involved in sexual differentiation as determined by functional analysis with GO annotation and KEGG pathway analysis. In conclusion, this work is the first report of sex-biased miRNAs expression in the budgerigar, and provides additional sequences to the avian miRNAome database which will foster further functional genomic research. PMID:29666766

Discovery and identification of candidate sex-related genes based on transcriptome sequencing of Russian sturgeon (Acipenser gueldenstaedtii) gonads.

PubMed

Chen, Yadong; Xia, Yongtao; Shao, Changwei; Han, Lei; Chen, Xuejie; Yu, Mengjun; Sha, Zhenxia

2016-07-01

As the Russian sturgeon (Acipenser gueldenstaedtii) is an important food and is the main source of caviar, it is necessary to discover the genes associated with its sex differentiation. However, the complicated life and maturity cycles of the Russian sturgeon restrict the accurate identification of sex in early development. To generate a first look at specific sex-related genes, we sequenced the transcriptome of gonads in different development stages (1, 2, and 5 yr old stages) with next-generation RNA sequencing. We generated >60 million raw reads, and the filtered reads were assembled into 263,341 contigs, which produced 38,505 unigenes. Genes involved in signal transduction mechanisms were the most abundant, suggesting that development of sturgeon gonads is under control of signal transduction mechanisms. Differentially expressed gene analysis suggests that more genes for protein synthesis, cytochrome c oxidase subunits, and ribosomal proteins were expressed in female gonads than in male. Meanwhile, male gonads expressed more transposable element transposase, reverse transcriptase, and transposase-related genes than female. In total, 342, 782, and 7,845 genes were detected in intersex, male, and female transcriptomes, respectively. The female gonad expressed more genes than the male gonad, and more genes were involved in female gonadal development. Genes (sox9, foxl2) are differentially expressed in different sexes and may be important sex-related genes in Russian sturgeon. Sox9 genes are responsible for the development of male gonads and foxl2 for female gonads. Copyright © 2016 the American Physiological Society.

[Gonadal ontogenesis and sex differentiation in the sea bass, Dicentrarchus labrax, under fish-farming conditions].

PubMed

Roblin, C; Bruslé, J

1983-01-01

The histology of the different stages of gonadal development (appearance of PGC, edification of gonad primordium, organization of an undifferentiated gonad, testicular or ovarian development) has been studied in fingerlings and juveniles of sea-bass in fish-culture conditions. Sex differentiation with a caudo-cranial gradient was direct and more in accordance with length than with age. Ovarian and testicular differentiation occurred in fish 11 to 23 months old and from 90 to 187 mm SL. Testis ova were frequently observed.

Gender role behavior in children with XY karyotype and disorders of sex development.

PubMed

Jürgensen, Martina; Hiort, Olaf; Holterhus, Paul-Martin; Thyen, Ute

2007-03-01

Children exhibit gender-typical preferences in play, toys, activities and interests, and playmates. Several studies suggest that high concentrations of pre- and postnatal androgens contribute to male-typical behavior development, whereas female-typical behavior develops in the absence of high androgens levels. This study aims to explore the consequences of hypoandrogenization on gender-typical behavior in children who have an XY karyotype and disorder of sex development (DSD). Participants included 33 children (ages 2-12 years) with an XY karyotype and DSD; 21 reared as girls and 12 reared as boys. Children's preferred activities and interests and playmate preferences were assessed with parent report questionnaires, a structured free-play task, and choice of a toy to keep as a gift. Participant's responses were compared to those of children recruited in a pre-school and elementary school survey (N=166). In this study, the degree of hypoandrogenization as indicated by genital stage and diagnosis showed a significant relationship to nearly all of the gender-related behaviors assessed, supporting the hypothesis that masculinization of gender role behavior is a function of prenatal androgen exposure. Despite the fact that children with partial androgen effects reared as girls showed increased "boyish" behaviors, they did not show increased signs of gender identity confusion or instability on a group level. We conclude that androgen exposure plays a decisive role in the development of gender-typical behavior in children with XY karyotype and DSD conditions.

XX/XY System of Sex Determination in the Geophilomorph Centipede Strigamia maritima

PubMed Central

Green, Jack E.; Dalíková, Martina; Sahara, Ken; Marec, František; Akam, Michael

2016-01-01

We show that the geophilomorph centipede Strigamia maritima possesses an XX/XY system of sex chromosomes, with males being the heterogametic sex. This is, to our knowledge, the first report of sex chromosomes in any geophilomorph centipede. Using the recently assembled Strigamia genome sequence, we identified a set of scaffolds differentially represented in male and female DNA sequence. Using quantitative real-time PCR, we confirmed that three candidate X chromosome-derived scaffolds are present at approximately twice the copy number in females as in males. Furthermore, we confirmed that six candidate Y chromosome-derived scaffolds contain male-specific sequences. Finally, using this molecular information, we designed an X chromosome-specific DNA probe and performed fluorescent in situ hybridization against mitotic and meiotic chromosome spreads to identify the Strigamia XY sex-chromosome pair cytologically. We found that the X and Y chromosomes are recognizably different in size during the early pachytene stage of meiosis, and exhibit incomplete and delayed pairing. PMID:26919730

Normal Levels of Sox9 Expression in the Developing Mouse Testis Depend on the TES/TESCO Enhancer, but This Does Not Act Alone.

PubMed

Gonen, Nitzan; Quinn, Alexander; O'Neill, Helen C; Koopman, Peter; Lovell-Badge, Robin

2017-01-01

During mouse sex determination, transient expression of the Y-linked gene Sry up-regulates its direct target gene Sox9, via a 3.2 kb testis specific enhancer of Sox9 (TES), which includes a core 1.4 kb element, TESCO. SOX9 activity leads to differentiation of Sertoli cells, rather than granulosa cells from the bipotential supporting cell precursor lineage. Here, we present functional analysis of TES/TESCO, using CRISPR/Cas9 genome editing in mice. Deletion of TESCO or TES reduced Sox9 expression levels in XY fetal gonads to 60 or 45% respectively relative to wild type gonads, and reduced expression of the SOX9 target Amh. Although human patients heterozygous for null mutations in SOX9, which are assumed to have 50% of normal expression, often show XY female sex reversal, mice deleted for one copy of Sox9 do not. Consistent with this, we did not observe sex reversal in either TESCO-/- or TES-/- XY embryos or adult mice. However, embryos carrying both a conditional Sox9 null allele and the TES deletion developed ovotestes. Quantitative analysis of these revealed levels of 23% expression of Sox9 compared to wild type, and a significant increase in the expression of the granulosa cell marker Foxl2. This indicates that the threshold in mice where sex reversal begins to be seen is about half that of the ~50% levels predicted in humans. Our results demonstrate that TES/TESCO is a crucial enhancer regulating Sox9 expression in the gonad, but point to the existence of additional enhancers that act redundantly.

Gene Expression Profiling Reveals Potential Players of Left-Right Asymmetry in Female Chicken Gonads.

PubMed

Wan, Zhiyi; Lu, Yanan; Rui, Lei; Yu, Xiaoxue; Yang, Fang; Tu, Chengfang; Li, Zandong

2017-06-20

Most female birds develop only a left ovary, whereas males develop bilateral testes. The mechanism underlying this process is still not completely understood. Here, we provide a comprehensive transcriptional analysis of female chicken gonads and identify novel candidate side-biased genes. RNA-Seq analysis was carried out on total RNA harvested from the left and right gonads on embryonic day 6 (E6), E12, and post-hatching day 1 (D1). By comparing the gene expression profiles between the left and right gonads, 347 differentially expressed genes (DEGs) were obtained on E6, 3730 were obtained on E12, and 2787 were obtained on D1. Side-specific genes were primarily derived from the autosome rather than the sex chromosome. Gene ontology and pathway analysis showed that the DEGs were most enriched in the Piwi-interactiing RNA (piRNA) metabolic process, germ plasm, chromatoid body, P granule, neuroactive ligand-receptor interaction, microbial metabolism in diverse environments, and methane metabolism. A total of 111 DEGs, five gene ontology (GO) terms, and three pathways were significantly different between the left and right gonads among all the development stages. We also present the gene number and the percentage within eight development-dependent expression patterns of DEGs in the left and right gonads of female chicken.

Acne in Klinefelter Syndrome-46XY/47XXY Mosaicism?

PubMed

Lakshmi, Chembolli; Swarnalakshimi, Selvaraj

2015-01-01

Klinefelter syndrome (KFS) is the most common non-heritable sex chromosome anomaly caused by nondisjunction during cell division and contains two or more X chromosomes. More than two third of all cases are homogenous (47XXY) and the remaining are mosaic (46XY/47XXY). Lower limb ulcers are frequently observed and attributed to impaired fibrinolysis. A case of KFS with post acne scars and leg ulcers is presented. The rarity of acne in this syndrome is explained by the phenomenon of mosaicism.

Familial Dandy-Walker malformation associated with macrocephaly, facial anomalies, developmental delay, and brain stem dysgenesis: prenatal diagnosis and postnatal outcome in brothers. A new syndrome?

PubMed

Chitayat, D; Moore, L; Del Bigio, M R; MacGregor, D; Ben-Zeev, B; Hodgkinson, K; Deck, J; Stothers, T; Ritchie, S; Toi, A

1994-10-01

Brothers are reported with an apparently new constellation of manifestations including Dandy-Walker complex (DWC), migrational brain disorder, macrocephaly, and facial anomalies. The first brother presented at birth, the second was detected prenatally with DWC and the pregnancy terminated. Fetal brain histopathology showed DWC associated with brainstem dysgenesis. Inheritance is likely autosomal or X-linked recessive. An extensive review of the differential diagnosis of DWC is provided.

The large Maf factor Traffic Jam controls gonad morphogenesis in Drosophila.

PubMed

Li, Michelle A; Alls, Jeffrey D; Avancini, Rita M; Koo, Karen; Godt, Dorothea

2003-11-01

Interactions between somatic and germline cells are critical for the normal development of egg and sperm. Here we show that the gene traffic jam (tj) produces a soma-specific factor that controls gonad morphogenesis and is required for female and male fertility. tj encodes the only large Maf factor in Drosophila melanogaster, an orthologue of the atypical basic Leu zipper transcription factors c-Maf and MafB/Kreisler in vertebrates. Expression of tj occurs in somatic gonadal cells that are in direct contact with germline cells throughout development. In tj mutant gonads, somatic cells fail to inter-mingle and properly envelop germline cells, causing an early block in germ cell differentiation. In addition, tj mutant somatic cells show an increase in the level of expression for several adhesion molecules. We propose that tj is a critical modulator of the adhesive properties of somatic cells, facilitating germline-soma interactions that are essential for germ cell differentiation.

Selected clinical features of the head and neck in women with Turner syndrome and the 45,X/46,XY karyotype.

PubMed

Frelich, Agnieszka; Frelich, Jakub; Jeż, Wacław; Irzyniec, Tomasz

2017-01-01

A 45,X/46,XY karyotype in women with Turner syndrome (TS) is very rare. The presence of a Y chromosome in the karyotype causes phenotypic differences and increased risk for neoplastic disease, compared to TS-women with other karyotypes. Our study addresses an issue: non-genital phenotypic differences between TS-patients with a Y-chromosome of their karyotype and TS-women without it. Results from patient history/physical examinations of the head and neck of eight TS-women and the 45,X/46,XY karyotype were compared with those observed in 164 TS-women and 30 controls. The heights of TS-groups: 142.5 ± 7.2 and 144.9 ± 7.2 cm were lower than controls (165.2 ± 6.6 cm). Participants were examined from 1995 to 2014. Among 28 study parameters, 15 were more frequently observed in TS women with the 45,X/46,XY karyotype compared to controls. Only abnormalities in the oral cavity and a history of childhood lymphoedema, differed significantly in the TS groups. With respect to the head and neck, the patient history and physical examination results of TS-women and the 45,X/46,XY karyotype and TS and other karyotypes revealed similar differences compared to controls. Compared to others TS patients, 45,X/46,XY individuals might more frequently have oral cavity soft tissue abnormalities and more rarely a history of childhood lymphoedema. (Endokrynol Pol 2017; 68 (1): 47-52).

Horseshoe kidney with growth retardation: Don't forget Turner syndrome.

PubMed

Arslansoyu-Çamlar, Seçil; Soylu, Alper; Abacı, Ayhan; Türkmen, Mehmet Atilla; Ülgenalp, Ayfer; Kavukçu, Salih

2016-01-01

Horseshoe kidney is the most frequent renal fusion anomaly that is usually asymptomatic and isolated malformation. However it can be seen with various syndromes and chromosomal anomalies. It was reported that 15-35% of Turner syndrome cases (TS) also display horseshoe kidney condition. TS is a chromosomal anomaly that had been characterized by delayed puberty, short body height and gonadal dysgenesis. In this report a five-year-old girl with horseshoe kidney, which has growth retardation during follow-up as only symptom of Turner syndrome.

Perrault's syndrome in two sisters.

PubMed

Bösze, P; Skripeczky, K; Gaál, M; Tóth, A; László, J

1983-10-01

We report on two sisters with Perrault's syndrome, i.e., autosomal recessive ovarian dysgenesis associated with sensorineural deafness. They were deaf-mute and of normal height with a few minor somatic anomalies. Both had streak gonads and an apparently normal female 46,XX chromosome constitution. The parents were apparently not consanguineous. The mother had normal hearing. Other relatives were not available for study. Epilepsy, which occurred in three relatives including one of the index patients, may have been inherited coincidentally from the mother's family.

Gonadal status and physical performance in older men.

PubMed

Maggio, Marcello; Ceda, Gian Paolo; Lauretani, Fulvio; Bandinelli, Stefania; Metter, Earl Jeffrey; Guralnik, Jack M; Basaria, Shehzad; Cattabiani, Chiara; Luci, Michele; Dall'Aglio, Elisabetta; Vignali, Alessandro; Volpi, Riccardo; Valenti, Giorgio; Ferrucci, Luigi

2011-03-01

To test the relationship between gonadal status and objective measures and determinants of physical performance in older men and their determinants. The study included 455 ≥ 65 year older men of InCHIANTI study, Italy, with complete data on testosterone levels, hand grip strength, cross-sectional muscle area (CSMA), short physical performance battery (SPPB). Linear models were used to test the relationship between gonadal status and determinants of physical performance. Three different groups of older men were created: (1) severely hypogonadal (N=23), total testosterone levels ≤ 230 ng /dl; (2) moderately hypogonadal (N=88), total testosterone >230 and < 350 ng/dl) and (3) eugonadal (N=344), testosterone levels ≥ 350 ng/dl. With increased severity of hypogonadal status, participants were significantly older while their BMI was substantially similar. In the age and BMI adjusted analysis, there was a significant difference in haemoglobin levels, hand grip strength and SPPB score (p for trend < 0.001) among three groups, with severely hypogonadal men having lower values of haemoglobin, muscle strength and physical performance. We found no association between testosterone group assignment and calf muscle mass and 4 m walking speed. In the multivariate analysis grip strength (p for trend = 0.004) and haemoglobin (p for trend < 0.0001) but not SPPB and other determinants of physical performance were significantly different between the three groups. In older men, gonadal status is independently associated with some determinants (haemoglobin and muscle strength) of physical performance.

Prostaglandin D2 Regulates SOX9 Nuclear Translocation during Gonadal Sex Determination in Tammar Wallaby, Macropus eugenii.

PubMed

Chen, Yu; Yu, Hongshi; Pask, Andrew J; Shaw, Geoff; Renfree, Marilyn B

2017-01-01

Sex determination and sexual differentiation pathways are highly conserved between marsupials and eutherians. There are 2 different pathways of prostaglandin D2 (PGD2) synthesis: prostaglandin D synthase (PTGDS) and haematopoietic prostaglandin D synthase (HPGDS). PGD2 regulates the subcellular localization of SOX9 during gonadal sexual differentiation. To investigate the function of PGD2 in the tammar gonad, we cultured undifferentiated male gonads in the presence of the HPGDS inhibitor HQL-79 and female gonads with exogenous PGD2 to mimic activation of the PTGDS-PGD2 pathway. Tammar PTGDS and HPGDS have only 50% similarity with mouse and human orthologues, but functional domains are conserved. The expression of SOX9 was unchanged by the treatments in cultured gonads, but its subcellular localization was markedly affected. SOX9 remained cytoplasmic in the Sertoli cells of testes treated with HQL-79. Treated testes developed a thickened ovary-like surface epithelium. In contrast, SOX9 became nuclear in the granulosa cells of developing ovaries treated with PGD2 and the surface epithelium was thin, as in testes. These results demonstrate that PGD2 regulates the subcellular localization of SOX9 and subsequent gonadal development in the developing marsupial gonads, as it does in mice, and that it must have been an ancestral mechanism. © 2017 S. Karger AG, Basel.

Utility of Ultrasound and Magnetic Resonance Imaging in Patients with Disorders of Sex Development Who Undergo Prophylactic Gonadectomy.

PubMed

Alaniz, V I; Kobernik, E K; Dillman, J; Quint, E H

2016-12-01

To evaluate ultrasonography and magnetic resonance imaging (MRI) in identifying gonads in patients with disorders of sex development (DSD) who undergo prophylactic gonadectomy, and to assess the capacity of preoperative imaging to detect premalignant and malignant transformation. Retrospective cohort at a tertiary referral center of 39 patients with DSD who underwent MRI and/or ultrasonography before prophylactic gonadectomy. None. Identification of gonads on preoperative imaging. Thirty-three patients underwent ultrasonography, which identified 54% (35/65) of gonads and 14 patients had MRI, which identified 41% (11/27) of gonads. There was no significant difference between imaging modalities in the proportion of gonads identified (P = .25). The proportion of pathology-confirmed dysgenetic gonads identified was higher on ultrasound compared with MRI (51% vs 8%; P = .02). There was no difference in the proportion of pathology-confirmed testes identified on ultrasound and MRI (54% vs 71%; P = .33). Eleven out of 39 patients (28%) were diagnosed with a premalignant lesion, and there were no distinguishing characteristics documented on imaging reports to suggest transformation. The only diagnosed malignancy in this series had imaging describing a "normal-sized ovary." Ultrasonography and MRI identified 40%-50% of gonads in patients with DSD who underwent prophylactic gonadectomy, with no significant difference between the 2 modalities. Clinicians should, therefore, consider ultrasonography as a first-line imaging modality. Premalignant lesions were not detected on either imaging modality. The only malignancy was described as a "normal-sized ovary" which should raise concern in a patient with complete gonadal dysgenesis expected to have streak gonads. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Sleep, Rhythms, and the Endocrine Brain: Influence of Sex and Gonadal Hormones

PubMed Central

Mong, Jessica A.; Baker, Fiona C.; Mahoney, Megan M.; Paul, Ketema N.; Schwartz, Michael D.; Semba, Kazue; Silver, Rae

2011-01-01

While much is known about the mechanisms that underlie sleep and circadian rhythms, the investigation into sex differences and gonadal steroid modulation of sleep and biological rhythms is in its infancy. There is a growing recognition of sex disparities in sleep and rhythm disorders. Understanding how neuroendocrine mediators and sex differences influence sleep and biological rhythms is central to advancing our understanding of sleep-related disorders. While it is known that ovarian steroids affect circadian rhythms in rodents, the role of androgen is less understood. Surprising findings that androgens, acting via androgen receptors in the master “circadian clock” within the suprachiasmatic nucleus (SCN), modulate photic effects on activity in males points to novel mechanisms of circadian control. Work in aromatase deficient (ArKO) mice suggests that some sex differences in photic responsiveness are independent of gonadal hormone effects during development. In parallel, aspects of sex differences in sleep are also reported to be independent of gonadal steroids and may involve sex chromosome complement. This a summary of recent work illustrating how sex differences and gonadal hormones influence sleep and circadian rhythms that was presented at a mini-symposium at the 2011 annual meeting of the Society for Neuroscience. PMID:22072663

Hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes: sex differences in regulation of stress responsivity.

PubMed

Oyola, Mario G; Handa, Robert J

2017-09-01

Gonadal hormones play a key role in the establishment, activation, and regulation of the hypothalamic-pituitary-adrenal (HPA) axis. By influencing the response and sensitivity to releasing factors, neurotransmitters, and hormones, gonadal steroids help orchestrate the gain of the HPA axis to fine-tune the levels of stress hormones in the general circulation. From early life to adulthood, gonadal steroids can differentially affect the HPA axis, resulting in sex differences in the responsivity of this axis. The HPA axis influences many physiological functions making an organism's response to changes in the environment appropriate for its reproductive status. Although the acute HPA response to stressors is a beneficial response, constant activation of this circuitry by chronic or traumatic stressful episodes may lead to a dysregulation of the HPA axis and cause pathology. Compared to males, female mice and rats show a more robust HPA axis response, as a result of circulating estradiol levels which elevate stress hormone levels during non-threatening situations, and during and after stressors. Fluctuating levels of gonadal steroids in females across the estrous cycle are a major factor contributing to sex differences in the robustness of HPA activity in females compared to males. Moreover, gonadal steroids may also contribute to epigenetic and organizational influences on the HPA axis even before puberty. Correspondingly, crosstalk between the hypothalamic-pituitary-gonadal (HPG) and HPA axes could lead to abnormalities of stress responses. In humans, a dysregulated stress response is one of the most common symptoms seen across many neuropsychiatric disorders, and as a result, such interactions may exacerbate peripheral pathologies. In this review, we discuss the HPA and HPG axes and review how gonadal steroids interact with the HPA axis to regulate the stress circuitry during all stages in life.

Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity

PubMed Central

Oyola, Mario G.; Handa, Robert J.

2018-01-01

Gonadal hormones play a key role in the establishment, activation, and regulation of the hypothalamic–pituitary–adrenal (HPA) axis. By influencing the response and sensitivity to releasing factors, neurotransmitters, and hormones, gonadal steroids help orchestrate the gain of the HPA axis to fine-tune the levels of stress hormones in the general circulation. From early life to adulthood, gonadal steroids can differentially affect the HPA axis, resulting in sex differences in the responsivity of this axis. The HPA axis influences many physiological functions making an organism’s response to changes in the environment appropriate for its reproductive status. Although the acute HPA response to stressors is a beneficial response, constant activation of this circuitry by chronic or traumatic stressful episodes may lead to a dysregulation of the HPA axis and cause pathology. Compared to males, female mice and rats show a more robust HPA axis response, as a result of circulating estradiol levels which elevate stress hormone levels during non-threatening situations, and during and after stressors. Fluctuating levels of gonadal steroids in females across the estrous cycle are a major factor contributing to sex differences in the robustness of HPA activity in females compared to males. Moreover, gonadal steroids may also contribute to epigenetic and organizational influences on the HPA axis even before puberty. Correspondingly, crosstalk between the hypothalamic–pituitary–gonadal (HPG) and HPA axes could lead to abnormalities of stress responses. In humans, a dysregulated stress response is one of the most common symptoms seen across many neuropsychiatric disorders, and as a result, such interactions may exacerbate peripheral pathologies. In this review, we discuss the HPA and HPG axes and review how gonadal steroids interact with the HPA axis to regulate the stress circuitry during all stages in life. PMID:28859530

Evidence That Intergenic Spacer Repeats of Drosophila Melanogaster Rrna Genes Function as X-Y Pairing Sites in Male Meiosis, and a General Model for Achiasmatic Pairing

PubMed Central

McKee, B. D.; Habera, L.; Vrana, J. A.

1992-01-01

In Drosophila melanogaster males, X-Y meiotic chromosome pairing is mediated by the nucleolus organizers (NOs) which are located in the X heterochromatin (Xh) and near the Y centromere. Deficiencies for Xh disrupt X-Y meiotic pairing and cause high frequencies of X-Y nondisjunction. Insertion of cloned rRNA genes on an Xh(-) chromosome partially restores normal X-Y pairing and disjunction. To map the sequences within an inserted, X-linked rRNA gene responsible for stimulating X-Y pairing, partial deletions were generated by P element-mediated destabilization of the insert. Complete deletions of the rRNA transcription unit did not interfere with the ability to stimulate X-Y pairing as long as most of the intergenic spacer (IGS) remained. Within groups of deletions that lacked the entire transcription unit and differed only in length of residual IGS material, pairing ability was proportional to the dose of 240-bp intergenic spacer repeats. Deletions of the complete rRNA transcription unit or of the 28S sequences alone blocked nucleolus formation, as determined by binding of an antinucleolar antibody, yet did not interfere with pairing ability, suggesting that X-Y pairing may not be mechanistically related to nucleolus formation. A model for achiasmatic pairing in Drosophila males based upon the combined action of topoisomerase I and a strand transferase is proposed. PMID:1330825

Acne in Klinefelter Syndrome-46XY/47XXY Mosaicism?

PubMed Central

Lakshmi, Chembolli; Swarnalakshimi, Selvaraj

2015-01-01

Klinefelter syndrome (KFS) is the most common non-heritable sex chromosome anomaly caused by nondisjunction during cell division and contains two or more X chromosomes. More than two third of all cases are homogenous (47XXY) and the remaining are mosaic (46XY/47XXY). Lower limb ulcers are frequently observed and attributed to impaired fibrinolysis. A case of KFS with post acne scars and leg ulcers is presented. The rarity of acne in this syndrome is explained by the phenomenon of mosaicism. PMID:26538700

On the role of germ cells in mammalian gonad development: quiet passengers or back-seat drivers?

PubMed

Rios-Rojas, Clarissa; Bowles, Josephine; Koopman, Peter

2015-04-01

In addition to their role as endocrine organs, the gonads nurture and protect germ cells, and regulate the formation of gametes competent to convey the genome to the following generation. After sex determination, gonadal somatic cells use several known signalling pathways to direct germ cell development. However, the extent to which germ cells communicate back to the soma, the molecular signals they use to do so and the significance of any such signalling remain as open questions. Herein, we review findings arising from the study of gonadal development and function in the absence of germ cells in a range of organisms. Most published studies support the view that germ cells are unimportant for foetal gonadal development in mammals, but later become critical for stabilisation of gonadal function and somatic cell phenotype. However, the lack of consistency in the data, and clear differences between mammals and other vertebrates and invertebrates, suggests that the story may not be so simple and would benefit from more careful analysis using contemporary molecular, cell biology and imaging tools. © 2015 Society for Reproduction and Fertility.

Sex Reversal and Analyses of Possible Involvement of Sex Steroids in Scallop Gonadal Development in Newly Established Organ-Culture Systems.

PubMed

Otani, Ayano; Nakajima, Tadaaki; Okumura, Tomomi; Fujii, Shiro; Tomooka, Yasuhiro

2017-04-01

Many molluscs perform sex reversal, and sex hormones may be involved in the process. In adult scallops, Patinopecten yessoensis, gonadotropin releasing hormone and 17β-estradiol (E 2 ) are involved in male sexual maturation, however, little is known about the effects of E 2 and testosterone (T) on the gonadal differentiation in young scallops. In the present study, scallop gonadal development was analyzed to determine the sex reversal stage in Funka bay, and effects of E 2 and T were examined. In Funka bay, almost all scallops were male at month 12. Scallops equipped with ambiguous gonads were 61.1% at month 16 and disappeared at month 18. Therefore, sex reversal in Funka bay occurs at around month 16. For establishment of organ culture systems for bivalves, Manila clam gonads were cultured in 15% L-15 medium diluted with HBSS containing 10% KSR on agarose gel at 10°C, and the gonads survived for 14 days. Scallop gonads were also able to be cultured in 30% L15 medium diluted with ASW containing 10% KSR on agarose gel for seven days. At mature stage, Foxl2 and Tesk were predominantly expressed in ovary and testis, respectively. When scallop gonads at sex reversal stage were organ-cultured, sex steroid treatment decreased Tesk expression in the majority of scallop gonads at sex reversal stage. However, no obvious change in Foxl2 and Tesk expression was detected in mature gonads in response to either E 2 or T in culture, suggesting sex steroid treatment might affect gonadal development at sex reversal stage.

Retinoic Acid Metabolic Genes, Meiosis, and Gonadal Sex Differentiation in Zebrafish

PubMed Central

Rodríguez-Marí, Adriana; Cañestro, Cristian; BreMiller, Ruth A.; Catchen, Julian M.; Yan, Yi-Lin; Postlethwait, John H.

2013-01-01

To help understand the elusive mechanisms of zebrafish sex determination, we studied the genetic machinery regulating production and breakdown of retinoic acid (RA) during the onset of meiosis in gonadogenesis. Results uncovered unexpected mechanistic differences between zebrafish and mammals. Conserved synteny and expression analyses revealed that cyp26a1 in zebrafish and its paralog Cyp26b1 in tetrapods independently became the primary genes encoding enzymes available for gonadal RA-degradation, showing lineage-specific subfunctionalization of vertebrate genome duplication (VGD) paralogs. Experiments showed that zebrafish express aldh1a2, which encodes an RA-synthesizing enzyme, in the gonad rather than in the mesonephros as in mouse. Germ cells in bipotential gonads of all zebrafish analyzed were labeled by the early meiotic marker sycp3, suggesting that in zebrafish, the onset of meiosis is not sexually dimorphic as it is in mouse and is independent of Stra8, which is required in mouse but was lost in teleosts. Analysis of dead-end knockdown zebrafish depleted of germ cells revealed the germ cell-independent onset and maintenance of gonadal aldh1a2 and cyp26a1 expression. After meiosis initiated, somatic cell expression of cyp26a1 became sexually dimorphic: up-regulated in testes but not ovaries. Meiotic germ cells expressing the synaptonemal complex gene sycp3 occupied islands of somatic cells that lacked cyp26a1 expression, as predicted by the hypothesis that Cyp26a1 acts as a meiosis-inhibiting factor. Consistent with this hypothesis, females up-regulated cyp26a1 in oocytes that entered prophase-I meiotic arrest, and down-regulated cyp26a1 in oocytes resuming meiosis. Co-expression of cyp26a1 and the pluripotent germ cell stem cell marker pou5f1(oct4) in meiotically arrested oocytes was consistent with roles in mouse to promote germ cell survival and to prevent apoptosis, mechanisms that are central for tipping the sexual fate of gonads towards the female

Gonadal Transcriptome Alterations in Response to Dietary Energy Intake: Sensing the Reproductive Environment

PubMed Central

Martin, Bronwen; Pearson, Michele; Brenneman, Randall; Golden, Erin; Wood, William; Prabhu, Vinayakumar; Becker, Kevin G.; Mattson, Mark P.; Maudsley, Stuart

2009-01-01

Reproductive capacity and nutritional input are tightly linked and animals' specific responses to alterations in their physical environment and food availability are crucial to ensuring sustainability of that species. We have assessed how alterations in dietary energy intake (both reductions and excess), as well as in food availability, via intermittent fasting (IF), affect the gonadal transcriptome of both male and female rats. Starting at four months of age, male and female rats were subjected to a 20% or 40% caloric restriction (CR) dietary regime, every other day feeding (IF) or a high fat-high glucose (HFG) diet for six months. The transcriptional activity of the gonadal response to these variations in dietary energy intake was assessed at the individual gene level as well as at the parametric functional level. At the individual gene level, the females showed a higher degree of coherency in gonadal gene alterations to CR than the males. The gonadal transcriptional and hormonal response to IF was also significantly different between the male and female rats. The number of genes significantly regulated by IF in male animals was almost 5 times greater than in the females. These IF males also showed the highest testosterone to estrogen ratio in their plasma. Our data show that at the level of gonadal gene responses, the male rats on the IF regime adapt to their environment in a manner that is expected to increase the probability of eventual fertilization of females that the males predict are likely to be sub-fertile due to their perception of a food deficient environment. PMID:19127293

Karyological and gonadal sex of eels (Anguilla anguilla) from the German Bight and the lower River Elbe

NASA Astrophysics Data System (ADS)

Passakas, T.; Tesch, F.-W.

1980-06-01

Yellow eels (Anguilla anguilla) taken during summer from random commercial trapnet samples in the littoral area of Helgoland (n=116) and from a freshwater area of the River Elbe near Hamburg (n=109) were examined with regard to their karyological (i.e. existence of female sex chromosomes) and gonadal sex. In 47 % and 21 % of the two samples, respectively, chromosomes were unidentifiable because of insufficient numbers of mitotic plates. All eels from Helgoland, except one phenotypically undetermined fish, exhibited female gonads: 48 had female sex chromosomes and 13 were karyologically males. As found previously in the River Elbe, eels with male gonads predominated (n=55); 25 were undifferentiated. Of the gonadal males 26 were karyological males and 16 karyological females; the rest could not be identified by chromosome patterns. In contrast, all but one of the Elbe eels with female gonads (n=28) had female sex chromosomes. Some aspects of the sex reversal documented in the eel are considered.

Randomly diluted xy and resistor networks near the percolation threshold

NASA Astrophysics Data System (ADS)

Harris, A. B.; Lubensky, T. C.

1987-05-01

A formulation based on that of Stephen for randomly diluted systems near the percolation threshold is analyzed in detail. By careful consideration of various limiting procedures, a treatment of xy spin models and resistor networks is given which shows that previous calculations (which indicate that these systems having continuous symmetry have the same crossover exponents as the Ising model) are in error. By studying the limit wherein the energy gap goes to zero, we exhibit the mathematical mechanism which leads to qualitatively different results for xy-like as contrasted to Ising-like systems. A distinctive feature of the results is that there is an infinite sequence of crossover exponents needed to completely describe the probability distribution for R(x,x'), the resistance between sites x and x'. Because of the difference in symmetry between the xy model and the resistor network, the former has an infinite sequence of crossover exponents in addition to those of the resistor network. The first crossover exponent φ1=1+ɛ/42 governs the scaling behavior of R(x,x') with ||x-x'||≡r: [R(x,x')]c~xφ1/ν, where [ ]c indicates a conditional average, subject to x and x' being in the same cluster, ν is the correlation length exponent for percolation, and ɛ=6-d, where d is the spatial dimensionality. We give a detailed analysis of the scaling properties of the bulk conductivity and the anomalous diffusion constant introduced by Gefen et al. Our results show conclusively that the Alexander-Orbach conjecture, while numerically quite accurate, is not exact, at least in high spatial dimension. We also evaluate various amplitude ratios associated with susceptibilities, χn involving the nth power of the resistance R(x,x'), e.g., &χ2χ0/χ21=2[1+(19ɛ/420)]. In an appendix we outline how the calculation can be extended to treat the diluted m-component spin model for m>2. As expected, the results for φ1 remain valid for m>2. The techniques described here have led to several

Disorders of sex development: a genetic study of patients in a multidisciplinary clinic

PubMed Central

Laino, Luigi; Majore, Silvia; Preziosi, Nicoletta; Grammatico, Barbara; De Bernardo, Carmelilia; Scommegna, Salvatore; Rapone, Anna Maria; Marrocco, Giacinto; Bottillo, Irene; Grammatico, Paola

2014-01-01

Sex development is a process under genetic control directing both the bi-potential gonads to become either a testis or an ovary, and the consequent differentiation of internal ducts and external genitalia. This complex series of events can be altered by a large number of genetic and non-genetic factors. Disorders of sex development (DSD) are all the medical conditions characterized by an atypical chromosomal, gonadal, or phenotypical sex. Incomplete knowledge of the genetic mechanisms involved in sex development results in a low probability of determining the molecular definition of the genetic defect in many of the patients. In this study, we describe the clinical, cytogenetic, and molecular study of 88 cases with DSD, including 29 patients with 46,XY and disorders in androgen synthesis or action, 18 with 46,XX and disorders in androgen excess, 17 with 46,XY and disorders of gonadal (testicular) development, 11 classified as 46,XX other, eight with 46,XX and disorders of gonadal (ovarian) development, and five with sex chromosome anomalies. In total, we found a genetic variant in 56 out of 88 of them, leading to the clinical classification of every patient, and we outline the different steps required for a coherent genetic testing approach. In conclusion, our results highlight the fact that each category of DSD is related to a large number of different DNA alterations, thus requiring multiple genetic studies to achieve a precise etiological diagnosis for each patient. PMID:25248670

Particle parameter analyzing system. [x-y plotter circuits and display

NASA Technical Reports Server (NTRS)

Hansen, D. O.; Roy, N. L. (Inventor)

1969-01-01

An X-Y plotter circuit apparatus is described which displays an input pulse representing particle parameter information, that would ordinarily appear on the screen of an oscilloscope as a rectangular pulse, as a single dot positioned on the screen where the upper right hand corner of the input pulse would have appeared. If another event occurs, and it is desired to display this event, the apparatus is provided to replace the dot with a short horizontal line.

The electronic and optical properties of quaternary GaAs1-x-y N x Bi y alloy lattice-matched to GaAs: a first-principles study.

PubMed

Ma, Xiaoyang; Li, Dechun; Zhao, Shengzhi; Li, Guiqiu; Yang, Kejian

2014-01-01

First-principles calculations based on density functional theory have been performed for the quaternary GaAs1-x-y N x Bi y alloy lattice-matched to GaAs. Using the state-of-the-art computational method with the Heyd-Scuseria-Ernzerhof (HSE) hybrid functional, electronic, and optical properties were obtained, including band structures, density of states (DOSs), dielectric function, absorption coefficient, refractive index, energy loss function, and reflectivity. It is found that the lattice constant of GaAs1-x-y N x Bi y alloy with y/x =1.718 can match to GaAs. With the incorporation of N and Bi into GaAs, the band gap of GaAs1-x-y N x Bi y becomes small and remains direct. The calculated optical properties indicate that GaAs1-x-y N x Bi y has higher optical efficiency as it has less energy loss than GaAs. In addition, it is also found that the electronic and optical properties of GaAs1-x-y N x Bi y alloy can be further controlled by tuning the N and Bi compositions in this alloy. These results suggest promising applications of GaAs1-x-y N x Bi y quaternary alloys in optoelectronic devices.

The "yin and yang" of the adrenal and gonadal systems in elite military men.

PubMed

Taylor, Marcus K; Hernández, Lisa M; Kviatkovsky, Shiloah A; Schoenherr, Matthew R; Stone, Michael S; Sargent, Paul

2017-05-01

We recently established daily, free-living profiles of the adrenal hormone cortisol, the (primarily adrenal) anabolic precursor dehydroepiandrosterone (DHEA) and the (primarily gonadal) anabolic hormone testosterone in elite military men. A prevailing view is that adrenal and gonadal systems reciprocally modulate each other; however, recent paradigm shifts prompted the characterization of these systems as parallel, cooperative processes (i.e. the "positive coupling" hypothesis). In this study, we tested the positive coupling hypothesis in 57 elite military men by evaluating associations between adrenal and gonadal biomarkers across the day. Salivary DHEA was moderately and positively coupled with salivary cortisol, as was salivary testosterone. Anabolic processes (i.e. salivary DHEA and testosterone) were also positively and reliably coupled across the day. In multivariate models, salivary DHEA and cortisol combined to account for substantial variance in salivary testosterone concentrations across the day, but this was driven almost exclusively by DHEA. This may reflect choreographed adrenal release of DHEA with testicular and/or adrenal release of testosterone, systemic conversion of DHEA to testosterone, or both. DHEA and testosterone modestly and less robustly predicted cortisol concentrations; this was confined to the morning, and testosterone was the primary predictor. Altogether, top-down co-activation of adrenal and gonadal hormone secretion may complement bottom-up counter-regulatory functions to foster anabolic balance and neuronal survival; hence, the "yin and yang" of adrenal and gonadal systems. This may be an adaptive process that is amplified by stress, competition, and/or dominance hierarchy.

A gonad-expressed opsin mediates light-induced spawning in the jellyfish Clytia

PubMed Central

Quiroga Artigas, Gonzalo; Lapébie, Pascal; Leclère, Lucas; Takeda, Noriyo; Deguchi, Ryusaku; Jékely, Gáspár

2018-01-01

Across the animal kingdom, environmental light cues are widely involved in regulating gamete release, but the molecular and cellular bases of the photoresponsive mechanisms are poorly understood. In hydrozoan jellyfish, spawning is triggered by dark-light or light-dark transitions acting on the gonad, and is mediated by oocyte maturation-inducing neuropeptide hormones (MIHs) released from the ectoderm. We determined in Clytia hemisphaerica that blue-cyan light triggers spawning in isolated gonads. A candidate opsin (Opsin9) was found co-expressed with MIH within specialised ectodermal cells. Opsin9 knockout jellyfish generated by CRISPR/Cas9 failed to undergo oocyte maturation and spawning, a phenotype reversible by synthetic MIH. Gamete maturation and release in Clytia is thus regulated by gonadal photosensory-neurosecretory cells that secrete MIH in response to light via Opsin9. Similar cells in ancestral eumetazoans may have allowed tissue-level photo-regulation of diverse behaviours, a feature elaborated in cnidarians in parallel with expansion of the opsin gene family. PMID:29303477

Gonadotropin-releasing hormone analogues inhibit leiomyoma extracellular matrix despite presence of gonadal hormones.

PubMed

Malik, Minnie; Britten, Joy; Cox, Jeris; Patel, Amrita; Catherino, William H

2016-01-01

To determine the effect of GnRH analogues (GnRH-a) leuprolide acetate (LA) and cetrorelix acetate on gonadal hormone-regulated expression of extracellular matrix in uterine leiomyoma three-dimensional (3D) cultures. Laboratory study. University research laboratory. Women undergoing hysterectomy for symptomatic leiomyomas. The 3D cell cultures, protein analysis, Western blot, immunohistochemistry. Expression of extracellular matrix proteins, collagen 1, fibronectin, and versican in leiomyoma cells 3D cultures exposed to E2, P, LA, cetrorelix acetate, and combinations for 24- and 72-hour time points. The 3D leiomyoma cultures exposed to E2 for 24 hours demonstrated an increased expression of collagen-1 and fibronectin, which was maintained for up to 72 hours, a time point at which versican was up-regulated significantly. Although P up-regulated collagen-1 protein (1.29 ± 0.04) within 24 hours of exposure, significant increase in all extracellular matrix (ECM) proteins was observed when the gonadal hormones were used concomitantly. Significant decrease in the amount of ECM proteins was observed on use of GnRH-a, LA and cetrorelix, with 24-hour exposure. Both the compounds also significantly decreased ECM protein concentration despite the presence of E2 or both gonadal hormones. This study demonstrates that GnRH-a directly affect the gonadal hormone-regulated collagen-1, fibronectin, and versican production in their presence. These findings suggest that localized therapy with GnRH-a may inhibit leiomyoma growth even in the presence of endogenous gonadal hormone exposure, thereby providing a mechanism to eliminate the hypoestrogenic side effects associated with GnRH-a therapy. Published by Elsevier Inc.

Detection of Spiroplasma and Wolbachia in the bacterial gonad community of Chorthippus parallelus.

PubMed

Martínez-Rodríguez, P; Hernández-Pérez, M; Bella, J L

2013-07-01

We have recently detected the endosymbiont Wolbachia in multiple individuals and populations of the grasshopper Chorthippus parallelus (Orthoptera: acrididae). This bacterium induces reproductive anomalies, including cytoplasmic incompatibility. Such incompatibilities may help explain the maintenance of two distinct subspecies of this grasshopper, C. parallelus parallelus and C. parallelus erythropus, which are involved in a Pyrenean hybrid zone that has been extensively studied for the past 20 years, becoming a model system for the study of genetic divergence and speciation. To evaluate whether Wolbachia is the sole bacterial infection that might induce reproductive anomalies, the gonadal bacterial community of individuals from 13 distinct populations of C. parallelus was determined by denaturing gradient gel electrophoresis analysis of bacterial 16S rRNA gene fragments and sequencing. The study revealed low bacterial diversity in the gonads: a persistent bacterial trio consistent with Spiroplasma sp. and the two previously described supergroups of Wolbachia (B and F) dominated the gonad microbiota. A further evaluation of the composition of the gonad bacterial communities was carried out by whole cell hybridization. Our results confirm previous studies of the cytological distribution of Wolbachia in C. parallelus gonads and show a homogeneous infection by Spiroplasma. Spiroplasma and Wolbachia cooccurred in some individuals, but there was no significant association of Spiroplasma with a grasshopper's sex or with Wolbachia infection, although subtle trends might be detected with a larger sample size. This information, together with previous experimental crosses of this grasshopper, suggests that Spiroplasma is unlikely to contribute to sex-specific reproductive anomalies; instead, they implicate Wolbachia as the agent of the observed anomalies in C. parallelus.

Traceable X,Y self-calibration at single nm level of an optical microscope used for coherence scanning interferometry

NASA Astrophysics Data System (ADS)

Ekberg, Peter; Mattsson, Lars

2018-03-01

Coherence scanning interferometry used in optical profilers are typically good for Z-calibration at nm-levels, but the X,Y accuracy is often left without further notice than typical resolution limits of the optics, i.e. of the order of ~1 µm. For the calibration of metrology tools we rely on traceable artefacts, e.g. gauge blocks for traditional coordinate measurement machines, and lithographically mask made artefacts for microscope calibrations. In situations where the repeatability and accuracy of the measurement tool is much better than the uncertainty of the traceable artefact, we are bound to specify the uncertainty based on the calibration artefact rather than on the measurement tool. This is a big drawback as the specified uncertainty of a calibrated measurement may shrink the available manufacturing tolerance. To improve the uncertainty in X,Y we can use self-calibration. Then, we do not need to know anything more than that the artefact contains a pattern with some nominal grid. This also gives the opportunity to manufacture the artefact in-house, rather than buying a calibrated and expensive artefact. The self-calibration approach we present here is based on an iteration algorithm, rather than the traditional mathematical inversion, and it leads to much more relaxed constrains on the input measurements. In this paper we show how the X,Y errors, primarily optical distortions, within the field of view (FOV) of an optical coherence scanning interferometry microscope, can be reduced with a large factor. By self-calibration we achieve an X,Y consistency in the 175  ×  175 µm2 FOV of ~2.3 nm (1σ) using the 50×  objective. Besides the calibrated coordinate X,Y system of the microscope we also receive, as a bonus, the absolute positions of the pattern in the artefact with a combined uncertainty of 6 nm (1σ) by relying on a traceable 1D linear measurement of a twin artefact at NIST.

Normal Levels of Sox9 Expression in the Developing Mouse Testis Depend on the TES/TESCO Enhancer, but This Does Not Act Alone

PubMed Central

O’Neill, Helen C.; Koopman, Peter; Lovell-Badge, Robin

2017-01-01

During mouse sex determination, transient expression of the Y-linked gene Sry up-regulates its direct target gene Sox9, via a 3.2 kb testis specific enhancer of Sox9 (TES), which includes a core 1.4 kb element, TESCO. SOX9 activity leads to differentiation of Sertoli cells, rather than granulosa cells from the bipotential supporting cell precursor lineage. Here, we present functional analysis of TES/TESCO, using CRISPR/Cas9 genome editing in mice. Deletion of TESCO or TES reduced Sox9 expression levels in XY fetal gonads to 60 or 45% respectively relative to wild type gonads, and reduced expression of the SOX9 target Amh. Although human patients heterozygous for null mutations in SOX9, which are assumed to have 50% of normal expression, often show XY female sex reversal, mice deleted for one copy of Sox9 do not. Consistent with this, we did not observe sex reversal in either TESCO-/- or TES-/- XY embryos or adult mice. However, embryos carrying both a conditional Sox9 null allele and the TES deletion developed ovotestes. Quantitative analysis of these revealed levels of 23% expression of Sox9 compared to wild type, and a significant increase in the expression of the granulosa cell marker Foxl2. This indicates that the threshold in mice where sex reversal begins to be seen is about half that of the ~50% levels predicted in humans. Our results demonstrate that TES/TESCO is a crucial enhancer regulating Sox9 expression in the gonad, but point to the existence of additional enhancers that act redundantly. PMID:28045957

Molecular Diagnosis of 5α-Reductase Type II Deficiency in Brazilian Siblings with 46,XY Disorder of Sex Development

PubMed Central

de Calais, Flávia Leme; Soardi, Fernanda Caroline; Petroli, Reginaldo José; Lusa, Ana Letícia Gori; de Paiva e Silva, Roberto Benedito; Maciel-Guerra, Andréa Trevas; Guerra-Júnior, Gil; de Mello, Maricilda Palandi

2011-01-01

The steroid 5α-reductase type II enzyme catalyzes the conversion of testosterone (T) to dihydrotestosterone (DHT), and its deficiency leads to undervirilization in 46,XY individuals, due to an impairment of this conversion in genital tissues. Molecular analysis in the steroid 5α-reductase type II gene (SRD5A2) was performed in two 46,XY female siblings. SRD5A2 gene sequencing revealed that the patients were homozygous for p.Gln126Arg missense mutation, which results from the CGA > CAA nucleotide substitution. The molecular result confirmed clinical diagnosis of 46,XY disorder of sex development (DSD) for the older sister and directed the investigation to other family members. Studies on SRD5A2 protein structure showed severe changes at NADPH binding region indicating that structural modeling analysis can be useful to evaluate the deleterious role of a mutation as causing 5α-reductase type II enzyme deficiency. PMID:22272144

XY sex chromosome complement, compared with XX, in the CNS confers greater neurodegeneration during experimental autoimmune encephalomyelitis

PubMed Central

Du, Sienmi; Itoh, Noriko; Askarinam, Sahar; Hill, Haley; Arnold, Arthur P.; Voskuhl, Rhonda R.

2014-01-01

Women are more susceptible to multiple sclerosis (MS) and have more robust immune responses than men. However, men with MS tend to demonstrate a more progressive disease course than women, suggesting a disconnect between the severity of an immune attack and the CNS response to a given immune attack. We have previously shown in an MS model, experimental autoimmune encephalomyelitis, that autoantigen-sensitized XX lymph node cells, compared with XY, are more encephalitogenic. These studies demonstrated an effect of sex chromosomes in the induction of immune responses, but did not address a potential role of sex chromosomes in the CNS response to immune-mediated injury. Here, we examined this possibility using XX versus XY bone marrow chimeras reconstituted with a common immune system of one sex chromosomal type. We found that experimental autoimmune encephalomyelitis mice with an XY sex chromosome complement in the CNS, compared with XX, demonstrated greater clinical disease severity with more neuropathology in the spinal cord, cerebellum, and cerebral cortex. A candidate gene on the X chromosome, toll-like receptor 7, was then examined. Toll-like receptor 7 expression in cortical neurons was higher in mice with XY compared with mice with XX CNS, consistent with the known neurodegenerative role for toll-like receptor 7 in neurons. These results suggest that sex chromosome effects on neurodegeneration in the CNS run counter to effects on immune responses, and may bear relevance to the clinical enigma of greater MS susceptibility in women but faster disability progression in men. This is a demonstration of a direct effect of sex chromosome complement on neurodegeneration in a neurological disease. PMID:24550311

XY sex chromosome complement, compared with XX, in the CNS confers greater neurodegeneration during experimental autoimmune encephalomyelitis.

PubMed

Du, Sienmi; Itoh, Noriko; Askarinam, Sahar; Hill, Haley; Arnold, Arthur P; Voskuhl, Rhonda R

2014-02-18

Women are more susceptible to multiple sclerosis (MS) and have more robust immune responses than men. However, men with MS tend to demonstrate a more progressive disease course than women, suggesting a disconnect between the severity of an immune attack and the CNS response to a given immune attack. We have previously shown in an MS model, experimental autoimmune encephalomyelitis, that autoantigen-sensitized XX lymph node cells, compared with XY, are more encephalitogenic. These studies demonstrated an effect of sex chromosomes in the induction of immune responses, but did not address a potential role of sex chromosomes in the CNS response to immune-mediated injury. Here, we examined this possibility using XX versus XY bone marrow chimeras reconstituted with a common immune system of one sex chromosomal type. We found that experimental autoimmune encephalomyelitis mice with an XY sex chromosome complement in the CNS, compared with XX, demonstrated greater clinical disease severity with more neuropathology in the spinal cord, cerebellum, and cerebral cortex. A candidate gene on the X chromosome, toll-like receptor 7, was then examined. Toll-like receptor 7 expression in cortical neurons was higher in mice with XY compared with mice with XX CNS, consistent with the known neurodegenerative role for toll-like receptor 7 in neurons. These results suggest that sex chromosome effects on neurodegeneration in the CNS run counter to effects on immune responses, and may bear relevance to the clinical enigma of greater MS susceptibility in women but faster disability progression in men. This is a demonstration of a direct effect of sex chromosome complement on neurodegeneration in a neurological disease.

Black carp vasa identifies embryonic and gonadal germ cells.

PubMed

Xue, Ting; Yu, Miao; Pan, Qihua; Wang, Yizhou; Fang, Jian; Li, Lingyu; Deng, Yu; Chen, Kai; Wang, Qian; Chen, Tiansheng

2017-07-01

Identification of molecular markers is an essential step in the study of germ cells. Vasa is an RNA helicase and a well-known germ cell marker that plays a crucial role in germ cell development. Here, we identified the Vasa homolog termed Mpvasa as the first germ cell marker in black carp (Mylopharyngodon piceus). First, a 2819-bp full-length Mpvasa complementary DNA (cDNA) was cloned by PCR using degenerated primers of conserved sequences and gene-specific primers. The Mpvasa cDNA sequence encodes a 637-amino acid protein that contains eight conserved characteristic motifs of the DEAD box protein family, and shares high identity to grass carp (81%) and zebrafish (74%) vasa homologs. Second, Mpvasa expression was restricted to the gonad in adulthood by RT-PCR and Western blot analysis. The dynamic patterns of temporal-spatial expression of Mpvasa during gametogenesis were examined by in situ hybridization, and Mpvasa transcripts were strictly detected in gonadal germ cells throughout oogenesis, predominantly in immature oocytes (stage I, II, and III oocytes). Third, Mpvasa transcripts were highly detected in unfertilized eggs and early embryos, and the signal indicated a dynamic migration of the primordial germ cells during embryogenesis, suggesting that Mpvasa transcripts were maternally inherited and specifically distributed in germ cells. Taken together, these results demonstrated that Mpvasa is an applicable molecular marker for identification of gonadal and embryonic germ cells, which facilitates the isolation and utilization of germ cells in black carp.

Gonadal and Sexual Dysfunction in Childhood Cancer Survivors.

PubMed

Yoon, Ju Young; Park, Hyeon Jin; Ju, Hee Young; Yoon, Jong Hyung; Chung, Jin Soo; Hwang, Sang Hyun; Lee, Dong Ock; Shim, Hye Young; Park, Byung-Kiu

2017-10-01

Few studies have addressed gonadal and sexual dysfunctions in childhood cancer survivors. We evaluated the prevalence rates and risk factors for gonadal failure among adolescent/young adult childhood cancer survivors and their sexual function. Subjects were childhood cancer survivors aged 15-29 years who had completed therapy more than 2 years ago. Demographic and medical characteristics were obtained from the patients' medical records. In addition, hormonal evaluation and semen analysis were performed and sexual function was evaluated via questionnaire. The study included 105 survivors (57 males, 48 females), of which 61 were adults (age > 19 years) and 44 were adolescents. In both males and females, the proportion of survivors with low sex hormone levels did not differ among age groups or follow-up period. Thirteen female subjects (27.1%) needed sex hormone replacement, while five males subjects (8.8%) were suspected of having hypogonadism, but none were receiving sex hormone replacement. Of 27 semen samples, 14 showed azospermia or oligospermia. The proportion of normospermia was lower in the high cyclophosphamide equivalent dose (CED) group (CED ≥ 8,000 mg/m2) than the low CED group (27.3% vs. 62.5%, p=0.047). Among adults, none were married and only 10 men (35.7%) and eight women (34.3%) were in a romantic relationship. Though a significant proportion (12.0% of males and 5.3% of females) of adolescent survivors had experienced sexual activity, 13.6% had not experienced sex education. The childhood cancer survivors in this study showed a high prevalence of gonadal/sexual dysfunction; accordingly, proper strategies are needed to manage these complications.

PlotXY: A High Quality Plotting System for the Herschel Interactive Processing Environment (HIPE) and the Astronomical Community

NASA Astrophysics Data System (ADS)

Panuzzo, P.; Li, J.; Caux, E.

2012-09-01

The Herschel Interactive Processing Environment (HIPE) was developed by the European Space Agency (ESA) in collaboration with NASA and the Herschel Instrument Control Centres, to provide the astronomical community a complete environment to process and analyze the data gathered by the Herschel Space Observatory. One of the most important components of HIPE is the plotting system (named PlotXY) that we present here. With PlotXY it is possible to produce easily high quality publication-ready 2D plots. It provides a long list of features, with fully configurable components, and interactive zooming. The entire code of HIPE is written in Java and is open source released under the GNU Lesser General Public License version 3. A new version of PlotXY is being developed to be independent from the HIPE code base; it is available to the software development community for the inclusion in other projects at the URL http://code.google.com/p/jplot2d/.

An SRY mutation causing human sex reversal resolves a general mechanism of structure-specific DNA recognition: application to the four-way DNA junction.

PubMed

Peters, R; King, C Y; Ukiyama, E; Falsafi, S; Donahoe, P K; Weiss, M A

1995-04-11

SRY, a genetic "master switch" for male development in mammals, exhibits two biochemical activities: sequence-specific recognition of duplex DNA and sequence-independent binding to the sharp angles of four-way DNA junctions. Here, we distinguish between these activities by analysis of a mutant SRY associated with human sex reversal (46, XY female with pure gonadal dysgenesis). The substitution (168T in human SRY) alters a nonpolar side chain in the minor-groove DNA recognition alpha-helix of the HMG box [Haqq, C.M., King, C.-Y., Ukiyama, E., Haqq, T.N., Falsalfi, S., Donahoe, P.K., & Weiss, M.A. (1994) Science 266, 1494-1500]. The native (but not mutant) side chain inserts between specific base pairs in duplex DNA, interrupting base stacking at a site of induced DNA bending. Isotope-aided 1H-NMR spectroscopy demonstrates that analogous side-chain insertion occurs on binding of SRY to a four-way junction, establishing a shared mechanism of sequence- and structure-specific DNA binding. Although the mutant DNA-binding domain exhibits > 50-fold reduction in sequence-specific DNA recognition, near wild-type affinity for four-way junctions is retained. Our results (i) identify a shared SRY-DNA contact at a site of either induced or intrinsic DNA bending, (ii) demonstrate that this contact is not required to bind an intrinsically bent DNA target, and (iii) rationalize patterns of sequence conservation or diversity among HMG boxes. Clinical association of the I68T mutation with human sex reversal supports the hypothesis that specific DNA recognition by SRY is required for male sex determination.

Two gonad-infecting species of Philometra (Nematoda: Philometridae) from groupers (Serranidae) off Tunisia, with a key to Philometra species infecting serranid gonads

PubMed Central

2016-01-01

Based on light and scanning electron microscopical studies of nematode specimens (males and mature females) collected from the ovary of groupers (Serranidae, Perciformes) in the Mediterranean Sea off Tunisia (near Tunis and Sfax), two gonad-infecting species of Philometra Costa, 1845 (Nematoda, Philometridae) are reported: Philometra inexpectata n. sp. from the mottled grouper Mycteroperca rubra and P. jordanoi (López-Neyra, 1951) from the dusky grouper Epinephelus marginatus. Identification of both fish species was confirmed by molecular barcoding. The new species is mainly characterized by the length of equally long spicules (147–165 μm), the gubernaculum (63–93 μm long) bearing at the tip two dorsolateral lamellar parts separated from each other by a smooth median field, a V-shaped mound on the male caudal extremity, the presence of a pair of large caudal papillae located posterior to the cloaca and by the body length of the males (1.97–2.43 mm). Philometra inexpectata n. sp. is the fifth known gonad-infecting philometrid species parasitizing serranid fishes in the Mediterranean region. The males of P. jordanoi were examined by scanning electron microscopy for the first time; this detailed study revealed some new taxonomically important morphological features, such as the number and arrangement of cephalic and caudal papillae, presence of amphids and phasmids and mainly the lamellate structures at the posterior end of the gubernaculum. A key to gonad-infecting species of Philometra parasitic in serranid fishes is provided. PMID:26956219

Epigenetic Control of Gonadal Aromatase (cyp19a1) in Temperature-Dependent Sex Determination of Red-Eared Slider Turtles

PubMed Central

Matsumoto, Yuiko; Buemio, Alvin; Chu, Randy; Vafaee, Mozhgon; Crews, David

2013-01-01

In the red-eared slider turtle (Trachemys scripta), a species with temperature-dependent sex determination (TSD), the expression of the aromatase gene during gonad development is strictly limited to the female-producing temperature. The underlying mechanism remains unknown. In this study, we identified the upstream 5′-flanking region of the aromatase gene, gonad-specific promoter, and the temperature-dependent DNA methylation signatures during gonad development in the red-eared slider turtle. The 5′-flanking region of the slider aromatase exhibited sequence similarities to the aromatase genes of the American alligator, chicken, quail, and zebra finch. A putative TATA box was located 31 bp upstream of the gonad-specific transcription start site. DNA methylation at the CpG sites between the putative binding sites of the fork head domain factor (FOX) and vertebrate steroidogenic factor 1 (SF1) and adjacent TATA box in the promoter region were significantly lower in embryonic gonads at the female-producing temperature compared the male-producing temperature. A shift from male- to female-, but not from female- to male-, producing temperature changed the level of DNA methylation in gonads. Taken together these results indicate that the temperature, particularly female-producing temperature, allows demethylation at the specific CpG sites of the promoter region which leads the temperature-specific expression of aromatase during gonad development. PMID:23762231

Control of molt in birds: association with prolactin and gonadal regression in starlings.

PubMed

Dawson, Alistair

2006-07-01

Despite the importance of molt to birds, very little is known about its environmental or physiological control. In starlings Sturnus vulgaris, and other species, under both natural conditions and experimental regimes, gonadal regression coincides with peak prolactin secretion. The prebasic molt starts at the same time. The aim of this series of experiments was to keep starlings on photo-schedules that would challenge the normally close relationship between gonadal regression and molt, to determine how closely the start of molt is associated with gonadal regression and/or associated changes in prolactin concentrations. In one series of experiments, photosensitive starlings were moved from a short photoperiod, 8 h light per day (8L), to 13 or 18L, and from 13 to 18L or 13 to 8L during testicular maturation. Later, photorefractory birds under 13L that had finished molting were moved to 18L. In another series of experiments, photorefractory starlings were moved from 18 to 8L for 7 weeks, 4 weeks, 2 weeks, 1 week, 3 days, 1 day, or 0 days, before being returned to 18L. There was no consistent relationship between photoperiod, or the increase in photoperiod, and the timing of the start of molt. Nor was there a consistent relationship with gonadal regression and the start of molt-molt could be triggered in the absence of a gonadal cycle. However, there was always an association between the start of molt and prolactin. In all cases where molt was induced, there had been an earlier increase in prolactin. However, the timing of molt was related to the time of peak prolactin, not the magnitude of that peak. This relationship between peak prolactin and the start of molt could explain the normally close relationship between the end of breeding activity and the start of molt.

Development of X-Y servo pneumatic-piezoelectric hybrid actuators for position control with high response, large stroke and nanometer accuracy.

PubMed

Chiang, Mao-Hsiung

2010-01-01

This study aims to develop a X-Y dual-axial intelligent servo pneumatic-piezoelectric hybrid actuator for position control with high response, large stroke (250 mm, 200 mm) and nanometer accuracy (20 nm). In each axis, the rodless pneumatic actuator serves to position in coarse stroke and the piezoelectric actuator compensates in fine stroke. Thus, the overall control systems of the single axis become a dual-input single-output (DISO) system. Although the rodless pneumatic actuator has relatively larger friction force, it has the advantage of mechanism for multi-axial development. Thus, the X-Y dual-axial positioning system is developed based on the servo pneumatic-piezoelectric hybrid actuator. In addition, the decoupling self-organizing fuzzy sliding mode control is developed as the intelligent control strategies. Finally, the proposed novel intelligent X-Y dual-axial servo pneumatic-piezoelectric hybrid actuators are implemented and verified experimentally.

Development of X-Y Servo Pneumatic-Piezoelectric Hybrid Actuators for Position Control with High Response, Large Stroke and Nanometer Accuracy

PubMed Central

Chiang, Mao-Hsiung

2010-01-01

This study aims to develop a X-Y dual-axial intelligent servo pneumatic-piezoelectric hybrid actuator for position control with high response, large stroke (250 mm, 200 mm) and nanometer accuracy (20 nm). In each axis, the rodless pneumatic actuator serves to position in coarse stroke and the piezoelectric actuator compensates in fine stroke. Thus, the overall control systems of the single axis become a dual-input single-output (DISO) system. Although the rodless pneumatic actuator has relatively larger friction force, it has the advantage of mechanism for multi-axial development. Thus, the X-Y dual-axial positioning system is developed based on the servo pneumatic-piezoelectric hybrid actuator. In addition, the decoupling self-organizing fuzzy sliding mode control is developed as the intelligent control strategies. Finally, the proposed novel intelligent X-Y dual-axial servo pneumatic-piezoelectric hybrid actuators are implemented and verified experimentally. PMID:22319266

MoXy fiber with active cooling cap for bovine prostate vaporization with high power 200W 532 nm laser

NASA Astrophysics Data System (ADS)

Peng, Steven Y.; Kang, Hyun Wook; Pirzadeh, Homa; Stinson, Douglas

2011-03-01

A novel MoXyTM fiber delivery device with Active Cooling Cap (ACCTM) is designed to transmit up to 180W of 532 nm laser light to treat benign prostatic hyperplasia (BPH). Under such high power tissue ablation, effective cooling is key to maintaining fiber power transmission and ensuring the reliability of the fiber delivery device To handle high power and reduce fiber degradation, the MoXy fiber features a larger core size (750 micrometer) and an internal fluid channel to ensure better cooling of the fiber tip to prevent the cap from burning, detaching, or shattering during the BPH treatment. The internal cooling channel was created with a metal cap and tubing that surrounds the optical fiber. In this study MoXy fibers were used to investigate the effect of power levels of 120 and 200 W on in-vitro bovine prostate ablation using a 532 nm XPSTM laser system. For procedures requiring more than 100 kJ, the MoXy fiber at 200W removed tissue at twice the rate of the current HPS fiber at 120W. The fiber maintained a constant tissue vaporization rate during the entire tissue ablation process. The coagulation at 200W was about 20% thicker than at 120W. In conclusion, the new fibers at 200W doubled the tissue removal rate, maintained vaporization efficiency throughout delivery of 400kJ energy, and induced similar coagulation to the existing HPS fiber at 120W.

Effects of incubation temperature and estrogen exposure on aromatase activity in the brain and gonads of embryonic alligators.

PubMed Central

Milnes, Matthew R; Roberts, Robert N; Guillette, Louis J

2002-01-01

During embryogenesis, incubation temperature and the hormonal environment influence gonadal differentiation of some reptiles, including all crocodilians. Current evidence suggests that aromatase, the enzyme that converts androgens to estrogens, has a role in sexual differentiation of species that exhibit temperature-dependent sex determination (TSD). During the temperature-sensitive period (TSP) of sex determination, we compared aromatase activity in the brain and gonads of putative male and female alligator embryos to determine if aromatase activity in the embryonic brain could provide the hormonal environment necessary for ovarian development in a TSD species. In addition, we assessed the pattern of aromatase activity in the brain and gonads of embryos treated with estradiol-17beta (E(2)) and incubated at male-producing temperatures to compare enzyme activity in E(2) sex-reversed females to control males and females. This has particular significance regarding wildlife species living in areas contaminated with suspected environmental estrogens. Gonadal aromatase activity remained low during the early stages of the TSP in both sexes and increased late in the TSP only in females. Aromatase activity in the brain increased prior to gonadal differentiation in both sexes. These results suggest that aromatase activity in the brain is not directly responsible for mediating differentiation of the gonad. E(2) exposure at male-producing temperatures resulted in sex-reversed females that had intermediate gonad function and masculinized brain activity. This study indicates the need to examine multiple end points and to determine the persistence of developmental alterations in contaminant-exposed wildlife populations. PMID:12060834

Expression profiling of c-kit and its impact after esiRNA silencing during gonadal development in catfish.

PubMed

Laldinsangi, C; Senthilkumaran, B

2018-04-03

C-kit receptor is a member of a family of growth factor receptors that have tyrosine kinase activity, and are involved in the transduction of growth regulatory signals across plasma membrane by activation of its ligand, kitl/scf. The present study analysed mRNA and protein expression profiles of c-kit in the gonads of catfish, Clarias gariepinus, using real time PCR, in situ hybridization and immunohistochemistry. Tissue distribution analysis revealed higher expression mainly in the catfish gonads. Ontogeny studies showed minimal expression during early developmental stages and highest during 50-75 days post hatch, and the dimorphic expression in gonads decreased gradually till adulthood, which might suggest an important role for this gene around later stages of sex differentiation and gonadal development. Expression of C-kit was analysed at various phases of gonadal cycle in both male and female, which showed minimal expression during the resting phase, and higher expression in male compared to females during the pre-spawning phase. In vitro and in vivo induction using human chorionic gonadotropin elevated the expression of c-kit indicating the regulatory influence of hypothalamo-hypophyseal axis. In vivo transient gene silencing using c-kit-esiRNA in adult catfish during gonadal recrudescence showed a decrease in c-kit expression, which affected the expression level of germ cell meiotic marker sycp3, as well as several factors and steroidogenic enzyme genes involved in germ cell development. Decrease in the levels of serum 11-KT and T were also observed after esiRNA silencing. The findings of this study suggest that c-kit has an important role in the process of germ cell proliferation, development and maturation during gonadal development and recrudescence in catfish. Copyright © 2018. Published by Elsevier Inc.

Neural, not gonadal, origin of brain sex differences in a gynandromorphic finch.

PubMed

Agate, Robert J; Grisham, William; Wade, Juli; Mann, Suzanne; Wingfield, John; Schanen, Carolyn; Palotie, Aarno; Arnold, Arthur P

2003-04-15

In mammals and birds, sex differences in brain function and disease are thought to derive exclusively from sex differences in gonadal hormone secretions. For example, testosterone in male mammals acts during fetal and neonatal life to cause masculine neural development. However, male and female brain cells also differ in genetic sex; thus, sex chromosome genes acting within cells could contribute to sex differences in cell function. We analyzed the sexual phenotype of the brain of a rare gynandromorphic finch in which the right half of the brain was genetically male and the left half genetically female. The neural song circuit on the right had a more masculine phenotype than that on the left. Because both halves of the brain were exposed to a common gonadal hormone environment, the lateral differences indicate that the genetic sex of brain cells contributes to the process of sexual differentiation. Because both sides of the song circuit were more masculine than that of females, diffusible factors such as hormones of gonadal or neural origin also likely played a role in sexual differentiation.

Bilateral congenital corneal keloids and anterior segment mesenchymal dysgenesis in a case of Rubinstein-Taybi syndrome.

PubMed

Rao, Srinivas K; Fan, Dorothy S P; Pang, C P; Li, Winnie W Y; Ng, Joan S K; Good, William V; Lam, Dennis S C

2002-01-01

To report the unusual association of bilateral corneal keloids and anterior segment mesenchymal dysgenesis in a child with Rubinstein-Taybi syndrome. Case report of a 2-year-old boy. Excision of the epicorneal mass in the right eye was followed by recurrence of the lesion. Multiple penetrating keratoplasties were unsuccessful in reconstructing the anterior segment because of recurrent corneal epithelial breakdown, suggesting limbal stem cell insufficiency. Histopathology and electron microscopy of the excised mass lesion showed features typical of a corneal keloid: thickened keratinized epithelium, absent Bowman's layer, and fibrovascular hyperplasia, with haphazard orientation of the collagen lamellae. Ultrasound biomicroscopy and intraoperative findings suggested a diagnosis of Peter anomaly, but genetic analysis did not show a PAX6 mutation. The findings in our patient add to the spectrum of ocular changes described in Rubinstein-Taybi syndrome and confirm earlier reports of poor ocular prognosis in corneal keloids and Rubinstein-Taybi syndrome.

Preliminary Study On Gonad Maturity Stages of the Sea Cucumber Paracaudina australis from Kenjeran Water, Surabaya, Indonesia

NASA Astrophysics Data System (ADS)

Widianingsih, Widianingsih; Zaenuri, Muhammad; Anggoro, Sutrisno; Pancasakti Kusumaningrum, Hermin; Hartati, Retno

2018-02-01

The holothurian Paracaudina australis is belong to family Caudinidae, ordo Molpadida and class Holothuroidea. This species is among the most common holothurian widely distributed in the tropical water. The purpose of this reseach is to do preliminary study on maturity stages of sea cucumber Paracaudina australis from Kenjeran Water, Surabaya, Indonesia. This research was conducted on April 2016. Samples were collected randomly on the Kenjeran Water, Surabaya. The result showed that there are five stages of gonad maturity. At the stage of maturity 1, the gonad was not clearly distinguished, there were unbranched small tubule. At the stage of maturity 2, there were small branched of tubules. At this stage, gonad can be differentiated between male and female. At the stage of maturity 3, tubule can been branched not only for male but also female. At the stage of maturity 4, the gonad was good mature, there were clearly branched tubule. At the stage of matury 5, there were generally had empty tubule except for a few relict unreleased spermatozoa. At female gonad, there were shrunken tubule and relict oocytes were presented in the lumen of the tubule.

Gonadal steroids modulate Fas-induced apoptosis of lactotropes and somatotropes.

PubMed

Jaita, Gabriela; Zárate, Sandra; Ferrari, Luciana; Radl, Daniela; Ferraris, Jimena; Eijo, Guadalupe; Zaldivar, Verónica; Pisera, Daniel; Seilicovich, Adriana

2011-02-01

We have previously reported that Fas activation induces apoptosis of anterior pituitary cells from rats at proestrus but not at diestrus and in an estrogen-dependent manner. In this study, we evaluated the effect of Fas activation on apoptosis of lactotropes and somatotropes during the estrous cycle and explored the action of gonadal steroids on Fas-induced apoptosis. Also, we studied whether changes in Fas expression are involved in the apoptotic response of anterior pituitary cells. Fas activation increased the percentage of TUNEL-positive lactotropes and somatotropes at proestrus but not at diestrus. FasL triggered apoptosis of somatotropes only when cells from ovariectomized rats were cultured in the presence of 17 β-estradiol (E2). Progesterone (P4) blocked the apoptotic action of the Fas/FasL system in lactotropes and somatotropes incubated with E2. Both E2 and P4 increased the percentage of cells expressing Fas at the cell membrane. Our results show that Fas activation induces apoptosis of lactotropes and somatotropes at proestrus but not at diestrus. Gonadal steroids may be involved in the apoptotic response of lactotropes and somatotropes, suggesting that Fas activation is implicated in the renewal of these pituitary subpopulations during the estrous cycle. The effect of gonadal steroids on Fas expression may be only partially involved in regulation of the Fas/FasL apoptotic pathway in the anterior pituitary gland.

A novel hybrid actuation mechanism based XY nanopositioning stage with totally decoupled kinematics

NASA Astrophysics Data System (ADS)

Zhu, Wu-Le; Zhu, Zhiwei; Guo, Ping; Ju, Bing-Feng

2018-01-01

This paper reports the design, analysis and testing of a parallel two degree-of-freedom piezo-actuated compliant stage for XY nanopositioning by introducing an innovative hybrid actuation mechanism. It mainly features the combination of two Scott-Russell and a half-bridge mechanisms for double-stage displacement amplification as well as moving direction modulation. By adopting the leaf-type double parallelogram (LTDP) structures at both input and output ends of the hybrid mechanism, the lateral stiffness and dynamic characteristics are significantly improved while the parasitic motions are greatly eliminated. The XY nanopositioning stage is constructed with two orthogonally configured hybrid mechanisms along with the LTDP mechanisms for totally decoupled kinematics at both input and output ends. An analytical model was established to describe the complete elastic deformation behavior of the stage, with further verification through the finite element simulation. Finally, experiments were implemented to comprehensively evaluate both the static and dynamic performances of the proposed stage. Closed-loop control of the piezoelectric actuators (PEA) by integrating strain gauges was also conducted to effectively eliminate the nonlinear hysteresis of the stage.

Correspondence between Gonadal Steroid Hormone Concentrations and Secondary Sexual Characteristics Assessed by Clinicians, Adolescents, and Parents

ERIC Educational Resources Information Center

Huang, Bin; Hillman, Jennifer; Biro, Frank M.; Ding, Lili; Dorn, Lorah D.; Susman, Elizabeth J.

2012-01-01

Adolescent sexual maturation is staged using Tanner criteria assessed by clinicians, parents, or adolescents. The physiology of sexual maturation is driven by gonadal hormones. We investigate Tanner stage progression as a function of increasing gonadal hormone concentration and compare performances of different raters. Fifty-six boys (mean age,…

Scattered dose to gonads and associated risks from radiotherapy for common pediatric malignancies : a phantom study.

PubMed

Mazonakis, Michalis; Zacharopoulou, Fotini; Kachris, Stefanos; Varveris, Charalambos; Damilakis, John; Gourtsoyiannis, Nicholas

2007-06-01

To measure the scattered dose to ovaries and testes from radiotherapy for common pediatric malignancies and to assess the relevant risks for radiation-induced gonadal damage and hereditary disorders in future generations. Radiotherapy for central nervous system tumors, acute leukemia, neuroblastoma, Hodgkin's disease, Wilms' tumor, and sarcoma was simulated on three humanoid phantoms representing patients of 5, 10, and 15 years of age. Ovarian and testicular dose measurements were performed using thermoluminescent dosimeters on a linear accelerator with multileaf collimator (MLC) producing 6-MV X-rays. The effect of lead block introduction into the primary beam on the gonadal dose was evaluated. Gonadal dose from radiotherapy for abdominal tumors was measured using an 18-MV photon beam. For a tumor dose range of 12-55 Gy, the scattered dose to ovaries was 0.5-62.4 cGy depending upon the patient's age (corresponding phantom) and treatment site. The corresponding dose to testes was 0.4-145.0 cGy. The use of blocks for field shaping can increase the gonadal dose up to a factor of 2.0 compared to that measured using MLC. Abdominal irradiation with 18-MV instead of 6-MV X-rays reduced the gonadal dose by more than 1.3 times. For female and male patients, the risk for induction of hereditary disorders was less than 81 x 10(-4) and 188 x 10(-4), respectively. The present dosimetric data suggest that pediatric radiotherapy is not associated with a risk for permanent damage to gonads excluded from the treatment volume. The risk for development of hereditary disorders in offspring conceived after exposure is low.

A novel mouse model of anterior segment dysgenesis (ASD): conditional deletion of Tsc1 disrupts ciliary body and iris development.

PubMed

Hägglund, Anna-Carin; Jones, Iwan; Carlsson, Leif

2017-03-01

Development of the cornea, lens, ciliary body and iris within the anterior segment of the eye involves coordinated interaction between cells originating from the ciliary margin of the optic cup, the overlying periocular mesenchyme and the lens epithelium. Anterior segment dysgenesis (ASD) encompasses a spectrum of developmental syndromes that affect these anterior segment tissues. ASD conditions arise as a result of dominantly inherited genetic mutations and result in both ocular-specific and systemic forms of dysgenesis that are best exemplified by aniridia and Axenfeld-Rieger syndrome, respectively. Extensive clinical overlap in disease presentation amongst ASD syndromes creates challenges for correct diagnosis and classification. The use of animal models has therefore proved to be a robust approach for unravelling this complex genotypic and phenotypic heterogeneity. However, despite these successes, it is clear that additional genes that underlie several ASD syndromes remain unidentified. Here, we report the characterisation of a novel mouse model of ASD. Conditional deletion of Tsc1 during eye development leads to a premature upregulation of mTORC1 activity within the ciliary margin, periocular mesenchyme and lens epithelium. This aberrant mTORC1 signalling within the ciliary margin in particular leads to a reduction in the number of cells that express Pax6, Bmp4 and Msx1 Sustained mTORC1 signalling also induces a decrease in ciliary margin progenitor cell proliferation and a consequent failure of ciliary body and iris development in postnatal animals. Our study therefore identifies Tsc1 as a novel candidate ASD gene. Furthermore, the Tsc1 -ablated mouse model also provides a valuable resource for future studies concerning the molecular mechanisms underlying ASD and acts as a platform for evaluating therapeutic approaches for the treatment of visual disorders. © 2017. Published by The Company of Biologists Ltd.

A novel mouse model of anterior segment dysgenesis (ASD): conditional deletion of Tsc1 disrupts ciliary body and iris development

PubMed Central

Hägglund, Anna-Carin; Jones, Iwan

2017-01-01

ABSTRACT Development of the cornea, lens, ciliary body and iris within the anterior segment of the eye involves coordinated interaction between cells originating from the ciliary margin of the optic cup, the overlying periocular mesenchyme and the lens epithelium. Anterior segment dysgenesis (ASD) encompasses a spectrum of developmental syndromes that affect these anterior segment tissues. ASD conditions arise as a result of dominantly inherited genetic mutations and result in both ocular-specific and systemic forms of dysgenesis that are best exemplified by aniridia and Axenfeld–Rieger syndrome, respectively. Extensive clinical overlap in disease presentation amongst ASD syndromes creates challenges for correct diagnosis and classification. The use of animal models has therefore proved to be a robust approach for unravelling this complex genotypic and phenotypic heterogeneity. However, despite these successes, it is clear that additional genes that underlie several ASD syndromes remain unidentified. Here, we report the characterisation of a novel mouse model of ASD. Conditional deletion of Tsc1 during eye development leads to a premature upregulation of mTORC1 activity within the ciliary margin, periocular mesenchyme and lens epithelium. This aberrant mTORC1 signalling within the ciliary margin in particular leads to a reduction in the number of cells that express Pax6, Bmp4 and Msx1. Sustained mTORC1 signalling also induces a decrease in ciliary margin progenitor cell proliferation and a consequent failure of ciliary body and iris development in postnatal animals. Our study therefore identifies Tsc1 as a novel candidate ASD gene. Furthermore, the Tsc1-ablated mouse model also provides a valuable resource for future studies concerning the molecular mechanisms underlying ASD and acts as a platform for evaluating therapeutic approaches for the treatment of visual disorders. PMID:28250050

Effect of SKI2670, a novel, orally active, non-peptide GnRH antagonist, on hypothalamic-pituitary-gonadal axis.

PubMed

Kim, Seon Mi; Yoo, Taekyung; Lee, So Young; Kim, Eun Jeong; Lee, Soo Min; Lee, Min Hee; Han, Min Young; Jung, Seung-Hyun; Choi, Jung-Hye; Ryu, Keun Ho; Kim, Hun-Taek

2015-10-15

Suppression of the hypothalamic-pituitary-gonadal axis has been widely utilized for the management of gonadal-hormone-dependent diseases such as endometriosis. Efforts to develop orally available gonadotropin-releasing hormone (GnRH) antagonists for the treatment of gonadal-hormone-dependent diseases led to the discovery of SKI2670, a novel non-peptide GnRH antagonist. The present study was undertaken to pharmacologically characterize SKI2670 in vitro and in vivo. We measured binding affinity and antagonistic activity of SKI2670 for the GnRH receptors. Immediate suppression of gonadotropins by single dosing of SKI2670 was examined in castrated monkeys. Subsequently, influence on gonadal hormones by prolonged administration of SKI2670 was assessed in naive female monkeys. To investigate in vivo efficacy of SKI2670, regression of ectopic implants by repeated administration of SKI2670 was examined in a rat endometriosis model. SKI2670 is a potent functional antagonist for the human GnRH receptor, with subnanomolar binding affinity. In castrated monkeys, single administration of SKI2670 lowered serum luteinizing hormone (LH) levels stronger with longer duration when compared to elagolix at equivalent doses. Moreover, repeated dosing of SKI2670 suppressed serum levels of gonadotropins and gonadal hormones in intact female monkeys while elagolix suppressed serum LH levels only. Finally, it exhibited regressive effects on ectopic implants in a rat endometriosis model without bone loss. Our findings demonstrate robust GnRH antagonistic efficacy of SKI2670 in animal models, suggesting that SKI2670-induced suppression of the hypothalamic-pituitary-gonadal axis may be beneficial for the treatment of gonadal-hormone-dependent diseases such as endometriosis in humans. Copyright © 2015 Elsevier Inc. All rights reserved.

Ascus dysgenesis in hybrid crosses of Neurospora and Sordaria (Sordariaceae).

PubMed

Kasbekar, Durgadas P

2017-07-01

When two lineages derived from a common ancestor become reproductively isolated (e.g. Neurospora crassa and N. tetrasperma), genes that have undergone mutation and adaptive evolution in one lineage can potentially become dysfunctional when transferred into the other, since other genes have undergone mutation and evolution in the second lineage, and the derived alleles were never 'tested' together before hybrid formation. Bateson (1909), Dobzhansky (1936), and Muller (1942) recognized that incompatibility between the derived alleles could potentially make the hybrid lethal, sterile, or display some other detriment. Alternatively, the detrimental effects seen in crosses with the hybrids may result from the silencing of ascus-development genes by meiotic silencing by unpaired DNA (MSUD). Aberrant transcripts from genes improperly paired in meiosis are processed into single-stranded MSUD-associated small interfering RNA (masiRNA), which is used to degrade complementary mRNA. Recently, backcrosses of N. crassa / N. tetrasperma hybrid translocation strains with wild-type N. tetrasperma were found to elicit novel ascus dysgenesis phenotypes. One was a transmission ratio distortion that apparently disfavoured the homokaryotic ascospores formed following alternate segregation. Another was the production of heterokaryotic ascospores in eight-spored asci. Lewis (1969) also had reported sighting rare eight-spored asci with heterokaryotic ascospores in interspecific crosses in Sordaria, a related genus. Ordinarily, in both Neurospora and Sordaria, the ascospores are partitioned at the eight-nucleus stage, and ascospores in eight-spored asci are initially uninucleate. Evidently, in hybrid crosses of the family Sordariaceae, ascospore partitioning can be delayed until after one or more mitoses following the postmeiotic mitosis.

New Anomalous Lieb-Robinson Bounds in Quasiperiodic XY Chains

NASA Astrophysics Data System (ADS)

Damanik, David; Lemm, Marius; Lukic, Milivoje; Yessen, William

2014-09-01

We announce and sketch the rigorous proof of a new kind of anomalous (or sub-ballistic) Lieb-Robinson (LR) bound for an isotropic XY chain in a quasiperiodic transversal magnetic field. Instead of the usual effective light cone |x|≤v|t|, we obtain |x|≤v|t|α for some 0<α <1. We can characterize the allowed values of α exactly as those exceeding the upper transport exponent αu+ of a one-body Schrödinger operator. To our knowledge, this is the first rigorous derivation of anomalous quantum many-body transport. We also discuss anomalous LR bounds with power-law tails for a random dimer field.

Mercury concentrations in gonad, liver, and muscle of white sturgeon Acipenser transmontanus in the lower Columbia River.

PubMed

Webb, M A H; Feist, G W; Fitzpatrick, M S; Foster, E P; Schreck, C B; Plumlee, M; Wong, C; Gundersen, D T

2006-04-01

This study determined the partitioning of total mercury in liver, gonad, and cheek muscle of white sturgeon (Acipenser transmonatus) in the lower Columbia River. The relationship between tissue mercury concentrations and various physiologic parameters was assessed. White sturgeon were captured in commercial fisheries in the estuary and Bonneville, The Dalles, and John Day Reservoirs. Condition factor (CF), relative weight (Wr), and gonadosomatic index (GSI) were determined for each fish (n = 57). Gonadal tissue was examined histologically to determine sex and stage of maturity. Liver (n = 49), gonad (n = 49), and cheek muscle (n = 57) were analyzed for total mercury using cold-vapor atomic fluorescence spectrophotometry. Tissue protein concentrations were measured by ultraviolet-visible spectroscopy. Plasma was analyzed for testosterone (T), 11-ketotestosterone (KT), and 17ss-estradiol (E2) using radioimmunoassay. Mean tissue mercury concentrations were higher in muscle compared with liver and gonad at all sampling locations, except Bonneville Reservoir where mean liver mercury content was the highest tissue concentration observed in the study. Significant negative correlations between plasma androgens (T and KT) and muscle mercury content and plasma E2 and liver mercury content were found. A significant positive linear relationship between white sturgeon age and liver mercury concentrations was evident. Significant negative correlations between CF and relative weight and gonad and liver mercury content were found. In addition, immature male sturgeon with increased gonad mercury content had decreased GSIs. These results suggest that mercury, in the form of methylmercury, may have an effect on the reproductive potential of white sturgeon.

Gonadal steroids and bone metabolism in men.

PubMed

Leder, Benjamin

2007-06-01

Over the past decade, our increasing awareness of the clinical importance of osteoporosis in men has stimulated intense interest in trying to better understand male skeletal physiology and pathophysiology. The present review focuses on a major focus of research in this area, namely the attempt to define the influence and therapeutic potential of gonadal steroids in male bone metabolism. Building on previous work defining the relative roles of androgens and estrogens in the developing male skeleton and in maintaining normal bone turnover, recent studies have begun to define these issues from epidemiologic, physiologic and therapeutic perspectives. With access to data from large prospectively defined populations of men, investigators are confirming and challenging existing hypotheses and forwarding new concepts. Clinical trials have expanded beyond standard androgen replacement studies to explore more complex hormonal interventions. Physiologic investigation has continued to probe the mechanisms underlying the differential and independent roles of androgens and estrogens in male bone metabolism. Recent work has added significantly to our understanding of the role of gonadal steroids in male skeletal physiology. Nonetheless, further research is necessary to build on these initial human studies and to capitalize on rapidly emerging advances in our understanding of the basic biology of bone metabolism.

Brainstem dysgenesis during the neonatal period: diagnosis and management.

PubMed

Castilla-Fernández, Yolanda; Boix, Héctor; Macaya, Alfons; Vázquez, Elida; Gratacòs, Margarida; Roig-Quilis, Manuel

2013-07-01

To report our neonatal management experience in patients who received a diagnosis of brainstem dysgenesis (BSD). This study retrospectively reviewed the medical records of 15 neonates with BSD diagnosed between 1984 and 2011. Data on the perinatal period, physical examination, laboratory findings, and management by systems were systematically analyzed. All cases were sporadic. Cocaine abuse and misoprostol use were recorded in two pregnancies. The reason for admission was prematurity (2 of 15), respiratory distress (8 of 15), gastroschisis (1 of 15), and abnormal neurological examination (4 of 15). Clinically, the most commonly affected cranial nerves were the 7th (13 of 15), 9th (11 of 15), 10th (8 of 15), 5th (7 of 15), 12th (7 of 15), 6th (3 of 15), 4th (1 of 15), and 3rd (1 of 15). Five patients required positive pressure ventilation during delivery room resuscitation, three had difficult airways, and two needed tracheostomy during admission. Most patients required nasogastric tube feeding shortly after birth, and four patients had a gastrostomy on discharge. Two patients died of respiratory and cardiac failure. Electromyography and nerve conduction velocity were used to exclude generalized neuromuscular disorders, and in conjunction with other neurophysiological and gastrointestinal tract studies, helped uncover the extent of brainstem involvement in most cases. Cranial magnetic resonance imaging supported the diagnosis in more than half of the patients. Early diagnosis of BSD is mainly clinical, difficult to establish unless suspected, and crucial to prevent complications. Neonatal care of patients with BSD requires a comprehensive approach that must take into consideration the etiological, anatomical, and pathogenic aspects contributing to the clinical manifestations of this disorder. Care should be provided by multidisciplinary teams, in which neonatologists, pediatric neurologists, nutritionists, physical therapists, and other professionals participate

Impact of a gestational exposure to diesel exhaust on offspring gonadal development: experimental study in the rabbit.

PubMed

Bourdon, M; Torres-Rovira, L; Monniaux, D; Faure, C; Levy, R; Tarrade, A; Rousseau-Ralliard, D; Chavatte-Palmer, P; Jolivet, G

2018-06-18

The aim of the present work was to address experimentally the possible impact of exposure to air pollution during gestation on the differentiation and function of the gonads of the offspring using a rabbit model. Rabbits were exposed daily to diluted diesel exhaust gas or filtered air from the 3rd until the 27th day of gestation, during which time germ cells migrate in genital ridges and divide, and fetal sex is determined. Offspring gonads were collected shortly before birth (28th day of gestation) or after puberty (7.5 months after birth). The structure of the gonads was analyzed by histological and immunohistological methods. Serum concentrations of testosterone and anti-Müllerian hormone were determined using ELISA. The morphology and the endocrine function of the gonads collected just at the arrest of the exposure were similar in polluted and control animals in both sexes. No differences were observed as well in gonads collected after puberty. Sperm was collected at the head of the epididymis in adults. Sperm motility and DNA fragmentation were measured. Among all parameters analyzed, only the sperm DNA fragmentation rate was increased three-fold in exposed males. Mechanisms responsible for these modifications and their physiological consequences are to be further clarified.

Disruption of apoptosis pathways involved in zebrafish gonad differentiation by 17α-ethinylestradiol and fadrozole exposures.

PubMed

Luzio, Ana; Matos, Manuela; Santos, Dércia; Fontaínhas-Fernandes, António A; Monteiro, Sandra M; Coimbra, Ana M

2016-08-01

Zebrafish (Danio rerio) sex determination seems to involve genetic factors (GSD) but also environmental factors (ESD), such as endocrine disrupting chemicals (EDCs) that are known to mimic endogenous hormones and disrupt gonad differentiation. Apoptosis has also been proposed to play a crucial role in zebrafish gonad differentiation. Nevertheless, the interactions between EDCs and apoptosis have received little attention. Thus, this study aimed to assess if and which apoptotic pathways are involved in zebrafish gonad differentiation and how EDCs may interfere with this process. With these purposes, zebrafish were exposed to 17α-ethinylestradiol (EE2, 4ng/L) and fadrozole (Fad, 50μg/L) from 2h to 35days post-fertilization (dpf). Afterwards, a gene expression analysis by qRT-PCR and a stereological analysis, based on systematic sampling and protein immunohistochemistry, were performed. The death receptors (FAS; TRADD), anti-apoptotic (BCL-2; MDM2), pro-apoptotic (CASP-2 and -6) and cell proliferation (BIRC5/survivin; JUN) genes and proteins were evaluated. In general, apoptosis was inhibited in females through the involvement of anti-apoptotic pathways, while in males apoptosis seemed to be crucial to the failure of the "juvenile ovary" development and the induction of testes transformation. The JUN protein was shown to be necessary in juvenile ovaries, while the BIRC5 protein seemed to be involved in zebrafish spermatogenesis. Both EDCs, EE2 and Fad, increased the apoptosis stimulus in zebrafish gonad. It was noticed that the few females that were resistant to Fad-induced sex reversal had increased anti-apoptotic factor levels, while males exposed to EE2 showed increased pro-apoptotic genes/proteins and were more advanced in gonad differentiation. Overall, our findings show that apoptosis pathways are involved in zebrafish gonad differentiation and that EDCs can disrupt this process. Copyright © 2016 Elsevier B.V. All rights reserved.

Random isotropic one-dimensional XY-model

NASA Astrophysics Data System (ADS)

Gonçalves, L. L.; Vieira, A. P.

1998-01-01

The 1D isotropic s = ½XY-model ( N sites), with random exchange interaction in a transverse random field is considered. The random variables satisfy bimodal quenched distributions. The solution is obtained by using the Jordan-Wigner fermionization and a canonical transformation, reducing the problem to diagonalizing an N × N matrix, corresponding to a system of N noninteracting fermions. The calculations are performed numerically for N = 1000, and the field-induced magnetization at T = 0 is obtained by averaging the results for the different samples. For the dilute case, in the uniform field limit, the magnetization exhibits various discontinuities, which are the consequence of the existence of disconnected finite clusters distributed along the chain. Also in this limit, for finite exchange constants J A and J B, as the probability of J A varies from one to zero, the saturation field is seen to vary from Γ A to Γ B, where Γ A(Γ B) is the value of the saturation field for the pure case with exchange constant equal to J A(J B) .

46,XY hypergonadotropic hypogonadism and myasthenia gravis.

PubMed

Lichiardopol, Corina; Herlea, V; Ioan, Virginia; Tomulescu, V; Mixich, F

2006-01-01

Both hypergonadotropic hypogonadism and myasthenia gravis can be parts of type II autoimmune polyendocrine syndrome and association between the two disorders has been reported in few cases. A 14 year old male patient with a personal history of bilateral cryptorchidism and ptosis was referred for delayed puberty. Clinical examination revealed eunuchoid habitus, small, soft testes, gynecomastia, ptosis, a myasthenic deficit score of 22.5 points and an IQ of 84 points. Decreased testosterone (0.064 ng/mL) and elevated LH (64.5 mUI/mL) were consistent with hypergonadotropic hypogonadism and karyotype was normal: 46,XY. Thyroid function, haematologic evaluation, BUN, electrolytes, and glycemia were in the normal range. Therapy consisted of anticholinesterase inhibitors, immunosuppressants, corticotherapy, testosterone; thoracoscopic thymectomy was performed showing thymic lymphoid hyperplasia on histopathologic examination. Myasthenic score improved (12.5 points), progressive virilization occurred, and a year later the patient presented with cushingoid features and obesity.

The influence of season on the gonad index and biochemical composition of the sea urchin Paracentrotus lividus from the Golf of Tunis.

PubMed

Arafa, Soumaya; Chouaibi, Moncef; Sadok, Saloua; El Abed, Amor

2012-01-01

Seasonal variation in the gonad weight and biochemical composition of the sea urchin Paracentrotus lividus from the Golf of Tunis (Tunisia) were studied between September 2003 and August 2004. The highest gonad indices occurred in March (16.71%). The spawning period occurred between April and July and resulted in a fall in gonad indices to low level (7.12 ± 0.12%). Protein constituted the main component of the gonad, and lipid and carbohydrate were found at appreciable amounts. Consistent with the gonad cycle, sea urchin biochemical components showed clear seasonal variation with a significant decrease during the spawning period. The polyunsaturated fatty acid (PUFA) group was found at high level (40% of the total fatty acids). Of the PUFA group, eicosapentaenoic (C20:5 n - 3) and eicosatetraenoic (C20:4 n - 3) were the most abundant gonadal lipids. The level of PUFA was significantly affected by temperature variation showing an increase during the cold months and a decrease in the hot months.

Regulation of gonadal sex ratios and pubertal development by the thyroid endocrine system in zebrafish (Danio rerio)

USGS Publications Warehouse

Sharma, Prakash; Patino, Reynaldo

2013-01-01

We examined associations between thyroid condition, gonadal sex and pubertal development in zebrafish. Seventy-two-hour postfertilization larvae were reared in untreated medium or in the presence of goitrogens (sodium perchlorate, 0.82 mM; methimazole, 0.15 and 0.3 mM) or thyroxine (1 and 10 nM) for 30 days. Thyrocyte height, gonadal sex and gonadal development were histologically determined at 45 and 60 days postfertilization (dpf). Thyrocyte hypertrophy, an index of hypothyroidism, was observed at 45 and 60 dpf in perchlorate-treated but only at 45 dpf in methimazole-treated fish. Similarly, gonadal sex ratios were biased toward ovaries relative to control animals at 45 and 60 dpf in perchlorate-treated fish but only at 45 dpf in methimazole-treated fish. Gonadal sex ratios were biased toward testes at 45 and 60 dpf in thyroxine-treated fish. Spermatogenesis was delayed in testes from goitrogen-treated fish at 60 dpf relative to control values, but was unaffected in testes from thyroxine-treated individuals. Oogenesis seemed to be nonspecifically delayed in all treatments relative to control at 60 dpf. This study confirmed the previously reported association between hypothyroid condition and ovarian-skewed ratios, and hyperthyroid condition and testicular-skewed ratios, and also showed that male pubertal development is specifically delayed by experimental hypothyroidism. The simultaneous recovery from the hypothyroid and ovary-inducing effects of methimazole by 60 dpf (27 days post-treatment) suggests that the ovary-skewing effect of goitrogens is reversible when thyroid conditions return to basal levels before developmental commitment of gonadal sex. Conversely, the masculinizing effect of hyperthyroidism seems to be stable and perhaps permanent.

Regulation of gonadal sex ratios and pubertal development by the thyroid endocrine system in zebrafish (Danio rerio).

PubMed

Sharma, Prakash; Patiño, Reynaldo

2013-04-01

We examined associations between thyroid condition, gonadal sex and pubertal development in zebrafish. Seventy-two-hour postfertilization larvae were reared in untreated medium or in the presence of goitrogens (sodium perchlorate, 0.82 mM; methimazole, 0.15 and 0.3 mM) or thyroxine (1 and 10 nM) for 30 days. Thyrocyte height, gonadal sex and gonadal development were histologically determined at 45 and 60 days postfertilization (dpf). Thyrocyte hypertrophy, an index of hypothyroidism, was observed at 45 and 60 dpf in perchlorate-treated but only at 45 dpf in methimazole-treated fish. Similarly, gonadal sex ratios were biased toward ovaries relative to control animals at 45 and 60 dpf in perchlorate-treated fish but only at 45 dpf in methimazole-treated fish. Gonadal sex ratios were biased toward testes at 45 and 60 dpf in thyroxine-treated fish. Spermatogenesis was delayed in testes from goitrogen-treated fish at 60 dpf relative to control values, but was unaffected in testes from thyroxine-treated individuals. Oogenesis seemed to be nonspecifically delayed in all treatments relative to control at 60 dpf. This study confirmed the previously reported association between hypothyroid condition and ovarian-skewed ratios, and hyperthyroid condition and testicular-skewed ratios, and also showed that male pubertal development is specifically delayed by experimental hypothyroidism. The simultaneous recovery from the hypothyroid and ovary-inducing effects of methimazole by 60 dpf (27 days post-treatment) suggests that the ovary-skewing effect of goitrogens is reversible when thyroid conditions return to basal levels before developmental commitment of gonadal sex. Conversely, the masculinizing effect of hyperthyroidism seems to be stable and perhaps permanent. Published by Elsevier Inc.

Range-Wide Sex-Chromosome Sequence Similarity Supports Occasional XY Recombination in European Tree Frogs (Hyla arborea)

PubMed Central

Brelsford, Alan; Perrin, Nicolas

2014-01-01

In contrast with mammals and birds, most poikilothermic vertebrates feature structurally undifferentiated sex chromosomes, which may result either from frequent turnovers, or from occasional events of XY recombination. The latter mechanism was recently suggested to be responsible for sex-chromosome homomorphy in European tree frogs (Hyla arborea). However, no single case of male recombination has been identified in large-scale laboratory crosses, and populations from NW Europe consistently display sex-specific allelic frequencies with male-diagnostic alleles, suggesting the absence of recombination in their recent history. To address this apparent paradox, we extended the phylogeographic scope of investigations, by analyzing the sequences of three sex-linked markers throughout the whole species distribution. Refugial populations (southern Balkans and Adriatic coast) show a mix of X and Y alleles in haplotypic networks, and no more within-individual pairwise nucleotide differences in males than in females, testifying to recurrent XY recombination. In contrast, populations of NW Europe, which originated from a recent postglacial expansion, show a clear pattern of XY differentiation; the X and Y gametologs of the sex-linked gene Med15 present different alleles, likely fixed by drift on the front wave of expansions, and kept differentiated since. Our results support the view that sex-chromosome homomorphy in H. arborea is maintained by occasional or historical events of recombination; whether the frequency of these events indeed differs between populations remains to be clarified. PMID:24892652

Involvement of Antizyme Characterized from the Small Abalone Haliotis diversicolor in Gonadal Development.

PubMed

Li, Wei-Dong; Huang, Min; Lü, Wen-Gang; Chen, Xiao; Shen, Ming-Hui; Li, Xiang-Min; Wang, Rong-Xia; Ke, Cai-Huan

2015-01-01

The small abalone Haliotis diversicolor is an economically important mollusk that is widely cultivated in Southern China. Gonad precocity may affect the aquaculture of small abalone. Polyamines, which are small cationic molecules essential for cellular proliferation, may affect gonadal development. Ornithine decarboxylase (ODC) and antizyme (AZ) are essential elements of a feedback circuit that regulates cellular polyamines. This paper presents the molecular cloning and characterization of AZ from small abalone. Sequence analysis showed that the cDNA sequence of H. diversicolor AZ (HdiODCAZ) consisted of two overlapping open reading frames (ORFs) and conformed to the +1 frameshift property of the frame. Thin Layer chromatography (TLC) analysis suggested that the expressed protein encoded by +1 ORF2 was the functional AZ that targets ODC to 26S proteasome degradation. The result demonstrated that the expression level of AZ was higher than that of ODC in the ovary of small abalone. In addition, the expression profiles of ODC and AZ at the different development stages of the ovary indicated that these two genes might be involved in the gonadal development of small abalone.

Nonequilibrium Phase Transition in a Periodically Driven XY Spin Chain

NASA Astrophysics Data System (ADS)

Prosen, Tomaž; Ilievski, Enej

2011-08-01

We present a general formulation of Floquet states of periodically time-dependent open Markovian quasifree fermionic many-body systems in terms of a discrete Lyapunov equation. Illustrating the technique, we analyze periodically kicked XY spin-(1)/(2) chain which is coupled to a pair of Lindblad reservoirs at its ends. A complex phase diagram is reported with reentrant phases of long range and exponentially decaying spin-spin correlations as some of the system’s parameters are varied. The structure of phase diagram is reproduced in terms of counting nontrivial stationary points of Floquet quasiparticle dispersion relation.

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

Comparing postnatal development of gonadal hormones and associated social behaviors in rats, mice, and humans.

PubMed

Bell, Margaret R

2018-05-14

Postnatal development includes dramatic changes in gonadal hormones and the many social behaviors they help regulate, both in rodents and humans. Parental care-seeking is the most salient social interaction in neonates and infants, play and pro-social behaviors are commonly studied in juveniles, and the development of aggression and sexual behavior begins in peripubertal stages but continues through late adolescence into adulthood. While parental behaviors are shown after reproductive success in adulthood, alloparenting behaviors are actually high in juveniles as well. These behaviors are sensitive to both early life organizational effects of gonadal hormones and later life activational regulation. However, changes in circulating gonadal hormones and the display of the above behaviors over development differs between rats, mice and humans. These endpoints are of interest to endocrinologist, toxicologists, neuroscientists because of their relevance to mental health disorders and their vulnerability to effects of endocrine disrupting chemical exposure. As such, the goal of this minireview is to succinctly describe and relate the postnatal development of gonadal hormones and social behaviors to each other, over time and across animal models. Ideally, this will help identify appropriate animal models and age ranges for continued study of both normative development and in contexts of environmental disruption.

One-norm geometric quantum discord and critical point estimation in the XY spin chain

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

Cheng, Chang-Cheng; Wang, Yao; Guo, Jin-Liang, E-mail: guojinliang80@163.com

2016-11-15

In contrast with entanglement and quantum discord (QD), we investigate the thermal quantum correlation in terms of Schatten one-norm geometric quantum discord (GQD) in the XY spin chain, and analyze their capabilities in detecting the critical point of quantum phase transition. We show that the one-norm GQD can reveal more properties about quantum correlation between two spins, especially for the long-range quantum correlation at finite temperature. Under the influences of site distance, anisotropy and temperature, one-norm GQD and its first derivative make it possible to detect the critical point efficiently for a general XY spin chain. - Highlights: • Comparingmore » with entanglement and QD, one-norm GQD is more robust versus the temperature. • One-norm GQD is more efficient in characterization of long-range quantum correlation between two distant qubits. • One-norm GQD performs well in highlighting the critical point of QPT at zero or low finite temperature. • One-norm GQD has a number of advantages over QD in detecting the critical point of the spin chain.« less

Gonadal sex differentiation and effects of dietary methyltestosterone treatment in sablefish (Anoplopoma fimbria).

PubMed

Luckenbach, J Adam; Fairgrieve, William T

2016-02-01

Methods for sex control are needed to establish monosex aquaculture of sablefish (Anoplopoma fimbria). Here we conducted the first characterization of sex differentiation by histology and hormonal sex reversal experiment in sablefish. Ovarian differentiation was first discernible at ~80 mm fork length (FL) and characterized by development of lamellar structures and onset of meiosis. Testes exhibited a dual-lobe appearance over much of their length and remained non-meiotic until males were ≥520 mm FL (2 years post-fertilization). Juveniles with undifferentiated gonads were provided diets containing 0 (control), 5 or 50 mg 17α-methyltestosterone (MT)/kg for 2 months. Following treatment, controls possessed either ovaries or non-meiotic testes, whereas MT-treated fish exhibited meiotic testes (60% of the fish), intersex gonads (~30%), or gonads that appeared sterile (~10%). A genetic sex marker revealed that all intersex fish were genetic females, although other females appeared to be completely sex reversed (i.e., neomales). One year after treatment, MT-treated fish possessed non-meiotic testes similar to control males or intersex gonads with reduced ovarian features, presumably due to atresia following MT withdrawal. Milt collected from neomales and genetic males 3 years post-treatment permitted sperm motility analyses; however, neomale sperm were virtually immotile. These results demonstrated that sablefish are differentiated gonochorists and that MT treatment from 76 to 196 mm FL induced permanent masculinization of a portion of the genetic females, but acquisition of sperm motility was impaired. Earlier administration of MT may be necessary to sex reverse a higher proportion of genetic females and reduce negative effects on fertility.

Gonadal disorder in the thinlip grey mullet (Liza ramada, Risso 1827) as a biomarker of environmental stress in surface waters.

PubMed

Tancioni, Lorenzo; Caprioli, Riccardo; Al-Khafaji, Ayad Hantoosh Dawood; Mancini, Laura; Boglione, Clara; Ciccotti, Eleonora; Cataudella, Stefano

2015-02-05

The aim of this study was to evaluate the use of gonadal alterations in the thinlip grey mullet (Liza ramada) as a biological indicator in assessing aquatic ecosystems health, with particular emphasis to river ecosystems exposed to sewage discharges. For this purpose, the reproductive status and the presence of gonadal alterations were studied in 206 mullets collected from two sites on the low course of the Tiber River, downstream of a large urban sewage treatment plant and in the estuarine area, and from an uncontaminated pond considered as reference site. Intersex and irregularly shaped gonads were observed in 20.8% of the mullets from the most polluted site, and intersex gonads in 10.3% of those from the estuarine area. No alterations were detected in the fish from the reference site, which also showed distinct stages of gonadal development. Conversely, unclear stages of testicular and ovary development were observed in the fish from the two polluted river sites. The results of this study suggest that L. ramada may represent a sentinel species in environmental risk assessment and support the use of gonadal alterations of this species as a bioindicator for extensive monitoring of pollution in lower stretches of rivers and estuarine areas.

Gonadal Disorder in the Thinlip Grey Mullet (Liza ramada, Risso 1827) as a Biomarker of Environmental Stress in Surface Waters

PubMed Central

Tancioni, Lorenzo; Caprioli, Riccardo; Dawood Al-Khafaji, Ayad Hantoosh; Mancini, Laura; Boglione, Clara; Ciccotti, Eleonora; Cataudella, Stefano

2015-01-01

The aim of this study was to evaluate the use of gonadal alterations in the thinlip grey mullet (Liza ramada) as a biological indicator in assessing aquatic ecosystems health, with particular emphasis to river ecosystems exposed to sewage discharges. For this purpose, the reproductive status and the presence of gonadal alterations were studied in 206 mullets collected from two sites on the low course of the Tiber River, downstream of a large urban sewage treatment plant and in the estuarine area, and from an uncontaminated pond considered as reference site. Intersex and irregularly shaped gonads were observed in 20.8% of the mullets from the most polluted site, and intersex gonads in 10.3% of those from the estuarine area. No alterations were detected in the fish from the reference site, which also showed distinct stages of gonadal development. Conversely, unclear stages of testicular and ovary development were observed in the fish from the two polluted river sites. The results of this study suggest that L. ramada may represent a sentinel species in environmental risk assessment and support the use of gonadal alterations of this species as a bioindicator for extensive monitoring of pollution in lower stretches of rivers and estuarine areas. PMID:25664693

Final height and gonad function after total body irradiation during childhood.

PubMed

Couto-Silva, A-C; Trivin, C; Esperou, H; Michon, J; Baruchel, A; Lemaire, P; Brauner, R

2006-09-01

Short stature and gonad failure can be a side effect of total body irradiation (TBI). The purpose of the study was to evaluate the factors influencing final height and gonad function after TBI. Fifty young adults given TBI during childhood were included. Twenty-seven had been treated with growth hormone (GH). Those given single 10 Grays (Gy) or fractionated 12 Gy TBI had similar characteristics, GH peaks, final heights and gonad function. After the end of GH treatment, 11/20 patients evaluated had GH peak >10 microg/l. Final height was <-2s.d. in 29 (58%). The height loss between TBI and final height (2.4+/-1.1 s.d.) was greater in those who were younger when irradiated (P<0.0001). When the GH-treated and -untreated patients were analyzed separately, this loss was correlated with the age at TBI at 4-8 years for the GH-treated and at 6-8 years for the untreated. Boys showed negative correlations between testicular volume and plasma follicle-stimulating hormone (FSH, P=0.0008) and between plasma FSH and inhibin B (P=0.005) concentrations. We concluded that the indications for GH treatment should be mainly based on the age at irradiation, taking into account the GH peak. The plasma FSH and inhibin B concentrations may predict sperm function. Published online 31 July 2006.

Method for observation of deembedded sections of fish gonad by scanning electron microscopy

NASA Astrophysics Data System (ADS)

Mao, Lian-Ju

2000-09-01

This article reports a method for examining the intracellular structure of fish gonads using a scanning electron microscope(SEM). The specimen preparation procedure is similar to that for transmission electron microscopy wherein samples cut into semi-thin sections are fixed and embedded in plastic. The embedment matrix was removed by solvents. Risen-free specimens could be observed by SEM. The morphology of matured sperms in the gonad was very clear, and the oocyte internal structures appeared in three-dimensional images. Spheroidal nucleoli and yolk vesicles and several bundles of filaments adhered on the nucleoli could be viewed by SEM for the first time.

Gonad development during the early life of Octopus maya (Mollusca: Cephalopoda).

PubMed

Avila-Poveda, Omar Hernando; Colin-Flores, Rafael Francisco; Rosas, Carlos

2009-02-01

Gonad development during the early life of Octopus maya is described in terms of histological, morphometric, oocytes growth, and somatic-oocyte relationship data obtained from octopus cultured at the UMDI-UNAM, in Sisal, Yucatan, Mexico. This study is the first publication on gonad development during the early life of Octopus maya. A total of 83 O. maya specimens were used; their sizes ranged from 6.5 to 76 mm of total length (TL), 4 to 28 mm of dorsal mantle length (DML), 2.5 to 20 mm of ventral mantle length (VML), and 0.0180 to 7.2940 g of fixed body weight (fBW). Animals were weighed and measured only after preservation. A loss of 10% of living weight was estimated for juvenile octopuses after formalin preservation. The relation of length to weight (VML, DML, TL/fBW) pooled for both sexes had a strong positive correlation (r), as shown by a potential power function that was quite close to 1. Compound images were produced from numerous microscopic fields. The histological examination revealed that, 4 months after hatching, male octopus (24.5 mm DML and 7.2940 g fBW) were in gonad stages 2 (maturing) to 3 (mature), with spermatogonia and spermatocytes in the tubule wall and abundant spermatids and spermatozoa in the central lumen of the seminiferous tubules, suggesting the occurrence of different phases of gonad development at different maturity stages. In contrast, females (22.5 mm DML and 4.8210 g fBW) at the same time since hatching were immature (stage 1), with many oogonia, few oocytes, and germinal epithelium. This suggests that males reach maturity earlier than females, indicating a probable onset of maturity for males at around 4 months of culture or 8 g of wet body weight. Our results indicate the possibility that the size-at-weight can be recognized early with a degree of certainty that allows the sexes to be separated for culture purposes; but more detailed studies on reproduction in relation to endocrinology and nutrition are needed.

Gonadal Status and physical performance in older men

PubMed Central

Maggio, Marcello; Ceda, Gian Paolo; Lauretani, Fulvio; Bandinelli, Stefania; Metter, E. Jeffrey; Guralnik, Jack M.; Basaria, Shehzad; Cattabiani, Chiara; Luci, Michele; Dall'Aglio, Elisabetta; Vignali, Alessandro; Volpi, Riccardo; Valenti, Giorgio; Ferrucci, Luigi

2011-01-01

Background Male aging is characterized by a progressive decline in serum testosterone levels and physical performance. Low testosterone levels may be implicated in the decline of physical performance and consequent mobility disability that occurs with aging. During the recent years many consensus reports have advocated that one of the potential effects of testosterone supplementation is the improvement in mobility. However, to the best of our knowledge no study has fully investigated the relationship between gonadal status and objective measures of physical performance in older men and their determinants. Methods We evaluated 455 ≥ 65 year old male participants of InCHIANTI study a population based study in two municipalities of Tuscany, Italy with complete data on testosterone levels, hand grip strength, cross-sectional muscle area (CSMA), short physical performance battery (SPPB). Linear models were used to test the relationship between gonadal status and determinants of physical performance. Results According to baseline serum levels of total testosterone, three different groups of older men were created: 1) severely hypogonadal (N= 23),total testosterone levels ≤230 ng /dl; 2) moderately hypogonadal (N=88), total testosterone >230 and <350 ng/dL), and 3) eugonadal (N=344), testosterone levels ≥350 ng/dL. With increased severity of hypogonadal status, participants were significantly older while their BMI was substantially similar. In the age and BMI adjusted analysis, there was a significant difference in hemoglobin levels, hand grip strength and SPPB score (p for trend<0.001) among −3 groups, with severely hypogonadal men having lower values of hemoglobin, muscle strength and physical performance. We found no association between testosterone group assignment and calf muscle mass and 4 meter walking speed. In the multivariate analysis grip strength (p for trend=0.004) and haemoglobin (p for trend <0.0001) but not SPPB and other determinants of physical

Sex differences in ischemic stroke sensitivity are influenced by gonadal hormones, not by sex chromosome complement.

PubMed

Manwani, Bharti; Bentivegna, Kathryn; Benashski, Sharon E; Venna, Venugopal Reddy; Xu, Yan; Arnold, Arthur P; McCullough, Louise D

2015-02-01

Epidemiologic studies have shown sex differences in ischemic stroke. The four core genotype (FCG) mouse model, in which the testes determining gene, Sry, has been moved from Y chromosome to an autosome, was used to dissociate the effects of sex hormones from sex chromosome in ischemic stroke outcome. Middle cerebral artery occlusion (MCAO) in gonad intact FCG mice revealed that gonadal males (XXM and XYM) had significantly higher infarct volumes as compared with gonadal females (XXF and XYF). Serum testosterone levels were equivalent in adult XXM and XYM, as was serum estrogen in XXF and XYF mice. To remove the effects of gonadal hormones, gonadectomized FCG mice were subjected to MCAO. Gonadectomy significantly increased infarct volumes in females, while no change was seen in gonadectomized males, indicating that estrogen loss increases ischemic sensitivity. Estradiol supplementation in gonadectomized FCG mice rescued this phenotype. Interestingly, FCG male mice were less sensitive to effects of hormones. This may be due to enhanced expression of the transgene Sry in brains of FCG male mice. Sex differences in ischemic stroke sensitivity appear to be shaped by organizational and activational effects of sex hormones, rather than sex chromosomal complement.

GPCRs Direct Germline Development and Somatic Gonad Function in Planarians

PubMed Central

Saberi, Amir; Beets, Isabel; Schoofs, Liliane; Newmark, Phillip A.

2016-01-01

Planarians display remarkable plasticity in maintenance of their germline, with the ability to develop or dismantle reproductive tissues in response to systemic and environmental cues. Here, we investigated the role of G protein-coupled receptors (GPCRs) in this dynamic germline regulation. By genome-enabled receptor mining, we identified 566 putative planarian GPCRs and classified them into conserved and phylum-specific subfamilies. We performed a functional screen to identify NPYR-1 as the cognate receptor for NPY-8, a neuropeptide required for sexual maturation and germ cell differentiation. Similar to NPY-8, knockdown of this receptor results in loss of differentiated germ cells and sexual maturity. NPYR-1 is expressed in neuroendocrine cells of the central nervous system and can be activated specifically by NPY-8 in cell-based assays. Additionally, we screened the complement of GPCRs with expression enriched in sexually reproducing planarians, and identified an orphan chemoreceptor family member, ophis, that controls differentiation of germline stem cells (GSCs). ophis is expressed in somatic cells of male and female gonads, as well as in accessory reproductive tissues. We have previously shown that somatic gonadal cells are required for male GSC specification and maintenance in planarians. However, ophis is not essential for GSC specification or maintenance and, therefore, defines a secondary role for planarian gonadal niche cells in promoting GSC differentiation. Our studies uncover the complement of planarian GPCRs and reveal previously unappreciated roles for these receptors in systemic and local (i.e., niche) regulation of germ cell development. PMID:27163480

GPCRs Direct Germline Development and Somatic Gonad Function in Planarians.

PubMed

Saberi, Amir; Jamal, Ayana; Beets, Isabel; Schoofs, Liliane; Newmark, Phillip A

2016-05-01

Planarians display remarkable plasticity in maintenance of their germline, with the ability to develop or dismantle reproductive tissues in response to systemic and environmental cues. Here, we investigated the role of G protein-coupled receptors (GPCRs) in this dynamic germline regulation. By genome-enabled receptor mining, we identified 566 putative planarian GPCRs and classified them into conserved and phylum-specific subfamilies. We performed a functional screen to identify NPYR-1 as the cognate receptor for NPY-8, a neuropeptide required for sexual maturation and germ cell differentiation. Similar to NPY-8, knockdown of this receptor results in loss of differentiated germ cells and sexual maturity. NPYR-1 is expressed in neuroendocrine cells of the central nervous system and can be activated specifically by NPY-8 in cell-based assays. Additionally, we screened the complement of GPCRs with expression enriched in sexually reproducing planarians, and identified an orphan chemoreceptor family member, ophis, that controls differentiation of germline stem cells (GSCs). ophis is expressed in somatic cells of male and female gonads, as well as in accessory reproductive tissues. We have previously shown that somatic gonadal cells are required for male GSC specification and maintenance in planarians. However, ophis is not essential for GSC specification or maintenance and, therefore, defines a secondary role for planarian gonadal niche cells in promoting GSC differentiation. Our studies uncover the complement of planarian GPCRs and reveal previously unappreciated roles for these receptors in systemic and local (i.e., niche) regulation of germ cell development.

The Influence of Season on the Gonad Index and Biochemical Composition of the Sea Urchin Paracentrotus lividus from the Golf of Tunis

PubMed Central

Arafa, Soumaya; Chouaibi, Moncef; Sadok, Saloua; El Abed, Amor

2012-01-01

Seasonal variation in the gonad weight and biochemical composition of the sea urchin Paracentrotus lividus from the Golf of Tunis (Tunisia) were studied between September 2003 and August 2004. The highest gonad indices occurred in March (16.71%). The spawning period occurred between April and July and resulted in a fall in gonad indices to low level (7.12 ± 0.12%). Protein constituted the main component of the gonad, and lipid and carbohydrate were found at appreciable amounts. Consistent with the gonad cycle, sea urchin biochemical components showed clear seasonal variation with a significant decrease during the spawning period. The polyunsaturated fatty acid (PUFA) group was found at high level (40% of the total fatty acids). Of the PUFA group, eicosapentaenoic (C20:5 n − 3) and eicosatetraenoic (C20:4 n − 3) were the most abundant gonadal lipids. The level of PUFA was significantly affected by temperature variation showing an increase during the cold months and a decrease in the hot months. PMID:22629206

Chromosome banding in Amphibia. XXVI. Coexistence of homomorphic XY sex chromosomes and a derived Y-autosome translocation in Eleutherodactylus maussi (Anura, Leptodactylidae).

PubMed

Schmid, M; Feichtinger, W; Steinlein, C; Haaf, T; Schartl, M; Visbal García, R; Manzanilla Pupo, J; Fernández Badillo, A

2002-01-01

A 15-year cytogenetic survey on one population of the leaf litter frog Eleutherodactylus maussi in northern Venezuela confirmed the existence of multiple XXAA male symbol /XAA(Y) female symbol sex chromosomes which originated by a centric (Robertsonian) fusion between the original Y chromosome and an autosome. 95% of the male individuals in this population are carriers of this Y-autosome fusion. In male meiosis the XAA(Y) sex chromosomes pair in the expected trivalent configuration. In the same population, 5% of the male animals still possess the original, free XY sex chromosomes. In a second population of E. maussi analyzed, all male specimens are characterized by these ancestral XY chromosomes which form normal bivalents in meiosis. E. maussi apparently represents the first vertebrate species discovered in which a derived Y-autosome fusion still coexists with the ancestral free XY sex chromosomes. The free XY sex chromosomes, as well as the multiple XA(Y) sex chromosomes are still in a very primitive (homomorphic) stage of differentiation. With no banding technique applied it is possible to distinguish the Y from the X. DNA flow cytometric measurements show that the genome of E. maussi is among the largest in the anuran family Leptodactylidae. The present study also supplies further data on differential chromosome banding and fluorescence in situ hybridization experiments in this amphibian species. Copyright 2003 S. Karger AG, Basel

Ultraprecision XY stage using a hybrid bolt-clamped Langevin-type ultrasonic linear motor for continuous motion.

PubMed

Lee, Dong-Jin; Lee, Sun-Kyu

2015-01-01

This paper presents a design and control system for an XY stage driven by an ultrasonic linear motor. In this study, a hybrid bolt-clamped Langevin-type ultrasonic linear motor was manufactured and then operated at the resonance frequency of the third longitudinal and the sixth lateral modes. These two modes were matched through the preload adjustment and precisely tuned by the frequency matching method based on the impedance matching method with consideration of the different moving weights. The XY stage was evaluated in terms of position and circular motion. To achieve both fine and stable motion, the controller consisted of a nominal characteristics trajectory following (NCTF) control for continuous motion, dead zone compensation, and a switching controller based on the different NCTFs for the macro- and micro-dynamics regimes. The experimental results showed that the developed stage enables positioning and continuous motion with nanometer-level accuracy.

Gender Identity and Coping in Female 46, XY Adults with Androgen Biosynthesis Deficiency (Intersexuality/DSD)

ERIC Educational Resources Information Center

Schweizer, Katinka; Brunner, Franziska; Schutzmann, Karsten; Schonbucher, Verena; Richter-Appelt, Hertha

2009-01-01

Individuals living with an intersex condition have not received much attention in counseling psychology, although a high need for psychosocial care is obvious. Using a mixed-methods multiple case study with qualitative and quantitative data, the authors explore coping and gender experiences in seven 46, XY intersexual persons with deficiencies of…

Homosexuality as a consequence of epigenetically canalized sexual development.

PubMed

Rice, William R; Friberg, Urban; Gavrilets, Sergey

2012-12-01

Male and female homosexuality have substantial prevalence in humans. Pedigree and twin studies indicate that homosexuality has substantial heritability in both sexes, yet concordance between identical twins is low and molecular studies have failed to find associated DNA makers. This paradoxical pattern calls for an explanation. We use published data on fetal androgen signaling and gene regulation via nongenetic changes in DNA packaging (epigenetics) to develop a new model for homosexuality. It is well established that fetal androgen signaling strongly influences sexual development. We show that an unappreciated feature of this process is reduced androgen sensitivity in XX fetuses and enhanced sensitivity in XY fetuses, and that this difference is most feasibly mused by numerous sex-specific epigenetic modifications ("epi-marks") originating in embryonic stem cells. These epi-marks buffer XX fetuses from masculinization due to excess fetal androgen exposure and similarly buffer XY fetuses from androgen underexposure. Extant data indicates that individual epi-marks influence some but not other sexually dimorphic traits, vary in strength across individuals, and are produced during ontogeny and erased between generations. Those that escape erasure will steer development of the sexual phenotypes they influence in a gonad-discordant direction in opposite sex offspring, mosaically feminizing XY offspring and masculinizing XX offspring. Such sex-specific epi-marks are sexually antagonistic (SA-epi-marks) because they canalize sexual development in the parent that produced them, but contribute to gonad-trait discordances in opposite-sex offspring when unerased. In this model, homosexuality occurs when stronger-than-average SA-epi-marks (influencing sexual preference) from an opposite-sex parent escape erasure and are then paired with a weaker-than-average de novo sex-specific epi-marks produced in opposite-sex offspring. Our model predicts that homosexuality is part of a

Steroid sex hormone dynamics during estradiol-17β induced gonadal differentiation in Paralichthys olivaceus (Teleostei)

NASA Astrophysics Data System (ADS)

Sun, Peng; You, Feng; Liu, Mengxia; Wu, Zhihao; Wen, Aiyun; Li, Jun; Xu, Yongli; Zhang, Peijun

2010-03-01

Steroid sex hormones, such as estradiol-17β (E2) and testosterone (T), are important regulators of sex change in fish. In this study, we examined the effects of E2 treatment on the dynamics of E2 and T during gonadal differentiation in the olive flounder Paralichthys olivaceus using histology and radioimmunoassay (RIA). Flounder larvae were divided into five groups (G0-G4), and fed with 0 (control), 0.2, 2, 20 and 100 mg E2/kg feed from 35 to 110 day post hatching (dph). Fish growth in the G1 and G2 groups was not significantly different from that of the control group ( P>0.05), while fish in the G3 and G4 groups were less active and showed growth depression and high mortality. The gonads of fish in the G3 and G4 groups were smaller and surrounded by hyperplastic connective tissue. The frequency of females in the G0-G4 groups was 54.5%, 75.0%, 100%, 100% and 93.3%, respectively. The RIA analyses of E2 and T showed that T levels decreased during gonadal differentiation, and increased slightly at the onset of ovarian differentiation, while E2 levels increased gradually and peaked at the onset of ovarian differentiation in the control group. In the E2-treated groups, T levels decreased before the onset of ovarian differentiation. E2 levels were high on the 48 dph, but declined to a lower level on the 54 dph, and then increased gradually during gonadal differentiation. And a sharp increase of E2 levels were observed in all E2-treated groups at the onset of ovarian differentiation. The data suggest that T and E2 play important roles during gonadal differentiation, and an E2 dose of 2 mg/kg feed could induce sex reversal in P. olivaceus.

Performance of Multiplexed XY Resistive Micromegas detectors in a high intensity beam

NASA Astrophysics Data System (ADS)

Banerjee, D.; Burtsev, V.; Chumakov, A.; Cooke, D.; Depero, E.; Dermenev, A. V.; Donskov, S. V.; Dubinin, F.; Dusaev, R. R.; Emmenegger, S.; Fabich, A.; Frolov, V. N.; Gardikiotis, A.; Gninenko, S. N.; Hösgen, M.; Karneyeu, A. E.; Ketzer, B.; Kirsanov, M. M.; Konorov, I. V.; Kramarenko, V. A.; Kuleshov, S. V.; Levchenko, E.; Lyubovitskij, V. E.; Lysan, V.; Mamon, S.; Matveev, V. A.; Mikhailov, Yu. V.; Myalkovskiy, V. V.; Peshekhonov, V. D.; Peshekhonov, D. V.; Polyakov, V. A.; Radics, B.; Rubbia, A.; Samoylenko, V. D.; Tikhomirov, V. O.; Tlisov, D. A.; Toropin, A. N.; Vasilishin, B.; Arenas, G. Vasquez; Ulloa, P.; Crivelli, P.

2018-02-01

We present the performance of multiplexed XY resistive Micromegas detectors tested in the CERN SPS 100 GeV/c electron beam at intensities up to 3 . 3 × 105e- /(s ṡcm2) . So far, all studies with multiplexed Micromegas have only been reported for tests with radioactive sources and cosmic rays. The use of multiplexed modules in high intensity environments was not explored due to the effect of ambiguities in the reconstruction of the hit point caused by the multiplexing feature. For the specific mapping and beam intensities analyzed in this work with a multiplexing factor of five, more than 50% level of ambiguity is introduced due to particle pile-up as well as fake clusters due to the mapping feature. Our results prove that by using the additional information of cluster size and integrated charge from the signal clusters induced on the XY strips, the ambiguities can be reduced to a level below 2%. The tested detectors are used in the CERN NA64 experiment for tracking the incoming particles bending in a magnetic field in order to reconstruct their momentum. The average hit detection efficiency of each module was found to be ∼96% at the highest beam intensities. By using four modules a tracking resolution of 1.1% was obtained with ∼85% combined tracking efficiency.

Effect of Diets Supplemented with Different Sources of Astaxanthin on the Gonad of the Sea Urchin Anthocidaris crassispina

PubMed Central

Peng, Juan; Yuan, Jian-Ping; Wang, Jiang-Hai

2012-01-01

The effect of the microalgae Haematococcus pluvialis and Chorella zofingiensis, and synthetic astaxanthin on the gonad of the sea urchin Anthocidaris crassispina was studied. The basal diet was supplemented with H. pluvialis, C. zofingiensis, or synthetic astaxanthin, at two levels of astaxanthin (approximately 400 mg/kg and 100 mg/kg), to obtain the experimental diets HP1, HP2, CZ1, CZ2, AST1, and AST2, respectively, for two months of feeding experiment. The results showed that the concentrations of astaxanthin in the gonads of the sea urchins fed these experimental diets ranged from 0.15 to 3.01 mg/kg dry gonad weight. The higher astaxanthin levels (>2.90 mg/kg) were found in the gonads of the sea urchins fed the diets HP1 (containing 380 mg/kg of astaxanthins, mostly mono- and diesters) and AST1 (containing 385 mg/kg of synthetic astaxanthin). The lowest astaxanthin level (0.15 mg/kg) was detected in the gonads of the sea urchins fed the diet CZ2 (containing 98 mg/kg of astaxanthins, mostly diesters). Furthermore, the highest canthaxanthin level (7.48 mg/kg) was found in the gonads of the sea urchins fed the diet CZ1 (containing 387 mg/kg of astaxanthins and 142 mg/kg of canthaxanthin), suggesting that astaxanthins, especially astaxanthin esters, might not be assimilated as easily as canthaxanthin by the sea urchins. Our results show that sea urchins fed diets containing astaxanthin pigments show higher incorporation of these known antioxidant constituents, with the resultant seafood products therefore being of potential higher nutritive value. PMID:23016124

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

The case of an Sry-negative XX male Pug with an inguinal gonad.

PubMed

Rota, A; Cucuzza, A Starvaggi; Iussich, S; Delorenzi, L; Parma, P

2010-08-01

A case of intersexuality in a Pug that was bought as a male in a pet shop is described. The dog was presented at the Veterinary Teaching Hospital, University of Turin, for a reddish mass protruding from the prepuce. The mass had the aspect of an enlarged clitoris, with a caudoventral direction and a dorsal urethral ostium. A gonad was palpable in the left inguinal region. Laparotomy confirmed ultrasound detection of an abdominal uterine structure together with the right gonad. The histology of both gonads was similar, showing an exclusively masculine character, with seminiferous tubules lined only by Sertoli cells; the uterus showed a normal histological structure. Karyological analysis revealed a female karyotype (78,XX), and polymerase chain reaction showed the absence of Sry. The diagnosis was an XX male. The pathogenesis of the XX sex reversal syndrome in dogs is not completely understood, as Sry, the master gene regulating testis differentiation, is not present; to date, no genetic cause has been identified for this phenotypic condition in dogs. This case is unusual because the dog showed an inguinal testis, implying a partial activity of the mechanisms leading to abdominal testis translocation along a gubernaculum and transinguinal migration.

Involvement of Antizyme Characterized from the Small Abalone Haliotis diversicolor in Gonadal Development

PubMed Central

Lü, Wen-Gang; Chen, Xiao; Shen, Ming-Hui; Li, Xiang-Min; Wang, Rong-Xia; Ke, Cai-Huan

2015-01-01

The small abalone Haliotis diversicolor is an economically important mollusk that is widely cultivated in Southern China. Gonad precocity may affect the aquaculture of small abalone. Polyamines, which are small cationic molecules essential for cellular proliferation, may affect gonadal development. Ornithine decarboxylase (ODC) and antizyme (AZ) are essential elements of a feedback circuit that regulates cellular polyamines. This paper presents the molecular cloning and characterization of AZ from small abalone. Sequence analysis showed that the cDNA sequence of H. diversicolor AZ (HdiODCAZ) consisted of two overlapping open reading frames (ORFs) and conformed to the +1 frameshift property of the frame. Thin Layer chromatography (TLC) analysis suggested that the expressed protein encoded by +1 ORF2 was the functional AZ that targets ODC to 26S proteasome degradation. The result demonstrated that the expression level of AZ was higher than that of ODC in the ovary of small abalone. In addition, the expression profiles of ODC and AZ at the different development stages of the ovary indicated that these two genes might be involved in the gonadal development of small abalone. PMID:26313647

Biogenic acidification reduces sea urchin gonad growth and increases susceptibility of aquaculture to ocean acidification.

PubMed

Mos, Benjamin; Byrne, Maria; Dworjanyn, Symon A

2016-02-01

Decreasing oceanic pH (ocean acidification) has emphasised the influence of carbonate chemistry on growth of calcifying marine organisms. However, calcifiers can also change carbonate chemistry of surrounding seawater through respiration and calcification, a potential limitation for aquaculture. This study examined how seawater exchange rate and stocking density of the sea urchin Tripneustes gratilla that were reproductively mature affected carbonate system parameters of their culture water, which in turn influenced growth, gonad production and gonad condition. Growth, relative spine length, gonad production and consumption rates were reduced by up to 67% by increased density (9-43 individuals.m(-2)) and reduced exchange rates (3.0-0.3 exchanges.hr(-1)), but survival and food conversion efficiency were unaffected. Analysis of the influence of seawater parameters indicated that reduced pH and calcite saturation state (ΩCa) were the primary factors limiting gonad production and growth. Uptake of bicarbonate and release of respiratory CO2 by T. gratilla changed the carbonate chemistry of surrounding water. Importantly total alkalinity (AT) was reduced, likely due to calcification by the urchins. Low AT limits the capacity of culture water to buffer against acidification. Direct management to counter biogenic acidification will be required to maintain productivity and reproductive output of marine calcifiers, especially as the ocean carbonate system is altered by climate driven ocean acidification. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Recreational Drug Ecstasy Disrupts the Hypothalamic-Pituitary-Gonadal Reproductive Axis in Adult Male Rats

PubMed Central

Dickerson, Sarah M.; Walker, Deena M.; Reveron, Maria E.; Duvauchelle, Christine L.; Gore, Andrea C.

2009-01-01

Reproductive function involves an interaction of three regulatory levels: hypothalamus, pituitary, and gonad. The primary drive upon this system comes from hypothalamic gonadotropin-releasing hormone (GnRH) neurosecretory cells, which receive afferent inputs from other neurotransmitter systems in the central nervous system to result in the proper coordination of reproduction and the environment. Here, we hypothesized that the recreational drug ±-3,4-Methylenedioxymethamphetamine (MDMA; “ecstasy”), which acts through several of the neurotransmitter systems that affect GnRH neurons, suppresses the hypothalamic-pituitary-gonadal (HPG) reproductive axis of male rats. Adult male Sprague-Dawley rats self-administered saline or MDMA or saline either once (acute) or for 20 days (chronic), and were euthanized 7 days following last administration. We quantified hypothalamic GnRH mRNA, serum luteinizing hormone (LH) concentrations, and serum testosterone levels, as indices of hypothalamic, pituitary, and gonadal functions, respectively. The results indicate that the hypothalamic and gonadal levels of the HPG axis are significantly altered by MDMA, with GnRH mRNA and serum testosterone levels suppressed in rats administered MDMA compared to saline. Furthermore, our finding that hypothalamic GnRH mRNA levels are suppressed in the context of low testosterone concentrations suggests that the central GnRH neurosecretory system may be a primary target of inhibitory regulation by MDMA usage. PMID:18309234

21 CFR 1000.50 - Recommendation for the use of specific area gonad shielding on patients during medical diagnostic...

Code of Federal Regulations, 2014 CFR

2014-04-01

... shielding on patients during medical diagnostic x-ray procedures. 1000.50 Section 1000.50 Food and Drugs... shielding on patients during medical diagnostic x-ray procedures. Specific area gonad shielding covers an... that may cause genetic mutations during many medical x-ray procedures in which the gonads lie within or...

21 CFR 1000.50 - Recommendation for the use of specific area gonad shielding on patients during medical diagnostic...

Code of Federal Regulations, 2011 CFR

2011-04-01

... shielding on patients during medical diagnostic x-ray procedures. 1000.50 Section 1000.50 Food and Drugs... shielding on patients during medical diagnostic x-ray procedures. Specific area gonad shielding covers an... that may cause genetic mutations during many medical x-ray procedures in which the gonads lie within or...

21 CFR 1000.50 - Recommendation for the use of specific area gonad shielding on patients during medical diagnostic...

Code of Federal Regulations, 2013 CFR

2013-04-01

... shielding on patients during medical diagnostic x-ray procedures. 1000.50 Section 1000.50 Food and Drugs... shielding on patients during medical diagnostic x-ray procedures. Specific area gonad shielding covers an... that may cause genetic mutations during many medical x-ray procedures in which the gonads lie within or...

21 CFR 1000.50 - Recommendation for the use of specific area gonad shielding on patients during medical diagnostic...

Code of Federal Regulations, 2012 CFR

2012-04-01

... shielding on patients during medical diagnostic x-ray procedures. 1000.50 Section 1000.50 Food and Drugs... shielding on patients during medical diagnostic x-ray procedures. Specific area gonad shielding covers an... that may cause genetic mutations during many medical x-ray procedures in which the gonads lie within or...

21 CFR 1000.50 - Recommendation for the use of specific area gonad shielding on patients during medical diagnostic...

Code of Federal Regulations, 2010 CFR

2010-04-01

... shielding on patients during medical diagnostic x-ray procedures. 1000.50 Section 1000.50 Food and Drugs... shielding on patients during medical diagnostic x-ray procedures. Specific area gonad shielding covers an... that may cause genetic mutations during many medical x-ray procedures in which the gonads lie within or...

Gender Issues and Related Social Stigma Affecting Patients with a Disorder of Sex Development in India.

PubMed

Joseph, Angela Ann; Kulshreshtha, Bindu; Shabir, Iram; Marumudi, Eunice; George, Tony Sam; Sagar, Rajesh; Mehta, Manju; Ammini, Ariachery C

2017-02-01

Children with disorders of sex development (DSD) manifest at birth with malformed genitalia or later with atypical pubertal development. Those born with malformed genitalia are often diagnosed at birth. However, in resource-poor countries like India, where not all births are supervised by healthcare workers, some of these children remain undiagnosed until puberty or even later. The aim of this study was to assess the gender issues and psychosocial problems of children with DSD. Participants included 205 children with DSD (103 with 46,XX DSD and 102 with 46,XY DSD). Both the children with DSD and their parents underwent semistructured interviews by a clinical psychologist. The birth of a child with DSD was perceived as a major medical and social problem by parents from all socioeconomic strata. Mothers were distressed as many believed the DSD condition was transmitted through the mother. Children who were not diagnosed and treated during infancy or early childhood experienced considerable social discrimination not only from relatives and friends but also from medical and paramedical staff in hospitals. Several patients had been operated during infancy without an etiological diagnosis and without provision of adequate information to the parents. Some children had problems related to complications of surgery. Most teenage patients with 5α-reductase-2 deficiency reared as females presented with gender dysphoria, while children with androgen insensitivity (except for one) or with gonadal dysgenesis developed a gender identity concordant with their gender of rearing. Parents of children with DSD preferred a male gender assignment for their children (if that was possible) because of the social advantages of growing up male in a patriarchal society.

Structure-Function Relationships in Human Testis-determining Factor SRY

PubMed Central

Racca, Joseph D.; Chen, Yen-Shan; Maloy, James D.; Wickramasinghe, Nalinda; Phillips, Nelson B.; Weiss, Michael A.

2014-01-01

Human testis determination is initiated by SRY, a Y-encoded architectural transcription factor. Mutations in SRY cause 46 XY gonadal dysgenesis with female somatic phenotype (Swyer syndrome) and confer a high risk of malignancy (gonadoblastoma). Such mutations cluster in the SRY high mobility group (HMG) box, a conserved motif of specific DNA binding and bending. To explore structure-function relationships, we constructed all possible substitutions at a site of clinical mutation (W70L). Our studies thus focused on a core aromatic residue (position 15 of the consensus HMG box) that is invariant among SRY-related HMG box transcription factors (the SOX family) and conserved as aromatic (Phe or Tyr) among other sequence-specific boxes. In a yeast one-hybrid system sensitive to specific SRY-DNA binding, the variant domains exhibited reduced (Phe and Tyr) or absent activity (the remaining 17 substitutions). Representative nonpolar variants with partial or absent activity (Tyr, Phe, Leu, and Ala in order of decreasing side-chain volume) were chosen for study in vitro and in mammalian cell culture. The clinical mutation (Leu) was found to markedly impair multiple biochemical and cellular activities as respectively probed through the following: (i) in vitro assays of specific DNA binding and protein stability, and (ii) cell culture-based assays of proteosomal degradation, nuclear import, enhancer DNA occupancy, and SRY-dependent transcriptional activation. Surprisingly, however, DNA bending is robust to this or the related Ala substitution that profoundly impairs box stability. Together, our findings demonstrate that the folding, trafficking, and gene-regulatory function of SRY requires an invariant aromatic “buttress” beneath its specific DNA-bending surface. PMID:25258310

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.

Action of the Metalloproteinases in Gonadal Remodeling during Sex Reversal in the Sequential Hermaphroditism of the Teleostei Fish Synbranchus marmoratus (Synbranchiformes: Synbranchidae)

PubMed Central

Mazzoni, Talita Sarah; Lo Nostro, Fabiana Laura; Antoneli, Fernanda Natália; Quagio-Grassiotto, Irani

2018-01-01

Teleostei present great plasticity regarding sex change. During sex reversal, the whole gonad including the germinal epithelium undergoes significant changes, remodeling, and neoformation. However, there is no information on the changes that occur within the interstitial compartment. Considering the lack of information, especially on the role played by metalloproteinases (MMPs) in fish gonadal remodeling, the aim of this study was to evaluate the action of MMPs on gonads of sex reversed females of Synbranchus marmoratus, a fresh water protogynic diandric fish. Gonads were processed for light microscopy and blood samples were used for the determination of plasma sex steroid levels. During sex reversal, degeneration of the ovaries occurred and were gradually replaced by the germinal tissue of the male. The action of the MMPs induces significant changes in the interstitial compartment, allowing the reorganization of germinal epithelium. Leydig cells also showed an important role in female to male reversion. The gonadal transition coincides with changes in circulating sex steroid levels throughout sex reversion. The action of the MMPs, in the gonadal remodeling, especially on the basement membrane, is essential for the establishment of a new functional germinal epithelium. PMID:29695033

Roles of GATA6 during Gonadal Development in Japanese Flounder: Gonadogenesis, Regulation of Gender-Related Genes, Estrogen Formation and Gonadal Function Maintenance.

PubMed

Li, Zan; Liu, Xiumei; Sun, Yan; Liu, Jinxiang; Liu, Yuezhong; Wang, Mengxun; Zhang, Quanqi; Wang, Xubo

2017-01-16

GATA-binding protein 6 (GATA6), a highly-conserved transcription factor of the GATA family plays an important role in gonadal cell proliferation, differentiation and endoderm development. In this study, the full-length cDNA of GATA6 of Paralichthys olivaceus (Japanese flounder) was obtained. Phylogenetic, gene structure and synteny analyses demonstrated that GATA6 of P. olivaceus is homologous to that of teleosts and tetrapods. The P. olivaceus GATA6 transcript showed higher expression in testis than in ovary, demonstrating a sexually dimorphic gene expression. During embryonic development, the expression of P. olivaceus GATA6 increased at the blastula stage, demonstrating that GATA6 is involved in morphogenesis. Results of in situ hybridization showed that GATA6 signals were detected in Sertoli cells, oogonia and oocytes. Moreover, 17α methyl testosterone, a male hormone, could moderately upregulate P. olivaceus GATA6 and downregulate P. olivaceus aromatase CYP19A1 in testis cells. These results suggest that GATA6 may play an important role in gonadal development in P. olivaceus . This study provides valuable information on the function of P. olivaceus GATA6, laying the foundation for further development of breeding techniques in this species.

Roles of GATA6 during Gonadal Development in Japanese Flounder: Gonadogenesis, Regulation of Gender-Related Genes, Estrogen Formation and Gonadal Function Maintenance

PubMed Central

Li, Zan; Liu, Xiumei; Sun, Yan; Liu, Jinxiang; Liu, Yuezhong; Wang, Mengxun; Zhang, Quanqi; Wang, Xubo

2017-01-01

GATA-binding protein 6 (GATA6), a highly-conserved transcription factor of the GATA family plays an important role in gonadal cell proliferation, differentiation and endoderm development. In this study, the full-length cDNA of GATA6 of Paralichthys olivaceus (Japanese flounder) was obtained. Phylogenetic, gene structure and synteny analyses demonstrated that GATA6 of P. olivaceus is homologous to that of teleosts and tetrapods. The P. olivaceus GATA6 transcript showed higher expression in testis than in ovary, demonstrating a sexually dimorphic gene expression. During embryonic development, the expression of P. olivaceus GATA6 increased at the blastula stage, demonstrating that GATA6 is involved in morphogenesis. Results of in situ hybridization showed that GATA6 signals were detected in Sertoli cells, oogonia and oocytes. Moreover, 17α methyl testosterone, a male hormone, could moderately upregulate P. olivaceus GATA6 and downregulate P. olivaceus aromatase CYP19A1 in testis cells. These results suggest that GATA6 may play an important role in gonadal development in P. olivaceus. This study provides valuable information on the function of P. olivaceus GATA6, laying the foundation for further development of breeding techniques in this species. PMID:28275215

Treosulfan induces distinctive gonadal toxicity compared with busulfan

PubMed Central

Levi, Mattan; Stemmer, Salomon M.; Stein, Jerry; Shalgi, Ruth; Ben-Aharon, Irit

2018-01-01

Treosulfan (L-treitol-1,4-bis-methanesulfonate) has been increasingly incorporated as a main conditioning protocol for hematopoietic stem cell transplantation in pediatric malignant and non-malignant diseases. Treosulfan presents lower toxicity profile than other conventional alkylating agents containing myeloablative and immunosuppressive traits such as busulfan. Yet, whereas busulfan is considered highly gonadotoxic, the gonadal toxicity profile of treosulfan remains to be elucidated. To study the gonadotoxicity of treosulfan, pubertal and prepubertal male and female mice were injected with treosulfan or busulfan and sacrificed one week, one month or six months later. Testicular function was assessed by measurements of sperm properties, testes and epididymides weights as well as markers for testicular reserve, proliferation and apoptosis. Ovarian function was assessed by measurements of ovary weight and markers for ovarian reserve, proliferation and apoptosis. Treosulfan testicular toxicity was milder than that of busulfan toxicity; possibly by sparing the stem spermatogonia in the testicular sanctuary. By contrast, ovarian toxicity of both treosulfan and busulfan was severe and permanent and displayed irreversible reduction of reserve primordial follicles in the ovaries. Our data indicate that treosulfan exerts a different gonadal toxicity profile from busulfan, manifested by mild testicular toxicity and severe ovarian toxicity. PMID:29721205

Critical behavior of the XY-rotor model on regular and small-world networks

NASA Astrophysics Data System (ADS)

De Nigris, Sarah; Leoncini, Xavier

2013-07-01

We study the XY rotors model on small networks whose number of links scales with the system size Nlinks˜Nγ, where 1≤γ≤2. We first focus on regular one-dimensional rings in the microcanonical ensemble. For γ<1.5 the model behaves like a short-range one and no phase transition occurs. For γ>1.5, the system equilibrium properties are found to be identical to the mean field, which displays a second-order phase transition at a critical energy density ɛ=E/N,ɛc=0.75. Moreover, for γc≃1.5 we find that a nontrivial state emerges, characterized by an infinite susceptibility. We then consider small-world networks, using the Watts-Strogatz mechanism on the regular networks parametrized by γ. We first analyze the topology and find that the small-world regime appears for rewiring probabilities which scale as pSW∝1/Nγ. Then considering the XY-rotors model on these networks, we find that a second-order phase transition occurs at a critical energy ɛc which logarithmically depends on the topological parameters p and γ. We also define a critical probability pMF, corresponding to the probability beyond which the mean field is quantitatively recovered, and we analyze its dependence on γ.

2d affine XY-spin model/4d gauge theory duality and deconfinement

NASA Astrophysics Data System (ADS)

Anber, Mohamed M.; Poppitz, Erich; Ünsal, Mithat

2012-04-01

We introduce a duality between two-dimensional XY-spin models with symmetry-breaking perturbations and certain four-dimensional SU(2) and SU(2)/ {{Z}_2} gauge theories, compactified on a small spatial circle {{R}^{{^{{{1},{2}}}}}} × {{S}^{{^{{1}}}}} , and considered at temperatures near the deconfinement transition. In a Euclidean set up, the theory is defined on {{R}^{{^{{2}}}}} × {{T}^{{^{{2}}}}} . Similarly, thermal gauge theories of higher rank are dual to new families of "affine" XY-spin models with perturbations. For rank two, these are related to models used to describe the melting of a 2d crystal with a triangular lattice. The connection is made through a multi-component electric-magnetic Coulomb gas representation for both systems. Perturbations in the spin system map to topological defects in the gauge theory, such as monopole-instantons or magnetic bions, and the vortices in the spin system map to the electrically charged W-bosons in field theory (or vice versa, depending on the duality frame). The duality permits one to use the two-dimensional technology of spin systems to study the thermal deconfinement and discrete chiral transitions in four-dimensional SU( N c ) gauge theories with n f ≥1 adjoint Weyl fermions.

Transcription of key genes regulating gonadal steroidogenesis in control and ketoconazole- or vinclozolin-exposed fathead minnows

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

Villeneuve, Daniel L.; Blake, Lindsey S.; Brodin, Jeffrey

2007-08-01

This study evaluated changes in the expression of steroidogenesis-related genes in male fathead minnows exposed to ketoconazole (KTC) or vinclozolin (VZ) for 21 days. The aim was to evaluate links between molecular changes and higher level outcomes after exposure to endocrine-active chemicals (EACs) with different modes of action. To aid our analysis and interpretation of EAC-related effects, we first examined variation in the relative abundance of steroidogenesis-related gene transcripts in the gonads of male and female fathead minnows as a function of age, gonad development, and spawning status, independent of EAC exposure. Gonadal expression of several genes varied with agemore » and/or gonadal somatic index in either males or females. However, with the exception of aromatase, steroidogenesis-related gene expression did not vary with spawning status. Following the baseline experiments, expression of the selected genes in male fathead minnows exposed to KTC or VZ was evaluated in the context of effects observed at higher levels of organization. Exposure to KTC elicited changes in gene transcription that were consistent with an apparent compensatory response to the chemical's anticipated direct inhibition of steroidogenic enzyme activity. Exposure to VZ, an antiandrogen expected to indirectly impact steroidogenesis, increased pituitary expression of follicle-stimulating hormone beta-subunit as well as testis expression of 20beta-hydroxysteroid dehydrogenase and luteinizing hormone receptor transcripts. Results of this study contribute to ongoing research aimed at understanding responses of the teleost hypothalamic-pituitary-gonadal axis to different types of EACs and how changes in molecular endpoints translate into apical outcomes reflective of either adverse effect or compensation.« less

Immunohistochemical localization of FMRFamide-containing neurons and nerve fibers in the ganglia and the gonad wall of the scallop, Pecten maximus (L).

PubMed

Henry, M; Benlinmame, N; Belhsen, O K; Jule, Y; Mathieu, M

1995-02-01

The Phe-Met-Arg-Phe NH2 (FMRFamide)-like immunoreactivity was detected in neurons of the cerebro-pedal and visceral ganglia of the scallop Pecten maximus using immunohistochemical techniques. FMRFamide-like immunoreactivity was also found in nerve fibers localized in the connective tissue and the epithelial wall of the gonad. Electron microscopy study carried out on the gonads indicates the existence of numerous nerve fibers crossing the connective tissue; nerve terminals apposed to highly secretory cells were seen in the gonad wall. All in all, the present immunohistochemical and electron microscopic data suggest that FMRFamide might play an unusual secretagogue role in the gonad wall.

Characterization of gonadal soma-derived factor expression during sex change in the protogynous wrasse, Halichoeres trimaculatus.

PubMed

Horiguchi, Ryo; Nozu, Ryo; Hirai, Toshiaki; Kobayashi, Yasuhisa; Nagahama, Yoshitaka; Nakamura, Masaru

2013-04-01

Sex change in fishes provides a good experimental model for understanding the mechanisms and plasticity of sex determination and differentiation. The three-spot wrasse, Halichoeres trimaculatus is a protogynous hermaphrodite. During sex change from female to male, the ovary is replaced by the testis through the degeneration of oocytes and subsequent spermatogenesis. In the present study, we cloned a cDNA-encoding gonadal soma-derived factor (GSDF) from protogynous wrasse and examined its expression pattern in the sexually mature gonads and the sex-changing gonad induced experimentally by aromatase inhibition. Expression of gsdf was predominantly observed in the testis, and it was mainly localized to the supporting cells surrounding the spermatogonia. In the ovary, only slight expression of gsdf was observed in morphologically undifferentiated supporting cells in contact with oogonia. During sex change, strong expression of gsdf appeared first in the supporting cells surrounding the gonial germ cells before the onset of spermatogenesis. Thereafter, the expression of gsdf continually increased in the supporting cells surrounding the proliferating spermatogonia throughout the sex change. These results suggest that gsdf is involved in the proliferation of spermatogonia and subsequent spermatogenesis in both the testis and the gonad in the early stages of sex change. Copyright © 2013 Wiley Periodicals, Inc.

Ultraprecision XY stage using a hybrid bolt-clamped Langevin-type ultrasonic linear motor for continuous motion

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

Lee, Dong-Jin; Lee, Sun-Kyu, E-mail: skyee@gist.ac.kr

2015-01-15

This paper presents a design and control system for an XY stage driven by an ultrasonic linear motor. In this study, a hybrid bolt-clamped Langevin-type ultrasonic linear motor was manufactured and then operated at the resonance frequency of the third longitudinal and the sixth lateral modes. These two modes were matched through the preload adjustment and precisely tuned by the frequency matching method based on the impedance matching method with consideration of the different moving weights. The XY stage was evaluated in terms of position and circular motion. To achieve both fine and stable motion, the controller consisted of amore » nominal characteristics trajectory following (NCTF) control for continuous motion, dead zone compensation, and a switching controller based on the different NCTFs for the macro- and micro-dynamics regimes. The experimental results showed that the developed stage enables positioning and continuous motion with nanometer-level accuracy.« less

Gonadal steroids regulate the expression of aggrecanases in human endometrial stromal cells in vitro

PubMed Central

Wen, Jiadi; Zhu, Hua; Leung, Peter CK

2013-01-01

The human endometrium undergoes cyclic change during each menstrual cycle in response to gonadal steroids. Proteolysis of endometrial extracellular matrix (ECM) is necessary to prepare this dynamic tissue for pregnancy. Proteolytic enzymes such as matrix metalloproteinase (MMP) and closely related a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) have been assigned key roles in the highly regulated cyclic remodelling of the endometrial ECM. We have previously shown that ADAMTS-1 undergoes spatiotemporal changes in human endometrial stromal cells under the regulation of gonadal steroids. This suggests that other ADAMTS subtypes, known as aggrecanases, may contribute to the ECM remodelling events that occur in female physiological cycles and in preparation for pregnancy. To determine whether progesterone (P4), 17β-estradiol (E2), or dihydrotestosterone (DHT), alone or in combination, are capable of regulating ADAMTS-4, -5, -8 or -9 expression in human endometrial stromal cells in vitro. Real-time quantitative PCR and Western blot analysis were used to measure ADAMTSs mRNA and protein levels in primary cultures of human endometrial stromal cells (n = 12). P4, DHT but not E2 have regulatory effects on ADAMTS-8, -9 and -5 expression. Combined treatment with gonadal steroids did not show any synergistic or antagonistic effects. However, the synthetic steroid antagonists RU486 and hydroxyflutamide specifically inhibited the P4- or DHT-mediated regulatory effects on ADAMTS expression. These studies provide evidence that the regulation of aggrecanases by gonadal steroids in human endometrial stromal cells may play an important role during decidualization. PMID:23947778

Adaptive Response in Female Modeling of the Hypothalamic-pituitary-gonadal Axis

EPA Science Inventory

Exposure to endocrine disrupting chemicals can affect reproduction and development in both humans and wildlife. We are developing a mechanistic computational model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict dose-response and time-course ...

Hypoplastic uterus and clitoris enlargement in Swyer syndrome.

PubMed

Hétu, Valérie; Caron, Evelyne; Francoeur, Diane

2010-02-01

Swyer syndrome is associated with absent testicular differentiation in a 46XY phenotypic female. A 17-year-old female presented with primary amenorrhea and 46XY karyotype. Breast and pubic hair development were Tanner 2, and clitoral enlargement was noted. Magnetic resonance imaging revealed a hypoplastic uterus and 2 "normal ovaries." Serum follicle-stimulating hormone and luteinizing hormone were elevated. Testosterone and androstenedione were in the female range. Dehydroepiandrosterone sulfate was slightly elevated. Laparoscopic bilateral gonadectomy was performed. Pathology reports showed bilateral microscopic benign hilar cell tumors. The diagnosis was a real puzzle for the clinicians because of the association of clitoral hypertrophy without hirsutism, female internal genitalia, and a 46XY karyotype. Clitoral enlargement can be explained by transient androgen secretion by the hilar cells found in the resected gonads. Copyright 2010 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Homonuclear Hartmann-Hahn transfer with reduced relaxation losses by use of the MOCCA-XY16 multiple pulse sequence

NASA Astrophysics Data System (ADS)

Furrer, Julien; Kramer, Frank; Marino, John P.; Glaser, Steffen J.; Luy, Burkhard

2004-01-01

Homonuclear Hartmann-Hahn transfer is one of the most important building blocks in modern high-resolution NMR. It constitutes a very efficient transfer element for the assignment of proteins, nucleic acids, and oligosaccharides. Nevertheless, in macromolecules exceeding ˜10 kDa TOCSY-experiments can show decreasing sensitivity due to fast transverse relaxation processes that are active during the mixing periods. In this article we propose the MOCCA-XY16 multiple pulse sequence, originally developed for efficient TOCSY transfer through residual dipolar couplings, as a homonuclear Hartmann-Hahn sequence with improved relaxation properties. A theoretical analysis of the coherence transfer via scalar couplings and its relaxation behavior as well as experimental transfer curves for MOCCA-XY16 relative to the well-characterized DIPSI-2 multiple pulse sequence are given.

Homonuclear Hartmann-Hahn transfer with reduced relaxation losses by use of the MOCCA-XY16 multiple pulse sequence.

PubMed

Furrer, Julien; Kramer, Frank; Marino, John P; Glaser, Steffen J; Luy, Burkhard

2004-01-01

Homonuclear Hartmann-Hahn transfer is one of the most important building blocks in modern high-resolution NMR. It constitutes a very efficient transfer element for the assignment of proteins, nucleic acids, and oligosaccharides. Nevertheless, in macromolecules exceeding approximately 10 kDa TOCSY-experiments can show decreasing sensitivity due to fast transverse relaxation processes that are active during the mixing periods. In this article we propose the MOCCA-XY16 multiple pulse sequence, originally developed for efficient TOCSY transfer through residual dipolar couplings, as a homonuclear Hartmann-Hahn sequence with improved relaxation properties. A theoretical analysis of the coherence transfer via scalar couplings and its relaxation behavior as well as experimental transfer curves for MOCCA-XY16 relative to the well-characterized DIPSI-2 multiple pulse sequence are given.

Effective equilibrium picture in the xy model with exponentially correlated noise.

PubMed

Paoluzzi, Matteo; Marconi, Umberto Marini Bettolo; Maggi, Claudio

2018-02-01

We study the effect of exponentially correlated noise on the xy model in the limit of small correlation time, discussing the order-disorder transition in the mean field and the topological transition in two dimensions. We map the steady states of the nonequilibrium dynamics into an effective equilibrium theory. In the mean field, the critical temperature increases with the noise correlation time τ, indicating that memory effects promote ordering. This finding is confirmed by numerical simulations. The topological transition temperature in two dimensions remains untouched. However, finite-size effects induce a crossover in the vortices proliferation that is confirmed by numerical simulations.

Comparative biochemical composition in gonad and adductor muscle of triploid and diploid catarina scallop (Argopecten ventricosus Sowerby II, 1842).

PubMed

Ruiz-Verdugo, C A.; Racotta, I S.; Ibarra, A M.

2001-05-15

Biochemical components of gonad and adductor muscle for diploid and triploid catarina scallop, Argopecten ventricosus, were evaluated and compared at four periods in 1 year (January, April, June, and October). Two comparisons were done. The first one compared an untreated control (diploid) vs. a triploidy-treated group for which the percentage of triploids was 57%. The second comparison was done on a group derived from within the triploidy-treated group, separating diploids (internal control) from triploids ('putative triploids'). Regardless of which comparison, in the gonad diploid scallops had larger concentrations of proteins, carbohydrates, lipids, and acylglycerols than triploid scallops. This reflects the maturation processes in diploid scallops vs. the sterility seen in most triploid scallops, and it is particularly supported by the consistently larger concentration of acylglycerols in gonads of diploids than in triploids. The gonad index of the internal control (diploid) group was significantly larger than that seen in the putative triploid group at all sampling periods but October, when none of the gonad biochemical components were different between ploidy groups.Triploid scallops had a significantly larger muscle index than diploids from April to October. This can be caused by a larger gain in muscle tissue in triploids than diploids from January to June. However, there were no consistent differences in any of the biochemical components evaluated in adductor muscle of diploids and triploids. The use of freshly ingested food rather than reserve mobilization from muscle in diploids is suggested by these results. Nutrients derived from ingested food are apparently used for muscle growth in triploids, whereas in diploids those nutrients serve primarily for gonad development. The importance of freshly ingested food for maintenance and growth is suggested because the decline in biochemical components seen in October in both muscle and gonad was paired with a

Global DNA Methylation Changes in Nile Tilapia Gonads during High Temperature-Induced Masculinization

PubMed Central

Wang, Hui; Li, Ning

2016-01-01

In some fish species, high or low temperature can switch the sex determination mechanisms and induce fish sex reversal when the gonads are undifferentiated. During this high or low temperature-induced sex reversal, the expressions of many genes are altered. However, genome-wide DNA methylation changes in fish gonads after high or low temperature treatment are unclear. Herein, we compared the global DNA methylation changes in the gonads from control females (CF), control males (CM), high temperature-treated females (TF), and high temperature-induced males (IM) from the F8 family of Nile tilapia (Oreochromis niloticus) using methylated DNA immunoprecipitation sequencing. The DNA methylation level in CF was higher than that in CM for various chromosomes. Both females and males showed an increase in methylation levels on various chromosomes after high-temperature induction. We identified 64,438 (CF/CM), 63,437 (TF/IM), 98,675 (TF/CF), 235,270 (IM/CM) and 119,958 (IM/CF) differentially methylated regions (DMRs) in Nile tilapia gonads, representing approximately 0.70% (CF/CM), 0.69% (TF/IM), 1.07% (TF/CF), 2.56% (IM/CM), and 1.30% (IM/CF)of the length of the genome. A total of 89 and 65 genes that exhibited DMRs in their gene bodies and promoters were mapped to the Nile tilapia genome. Furthermore, more than half of the genes with DMRs in the gene body in CF/CM were also included in the IM/CM, TF/CF, TF/IM, and IM/CF groups. Additionally, many important pathways, including neuroactive ligand-receptor interaction, extracellular matrix-receptor interaction, and biosynthesis of unsaturated fatty acids were identified. This study provided an important foundation to investigate the molecular mechanism of high temperature-induced sex reversal in fish species. PMID:27486872

Influence of Xenorhabdus (Gamma-Proteobacteria: Enterobacteriaceae) symbionts on gonad postembryonic development in Steinernema (Nematoda: Steinernematidae) nematodes.

PubMed

Roder, Alexandra C; Stock, S Patricia

2018-03-01

Steinernema nematodes and their Xenorhabdus partners form an obligate mutualistic association. This partnership is insecticidal to a wide range of insects. Steinernema rely on their Xenorhabdus partner to produce toxins inside the insect cadaver to liberate nutrients from the insect, as well as antimicrobials to sterilize the cadaver, thus creating a suitable environment for reproduction. In return, Steinernema vector their Xenorhabdus between insect hosts. Disruption of this partnership may affect the success of both partners. For instance, when Steinernema associates with non-cognate symbionts, their virulence and reproductive fitness are affected. In this study, we examined the effect of symbiotic (cognate and non-cognate) and non-symbiotic bacteria on maturation time, gonad postembryonic development, and sex ratio of first-generation Steinernema adults. Two Steinernema spp. were considered: S. feltiae SN and S. carpocapsae All. In vitro assays were carried out by pairing each nematode sp. with symbiotic (cognate and non-cognate) Xenorhabdus, and with non-symbiotic bacteria (Serratia proteamaculans). Additionally, for comparative purposes, we also considered adult nematodes reared in vivo in Galleria mellonella larvae to assess nematode development under natural conditions. Results from this study showed non-symbiotic Serratia proteamaculans did not support adult development of S. feltiae but it allowed development of S. carpocapsae adults. Sex ratio decreased from 2:1 to 1:1 (female: male) when S. carpocapsae adults were reared with the non-symbiotic S. proteamaculans. Cognate or non-cognate Xenorhabdus spp. and/or strains did not change the sex ratio of any of either Steinernema spp. tested. Morphometric analysis also revealed that bacterial conditions influenced adult size and gonad postembryonic development in both Steinernema species. Body size (length and width), and gonad length in both S. feltiae males and females, were significantly reduced when reared

Elucidation of the transcription network governing mammalian sex determination by exploiting strain-specific susceptibility to sex reversal

PubMed Central

Munger, Steven C.; Aylor, David L.; Syed, Haider Ali; Magwene, Paul M.; Threadgill, David W.; Capel, Blanche

2009-01-01

Despite the identification of some key genes that regulate sex determination, most cases of disorders of sexual development remain unexplained. Evidence suggests that the sexual fate decision in the developing gonad depends on a complex network of interacting factors that converge on a critical threshold. To elucidate the transcriptional network underlying sex determination, we took the first expression quantitative trait loci (eQTL) approach in a developing organ. We identified reproducible differences in the transcriptome of the embryonic day 11.5 (E11.5) XY gonad between C57BL/6J (B6) and 129S1/SvImJ (129S1), indicating that the reported sensitivity of B6 to sex reversal is consistent with a higher expression of a female-like transcriptome in B6. Gene expression is highly variable in F2 XY gonads from B6 and 129S1 intercrosses, yet strong correlations emerged. We estimated the F2 coexpression network and predicted roles for genes of unknown function based on their connectivity and position within the network. A genetic analysis of the F2 population detected autosomal regions that control the expression of many sex-related genes, including Sry (sex-determining region of the Y chromosome) and Sox9 (Sry-box containing gene 9), the key regulators of male sex determination. Our results reveal the complex transcription architecture underlying sex determination, and provide a mechanism by which individuals may be sensitized for sex reversal. PMID:19884258

NR5A1 is a novel disease gene for 46,XX testicular and ovotesticular disorders of sex development.

PubMed

Baetens, Dorien; Stoop, Hans; Peelman, Frank; Todeschini, Anne-Laure; Rosseel, Toon; Coppieters, Frauke; Veitia, Reiner A; Looijenga, Leendert H J; De Baere, Elfride; Cools, Martine

2017-04-01

We aimed to identify the genetic cause in a cohort of 11 unrelated cases and two sisters with 46,XX SRY-negative (ovo)testicular disorders of sex development (DSD). Whole-exome sequencing (n = 9), targeted resequencing (n = 4), and haplotyping were performed. Immunohistochemistry of sex-specific markers was performed on patients' gonads. The consequences of mutation were investigated using luciferase assays, localization studies, and RNA-seq. We identified a novel heterozygous NR5A1 mutation, c.274C>T p.(Arg92Trp), in three unrelated patients. The Arg92 residue is highly conserved and located in the Ftz-F1 region, probably involved in DNA-binding specificity and stability. There were no consistent changes in transcriptional activation or subcellular localization. Transcriptomics in patient-derived lymphocytes showed upregulation of MAMLD1, a direct NR5A1 target previously associated with 46,XY DSD. In gonads of affected individuals, ovarian FOXL2 and testicular SRY-independent SOX9 expression observed. We propose NR5A1, previously associated with 46,XY DSD and 46,XX primary ovarian insufficiency, as a novel gene for 46,XX (ovo)testicular DSD. We hypothesize that p.(Arg92Trp) results in decreased inhibition of the male developmental pathway through downregulation of female antitestis genes, thereby tipping the balance toward testicular differentiation in 46,XX individuals. In conclusion, our study supports a role for NR5A1 in testis differentiation in the XX gonad.Genet Med 19 4, 367-376.

Fine Time Course Expression Analysis Identifies Cascades of Activation and Repression and Maps a Putative Regulator of Mammalian Sex Determination

PubMed Central

Looger, Loren L.; Ohler, Uwe; Capel, Blanche

2013-01-01

In vertebrates, primary sex determination refers to the decision within a bipotential organ precursor to differentiate as a testis or ovary. Bifurcation of organ fate begins between embryonic day (E) 11.0–E12.0 in mice and likely involves a dynamic transcription network that is poorly understood. To elucidate the first steps of sexual fate specification, we profiled the XX and XY gonad transcriptomes at fine granularity during this period and resolved cascades of gene activation and repression. C57BL/6J (B6) XY gonads showed a consistent ∼5-hour delay in the activation of most male pathway genes and repression of female pathway genes relative to 129S1/SvImJ, which likely explains the sensitivity of the B6 strain to male-to-female sex reversal. Using this fine time course data, we predicted novel regulatory genes underlying expression QTLs (eQTLs) mapped in a previous study. To test predictions, we developed an in vitro gonad primary cell assay and optimized a lentivirus-based shRNA delivery method to silence candidate genes and quantify effects on putative targets. We provide strong evidence that Lmo4 (Lim-domain only 4) is a novel regulator of sex determination upstream of SF1 (Nr5a1), Sox9, Fgf9, and Col9a3. This approach can be readily applied to identify regulatory interactions in other systems. PMID:23874228

Testis development requires the repression of Wnt4 by Fgf signaling

PubMed Central

Jameson, Samantha A.; Lin, Yi-Tzu; Capel, Blanche

2013-01-01

The bipotential gonad expresses genes associated with both the male and female pathways. Adoption of the male testicular fate is associated with the repression of many female genes including Wnt4. However, the importance of repression of Wnt4 to the establishment of male development was not previously determined. Deletion of either Fgf9 or Fgfr2 in an XY gonad resulted in up-regulation of Wnt4 and male-to-female sex reversal. We investigated whether the deletion if Wnt4 could rescue sex reversal in Fgf9 and Fgfr2 mutants. XY Fgf9/Wnt4 and Fgfr2/Wnt4 double mutants developed testes with male somatic and germ cells present, suggesting that the primary role of Fgf signaling is the repression of female-promoting genes. Thus, the decision to adopt the male fate is based not only on whether male genes, such as Sox9, are expressed, but also on the active repression of female genes, such as Wnt4. Because loss of Wnt4 results in the up-regulation of Fgf9, we also tested the possibility that derepression of Fgf9 was responsible for the aspects of male development observed in XX Wnt4 mutants. However, we found that the relationship between these two signaling factors is not symmetric: loss of Fgf9 in XX Wnt4−/− gonads does not rescue their partial female-to-male sex-reversal. PMID:22705479

The sensitive period for male-to-female sex reversal begins at the embryonic stage in the Nile tilapia and is associated with the sexual genotype.

PubMed

Gennotte, Vincent; Mélard, Charles; D'Cotta, Helena; Baroiller, Jean-François; Rougeot, Carole

2014-12-01

In this study, we sought to determine the mechanism of early sex reversal in a teleost by applying 4 hr feminization treatments to XY (17α-ethynylestradiol 2000 μg L(-1) ) and YY (6500 μg L(-1) ) Nile tilapia embryos on the first day post-fertilization (dpf). We then searched for changes in the expression profiles of some sex-differentiating genes in the brain (cyp19a1b, foxl2, and amh) and in sex steroids (testosterone, 17β-estradiol, and 11-ketotestosterone) concentrations during embryogenesis and gonad differentiation. No sex reversal was observed in YY individuals, whereas sex-reversal rates in XY progeny ranged from 0-60%. These results, together with the clearance profile of 17α-ethynylestradiol, confirmed the existence of an early sensitive period for sex determination that encompasses embryonic and larval development and is active prior to any sign of gonad differentiation. Estrogen treatment induced elevated expression of cyp19a1b and higher testosterone and 17β-estradiol concentrations at 4 dpf in both XY and YY individuals. foxl2 and amh were repressed at 4 dpf and their expression levels were not different between treated and control groups at 14 dpf, suggesting that foxl2 did not control cyp19a1b in the brains of tilapia embryos. Increased cyp19a1b expression in treated embryos could reflect early brain sexualization, although this difference alone cannot account for the observed sex reversal as the treatment was ineffective in YY individuals. The differential sensitivity of XY and YY genotypes to embryonic induced-feminization suggests that a sex determinant on the sex chromosomes, such as a Y repressor or an X activator, may influence sex reversal during the first steps of tilapia embryogenesis. © 2014 Wiley Periodicals, Inc.

A case report of severe panhypopituitarism in a newborn delivered by a women with Turner syndrome.

PubMed

Olszewska, Marta; Kiełbasa, Grzegorz; Wójcik, Małgorzata; Zygmunt-Górska, Agata; Starzyk, Jerzy B

2015-01-01

Turner syndrome (TS) is a congenital disease caused by absence or structural abnormalities of sex chromosomes resulting in gonadal dysgenesis. Spontaneous pregnancies occur in 2-8% of patients, especially with mosaic kariotypes, however they are associated with increased risk of poor outcome both for mother and fetus. We report a 4-day-old male infant delivered by women with mosaic TS who was admitted to the pediatric intensive care unit and presented with severe panhypopituitarism as the early manifestation of pituitary stalk interruption syndrome (PSIS). To the best of our knowledge this is the first report of severe panhypopituitarism in a newborn borne by women with TS.

Obesity independently influences gonadal function in very long-term adult male survivors of childhood cancer.

PubMed

Blijdorp, Karin; van Dorp, Wendy; Laven, Joop S E; Pieters, Rob; de Jong, Frank H; Pluijm, Saskia M F; van der Lely, Aart Jan; van den Heuvel-Eibrink, Marry M; Neggers, Sebastian J C M M

2014-08-01

Although obesity is associated with gonadal dysfunction in the general population, gonadotoxic treatment might diminish the impact of obesity in childhood cancer survivors (CCS). The aim was to evaluate whether altered body composition is associated with gonadal dysfunction in male CCS, independent of gonadotoxic cancer treatment. Three hundred fifty-one male CCS were included. Median age at diagnosis was 5.9 years (0-17.8) and median age at follow-up 25.6 years (18.0-45.8). Total and non-SHBG-bound testosterone, sex hormone-binding globulin, inhibin B, and follicle-stimulating hormone (FSH) were studied. Potential determinants were BMI, waist circumference, waist-hip ratio, and body composition measures (dual energy X-ray absorptiometry). Non-SHBG-bound testosterone was significantly decreased in survivors with BMI ≥ 30 kg/m(2) (adjusted mean 9.1 nmol/L vs. 10.2 nmol/L, P = 0.015), high fat percentage (10.0 vs. 11.2, P = 0.004), and high waist circumference (>102 cm) (9.0 vs. 11.0, P = 0.020). Survivors with high fat percentage (≥25%) had significantly lower inhibin B/FSH ratios (inhibin B/FSH ratio: β -34%, P = 0.041). Obesity is associated with gonadal dysfunction in male CCS, independent of the irreversible effect of previous cancer treatment. Randomized controlled trials are required to evaluate whether weight normalization could improve gonadal function, especially in obese survivors with potential other mechanisms than lifestyle causing their obesity. Copyright © 2014 The Obesity Society.

Emergence, development, and maturity of the gonad of two species of chitons "sea cockroach" (Mollusca: Polyplacophora) through the early life stages.

PubMed

Avila-Poveda, Omar Hernando; Abadia-Chanona, Quetzalli Yasú

2013-01-01

This study describes and recognises, using histological and microscopical examinations on a morphometrical basis, several gonad traits through the early life stages of Chiton articulatus and C. albolineatus. Gonadal ontogenesis, gonad development stages, sexual differentiation, onset of the first sexual maturity, and growth sequences or "early life stages" were determined. In addition, allometry between lengths and body weight pooled for both sexes per each chiton were calculated using equation Y = aX(b) . A total of 125 chitons (4≤TL≤40 mm, in total length "TL") were used. All allometric relations showed a strong positive correlation (r), close to 1, with b-values above three, indicating an isometric growth. Gonadal ontogenesis and gonad development stages were categorised into three periods ("Pw" without gonad, "Pe" gonad emergence, and "Pf" gonadal sac formed) and four stages ("S0" gametocytogenesis, "S1" gametogenesis, "S2" mature, and "S3" spawning), respectively. Compound digital images were attained for each process. Periods and stages are overlapped among them and between species, with the following overall confidence intervals in TL: Pw 6.13-14.32 mm, Pe 10.32-16.93 mm, Pf 12.99-25.01 mm, S0 16.08-24.34 mm (females) and 19.51-26.60 mm (males), S1 27.15-35.63 mm (females) and 23.45-32.27 mm (males), S2 24.48-40.24 mm (females) and 25.45-32.87 mm (males). Sexual differentiation (in S0) of both chitons occurs first as a female then as a male; although, males reach the onset of the first sexual maturity earlier than females, thus for C. articulatus males at 17 mm and females at 32 mm, and for C. albolineatus males at 23.5 mm and females at 28 mm, all in TL. Four early life stages (i.e., subjuvenile, juvenile, subadult, and adult) are described and proposed to distinguish growth sequences. Our results may be useful to diverse disciplines, from developmental biology to fisheries management.

Sex hormones alter sex ratios in the Indian skipper frog, Euphlyctis cyanophlyctis: Determining sensitive stages for gonadal sex reversal.

PubMed

Phuge, S K; Gramapurohit, N P

2015-09-01

In amphibians, although genetic factors are involved in sex determination, gonadal sex differentiation can be modified by exogenous steroid hormones suggesting a possible role of sex steroids in regulating the process. We studied the effect of testosterone propionate (TP) and estradiol-17β (E2) on gonadal differentiation and sex ratio at metamorphosis in the Indian skipper frog, Euphlyctis cyanophlyctis with undifferentiated type of gonadal differentiation. A series of experiments were carried out to determine the optimum dose and sensitive stages for gonadal sex reversal. Our results clearly indicate the importance of sex hormones in controlling gonadal differentiation of E. cyanophlyctis. Treatment of tadpoles with 10, 20, 40, and 80μg/L TP throughout larval period resulted in the development of 100% males at metamorphosis at all concentrations. Similarly, treatment of tadpoles with 40μg/L TP during ovarian and testicular differentiation resulted in the development of 90% males, 10% intersexes and 100% males respectively. Treatment of tadpoles with 10, 20, 40, and 80μg/L E2 throughout larval period likewise produced 100% females at all concentrations. Furthermore, exposure to 40μg/L E2 during ovarian and testicular differentiation produced 95% females, 5% intersexes and 91% females, 9% intersexes respectively. Both TP and E2 were also effective in advancing the stages of gonadal development. Present study shows the effectiveness of both T and E2 in inducing complete sex reversal in E. cyanophlyctis. Generally, exposure to E2 increased the larval period resulting in significantly larger females than control group while the larval period of control and TP treated groups was comparable. Copyright © 2014 Elsevier Inc. All rights reserved.

Discovery and functional characterization of microRNAs and their potential roles for gonadal development in spotted knifejaw, Oplegnathus punctatus.

PubMed

Du, Xinxin; Liu, Xiaobing; Zhang, Kai; Liu, Yuxiang; Cheng, Jie; Zhang, Quanqi

2018-05-16

The spotted knifejaw (Oplegnathus punctatus) is a newly emerging economical fishery species in China. Studies focused on the regulation of gonadal development and gametogenesis of spotted knifejaw are still insufficient. As a key post-transcriptional regulator, miRNAs have been shown to play important roles in development and reproduction systems. In this study, small RNA deep sequencing in ovary and testis of spotted knifejaw were performed to screen miRNA expression patterns. After sequencing and bioinformatics analysis, a total of 247 conserved known miRNAs and 41 novel miRNAs were identified in spotted knifejaw gonads for the first time. In addition, 36 miRNAs were differentially expressed between testis and ovary. The putative target genes of differentially expressed (DE) miRNAs were significantly enriched in several pathways related to sexual differentiation and gonadal development, such as steroid hormone biosynthesis. Sequencing data was validated through qRT-PCR analysis of selected DE miRNAs. Dual-luciferase reporter analyses of filtered miRNA-target gene pairs confirmed that opu-miR-27b-3p targeted in piwi2 and mov10l1 3' UTRs and down-regulated their expressions in spotted knifejaw. The notion that mov10l1 and piwi2 enhance germ cells proliferation and regulate gonadal development and gametogenesis suggests that opu-miR-27b-3p may attenuated this process in the gonads of spotted knifejaw. These findings provided insights into regulatory roles of gonadal miRNAs and supplied fundamental resources for further studies on miRNA-mediated post-transcriptional regulation in reproductive system of spotted knifejaw. Copyright © 2018. Published by Elsevier Inc.

Prevalence and Physical Distribution of SRY in the Gonads of a Woman with Turner Syndrome: Phenotypic Presentation, Tubal Formation, and Malignancy Risk.

PubMed

Baer, Tamar G; Freeman, Christopher E; Cujar, Claudia; Mansukhani, Mahesh; Singh, Bahadur; Chen, Xiaowei; Abellar, Rosanna; Oberfield, Sharon E; Levy, Brynn

2017-01-01

Although monosomy X is the most common karyotype in patients with Turner syndrome, the presence of Y chromosome material has been observed in about 10% of patients. Y chromosome material in patients with Turner syndrome poses an increased risk of gonadoblastoma and malignant transformation. We report a woman with a diagnosis of Turner syndrome at 12 years of age, without signs of virilization, and karyotype reported as 46,X,del(X)(q13). At 26 years, cytogenetic studies indicated the patient to be mosaic for monosomy X and a cell line that contained a du-plicated Yq chromosome. Bilateral gonadectomy was performed and revealed streak gonads, without evidence of gonadoblastoma. Histological analysis showed ovarian stromal cells with few primordial tubal structures. FISH performed on streak gonadal tissue showed a heterogeneous distribution of SRY, with exclusive localization to the primordial tubal structures. DNA extraction from the gonadal tissue showed a 6.5% prevalence of SRY by microarray analysis, contrasting the 86% prevalence in the peripheral blood sample. This indicates that the overall gonadal sex appears to be determined by the majority gonosome complement in gonadal tissue in cases of sex chromosome mosaicism. This case also raises questions regarding malignancy risk associated with Y prevalence and tubal structures in gonadal tissue. © 2017 S. Karger AG, Basel.

Identification of gonadal soma-derived factor involvement in Monopterus albus (protogynous rice field eel) sex change.

PubMed

Zhu, Yefei; Wang, Chunlei; Chen, Xiaowu; Guan, Guijun

2016-07-01

We studied molecular events and potential mechanisms underlying the process of female-to-male sex transformation in the rice field eel (Monopterus albus), a protogynous hermaphrodite fish in which the gonad is initially a female ovary and transforms into male testes. We cloned and identified a novel gonadal soma derived factor (GSDF), which encodes a member of the transforming growth factor-beta superfamily. gsdf expression was measured in gonads of female, intersex and male with reverse transcription-PCR and gsdf's role in sex transformation was studied with qPCR, histological analysis and dual-color in situ hybridization assays and compared to other sex-related genes. gsdf was correlated to Sertoli cell differentiation, indicating involvement in testicular differentiation and sex transformation from female to male in this species. A unique expression pattern reveals a potential role of gsdf essential for the sex transformation of rice field eels.

A variant Klinefelter syndrome patient with an XXY/XX/XY karyotype studied by GTG-banding and fluorescence in situ hybridization.

PubMed

Mark, H F; Bai, H; Sotomayor, E; Mark, S; Zolnierz, K; Airall, E; Sigman, M

1999-09-01

Klinefelter syndrome is the first human sex chromosomal abnormality to be reported. The majority of Klinefelter syndrome patients have the XXY karyotype. Approximately 15% of Klinefelter patients, however, are mosaics with variable phenotypes. Among the variant Klinefelter genotypes are such karyotypes as XY/XXY and XX/XXY. The variation in phenotypes most likely depends on the number of abnormal cells and their location in body tissues. In this paper we report the case of a 42-year-old patient with Klinefelter syndrome and a rare variant mosaic XXY/XX karyotype initially identified by GTG-banding. This was confirmed by fluorescence in situ hybridization (FISH) using a dual-color X/Y probe. The patient presented with erectile dysfunction and few other physical findings. Thus, this case illustrates a rare variant of Klinefelter syndrome with a relatively mild phenotype. It also illustrates the utility of FISH as an adjunct to conventional cytogenetics in assessing the chromosome copy number in each cell line of a mosaic. In our case, FISH also detected the presence of a small population of cells with the XY karyotype not previously detected in the initial 30-cell GTG-banding analysis. Thus, through a combination of GTG-banding and FISH, the patient was determined to be an XXY/XX/XY mosaic. Given that most individuals with Klinefelter syndrome are infertile, and that these individuals may wish to reproduce with the aid of modern reproductive technology, such as testicular fine needle aspiration and intracytoplasmic sperm injection, it is important that accurate estimation of the frequency of abnormal cells be obtained for accurate risk estimation and genetic counseling, as recent studies in patients with mosaic Klinefelter syndrome revealed that germ cells with sex chromosomal abnormalities were nevertheless capable of completing meiosis. Copyright 1999 Academic Press.

Realizing various approximate quantum cloning with XY-type exchange interactions of flux qubits

NASA Astrophysics Data System (ADS)

Li, Na; Ye, Liu

2014-03-01

In this paper, we realize all kinds of 1 → 2 approximate quantum cloning, including optimal 1 → 2 symmetric (or asymmetric) universal quantum cloning (UQC) and phase-covariant cloning (PCC), symmetric economical phase-covariant cloning (EPCC) and real state quantum cloning, with the XY-type exchange interactions of the flux qubits which are coupled by dc superconducting quantum interference devices (SQUIDs). It is shown that our schemes can be realized with the current experimental technology.

High frequency fo X-Y chromosome dissociation in primary spermatocytes of F1 hybrids between Japanese wild mice (Mus musculus molossinus) and inbred laboratory mice.

PubMed

Imai, H T; Matsuda, Y; Shiroishi, T; Moriwaki, K

1981-01-01

In the hybrids between Japanese wild mice (Mus musculus molossinus) and inbred laboratory mice (BALB/c and B10.BR, which were probably derived from M. m. domesticus), the X and Y chromosomes dissociated precociously at the first meiotic metaphase in some 70% of spermatocytes; that percentage was only 8.9% in inbred laboratory mice and 21.1% in wild mice. X-Y dissociation began at least at early diakinesis and continued during metaphase I (MI). Some autosomes of the hybrid (10.1%) and BALB/c (10.6%) mice also dissociated precociously, but there was no distinctive correlation between X-Y and autosomal dissociation. In B10 or B6 congenic lines with a Y chromosome from wild M. m. molossinus, there was an apparent tendency for the percentage of precocious X-Y dissociation to decrease with an increasing number of back cross generations. Based on these observations we concluded that: 1. the X-Y dissociation found is genetically controlled, perhaps by multiple genes; 2. these genes are located on autosomes and are active only when they are heterozygous; 3. the frequent dissociation of the sex chromosomes neither affects male fertility nor induces non-disjunction of the X and Y chromosomes, though it significantly reduces testes weight.

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.

Multiscale mathematical modeling of the hypothalamo-pituitary-gonadal axis.

PubMed

Clément, Frédérique

2016-07-01

Although the fields of systems and integrative biology are in full expansion, few teams are involved worldwide into the study of reproductive function from the mathematical modeling viewpoint. This may be due to the fact that the reproductive function is not compulsory for individual organism survival, even if it is for species survival. Alternatively, the complexity of reproductive physiology may be discouraging. Indeed, the hypothalamo-pituitary-gonadal (HPG) axis involves not only several organs and tissues but also intricate time (from the neuronal millisecond timescale to circannual rhythmicity) and space (from molecules to organs) scales. Yet, mathematical modeling, and especially multiscale modeling, can renew our approaches of the molecular, cellular, and physiological processes underlying the control of reproductive functions. In turn, the remarkable dynamic features exhibited by the HPG axis raise intriguing and challenging questions to modelers and applied mathematicians. In this article, we draw a panoramic review of some mathematical models designed in the framework of the female HPG, with a special focus on the gonadal and central control of follicular development. On the gonadal side, the modeling of follicular development calls to the generic formalism of structured cell populations, that allows one to make mechanistic links between the control of cell fate (proliferation, differentiation, or apoptosis) and that of the follicle fate (ovulation or degeneration) or to investigate how the functional interactions between the oocyte and its surrounding cells shape the follicle morphogenesis. On the central, mainly hypothalamic side, models based on dynamical systems with multiple timescales allow one to represent within a single framework both the pulsatile and surge patterns of the neurohormone GnRH. Beyond their interest in basic research investigations, mathematical models can also be at the source of useful tools to study the encoding and decoding of

Substrate Specificities of MexAB-OprM, MexCD-OprJ, and MexXY-OprM Efflux Pumps in Pseudomonas aeruginosa

PubMed Central

Masuda, Nobuhisa; Sakagawa, Eiko; Ohya, Satoshi; Gotoh, Naomasa; Tsujimoto, Hideto; Nishino, Takeshi

2000-01-01

To find the exact substrate specificities of three species of tripartite efflux systems of Pseudomonas aeruginosa, MexAB-OprM, MexCD-OprJ, and MexXY-OprM, we constructed a series of isogenic mutants, each of which constitutively overproduced one of the three efflux systems and lacked the other two, and their isogenic mutants, which lacked all these systems. Comparison of the susceptibilities of the constructed mutants to 52 antimicrobial agents belonging to various groups suggested the following substrate specificities. All of the efflux systems extrude a wide variety of antimicrobial agent groups, i.e., quinolones, macrolides, tetracyclines, lincomycin, chloramphenicol, most penicillins (all but carbenicillin and sulbenicillin), most cephems (all but cefsulodin and ceftazidime), meropenem, and S-4661, but none of them extrude polymyxin B or imipenem. Extrusion of aminoglycosides is specific to MexXY-OprM, and extrusion of a group of the β-lactams, i.e., carbenicillin, sulbenicillin, ceftazidime, moxalactam, and aztreonam, is specific to MexAB-OprM. Moreover, MexAB-OprM and MexCD-OprJ extrude novobiocin, cefsulodin, and flomoxef, while MexXY-OprM does not. These substrate specificities are distinct from those reported previously. PMID:11083635

Gonadal steroids regulate the expression of aggrecanases in human endometrial stromal cells in vitro.

PubMed

Wen, Jiadi; Zhu, Hua; Leung, Peter C K

2013-10-01

The human endometrium undergoes cyclic change during each menstrual cycle in response to gonadal steroids. Proteolysis of endometrial extracellular matrix (ECM) is necessary to prepare this dynamic tissue for pregnancy. Proteolytic enzymes such as matrix metalloproteinase (MMP) and closely related a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) have been assigned key roles in the highly regulated cyclic remodelling of the endometrial ECM. We have previously shown that ADAMTS-1 undergoes spatiotemporal changes in human endometrial stromal cells under the regulation of gonadal steroids. This suggests that other ADAMTS subtypes, known as aggrecanases, may contribute to the ECM remodelling events that occur in female physiological cycles and in preparation for pregnancy. To determine whether progesterone (P4), 17β-estradiol (E2), or dihydrotestosterone (DHT), alone or in combination, are capable of regulating ADAMTS-4, -5, -8 or -9 expression in human endometrial stromal cells in vitro. Real-time quantitative PCR and Western blot analysis were used to measure ADAMTSs mRNA and protein levels in primary cultures of human endometrial stromal cells (n = 12). P4, DHT but not E2 have regulatory effects on ADAMTS-8, -9 and -5 expression. Combined treatment with gonadal steroids did not show any synergistic or antagonistic effects. However, the synthetic steroid antagonists RU486 and hydroxyflutamide specifically inhibited the P4- or DHT-mediated regulatory effects on ADAMTS expression. These studies provide evidence that the regulation of aggrecanases by gonadal steroids in human endometrial stromal cells may play an important role during decidualization. © 2013 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

The C. elegans VAPB homolog VPR-1 is a permissive signal for gonad development

PubMed Central

Cole, Tim; Hoang, Hieu D.; Han, Sung Min

2017-01-01

VAMP/synaptobrevin-associated proteins (VAPs) contain an N-terminal major sperm protein domain (MSPd) that is associated with amyotrophic lateral sclerosis. VAPs have an intracellular housekeeping function, as well as an extracellular signaling function mediated by the secreted MSPd. Here we show that the C. elegans VAP homolog VPR-1 is essential for gonad development. vpr-1 null mutants are maternal effect sterile due to arrested gonadogenesis following embryo hatching. Somatic gonadal precursor cells and germ cells fail to proliferate fully and complete their respective differentiation programs. Maternal or zygotic vpr-1 expression is sufficient to induce gonadogenesis and fertility. Genetic mosaic and cell type-specific expression studies indicate that vpr-1 activity is important in the nervous system, germ line and intestine. VPR-1 acts in parallel to Notch signaling, a key regulator of germline stem cell proliferation and differentiation. Neuronal vpr-1 expression is sufficient for gonadogenesis induction during a limited time period shortly after hatching. These results support the model that the secreted VPR-1 MSPd acts at least in part on gonadal sheath cell precursors in L1 to early L2 stage hermaphrodites to permit gonadogenesis. PMID:28634273

Use of gene expression data to determine effects on gonad phenotype in Japanese medaka after exposure to trenbolone or estradiol.

PubMed

Flynn, Kevin; Swintek, Joe; Johnson, Rodney

2013-06-01

Various aquatic bioassays using one of several fish species have been developed or are in the process of being developed by organizations like the US Environmental Protection Agency and the Office of Economic Cooperation and Development for testing potential endocrine-disrupting chemicals (EDCs). Often, these involve assessment of the gonad phenotype of individuals as a key endpoint that is inputted into a risk or hazard assessment. Typically, gonad phenotype is determined histologically, which involves specialized and time-consuming techniques. The methods detailed here utilize an entirely different methodology, reverse-transcription quantitative polymerase chain reaction, to determine the relative expression levels of 4 genes after exposure to either 17β-estradiol or 17β-trenbolone and, by extension, the effects of EDCs on the phenotypic status of the gonad. The 4 genes quantified, Sox9b, protamine, Fig1α, and ZPC1, are all involved in gonad development and maintenance in Japanese medaka (Oryzias latipes); these data were then inputted into a permutational multivariate analysis of variance to determine whether significant differences exist between treatment groups. This information in conjunction with the sexual genotype, which can be determined in medaka, can be used to determine adverse effects of exposure to EDCs in a similar fashion to the histologically determined gonad phenotype. Copyright © 2013 SETAC.

RNAi-Mediated Gene Silencing in a Gonad Organ Culture to Study Sex Determination Mechanisms in Sea Turtle.

PubMed

Sifuentes-Romero, Itzel; Merchant-Larios, Horacio; Milton, Sarah L; Moreno-Mendoza, Norma; Díaz-Hernández, Verónica; García-Gasca, Alejandra

2013-06-07

The autosomal Sry-related gene, Sox9, encodes a transcription factor, which performs an important role in testis differentiation in mammals. In several reptiles, Sox9 is differentially expressed in gonads, showing a significant upregulation during the thermo-sensitive period (TSP) at the male-promoting temperature, consistent with the idea that SOX9 plays a central role in the male pathway. However, in spite of numerous studies, it remains unclear how SOX9 functions during this event. In the present work, we developed an RNAi-based method for silencing Sox9 in an in vitro gonad culture system for the sea turtle, Lepidochelys olivacea. Gonads were dissected as soon as the embryos entered the TSP and were maintained in organ culture. Transfection of siRNA resulted in the decrease of both Sox9 mRNA and protein. Furthermore, we found coordinated expression patterns for Sox9 and the anti-Müllerian hormone gene, Amh, suggesting that SOX9 could directly or indirectly regulate Amh expression, as it occurs in mammals. These results demonstrate an in vitro method to knockdown endogenous genes in gonads from a sea turtle, which represents a novel approach to investigate the roles of important genes involved in sex determination or differentiation pathways in species with temperature-dependent sex determination.

The effect of latitude on photoperiodic control of gonadal maturation, regression and molt in birds.

PubMed

Dawson, Alistair

2013-09-01

Photoperiod is the major cue used by birds to time breeding seasons and molt. However, the annual cycle in photoperiod changes with latitude. Within species, for temperate and high latitude species, gonadal maturation and breeding start earlier at lower latitudes but regression and molt both occur at similar times at different latitudes. Earlier gonadal maturation can be explained simply by the fact that considerable maturation occurs before the equinox when photoperiod is longer at lower latitudes - genetic differences between populations are not necessary to explain earlier breeding at lower latitudes. Gonadal regression is caused either by absolute photorefractoriness or, in some species with long breeding seasons, relative photorefractoriness. In either case, the timing of regression and molt cannot be explained by absolute prevailing photoperiod or rate of change in photoperiod - birds appear to be using more subtle cues from the pattern of change in photoperiod. However, there may be no difference between absolute and relative photorefractory species in how they utilise the annual cycle in photoperiod to time regression. Copyright © 2013 Elsevier Inc. All rights reserved.

Production, optimisation and characterisation of angiotensin converting enzyme inhibitory peptides from sea cucumber (Stichopus japonicus) gonad.

PubMed

Zhong, Chan; Sun, Le-Chang; Yan, Long-Jie; Lin, Yi-Chen; Liu, Guang-Ming; Cao, Min-Jie

2018-01-24

In this study, production of bioactive peptides with angiotensin converting enzyme (ACE) inhibitory activity from sea cucumber (Stichopus japonicus) gonad using commercial protamex was optimised by response surface methodology (RSM). As a result, the optimal condition to achieve the highest ACE inhibitory activity in sea cucumber gonad hydrolysate (SCGH) was hydrolysis for 1.95 h and E/S of 0.75%. For further characterisation, three individual peptides (EIYR, LF and NAPHMR) were purified and identified. The peptide NAPHMR showed the highest ACE inhibitory activity with IC 50 of 260.22 ± 3.71 μM. NAPHMR was stable against simulated gastrointestinal digestion and revealed no significant cytotoxicity toward Caco-2 cells. Molecular docking study suggested that Arg, His and Asn residues in NAPHMR interact with the S2 pocket or Zn 2+ binding motifs of ACE via hydrogen or π-bonds, potentially contributing to ACE inhibitory effect. Sea cucumber gonad is thus a potential resource to produce ACE inhibitory peptides for preparation of functional foods.

Gonadal Transcriptome Analysis of Male and Female Olive Flounder (Paralichthys olivaceus)

PubMed Central

Fan, Zhaofei; You, Feng; Wang, Lijuan; Weng, Shenda; Wu, Zhihao; Hu, Jinwei; Zou, Yuxia; Tan, Xungang; Zhang, Peijun

2014-01-01

Olive flounder (Paralichthys olivaceus) is an important commercially cultured marine flatfish in China, Korea, and Japan, of which female grows faster than male. In order to explore the molecular mechanism of flounder sex determination and development, we used RNA-seq technology to investigate transcriptomes of flounder gonads. This produced 22,253,217 and 19,777,841 qualified reads from ovary and testes, which were jointly assembled into 97,233 contigs. Among them, 23,223 contigs were mapped to known genes, of which 2,193 were predicted to be differentially expressed in ovary and 887 in testes. According to annotation information, several sex-related biological pathways including ovarian steroidogenesis and estrogen signaling pathways were firstly found in flounder. The dimorphic expression of overall sex-related genes provides further insights into sex determination and gonadal development. Our study also provides an archive for further studies of molecular mechanism of fish sex determination. PMID:25121093

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

Virtanen, H.E.; Rajpert-De Meyts, E.; Main, K.M.

Patients with 45,X0/46XY karyotype often present with intersex phenotype and testicular dysgenesis. These patients may also have undescended testes (cryptorchidism), hypospadias and their spermatogenesis is severely disrupted. They have a high risk for testicular cancer. These patients have the most severe form of testicular dysgenesis syndrome (TDS). We have hypothesized that testicular cancer, cryptorchidism, hypospadias and poor spermatogenesis are all signs of a developmental disturbance that was named as testicular dysgenesis syndrome. The hypothesis is based on clinical and epidemiological findings and on biological and experimental evidence. Signs of TDS share several risk factors, such as small birth weight (particularlymore » being small for gestational age), and they are risk factors for each other. All of them have background in fetal development. They show strong epidemiological links so that countries with high incidence of testicular cancer, such as Denmark, tend to also have high prevalence rates of cryptorchidism and hypospadias and poor semen quality. Vice versa, in countries with good male reproductive health, e.g., in Finland, all these aspects are better than in Denmark. Although genetic abnormalities can cause these disorders, in the majority of cases, the reasons remain unclear. Adverse trends in the incidence of male reproductive disorders suggest that environmental and life style factors contribute to the problem. Endocrine disrupters are considered as prime candidates for environmental influence. Fetal exposure to high doses of dibutyl phthalate was shown to cause a TDS-like phenotype in the rats. Studies are underway to assess whether there is any exposure-outcome relation with selected chemicals (persistent organic pollutants, pesticides, phthalates) and cryptorchidism00.« less

Brain nonapeptide and gonadal steroid responses to deprivation of heterosexual contact in the black molly

PubMed Central

Kulczykowska, Ewa; Kalamarz-Kubiak, Hanna; Nietrzeba, Marta; Gozdowska, Magdalena

2015-01-01

ABSTRACT Fish may respond to different social situations with changes in both physiology and behaviour. A unique feature of fish is that social interactions between males and females strongly affect the sexual characteristics of individuals. Here we provide the first insight into the endocrine background of two phenomena that occur in mono-sex groups of the black molly (Poecilia sphenops): masculinization in females and same-sex sexual behaviour, manifested by gonopodial displays towards same-sex tank mates and copulation attempts in males. In socially controlled situations, brain neurohormones impact phenotypic sex determination and sexual behaviour. Among these hormones are the nonapeptides arginine vasotocin (AVT) and isotocin (IT), counterparts of the well-known mammalian arginine vasopressin and oxytocin, respectively. To reveal potential hormone interactions, we measured the concentrations of bioactive AVT and IT in the brain, along with those of the sex steroids 17β-estradiol and 11-ketotestosterone in the gonads, of females, masculinized females, males displaying same-sex sexual behaviour and those who did not. These data were supplemented by morphological and histological analyses of the gonads. Correlations between brain nonapeptides and gonadal steroids strongly suggest a cross talk between hormonal systems. In the black molly, the masculinization process was associated with the production of brain AVT and gonadal steroids, whereas same-sex sexual behaviour involves both brain nonapeptides, but neither of the sex steroids. This study extends current knowledge of endocrine control of phenotypic sex and sexual behaviour in fish and for the first time links brain nonapeptides with the occurrence of male-male sexual behaviour in lower vertebrates. PMID:25527645

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

Morphology, sex steroid level and gene expression analysis in gonadal sex reversal of triploid female (XXX) rainbow trout (Oncorhynchus mykiss).

PubMed

Xu, Gefeng; Huang, Tianqing; Jin, Xian; Cui, Cunhe; Li, Depeng; Sun, Cong; Han, Ying; Mu, Zhenbo

2016-02-01

In non-mammalian vertebrates, estrogens and expressions of cyp19a1 and foxl2 play critical roles in maintaining ovary differentiation and development, while dmrt1 and sox9 are male-specific genes in testicular differentiation and are highly conserved. In order to deeply understand the morphological change, sex steroids level and molecular mechanism of triploid female gonadal reversal in rainbow trout, we studied the ovary morphology, tendency of estradiol-17β (E2) and testosterone (T) levels and the relative expressions of dmrt1, cyp19a1, sox9 and foxl2 in juvenile and adult fish. Our results demonstrated that the development of triploid female gonads in rainbow trout went through arrested development, oocytes dedifferentiation, ovary reconstruction and sex reversal finally. During early gonadal development (154-334 days post-fertilization), the expressions of foxl2 and cyp19a1 increased linearly, while expressions of dmrt1 and sox9 were extremely suppressed, and E2 level was higher, while T level was lower. During the mid-to-late period of triploid female gonadal development (574-964 days post-fertilization), the expressions of dmrt1 and sox9 remained high and were very close to the quantity of diploid male genes, and T levels were even reaching diploid male plasma concentrations, while expressions of cyp19a1 and foxl2 were decreased, leading to decrease in E2 level. We realized that the development model of rainbow trout triploid female gonads was extremely rare, and the regulatory mechanism was very special. Genes involved in gonadal development and endogenous estrogens are pivotal factors in fish natural sex reversal.

Novel mutations of the SRD5A2 and AR genes in Thai patients with 46, XY disorders of sex development.

PubMed

Ittiwut, Chupong; Pratuangdejkul, Jaturong; Supornsilchai, Vichit; Muensri, Sasipa; Hiranras, Yodporn; Sahakitrungruang, Taninee; Watcharasindhu, Suttipong; Suphapeetiporn, Kanya; Shotelersuk, Vorasuk

2017-01-01

Abnormalities of dihydrotestosterone conversion [5α-reductase deficiency: online Mendelian inheritance in man (OMIM) 607306] or actions of androgens [partial androgen insensitivity syndrome (PAIS): OMIM 312300] during the 8th-12th weeks of gestation cause varying degrees of undervirilized external genitalia in 46, XY disorders of sex development (DSD) with increased testosterone production. The objective of the study was to determine clinical and genetic characteristics of Thai patients with 46, XY DSD. A cross-sectional study was conducted in 46, XY DSD with increased testosterone production (n=43) evaluated by a human chorionic gonadotropin (hCG) stimulation test or clinical features consistent with 5α-reductase deficiency or PAIS. PCR sequencing of the entire coding regions of the SRD5A2 and AR genes was performed. Molecular modeling analysis of the androgen receptor-ligand-binding domain (AR-LBD) of a novel mutation was constructed. Mutations were found in seven patients (16.3%): five (11.6%) and two (4.7%) patients had mutations in SRD5A2 and AR, respectively. Two novel mutations, SRD5A2 c.383A>G (p.Y128C) and AR c.2176C>T (p.R726C), were identified. Dimensional structural analysis of the novel mutated AR (p.R726C) revealed that it affected the co-activator binding [binding function-3 (BF-3)], not the testosterone binding site. Short phallus length was associated with 5α-reductase deficiency. Around 16.3% of our patients with 46, XY DSD had 5α-reductase deficiency or PAIS. Two novel mutations of SRD5A2 and AR were identified. The novel mutated AR (p.R726C) might affect the co-activator binding (BF-3), not the testosterone binding site.

Cytoplasmic and nuclear localization of cadherin in honey bee (Apis mellifera L.) gonads.

PubMed

Florecki, Mônica M; Hartfelder, Klaus

2011-01-01

Cadherins are crucial molecules mediating cell-cell interactions between somatic and germline cells in insect and mammalian male and female gonads. We analysed the presence and localization of cadherins in ovaries of honeybee queens and in testes of drones. Transcripts representing two classical cadherins, E-cadherin (shotgun) and N-cadherin, as well as three protocadherins (Starry night, Fat and Fat-like) were detected in gonads of both sexes. Pan-cadherin antibodies, which most probably detect a honeybee N-cadherin, were used in immunolocalization analyses. In the germarium of ovarioles, cadherin-IR (cadherin immunoreactivity) was evidenced as homogeneously distributed in the cytoplasm and as nuclear foci, in both germline and somatic cells. It was also detected in polyfusomes and ring canals. In testiolar tubules, cadherin-IR showed a cytoplasmic and nuclear distributon alike in ovaries. The unexpected nuclear localization and cytoplasmic distribution in ovaries and testes were corroborated by immunogold electron microscopy, which revealed cadherin aggregates associated with electron-dense nuclear structures. With respect to cadherin localization, the honeybee differs from Drosophila, the model for gametogenesis in insects, raising the question as to how differences among solitary and social species may be built into and generated from the general architecture of polytrophic meroistic ovaries. It also indicates the possibility of divergent roles for cadherin in the functional architecture of insect gonads, in general, especially in taxa with high reproductive output.

Characterization of gonadal transcriptomes from the turbot (Scophthalmus maximus).

PubMed

Hu, Yulong; Huang, Meng; Wang, Weiji; Guan, Jiantao; Kong, Jie

2016-01-01

The mechanisms underlying sexual reproduction and sex ratio determination remains unclear in turbot, a flatfish of great commercial value. And there is limited information in the turbot database regarding genes related to the reproductive system. Here, we conducted high-throughput transcriptome profiling of turbot gonad tissues to better understand their reproductive functions and to supply essential gene sequence information for marker-assisted selection programs in the turbot industry. In this study, two gonad libraries representing sex differences in Scophthalmus maximus yielded 453 818 high-quality reads that were assembled into 24 611 contigs and 33 713 singletons by using 454 pyrosequencing, 13 936 contigs and singletons (CS) of which were annotated using BLASTx. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analyses revealed that various biological functions and processes were associated with many of the annotated CS. Expression analyses showed that 510 genes were differentially expressed in males versus females; 80% of these genes were annotated. In addition, 6484 and 6036 single nucleotide polymorphisms (SNPs) were identified in male and female libraries, respectively. This transcriptome resource will serve as the foundation for cDNA or SNP microarray construction, gene expression characterization, and sex-specific linkage mapping in turbot.

Effects of salinity on gonadal development, osmoregulation and metabolism of adult male Chinese mitten crab, Eriocheir sinensis

PubMed Central

Zhao, Lei; Ye, Haihui; Cheng, Yongxu; Zeng, Chaoshu

2017-01-01

As a catadromous species, salinity is a key parameter that affects gonadal development of Chinese mitten crab Eriocheir sinensis during reproductive migration. It is however unclear the effects of salinity on the gonadal development of male E. sinensis as well as their physiological responses to salinity during reproductive migration. This study investigated the effects of four salinities (0 ‰, 6 ‰, 12 ‰ and 18 ‰) on gonadal development, osmoregulation and metabolism of adult male E. sinensis over a 40-day period. The results showed that elevating salinity promote gonadal development, increase hemolymph osmolality and K+ and Mg2+ concentrations (P < 0.05). The 12 ‰ salinity resulted in the highest contents of taurine and arginine in the hemolymph while the highest contents of threonine, phenylalanine, lysine, ß-alanine, tryptophan, ornithine and total free amino acids were found for 0 ‰ treatment (P < 0.05). A decreasing trend was detected for the Na+/K+-ATPase activity and its mRNA expression level in the posterior gills with salinity (P < 0.05). Total saturated fatty acids in the anterior gills decreased with increasing salinity (P < 0.05); the 0 ‰ treatment had the highest total polyunsaturated fatty acids in the posterior gills while total n-6 polyunsaturated fatty acids increased with salinity (P < 0.05). The hemolymph glucose and uric acid showed a decreasing trend as salinity while an increasing trend was found for the hemolymph triglyceride and high-density lipoprotein cholesterol (P < 0.05). The 12 ‰ treatment had the highest levels of hemolymph malonaldehyde and hepatopancreatic γ-glutamyltranspeptidase (P < 0.05). In conclusion, these results suggested that the brackish water promote gonadal development of male E. sinensis, and increase osmolality and ionic concentrations in hemolymph while reduced the activity of Na+ /K+- ATPase and its mRNA expression in the posterior gills as well as metabolism. PMID:28628611

Estimation of gonad volume, fecundity, and reproductive stage of shovelnose sturgeon using sonography and endoscopy with application to the endangered pallid sturgeon

USGS Publications Warehouse

Bryan, J.L.; Wildhaber, M.L.; Papoulias, D.M.; DeLonay, A.J.; Tillitt, D.E.; Annis, M.L.

2007-01-01

Most species of sturgeon are declining in the Mississippi River Basin of North America including pallid (Scaphirhynchus albus F. and R.) and shovelnose sturgeons (S. platorynchus R.). Understanding the reproductive cycle of sturgeon in the Mississippi River Basin is important in evaluating the status and viability of sturgeon populations. We used non-invasive, non-lethal methods for examining internal reproductive organs of shovelnose and pallid sturgeon. We used an ultrasound to measure egg diameter, fecundity, and gonad volume; endoscope was used to visually examine the gonad. We found the ultrasound to accurately measure the gonad volume, but it underestimated egg diameter by 52%. After correcting for the measurement error, the ultrasound accurately measured the gonad volume but it was higher than the true gonad volume for stages I and II. The ultrasound underestimated the fecundity of shovelnose sturgeon by 5%. The ultrasound fecundity was lower than the true fecundity for stage III and during August. Using the endoscope, we viewed seven different egg color categories. Using a model selection procedure, the presence of four egg categories correctly predicted the reproductive stage ± one reproductive stage of shovelnose sturgeon 95% of the time. For pallid sturgeon, the ultrasound overestimated the density of eggs by 49% and the endoscope was able to view eggs in 50% of the pallid sturgeon. Individually, the ultrasound and endoscope can be used to assess certain reproductive characteristics in sturgeon. The use of both methods at the same time can be complementary depending on the parameter measured. These methods can be used to track gonad characteristics, including measuring Gonadosomatic Index in individuals and/or populations through time, which can be very useful when associating gonad characteristics with environmental spawning triggers or with repeated examinations of individual fish throughout the reproductive cycle.

The C. elegans VAPB homolog VPR-1 is a permissive signal for gonad development.

PubMed

Cottee, Pauline A; Cole, Tim; Schultz, Jessica; Hoang, Hieu D; Vibbert, Jack; Han, Sung Min; Miller, Michael A

2017-06-15

VAMP/synaptobrevin-associated proteins (VAPs) contain an N-terminal major sperm protein domain (MSPd) that is associated with amyotrophic lateral sclerosis. VAPs have an intracellular housekeeping function, as well as an extracellular signaling function mediated by the secreted MSPd. Here we show that the C. elegans VAP homolog VPR-1 is essential for gonad development. vpr-1 null mutants are maternal effect sterile due to arrested gonadogenesis following embryo hatching. Somatic gonadal precursor cells and germ cells fail to proliferate fully and complete their respective differentiation programs. Maternal or zygotic vpr-1 expression is sufficient to induce gonadogenesis and fertility. Genetic mosaic and cell type-specific expression studies indicate that vpr-1 activity is important in the nervous system, germ line and intestine. VPR-1 acts in parallel to Notch signaling, a key regulator of germline stem cell proliferation and differentiation. Neuronal vpr-1 expression is sufficient for gonadogenesis induction during a limited time period shortly after hatching. These results support the model that the secreted VPR-1 MSPd acts at least in part on gonadal sheath cell precursors in L1 to early L2 stage hermaphrodites to permit gonadogenesis. © 2017. Published by The Company of Biologists Ltd.

Extra-gonadal steroids modulate non-breeding territorial aggression in weakly electric fish.

PubMed

Jalabert, Cecilia; Quintana, Laura; Pessina, Paula; Silva, Ana

2015-06-01

The neuroendocrine control of intraspecific aggression is a matter of current debate. Although aggression in a reproductive context has been associated with high levels of circulating androgens in a broad range of species, it has also been shown to occur during the non-breeding season when gonads are regressed and plasma steroid hormone levels are low. In mammals and birds the aromatization of androgens into estrogens plays a key role in the regulation of aggression in both the breeding and non-breeding seasons. This is the first study in a teleost fish to explore the role of steroids in the modulation of non-breeding aggression. Gymnotus omarorum is a highly aggressive teleost fish that exhibits aggression all year-round. We analyzed male-male non-breeding agonistic behavior, compared circulating 11-Ketotestosterone (11-KT) levels between dominants and isolated males, assessed the regulatory role of aromatization of androgens into estrogens, and evaluated the gonads as a source of these sex steroids. We found that high levels of aggression occurred in the non-breeding season despite low plasma 11-KT levels, and that there was no difference in 11-KT levels between dominant and isolated males. We demonstrated that acute aromatase inhibition decreased aggression, distorted contest dynamics, and affected expected outcome. We also found that castrated individuals displayed aggressive behavior indistinguishable from non-castrated males. Our results show, for the first time in teleost fish, that territorial aggression of G. omarorum during the non-breeding season depends on a non-gonadal estrogenic pathway. Copyright © 2015 Elsevier Inc. All rights reserved.

Mortality, size of the gonads, and ultrastructure of primordial germ cell in chick embryos treated with gamma-irradiation or injected with donor cells.

PubMed

Maeda, T; Clark, M E; Etches, R J

1998-06-01

The effects of injection and/or gamma-irradiation prior to injection on mortality, size of the gonads, and ultrastructure of primordial germ cell (PGC) were examined after 5 d of incubation. The mortality of embryos injected with donor cells was significantly higher than that of control and irradiated embryos. All irradiated embryos were alive, although their development was delayed compared to those not exposed to irradiation. The size of the gonads of embryos injected with donor cells were similar to those of control embryos, however, the size of the gonads in irradiated embryos was significantly smaller than those of control embryos. The number of PGC in the gonads was significantly decreased by irradiation. There was no notable effect of irradiation or injection on the nuclei and cytoplasmic organelles in PGC.

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

NR5A1 is a novel disease gene for 46,XX testicular and ovotesticular disorders of sex development

PubMed Central

Baetens, Dorien; Stoop, Hans; Peelman, Frank; Todeschini, Anne-Laure; Rosseel, Toon; Coppieters, Frauke; Veitia, Reiner A.; Looijenga, Leendert H.J.; De Baere, Elfride; Cools, Martine

2017-01-01

Purpose: We aimed to identify the genetic cause in a cohort of 11 unrelated cases and two sisters with 46,XX SRY-negative (ovo)testicular disorders of sex development (DSD). Methods: Whole-exome sequencing (n = 9), targeted resequencing (n = 4), and haplotyping were performed. Immunohistochemistry of sex-specific markers was performed on patients' gonads. The consequences of mutation were investigated using luciferase assays, localization studies, and RNA-seq. Results: We identified a novel heterozygous NR5A1 mutation, c.274C>T p.(Arg92Trp), in three unrelated patients. The Arg92 residue is highly conserved and located in the Ftz-F1 region, probably involved in DNA-binding specificity and stability. There were no consistent changes in transcriptional activation or subcellular localization. Transcriptomics in patient-derived lymphocytes showed upregulation of MAMLD1, a direct NR5A1 target previously associated with 46,XY DSD. In gonads of affected individuals, ovarian FOXL2 and testicular SRY-independent SOX9 expression observed. Conclusions: We propose NR5A1, previously associated with 46,XY DSD and 46,XX primary ovarian insufficiency, as a novel gene for 46,XX (ovo)testicular DSD. We hypothesize that p.(Arg92Trp) results in decreased inhibition of the male developmental pathway through downregulation of female antitestis genes, thereby tipping the balance toward testicular differentiation in 46,XX individuals. In conclusion, our study supports a role for NR5A1 in testis differentiation in the XX gonad. Genet Med 19 4, 367–376. PMID:27490115

Emergence, Development, and Maturity of the Gonad of Two Species of Chitons “Sea Cockroach” (Mollusca: Polyplacophora) through the Early Life Stages

PubMed Central

Avila-Poveda, Omar Hernando; Abadia-Chanona, Quetzalli Yasú

2013-01-01

This study describes and recognises, using histological and microscopical examinations on a morphometrical basis, several gonad traits through the early life stages of Chiton articulatus and C. albolineatus. Gonadal ontogenesis, gonad development stages, sexual differentiation, onset of the first sexual maturity, and growth sequences or “early life stages” were determined. In addition, allometry between lengths and body weight pooled for both sexes per each chiton were calculated using equation Y = aXb. A total of 125 chitons (4≤TL≤40 mm, in total length “TL”) were used. All allometric relations showed a strong positive correlation (r), close to 1, with b-values above three, indicating an isometric growth. Gonadal ontogenesis and gonad development stages were categorised into three periods (“Pw” without gonad, “Pe” gonad emergence, and “Pf” gonadal sac formed) and four stages (“S0” gametocytogenesis, “S1” gametogenesis, “S2” mature, and “S3” spawning), respectively. Compound digital images were attained for each process. Periods and stages are overlapped among them and between species, with the following overall confidence intervals in TL: Pw 6.13–14.32 mm, Pe 10.32–16.93 mm, Pf 12.99–25.01 mm, S0 16.08–24.34 mm (females) and 19.51–26.60 mm (males), S1 27.15–35.63 mm (females) and 23.45–32.27 mm (males), S2 24.48–40.24 mm (females) and 25.45–32.87 mm (males). Sexual differentiation (in S0) of both chitons occurs first as a female then as a male; although, males reach the onset of the first sexual maturity earlier than females, thus for C. articulatus males at 17 mm and females at 32 mm, and for C. albolineatus males at 23.5 mm and females at 28 mm, all in TL. Four early life stages (i.e., subjuvenile, juvenile, subadult, and adult) are described and proposed to distinguish growth sequences. Our results may be useful to diverse disciplines, from developmental biology to fisheries management. PMID:23936353

Intersex gonads in frogs: understanding the time course of natural development and role of endocrine disruptors.

PubMed

Storrs-Méndez, Sara I; Semlitsch, Raymond D

2010-01-15

The paucity of data on sexual development of anuran amphibians has played an important role in the recent controversy over atrazine exposure. Although some studies have demonstrated the presence of abnormal gonads in control treatments, others have not, leading to varying interpretations of the effects of atrazine exposure on sexual development. However, the timing of development varies among anuran amphibians such that, at any snapshot in time, different species may exhibit different stages of sexual differentiation. We examined three species representing each of the differentiation rates (Bufo americanus=retarded rate; Hyla versicolor=basic rate; Rana sphenocephala=accelerated rate), to examine the natural time course of sexual development along with the influence of atrazine exposure. For each species, exposure to atrazine (1, 3, 10, 30 parts per billion), 17-beta-estradiol or control water occurred throughout larval life. Gonad histology was performed at 3-week intervals during the larval period or at a juvenile stage to examine the proportion of males, females, underdeveloped testes, testicular oocytes (TO; testes with 0-30% oocytes), and ovotestes (OVTs; testes with>30% oocytes). Our results illustrate that a phase of intersex gonads (TO or OVT) is normal during R. sphenocephala sexual development, a species representing the accelerated differentiation rate. Further, intersex gonads were found in juvenile stages of B. americanus and H. versicolor, representing retarded and basic rates, respectively, suggesting that a phase of intersex may be common regardless of differentiation rate. Moreover, these data highlight the importance of longitudinal studies rather than snapshots in time. (c) 2009 Wiley-Liss, Inc.

Long-term preservation of eri and ailanthus silkworms using frozen gonads.

PubMed

Fukumori, Hisayoshi; Lee, Jung; Fujii, Tsuguru; Kajiura, Zenta; Banno, Yutaka

2017-08-01

Cryopreservation of eri and ailanthus silkworms using frozen gonads was investigated. First, we evaluated the freeze tolerance of ovary and testis in the eri silkworm, which showed high tolerance. Mating between frozen ovary-transplanted females and frozen testis-transplanted males produced 163.0 eggs, yielding 105.7 larvae per moth. In a second experiment, we tested the use of the eri silkworm as a host insect for gonad transplantation from ailanthus silkworm donors. A high success ratio for laid and hatched eggs was demonstrated for ovary transplantation (97.8 and 51.3 eggs per moth, respectively). For testis transplantation, however, the average number of hatched larvae was low (12.0). Mating between host eri females and males in which both frozen ovary and testis of the ailanthus silkworm had been transplanted produced 6.4 fertilized eggs per host moth. Our success in using cross subspecies cryopreservation between these wild silkworms could lead to the alternative use of hosts between species in other insects. Copyright © 2017 Elsevier Inc. All rights reserved.

Local conservation laws in spin-\\frac{1}{2} XY chains with open boundary conditions

NASA Astrophysics Data System (ADS)

Fagotti, Maurizio

2016-06-01

We revisit the conserved quantities of the spin-\\frac{1}{2} XY model with open boundary conditions. In the absence of a transverse field, we find new families of local charges and show that half of the seeming conservation laws are conserved only if the number of sites is odd. In even chains the set of noninteracting charges is abelian, like in the periodic case when the number of sites is odd. In odd chains the set is doubled and becomes non-abelian, like in even periodic chains. The dependence of the charges on the parity of the chain’s size undermines the common belief that the thermodynamic limit of diagonal ensembles exists. We consider also the transverse-field Ising chain, where the situation is more ordinary. The generalization to the XY model in a transverse field is not straightforward and we propose a general framework to carry out similar calculations. We conjecture the form of the bulk part of the local charges and discuss the emergence of quasilocal conserved quantities. We provide evidence that in a region of the parameter space there is a reduction of the number of quasilocal conservation laws invariant under chain inversion. As a by-product, we study a class of block-Toeplitz-plus-Hankel operators and identify the conditions that their symbols satisfy in order to commute with a given block-Toeplitz.

Transfer and detection of freshly isolated or cultured chicken (Gallus gallus) and exotic species' embryonic gonadal germ stem cells in host embryos.

PubMed

Imus, Nastassja; Roe, Mandi; Charter, Suellen; Durrant, Barbara; Jensen, Thomas

2014-06-01

The management of captive avian breeding programs increasingly utilizes various artificial reproductive technologies, including in ovo sexing of embryos to adjust population sex ratios. Currently, however, no attention has been given to the loss of genetic diversity following sex-selective incubation, even with respect to individuals from critically endangered species. This project evaluated the possibility of using xenotransfer of embryonic gonadal germline stem cells (GGCs) for future reintroduction of their germplasm into the gene pool. We examined and compared the host gonad colonization of freshly isolated and 3 day (3d) cultured donor GGCs from chicken and 13 species of exotic embryos. Following 3d-culture of GGCs, there was a significant increase in the percentage of stem cell marker (SSEA-1, -3, -4) positive cells. However, the percentage of positive host gonads with chicken donor-derived cells decreased from 68% (fresh) to 22% (3d), while the percentage of exotic species donor-cells positive host gonads decreased from 61% (fresh) to 49% (3d-cultured). Donor GGCs from both chicken and exotic species were localized within the caudal endoderm, including the region encompassing the gonadal ridge by 16 hours post-injection. Furthermore, donor-derived cells isolated from stage 36 host embryos were antigenic for anti SSEA-1, VASA/DDX4 and EMA-1 antibodies, presumably indicating maintenance of stem cell identity. This study demonstrates that GGCs from multiple species can migrate to the gonadal region and maintain presumed stemness following xenotransfer into a chicken host embryo, suggesting that germline stem cell migration is highly conserved in birds.

A subject with abnormally short stature from Imperial Rome.

PubMed

Ottini, L; Minozzi, S; Pantano, W B; Maucci, C; Gazzaniga, V; Angeletti, L R; Catalano, P; Mariani-Costantini, R

2001-01-01

In spite of the rich iconographic and literary documentation from ancient sources, the skeletal evidence concerning individuals of abnormally short stature in the Greco-Roman world is scarce. The necropolis of Viale della Serenissima/Via Basiliano in Rome, mostly referable to the II century AD, recently yielded the skeleton of an individual characterized by proportionate short stature, gracile features suggesting female gender, and delayed epiphysial closure, associated with full maturation of the permanent dentition. These characteristics could be compatible with the phenotype associated with female gonadal dysgenesis. The skeletal individual described here, although poorly preserved, represents the first evidence of a paleopathologic condition affecting skeletal growth documented for the population of ancient Rome.

The Turner syndrome in patient with 45X/47XXX mosaic karyotype--case report.

PubMed

Maciejewska-Jeske, Marzena; Czyzyk, Adam; Meczekalski, Blazej

2015-07-01

Turner syndrome (TS) is a gonadal dysgenesis related to partial or total lack of one of the X chromosomes. It this report we describe a young patient presenting some somatic features of TS, who underwent spontaneous puberty and was eumenoorheic up to the age of 23. Using fluorescent in situ hybridization (FISH) mosaic karyotype (45X[131]/47XXX[9]) of TS and triple X syndrome was found. She presented uncommon for TS somatic hemihypotrophy and underwent growth hormone and surgical therapy. The patient was diagnosed with premature ovarian failure when she was 23, with absent follicular reserve. Clinical features of this case and a few published cases will be reviewed briefly.

Global Application of the Assessment of Communication Skills of Paediatric Endocrinology Fellows in the Management of Differences in Sex Development Using the ESPE E-Learning.Org Portal.

PubMed

Kranenburg, Laura J C; Reerds, Sam T H; Cools, Martine; Alderson, Julie; Muscarella, Miriam; Magrite, Ellie; Kuiper, Martijn; Abdelgaffar, Shereen; Balsamo, Antonio; Brauner, Raja; Chanoine, Jean Pierre; Deeb, Asma; Fechner, Patricia; German, Alina; Holterhus, Paul Martin; Juul, Anders; Mendonca, Berenice B; Neville, Kristen; Nordenstrom, Anna; Oostdijk, Wilma; Rey, Rodolfo A; Rutter, Meilan M; Shah, Nalini; Luo, Xiaoping; Grijpink, Kalinka; Drop, Stenvert L S

2017-01-01

Information sharing in chronic conditions such as disorders of/differences in sex development (DSD) is essential for a comprehensive understanding by parents and patients. We report on a qualitative analysis of communication skills of fellows undergoing training in paediatric endocrinology. Guidelines are created for the assessment of communication between health professionals and individuals with DSD and their parents. Paediatric endocrinology fellows worldwide were invited to study two interactive online cases (www.espe-elearning.org) and to describe a best practice communication with (i) the parents of a newborn with congenital adrenal hyperplasia and (ii) a young woman with 46,XY gonadal dysgenesis. The replies were analysed regarding completeness, quality, and evidence of empathy. Guidelines for structured assessment of responses were developed by 22 senior paediatric endocrinologists worldwide who assessed 10 selected replies. Consensus of assessors was established and the evaluation guidelines were created. The replies of the fellows showed considerable variation in completeness, quality of wording, and evidence of empathy. Many relevant aspects of competent clinical communication were not mentioned; 15% (case 1) and 17% (case 2) of the replies were considered poor/insufficient. There was also marked variation between 17 senior experts in the application of the guidelines to assess communication skills. The guidelines were then adjusted to a 3-level assessment with empathy as a separate key item to better reflect the qualitative differences in the replies and for simplicity of use by evaluators. E-learning can play an important role in assessing communication skills. A practical tool is provided to assess how information is shared with patients with DSD and their families and should be refined by all stakeholders, notably interdisciplinary health professionals and patient representatives. © 2017 S. Karger AG, Basel.

Retracted: Aetiology and clinical profile of children with 46, XY differences of sex development at an Indian referral centre.

PubMed

Chauhan, V; Dada, R; Jain, V

2017-11-01

Retraction: 'Aetiology and clinical profile of children with 46, XY differences of sex development at an Indian referral centre' by Vasundhera Chauhan, Rima Dada, Vandana Jain The above article, published online on 8 August 2016 in Wiley Online Library (http://wileyonlinelibrary.com), has been retracted by agreement between the authors, the Journal Editors-in-Chief, Wolf-Bernhard Schill and Ralf Henkel, and Blackwell Verlag GmbH. The retraction has been agreed as the result of an unresolved dispute between the first author and a colleague research fellow due to the inclusion of data from patients who were simultaneously enrolled in two studies being conducted separately by the two parties. Reference Chauhan, V., Dada, R. and Jain, V. (2016), Aetiology and clinical profile of children with 46, XY differences of sex development at an Indian referral centre. Andrologia. doi:10.1111/and.12663. © 2016 Blackwell Verlag GmbH.

Genetics of Gonadal Stem Cell Renewal

PubMed Central

Greenspan, Leah Joy; de Cuevas, Margaret

2015-01-01

Stem cells are necessary for the maintenance of many adult tissues. Signals within the stem cell microenvironment, or niche, regulate the self-renewal and differentiation capability of these cells. Misregulation of these signals through mutation or damage can lead to overgrowth or depletion of different stem cell pools. In this review, we focus on the Drosophila testis and ovary, both of which contain well-defined niches, as well as the mouse testis, which has become a more approachable stem cell system with recent technical advances. We discuss the signals that regulate gonadal stem cells in their niches, how these signals mediate self-renewal and differentiation under homeostatic conditions, and how stress, whether from mutations or damage, can cause changes in cell fate and drive stem cell competition. PMID:26355592

The interactive effect of dietary protein and vitamin levels on the depression of gonadal development in growing male rats kept under disturbed daily rhythm.

PubMed

Hanai, Miho; Esashi, Takatoshi

2007-04-01

The purpose of this study was to clarify the effects of nutrients on the gonadal development of male rats kept under constant darkness as a model of disturbed daily rhythm. The present study examined protein and vitamins, and their interactions. This study was based on three-way ANOVA; the three factors were lighting conditions, dietary protein and dietary vitamins, respectively. The levels of dietary protein were low or normal: 9% casein or 20% casein. The levels of dietary vitamins were low, normal or high: 1/3.3 of normal (AIN-93G diet) content, normal content, or three times the normal content, respectively. Other compositions were the same as those of the AIN-93G diet, and six kinds of experimental diet were prepared. Four-week-old rats (Fischer 344 strain) were kept under constant darkness or normal lighting (12-h light/dark cycle) for 4 wk. After 4 wk, the gonadal weights and serum testosterone content were evaluated. In the constant darkness groups (D-groups), the low-protein diet induced reduction of gonadal organ weights and serum testosterone concentrations. This reduction of gonadal organ weights was exacerbated by progressively higher levels of dietary vitamins. In the case of a normal-protein diet, the depression of gonadal development was not accelerated by high-vitamin intake. In the normal lighting groups (N-groups), the low-protein and high-vitamin diet slightly depressed gonadal development. These results suggest that the metabolism of protein and vitamins is different in rats being kept under constant darkness, and that excess dietary vitamins have an adverse effect on gonadal development in rats fed a low-protein diet.

Prey resources before spawning influence gonadal investment of female, but not male, white crappie

USGS Publications Warehouse

Bunnell, D.B.; Thomas, S.E.; Stein, R.A.

2007-01-01

In this study, an outdoor pool experiment was used to evaluate the effect of prey resources during 4 months before spawning on the gonadal investments of male and female white crappie Pomoxis annularis, a popular freshwater sportfish that exhibits erratic recruitment. Fish were assigned one of three feeding treatments: starved, fed once every 5 days (intermediate) or fed daily (high). All measurements of male testes (i.e. wet mass, energy density and spermatocrit) were similar across treatments. Conversely, high-fed females produced larger ovaries than those of intermediate-fed and starved fish, and invested more energy in their ovaries than starved fish. Compared to pre-experiment fish, starved and intermediate-fed females appeared to increase their ovary size by relying on liver energy stores (‘capital’ spawning). Conversely, high-fed females increased liver and gonad mass, implying an ‘income’-spawning strategy (where gonads are built from recently acquired energy). Fecundity did not differ among treatments, but high-fed fish built larger eggs than those starved. Females rarely ‘skipped’ spawning opportunities when prey resources were low, as only 8% of starved females and 8% of intermediate-fed females lacked vitellogenic eggs. These results suggest that limited prey resources during the months before spawning can limit ovary production, which, in turn, can limit reproductive success of white crappies.

Gonadal function and psychosexual adjustment in male long-term survivors of bone marrow transplantation.

PubMed

Molassiotis, A; van den Akker, O B; Milligan, D W; Boughton, B J

1995-08-01

Gonadal function and psychosexual adjustment were evaluated in 29 male patients after autologous and allogeneic BMT (mean post-BMT time 35.6 months). Patients were divided into groups according to their interval from transplant in order to evaluate gonadal function throughout the post-BMT years. Thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were normal throughout the post-BMT years. Follicle-stimulating hormone (FSH) and luteinising hormone (LH) were increased throughout the years after BMT, suggesting moderate compensated hypogonadism. Hyperprolactinaemia was observed only in the 2nd year post-BMT and testosterone levels were normal, suggesting that Leydig cells can withstand alkylating agents or TBI. Psychosexual functioning in BMT survivors was compared with that of a group of mixed-diagnosis cancer patients (n = 30) and a group of healthy young subjects (n = 119). Long-term BMT survivors had similar psychosexual adjustment to that of other cancer patients who had received less intensive chemotherapy. Half the patients were dissatisfied with their current sex life. Major problems included impotence/erectile difficulties (37.9%), low sexual desire (37.9%) and altered body image (20.7%). However, both BMT survivors and cancer patients had significantly higher psychosexual dysfunction compared with healthy subjects. The type of chemotherapy, TBI (either single-dose or fractionated), type of transplant and post-BMT time did not correlate with either gonadal or psychosexual functioning.

Gonadal and extra-gonadal sperm reserves and sperm production of pubertal rabbits fed dietary fumonisin B1.

PubMed

Ewuola, E O; Egbunike, G N

2010-06-01

The influence of fumonisin B(1) (a mycotoxin produced by Fusarium verticillioides) on sperm reserves and production of crossbred pubertal rabbits was studied using an experimental model that lasted 28 weeks. Forty-eight male rabbits, 7 weeks old and with average weight of 757.50+/-0.50 g, were allotted to four dietary fumonisin B(1) concentrations of 0.13, 5.0, 7.5 and 10.0 mg kg(-1) constituting diets 1 (control), 2, 3 and 4, respectively. The paired testes weight of rabbits fed diet 3 was significantly (P<0.05) higher than those fed diet 2 and the control. However, the epididymal weight was significantly (P<0.05) lower in rabbits fed the control diet as compared to others on test diets. The gonadal sperm reserves of the animals were significantly (P<0.05) reduced by the toxin with increased concentrations of the toxin in the diets. The sperm reserves per testis and per gram testis were significantly (P<0.05) higher in the control rabbits than those fed diets 3 and 4. The sperm reserves in caput, corpus and caudal epididymis declined significantly with each increase in the fumonisin concentration in the diets. The number of spermatozoa in total caput, corpus and cauda was significantly (P<0.05) higher in rabbits fed the control diet and the least in rabbits fed diet 4 containing 10.0mg fumonisin B(1)/kg. Extra-gonadal sperm reserves significantly decreased (P<0.05) in rabbits fed diets 3 and 4 compared to the control. The daily sperm production of the animals fed diets 2, 3 and 4 declined significantly to 67, 59 and 36% relative to those animals fed the control diet. This study suggests that exposure of breeding male rabbits to diets contaminated with fumonisin B(1) up to 7.5 mg fumonisin B(1)/kg will depress testicular and epididymal sperm reserves and sperm production and potentially impair reproduction in the animals. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Effects of simvastatin and pravastatin on gonadal function in male hypercholesterolemic patients.

PubMed

Dobs, A S; Miller, S; Neri, G; Weiss, S; Tate, A C; Shapiro, D R; Musliner, T A

2000-01-01

Inhibition of cholesterol biosynthesis by hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors could, in theory, adversely affect male gonadal function because cholesterol is a precursor of steroid hormones. The objective of this randomized double-blind trial was to compare the effects of simvastatin, pravastatin, and placebo on gonadal testosterone production and spermatogenesis. After a 6-week placebo and lipid-lowering diet run-in period, 159 male patients aged 21 to 55 years with type IIa or IIb hypercholesterolemia, low-density lipoprotein (LDL) cholesterol between 145 and 240 mg/dL, and normal basal levels of testosterone were randomly assigned to treatment with simvastatin 20 mg (n = 40), simvastatin 40 mg (n = 41), pravastatin 40 mg (n = 39), or placebo (n = 39) once daily. After 24 weeks of treatment, mean total cholesterol levels were decreased 24% to 27% and mean LDL cholesterol was decreased 30% to 34% in the 3 active-treatment groups (P < .001 for all comparisons to placebo). At 24 weeks, there were no statistically significant differences between the placebo group and any of the active-treatment groups for the change from baseline in testosterone, human chorionic gonadotropin (hCG)stimulated testosterone, free testosterone index, follicle-stimulating hormone (FSH), luteinizing hormone (LH), or sex hormone-binding globulin (SHBG). Moreover, there were no statistically significant differences at week 12 or week 24 for the change from baseline in sperm concentration, ejaculate volume, or sperm motility for any active treatment relative to placebo. Both simvastatin and pravastatin were well tolerated. In summary, we found no evidence for clinically meaningful effects of simvastatin or pravastatin on gonadal testosterone production, testosterone reserve, or multiple parameters of semen quality.

Relationship between gonad maturation and heavy metal accumulation in the clam, Galatea paradoxa (Born 1778) from the Volta estuary, Ghana.

PubMed

Adjei-Boateng, D; Obirikorang, K A; Amisah, S; Madkour, H A; Otchere, F A

2011-12-01

The relationship between gonadal development and the concentrations of four heavy metals Mn, Zn, Fe and Hg in the tissues of the clam Galatea paradoxa was evaluated at the Volta estuary, Ghana, over an 18-month period. Metal concentrations in the clam tissues were highly variable over the sampling period and seemed to be influenced by the reproductive cycle of the clam. Mn concentrations varied over a wide range from 49 to 867 μg/g and exhibited a significant positive correlation with gonadal development (p = 0.0146, r(2) = 0.3190). Zn and Fe concentrations ranged from 13 to 59 μg/g and 79 to 484 μg/g, respectively and both revealed negative relationships between gonad development and metal accumulation (Zn (p = 0.0554, r(2) = 0.0554) and Fe (p = 0.1040, r(2) = 0.1567)). Hg concentrations ranged from 0.026 to 0.059 μg/g over the sampling period and exhibited a slight positive relationship between gonadal development and metal accumulation (p = 0.0861, r(2) = 0.1730).

Frequency doubling of a tunable ytterbium-doped fibre laser in KTP crystals phase-matched in the XY and YZ planes

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

Akulov, V A; Kablukov, S I; Babin, Sergei A

2012-02-28

This paper presents an experimental study of frequency doubling of a tunable ytterbium-doped fibre laser in KTP crystals phase-matched in the XY and YZ planes. In the XY plane, we obtained continuous tuning in the range 528 - 540 nm through intracavity frequency doubling. The second-harmonic power reached 450 mW for 18 W of multimode diode pump power, which was five times higher in comparison with single-pass frequency doubling. In a single-pass configuration in the YZ plane, we obtained a wide tuning range (527 - 551 nm) in the green spectral region and a second-harmonic power of {approx}10 mW. Themore » tuning range was only limited by the mechanical performance of the fibre Bragg grating and can potentially be extended to the entire lasing range of the ytterbium-doped fibre laser.« less

Familial ring (18) mosaicism in a 23-year-old young adult with 46,XY,r(18) (::p11→q21::)/46,XY karyotype, intellectual disability, motor retardation and single maxillary incisor and in his phenotypically normal mother, karyotype 47,XX,+r(18)(::p11→q21::)/46,XX.

PubMed

Balci, Sevim; Tümer, Celal; Karaca, Ciğdem; Bartsch, Oliver

2011-05-01

We report on a 23-year-old man with craniofacial findings of the holoprosencephaly spectrum disorder (microcephaly, hypotelorism, depressed nasal bridge, single median maxillary central incisor), fusion of C2-C3 vertebrae, intellectual disability, and severe sleep apnea. Chromosome analysis of blood lymphocytes showed 75% ring (18) cells and 25% normal cells, karyotype mos 46,XY,r(18)(::p11→q21::)[75]/46,XY[25]. His mother was phenotypically normal except for a double ureter and bifid renal pelvis as in his son. She had a supernumerary ring (18) in 10% of blood lymphocytes, karyotype mos 47,XX,+r(18)(::p11→q21::)[10]/46,XX[90]. Familial ring (18) is a rare cytogenetic abnormality. This is the first report of a mother with a supernumerary ring (18) and a son with ring (18) mosaicism. Interestingly, the son showed a true mosaicism (mixoploidy) of ring (18) and normal cells. The mother's 46,XX cells could be easily explained by mitotic instability and ring loss during cell division. However, the coexistence of ring (18) and normal cells in the son is unusual. Possibly, during early postzygotic divisions of a 47,XY,+r(18) zygote, two (possibly subsequent) genetic events could have occurred, one when one normal chromosome 18 was lost (resulting in a cell line with ring 18), and one when the ring 18 was lost (resulting in a cell line without ring, "escape to normal"). Alternatively, the zygote of the son could have been 46,XY,r(18), and postzygotic loss of the ring 18 could have resulted in monosomy 18 cells followed by duplication of chromosome 18 in these cells (a rare mechanism for cell survival previously described as "compensatory" isodisomy). Copyright © 2011 Wiley-Liss, Inc.

Identification of deletions in children with congenital hypothyroidism and thyroid dysgenesis with the use of multiplex ligation-dependent probe amplification.

PubMed

Kumorowicz-Czoch, Malgorzata; Madetko-Talowska, Anna; Tylek-Lemanska, Dorota; Pietrzyk, Jacek J; Starzyk, Jerzy

2015-01-01

Thyroid dysgenesis (TD) is the most common cause of congenital hypothyroidism (CH). Important genetic factors possibly contributing to TD etiologies include mutations of thyroid transcription factors and TSHR-encoding genes. Our objective was to determine multiplex ligation-dependent probe amplification (MLPA) utility in detecting the copy number changes in patients with CH and TD. The study included 45 children from southeastern Poland selected via already established neonatal screening for CH. Genomic DNA was extracted from peripheral blood samples and used in MLPA analysis. Genetic variations were analyzed within selected fragments of the PAX8, FOXE1, NKX2-1, thyroid stimulating hormone receptor (TSHR), and TPO genes. Three heterozygous deletion types in probe hybridization regions were identified for the following genes: PAX8 (exon 7), TSHR (exon 2), and FOXE1 (exon 1). Monoallelic deletions were identified in 5/45 TD subjects. MLPA is a useful tool for copy number changes detection and might both improve and expand genetic analysis for CH and TD.

Phenotypic Variation in 46,XX Disorders of Sex Development due to the NR5A1 p.R92W Variant: A Sibling Case Report and Literature Review.

PubMed

Takasawa, Kei; Igarashi, Maki; Ono, Makoto; Takemoto, Akira; Takada, Shuji; Yamataka, Atsuyuki; Ogata, Tsutomu; Morio, Tomohiro; Fukami, Maki; Kashimada, Kenichi

2017-01-01

Recently, a heterozygous missense mutation in NR5A1, p.R92W, was identified as a cause of 46,XX testicular/ovo-testicular disorders of sexual development (DSD). We report a sibling pair with 46,XX DSD due to an NR5A1 mutation with distinct phenotypes, including external and internal genitalia and gonads, for whom different rearing sexes were selected. Thus, the phenotypes of p.R92W vary, even within a family. The father of the patients showed oligozoospermia with the p.R92W mutation, suggesting that in 46,XY individuals, the mutation would cause various gonadal phenotypes. We review and discuss the general role of the R92W mutation in sexual development. © 2018 S. Karger AG, Basel.

Age, sex, and gonadal hormones differently influence anxiety- and depression-related behavior during puberty in mice.

PubMed

Boivin, Josiah R; Piekarski, David J; Wahlberg, Jessica K; Wilbrecht, Linda

2017-11-01

Anxiety and depression symptoms increase dramatically during adolescence, with girls showing a steeper increase than boys after puberty onset. The timing of the onset of this sex bias led us to hypothesize that ovarian hormones contribute to depression and anxiety during puberty. In humans, it is difficult to disentangle direct effects of gonadal hormones from social and environmental factors that interact with pubertal development to influence mental health. To test the role of gonadal hormones in anxiety- and depression-related behavior during puberty, we manipulated gonadal hormones in mice while controlling social and environmental factors. Similar to humans, we find that mice show an increase in depression-related behavior from pre-pubertal to late-pubertal ages, but this increase is not dependent on gonadal hormones and does not differ between sexes. Anxiety-related behavior, however, is more complex during puberty, with differences that depend on sex, age, behavioral test, and hormonal status. Briefly, males castrated before puberty show greater anxiety-related behavior during late puberty compared to intact males, while pubertal females are unaffected by ovariectomy or hormone injections in all assays except the marble burying test. Despite this sex-specific effect of pubertal hormones on anxiety-related behavior, we find no sex differences in intact young adults, suggesting that males and females use separate mechanisms to converge on a similar behavioral phenotype. Our results are consistent with anxiolytic effects of testicular hormones during puberty in males but are not consistent with a causal role for ovarian hormones in increasing anxiety- and depression-related behavior during puberty in females. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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).

Sex, stress, and mood disorders: at the intersection of adrenal and gonadal hormones.

PubMed

Fernández-Guasti, A; Fiedler, J L; Herrera, L; Handa, R J

2012-07-01

The risk for neuropsychiatric illnesses has a strong sex bias, and for major depressive disorder (MDD), females show a more than 2-fold greater risk compared to males. Such mood disorders are commonly associated with a dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis. Thus, sex differences in the incidence of MDD may be related with the levels of gonadal steroid hormone in adulthood or during early development as well as with the sex differences in HPA axis function. In rodents, organizational and activational effects of gonadal steroid hormones have been described for the regulation of HPA axis function and, if consistent with humans, this may underlie the increased risk of mood disorders in women. Other developmental factors, such as prenatal stress and prenatal overexposure to glucocorticoids can also impact behaviors and neuroendocrine responses to stress in adulthood and these effects are also reported to occur with sex differences. Similarly, in humans, the clinical benefits of antidepressants are associated with the normalization of the dysregulated HPA axis, and genetic polymorphisms have been found in some genes involved in controlling the stress response. This review examines some potential factors contributing to the sex difference in the risk of affective disorders with a focus on adrenal and gonadal hormones as potential modulators. Genetic and environmental factors that contribute to individual risk for affective disorders are also described. Ultimately, future treatment strategies for depression should consider all of these biological elements in their design. © Georg Thieme Verlag KG Stuttgart · New York.

Gonad dose in AP pelvis radiography: Impact of anode heel orientation.

PubMed

Mraity, H A A B; England, A; Hogg, P

2017-02-01

For antero posterior (AP) pelvis radiographic examination, determine the impact of anode heel orientation on female/male gonad dose. High sensitivity thermo-luminescent dosimeters (TLDs) were used with an ATOM dosimetry phantom; the phantom was positioned for AP pelvis. TLDs were placed into the testes and ovaries. Radiation dose received by these organs was measured with the feet toward anode and feet toward the cathode. kVp, mAs and SID were manipulated to generate a range of exposures. A dose profile was also generated using Unfors Mult-O-Meter 401 along the long axis of the phantom. A decrease in dose from the central ray toward the anode was noted, with a marked increase toward the cathode. A significant reduction in dose was received by the testes with feet towards the anode compared with feet towards cathode (P˂0.001). No difference was seen for ovarian dose (P˃0.05). kVp, mAs and SID all have an effect on male and female gonad dose. For male pelvis imaging, placing feet towards the anode can be used as a simple dose reduction method. Copyright © 2016 The College of Radiographers. Published by Elsevier Ltd. All rights reserved.

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.

Germ Cells Are Not Required to Establish the Female Pathway in Mouse Fetal Gonads

PubMed Central

Maatouk, Danielle M.; Mork, Lindsey; Hinson, Ashley; Kobayashi, Akio; McMahon, Andrew P.; Capel, Blanche

2012-01-01

The fetal gonad is composed of a mixture of somatic cell lineages and germ cells. The fate of the gonad, male or female, is determined by a population of somatic cells that differentiate into Sertoli or granulosa cells and direct testis or ovary development. It is well established that germ cells are not required for the establishment or maintenance of Sertoli cells or testis cords in the male gonad. However, in the agametic ovary, follicles do not form suggesting that germ cells may influence granulosa cell development. Prior investigations of ovaries in which pre-meiotic germ cells were ablated during fetal life reported no histological changes during stages prior to birth. However, whether granulosa cells underwent normal molecular differentiation was not investigated. In cases where germ cell loss occurred secondary to other mutations, transdifferentiation of granulosa cells towards a Sertoli cell fate was observed, raising questions about whether germ cells play an active role in establishing or maintaining the fate of granulosa cells. We developed a group of molecular markers associated with ovarian development, and show here that the loss of pre-meiotic germ cells does not disrupt the somatic ovarian differentiation program during fetal life, or cause transdifferentiation as defined by expression of Sertoli markers. Since we do not find defects in the ovarian somatic program, the subsequent failure to form follicles at perinatal stages is likely attributable to the absence of germ cells rather than to defects in the somatic cells. PMID:23091613

Gonad Transcriptome Analysis of the Pacific Oyster Crassostrea gigas Identifies Potential Genes Regulating the Sex Determination and Differentiation Process.

PubMed

Yue, Chenyang; Li, Qi; Yu, Hong

2018-04-01

The Pacific oyster Crassostrea gigas is a commercially important bivalve in aquaculture worldwide. C. gigas has a fascinating sexual reproduction system consisting of dioecism, sex change, and occasional hermaphroditism, while knowledge of the molecular mechanisms of sex determination and differentiation is still limited. In this study, the transcriptomes of male and female gonads at different gametogenesis stages were characterized by RNA-seq. Hierarchical clustering based on genes differentially expressed revealed that 1269 genes were expressed specifically in female gonads and 817 genes were expressed increasingly over the course of spermatogenesis. Besides, we identified two and one gene modules related to female and male gonad development, respectively, using weighted gene correlation network analysis (WGCNA). Interestingly, GO and KEGG enrichment analysis showed that neurotransmitter-related terms were significantly enriched in genes related to ovary development, suggesting that the neurotransmitters were likely to regulate female sex differentiation. In addition, two hub genes related to testis development, lncRNA LOC105321313 and Cg-Sh3kbp1, and one hub gene related to ovary development, Cg-Malrd1-like, were firstly investigated. This study points out the role of neurotransmitter and non-coding RNA regulation during gonad development and produces lists of novel relevant candidate genes for further studies. All of these provided valuable information to understand the molecular mechanisms of C. gigas sex determination and differentiation.

Function of the hypothalamic-pituitary-gonadal axis in long-term survivors of hematopoietic stem cell transplantation for hematological diseases.

PubMed

Somali, Maria; Mpatakoias, Vassilios; Avramides, Avraam; Sakellari, Ioanna; Kaloyannidis, Panayotis; Smias, Christos; Anagnostopoulos, Achilleas; Kourtis, Anargyros; Rousso, David; Panidis, Dimitrios; Vagenakis, Apostolos

2005-07-01

Gonadal dysfunction in adult long-term survivors of hematopoietic stem cell transplantation (HSCT) is an adverse effect of conditioning regimens consisting of chemotherapy and total body irradiation (TBI). The impact of conditioning regimens consisting of chemotherapy alone on the function of the hypothalamic-pituitary-gonadal (HPG) axis was evaluated in a series of 41 female and 31 male patients who had undergone either autologous or allogeneic bone marrow/peripheral blood stem cell transplantation; mean age at transplantation was 32.6 years and mean time interval from transplantation was 1.5 years (range 0.2-9.8 years). Provocative testing of the HPG axis by administration of luteinizing hormone-releasing hormone was included in the first endocrinological evaluation. The follow-up period extended to three consecutive years. Gonadal dysfunction was not reported by any of the patients prior to their underlying illness. Hypergonadotrophic hypogonadism was observed in 97% of female and 19% of male patients. Leydig cell strain (normal testosterone, high luteinizing hormone levels) was evident in 32% and spermatogenesis damage (high follicle-stimulating hormone levels) in 68% of the male population. At the conclusion of the study four women (10%) had regained spontaneous menses and all hypogonadal men had resumed normal testosterone levels. Our results indicate a high incidence of gonadal dysfunction due to target organ failure in HSCT recipients not treated by TBI.

Both nuclear and cytoplasmic components are defective in oocytes of the B6.Y(TIR) sex-reversed female mouse.

PubMed

Amleh, A; Smith, L; Chen, H; Taketo, T

2000-03-15

In the mammalian gonadal primordium, activation of the Sry gene on the Y chromosome initiates a cascade of genetic events leading to testicular organization whereas its absence results in ovarian differentiation. An exception occurs when the Y chromosome of Mus musculus domesticus from Tirano, Italy (Y(TIR)), is placed on the C57BL/6J (B6) genetic background. The B6.Y(TIR) progeny develop only ovaries or ovotestes despite Sry transcription in fetal life. Consequently, the XY offspring with bilateral ovaries develop into apparently normal females, but their eggs fail to develop after fertilization. Our previous studies have shown that the primary cause of infertility can be attributed to oocytes rather than their surrounding somatic cells in the XY ovary. This study attempted to identify the defects in oocytes from the B6.Y(TIR) female mouse. We examined the developmental potential of embryos from XY and XX females after exchanging their nuclear components by microsurgery following in vitro maturation and fertilization. The results suggest that both nuclear and cytoplasmic components are defective in oocytes from XY females. In the XY fetal ovary, most germ cells entered meiosis and their autosomes appeared to synapse normally while the X and Y chromosomes remained unpaired during meiotic prophase. This lack of X-Y pairing probably caused aneuploidy in some secondary oocytes following in vitro maturation. However, normal numbers of chromosomes in the rest of the secondary oocytes indicate that aneuploidy alone can not explain the nuclear defect in oocytes. Copyright 2000 Academic Press.

Chromosome banding in Amphibia. XXVIII. Homomorphic XY sex chromosomes and a derived Y-autosome translocation in Eleutherodactylus riveroi (Anura, Leptodactylidae).

PubMed

Schmid, M; Feichtinger, W; Steinlein, C; Visbal García, R; Fernández Badillo, A

2003-01-01

Extensive cytogenetic analyses on a population of the leptodactylid frog Eleutherodactylus riveroi in northern Venezuela revealed the existence of multiple XXAA male/XYAA female/XAA(Y) female sex chromosomes. The XAA(Y) karyotype originated by a centric (Robertsonian) fusion between the original, free Y chromosome and an autosome. 46.2% of the male individuals in this population are carriers of this Y-autosome fusion. In male meiosis the XAA(Y) sex chromosomes pair in the expected trivalent configuration. In the same population 53.8% of the male animals still possess the original, free XY sex chromosomes. E. riveroi is only the second vertebrate species discovered in which a derived Y-autosome fusion coexists with the ancestral free XY sex chromosomes. The free XY sex chromosomes, as well as the multiple XA(Y) sex chromosomes are still in a very primitive (homomorphic) stage of differentiation. With no banding technique applied it is possible to distinguish the Y from the X. Various banding techniques and in situ hybridizations have been carried out to characterize the karyotypes. DNA flow cytometric measurements show that the genome size of E. riveroi resembles that of other Eleutherodactylus species. The cytogenetic data obtained in E. riveroi are compared with those of the sole other vertebrate known to possess the extremely rare, multiple XXAA male/XYAA female/XAA(Y) female sex chromosomes. Surprisingly enough, this vertebrate again is a frog belonging to the genus Eleutherodactylus [E. ((maussi) biporcatus] which lives exactly in the same habitat in northern Venezuela as does E. riveroi. Copyright 2003 S. Karger AG, Basel

Adaptive Responses to Prochloraz Exposure in the Hypothalamic-Pituitary Gonadal Axis of Fathead Minnows

EPA Science Inventory

Exposure to endocrine disrupting chemicals can affect reproduction and development in both humans and wildlife. We are developing a mechanistic mathematical model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict doseresponse and time-course ...

Zebrafish monosex population reveals female dominance in sex determination and earliest events of gonad differentiation.

PubMed

Tong, Sok-Keng; Hsu, Hwei-Jan; Chung, Bon-chu

2010-08-15

The zebrafish is a popular model for genetic analysis and its sex differentiation has been the focus of attention for breeding purposes. Despite numerous efforts, very little is known about the mechanism of zebrafish sex determination. The lack of discernible sex chromosomes and the difficulty of distinguishing the sex of juvenile fish are two major obstacles that hamper the progress in such studies. To alleviate these problems, we have developed a scheme involving methyltestosterone treatment followed by natural mating to generate fish with predictable sex trait. Female F1 fish that gave rise to all-female offspring were generated. This predictable sex trait enables characterization of gonadal development in juvenile fish by histological examination and gene expression analysis. We found the first sign of zebrafish sex differentiation to be ovarian gonocyte proliferation and differentiation at 10 to 12 days post-fertilization (dpf). Somatic genes were expressed indifferently at 10 to 17 dpf, and then became sexually dimorphic at three weeks. This result indicates clear distinction of male and female gonads derived independently from primordial gonads. We classified the earliest stages of zebrafish sex determination into the initial preparation followed by female germ cell growth, oocyte differentiation, and somatic differentiation. Our genetic selection scheme matches the prediction that female-dominant genetic factors are required to determine zebrafish sex. Copyright 2010 Elsevier Inc. All rights reserved.

A long serendipitous XMM-Newton observation of the intermediate polar XY Ari1

NASA Astrophysics Data System (ADS)

Zengin Ćamurdan, D.; Balman, Ş.; Burwitz, V.

2018-07-01

XY Ari is one of the few known eclipsing intermediate polars. We present results from a detailed analysis of an unpublished archival observation using XMM-Newton EPIC pn and MOS data in a quiescent state of XY Ari. The X-ray orbital modulation and spin-pulse variations were investigated for energy-dependent modulations in different energy bands. The broad orbital modulation observed with various observations was confirmed with XMM-Newton in the hard X-ray (>1.6 keV). The EPIC light curves folded at the spin phases show a double-peak profile, as expected from two-pole accretion. The pulse profile is found to be energy-dependent. Hardness-ratio variations and energy modulation depth during spin modulation can be explained by photoelectric absorption. The simultaneously fitted EPIC spectra with a multi-temperature plasma emission model (CEVMKL) model yield a maximum plasma temperature of 28^{+3.1}_{-2.9} keV with an iron abundance Fe/Fe_{⊙}=0.37^{+0.06}_{-0.05}. We find two intrinsic partial covering absorption columns of 6.2^{+1.0}_{-0.9} × 10^{22} and 105.3^{+35.4}_{-30.4} × 10^{22} cm^{-2} with covering fractions of 0.53^{+0.05}_{-0.04}, 0.41^{+0.14}_{-0.13}, respectively. In addition, a Gaussian emission line at 6.43^{+0.01}_{-0.02} keV with an equivalent width of 51^{+12}_{-10} eV is required to account for fluorescent emission from neutral iron. The X-ray luminosity of the source is 4.2 × 1032 erg s-1 in the 0.2-10.0 keV energy band.

Experiment K-7-19: Pineal Physiology After Spaceflight: Relation to Rat Gonadal Function

NASA Technical Reports Server (NTRS)

Holley, D. C.; Soliman, M. R. I.; Krasnov, I.; Asadi, H.

1994-01-01

The function of pineal exposed to microgravity and spaceflight is studied. It is found that the spaceflight resulted in a stress response as indicated by adrenal hypertrophy, that gonadal function was compromised, and that the pineal may be linked as part of the mechanisms of the response noted.

Characterization of mutations in the FOXE1 gene in a cohort of unrelated Malaysian patients with congenital hypothyroidism and thyroid dysgenesis.

PubMed

Kang, In-Nee; Musa, Maslinda; Harun, Fatimah; Junit, Sarni Mat

2010-02-01

The FOXE1 gene was screened for mutations in a cohort of 34 unrelated patients with congenital hypothyroidism, 14 of whom had thyroid dysgenesis and 18 were normal (the thyroid status for 2 patients was unknown). The entire coding region of the FOXE1 gene was PCR-amplified, then analyzed using single-stranded conformational polymorphism, followed by confirmation by direct DNA sequencing. DNA sequencing analysis revealed a heterozygous A>G transition at nucleotide position 394 in one of the patients. The nucleotide transition changed asparagine to aspartate at codon 132 in the highly conserved region of the forkhead DNA binding domain of the FOXE1 gene. This mutation was not detected in a total of 104 normal healthy individuals screened. The binding ability of the mutant FOXE1 protein to the human thyroperoxidase (TPO) promoter was slightly reduced compared with the wild-type FOXE1. The mutation also caused a 5% loss of TPO transcriptional activity.

Natural reversal of left-right gut/gonad asymmetry in C. elegans males is independent of embryonic chirality.

PubMed

Callander, Davon C; Alcorn, Melissa R; Birsoy, Bilge; Rothman, Joel H

2014-06-01

Anatomical left-right (L/R) asymmetry in C. elegans is established in the four-cell embryo as a result of anteroposterior skewing of transverse mitotic spindles with a defined handedness. This event creates a chiral embryo and ultimately an adult body plan with fixed L/R positioning of internal organs and components of the nervous system. While this "dextral" configuration is invariant in hermaphrodites, it can be reversed by physical manipulation of the early embryo or by mutations that interfere with mitotic spindle orientation, which leads to viable, mirror-reversed (sinistral) animals. During normal development of the C. elegans male, the gonad develops on the right of the midline, with the gut bilaterally apposed on the left. However, we found that in males of the laboratory N2 strain and Hawaiian ("Hw") wild isolate, the gut/gonad asymmetry is frequently reversed in a temperature-dependent manner, independent of normal embryonic chirality. We also observed sporadic errors in gonad migration occurring naturally during early larval stages of these and other wild strains; however, the incidence of such errors does not correlate with the frequency of L/R gut/gonad reversals in these strains. Analysis of N2/Hw hybrids and recombinant inbred advanced intercross lines (RIAILs) indicate that the L/R organ reversals are likely to result from recessively acting variations in multiple genes. Thus, unlike the highly reproducible L/R asymmetries of most structures in hermaphrodites, the L/R asymmetry of the male C. elegans body plan is less rigidly determined and subject to natural variation that is influenced by a multiplicity of genes. © 2014 Wiley Periodicals, Inc.

Subcutaneous and gonadal adipose tissue transcriptome differences in lean and obese female dogs.

PubMed

Grant, Ryan W; Vester Boler, Brittany M; Ridge, Tonya K; Graves, Thomas K; Swanson, Kelly S

2013-12-01

Canine obesity leads to shortened life span and increased disease incidence. Adipose tissue depots are known to have unique metabolic and gene expression profiles in rodents and humans, but few comparisons of depot gene expression have been performed in the dog. Using microarray technology, our objective was to identify differentially expressed genes and enriched functional pathways between subcutaneous and gonadal adipose of lean and obese dogs to better understand the pathogenesis of obesity in the dog. Because no depot × body weight status interactions were identified in the microarray data, depot differences were the primary focus. A total of 946 and 703 transcripts were differentially expressed (FDR P < 0.05) between gonadal and subcutaneous adipose tissue in obese and lean dogs respectively. Of the adipose depot-specific differences in gene expression, 162 were present in both lean and obese dogs, with the majority (85%) expressed in the same direction. Both lean and obese dog gene lists had enrichment of the complement and coagulation cascade and systemic lupus erythematosus pathways. Obese dogs had enrichment of lysosome, extracellular matrix-receptor interaction, renin-angiotensin system and hematopoietic cell lineage pathways. Lean dogs had enrichment of glutathione metabolism and synthesis and degradation of ketone bodies. We have identified a core set of genes differentially expressed between subcutaneous and gonadal adipose tissue in dogs regardless of body weight. These genes contribute to depot-specific differences in immune function, extracellular matrix remodeling and lysosomal function and may contribute to the physiological differences noted between depots. © 2013 The Authors, Animal Genetics © 2013 Stichting International Foundation for Animal Genetics.

Quantum critical singularities in two-dimensional metallic XY ferromagnets

NASA Astrophysics Data System (ADS)

Varma, Chandra M.; Gannon, W. J.; Aronson, M. C.; Rodriguez-Rivera, J. A.; Qiu, Y.

2018-02-01

An important problem in contemporary physics concerns quantum-critical fluctuations in metals. A scaling function for the momentum, frequency, temperature, and magnetic field dependence of the correlation function near a 2D-ferromagnetic quantum-critical point (QCP) is constructed, and its singularities are determined by comparing to the recent calculations of the correlation functions of the dissipative quantum XY model (DQXY). The calculations are motivated by the measured properties of the metallic compound YFe2Al10 , which is a realization of the DQXY model in 2D. The frequency, temperature, and magnetic field dependence of the scaling function as well as the singularities measured in the experiments are given by the theory without adjustable exponents. The same model is applicable to the superconductor-insulator transitions, classes of metallic AFM-QCPs, and as fluctuations of the loop-current ordered state in hole-doped cuprates. The results presented here lend credence to the solution found for the 2D-DQXY model and its applications in understanding quantum-critical properties of diverse systems.

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

[Rare or little known syndromes in gynecology and obstetrics].

PubMed

Dumont, M

1986-04-01

The author presents fourty-three years' experience of rare syndromes or those which he considers are poorly understood in the area of gynecologic obstetrics. He briefly reviews: spontaneous post-cesarian perforation of the cecum, post-partum paralysis of the external popliteal sciatic, carpal canal syndrome in pregnacy, meralgia paresthetica in pregnant women, diaphragmatic hernia and its complications during pregnancy and labor, post-mortem cesarian, the "molar lung", early pregnancy and late pregnancy, fulguration and electroshock in pregnant women, the "acrobatic fetus", the rupture of an aneurysm of the splenic artery, geophagia or "pica", extramucous ruptures of the uterus, "virtually pure" type XX familial gonadic dysgenesis with deaf-muteness, gynecologic pathomimesis, genital perihepatitis or Fitz-Hugh-Curtis syndrome, vulvar mammary ectopism, post-hysterectomic pregnancy, recurrent hydramnios, locoregional ecchymatosis.

vasa is expressed in somatic cells of the embryonic gonad in a sex-specific manner in Drosophila melanogaster.

PubMed

Renault, Andrew D

2012-10-15

Vasa is a DEAD box helicase expressed in the Drosophila germline at all stages of development. vasa homologs are found widely in animals and vasa has become the gene of choice in identifying germ cells. I now show that Drosophila vasa expression is not restricted to the germline but is also expressed in a somatic lineage, the embryonic somatic gonadal precursor cells. This expression is sexually dimorphic, being maintained specifically in males, and is regulated post-transcriptionally. Although somatic Vasa expression is not required for gonad coalescence, these data support the notion that Vasa is not solely a germline factor.

vasa is expressed in somatic cells of the embryonic gonad in a sex-specific manner in Drosophila melanogaster

PubMed Central

Renault, Andrew D.

2012-01-01

Summary Vasa is a DEAD box helicase expressed in the Drosophila germline at all stages of development. vasa homologs are found widely in animals and vasa has become the gene of choice in identifying germ cells. I now show that Drosophila vasa expression is not restricted to the germline but is also expressed in a somatic lineage, the embryonic somatic gonadal precursor cells. This expression is sexually dimorphic, being maintained specifically in males, and is regulated post-transcriptionally. Although somatic Vasa expression is not required for gonad coalescence, these data support the notion that Vasa is not solely a germline factor. PMID:23213382

Expression profile of doublesex/male abnormal-3-related transcription factor-1 during gonadal sex change in the protogynous wrasse, Halichoeres trimaculatus.

PubMed

Nozu, Ryo; Horiguchi, Ryo; Kobayashi, Yasuhisa; Nakamura, Masaru

2015-11-01

Sex change in fish involves a dramatic transformation of gonadal tissue and a switch in gametogenesis. Doublesex/male abnormal-3-related transcription factor-1 (DMRT1), encoded by the DMRT1 gene, is involved in testicular differentiation in a wide range of vertebrates as well as in sexual differentiation and gonadal sex change. In the present study, we investigated changes in the expression of dmrt1 during artificial gonadal sex change in the three-spot wrasse, Halichoeres trimaculatus, by real-time quantitative PCR and immunolocalization, using an anti-wrasse-Dmrt1 antibody that we prepared. We found that dmrt1 expression was predominantly observed in the testes, and that Dmrt1 was expressed in Sertoli cells of testes and a few granulosa cells surrounding vitellogenic oocytes of the ovary. Additionally, the upregulation of dmrt1 expression was consistent with an increase in spermatogenic cyst quantity rather than proliferation of presumptive spermatogonia, suggesting that dmrt1 is involved in the progression of spermatogenesis during sex change. Changes in the localization of Dmrt1 during gonadal sex change further implied that Sertoli cells originate from somatic cells adjacent to gonial germ cells during testicular formation in the three-spot wrasse. © 2015 Wiley Periodicals, Inc.

Human MAMLD1 Gene Variations Seem Not Sufficient to Explain a 46,XY DSD Phenotype.

PubMed

Camats, Núria; Fernández-Cancio, Mónica; Audí, Laura; Mullis, Primus E; Moreno, Francisca; González Casado, Isabel; López-Siguero, Juan Pedro; Corripio, Raquel; Bermúdez de la Vega, José Antonio; Blanco, José Antonio; Flück, Christa E

2015-01-01

MAMLD1 is thought to cause disordered sex development in 46,XY patients. But its role is controversial because some MAMLD1 variants are also detected in normal individuals, several MAMLD1 mutations have wild-type activity in functional tests, and the male Mamld1-knockout mouse has normal genitalia and reproduction. Our aim was to search for MAMLD1 variations in 108 46,XY patients with disordered sex development, and to test them functionally. We detected MAMDL1 variations and compared SNP frequencies in controls and patients. We tested MAMLD1 transcriptional activity on promoters involved in sex development and assessed the effect of MAMLD1 on androgen production. MAMLD1 expression in normal steroid-producing tissues and mutant MAMLD1 protein expression were also assessed. Nine MAMLD1 mutations (7 novel) were characterized. In vitro, most MAMLD1 variants acted similarly to wild type. Only the L210X mutation showed loss of function in all tests. We detected no effect of wild-type or MAMLD1 variants on CYP17A1 enzyme activity in our cell experiments, and Western blots revealed no significant differences for MAMLD1 protein expression. MAMLD1 was expressed in human adult testes and adrenals. In conclusion, our data support the notion that MAMLD1 sequence variations may not suffice to explain the phenotype in carriers and that MAMLD1 may also have a role in adult life.

Human MAMLD1 Gene Variations Seem Not Sufficient to Explain a 46,XY DSD Phenotype

PubMed Central

Audí, Laura; Mullis, Primus E.; Moreno, Francisca; González Casado, Isabel; López-Siguero, Juan Pedro; Corripio, Raquel; Bermúdez de la Vega, José Antonio; Blanco, José Antonio; Flück, Christa E.

2015-01-01

MAMLD1 is thought to cause disordered sex development in 46,XY patients. But its role is controversial because some MAMLD1 variants are also detected in normal individuals, several MAMLD1 mutations have wild-type activity in functional tests, and the male Mamld1-knockout mouse has normal genitalia and reproduction. Our aim was to search for MAMLD1 variations in 108 46,XY patients with disordered sex development, and to test them functionally. We detected MAMDL1 variations and compared SNP frequencies in controls and patients. We tested MAMLD1 transcriptional activity on promoters involved in sex development and assessed the effect of MAMLD1 on androgen production. MAMLD1 expression in normal steroid-producing tissues and mutant MAMLD1 protein expression were also assessed. Nine MAMLD1 mutations (7 novel) were characterized. In vitro, most MAMLD1 variants acted similarly to wild type. Only the L210X mutation showed loss of function in all tests. We detected no effect of wild-type or MAMLD1 variants on CYP17A1 enzyme activity in our cell experiments, and Western blots revealed no significant differences for MAMLD1 protein expression. MAMLD1 was expressed in human adult testes and adrenals. In conclusion, our data support the notion that MAMLD1 sequence variations may not suffice to explain the phenotype in carriers and that MAMLD1 may also have a role in adult life. PMID:26580071

Seasonal expression of arginine vasotocin mRNA and its correlations to gonadal steroidogenic enzymes and sexually dimorphic coloration during sex reversal in the gilthead seabream (Sparus aurata).

PubMed

Reyes-Tomassini, José J; Wong, Ten-Tsao; Zohar, Yonathan

2017-06-01

Arginine vasotocin is a hormone produced in the hypothalamus of teleost fish that has been shown to regulate gonad development and sexual behavior. To study the role of arginine vasotocin in the gonadal cycle of the hermaphrodite gilthead seabream, Sparus aurata, we cloned the seabream arginine vasotocin (avt) complementary DNA (cDNA). We investigated the expression of brain avt throughout the gonad cycle using real-time quantitative PCR and compared its expression levels to the expression levels of two key gonadal steroidogenic enzymes, cyp19a1a and cyp11b2. In July, when the process of sex reversal is thought to begin, avt expression was elevated over the previous 2 months. Avt in the brain remained at or above the level of July until November then peaked again in December. There was no difference between males and females in the expression levels of brain avt throughout the year. However, only in ambisexual fish was the expression of the cyp19a1a gonadal aromatase correlated to the expression of avt in the brain. Cyp11b2 did not show any correlation to brain avt expression. We also found that females had more intense body coloration than males and that this intensity peaked prior to spawning. Avt expression and female coloration were positively correlated. The fact that brain avt expression was lowest during gonad quiescence, together with the observation of a correlation between brain avt with gonadal cyp19a1a and body coloration during that time suggests that avt may play a role during the process of sex reversal and spawning of the gilthead seabream.

46,XY disorder of sex development (DSD) due to 17β-hydroxysteroid dehydrogenase type 3 deficiency.

PubMed

Mendonca, Berenice B; Gomes, Nathalia Lisboa; Costa, Elaine M F; Inacio, Marlene; Martin, Regina M; Nishi, Mirian Y; Carvalho, Filomena Marino; Tibor, Francisco Denes; Domenice, Sorahia

2017-01-01

17β-hydroxysteroid dehydrogenase 3 deficiency consists of a defect in the last phase of steroidogenesis, in which androstenedione is converted into testosterone and estrone into estradiol. External genitalia range from female-like to atypical genitalia and most affected males are raised as females. Virilization in subjects with 17β-HSD3 deficiency occurs at the time of puberty and several of them change to male social sex. In male social sex patients, testes can be safely maintained, as long as they are positioned inside the scrotum The phenotype of 46,XY DSD due to 17β-HSD3 deficiency is extremely variable and clinically indistinguishable from other causes of 46,XY DSD such as partial androgen insensitivity syndrome and 5α-reductase 2 deficiency. Laboratory diagnosis is based on a low testosterone/androstenedione ratio due to high serum levels of androstenedione and low levels of testosterone. The disorder is caused by a homozygous or compound heterozygous mutations in the HSD17B3 gene that encodes the 17β-HSD3 isoenzyme leading to an impairment of the conversion of 17-keto into 17-hydroxysteroids. Molecular genetic testing confirms the diagnosis and provides the orientation for genetic counseling. Our proposal in this article is to review the previously reported cases of 17β-HSD3 deficiency adding our own cases. Copyright © 2016. Published by Elsevier Ltd.

First analysis of eight Algol-type binaries: EI Aur, XY Dra, BP Dra, DD Her, VX Lac, WX Lib, RZ Lyn, and TY Tri

NASA Astrophysics Data System (ADS)

Zasche, P.

2016-01-01

The available photometry from the online databases were used for the first light curve analysis of eight eclipsing binary systems EI Aur, XY Dra, BP Dra, DD Her, VX Lac, WX Lib, RZ Lyn, and TY Tri. All these stars are of Algol-type, having the detached components and the orbital periods from 0.92 to 6.8 days. For the systems EI Aur and BP Dra the large amount of the third light was detected during the light curve solution. Moreover, 468 new times of minima for these binaries were derived, trying to identify the period variations. For the systems XY Dra and VX Lac the third bodies were detected with the periods 17.7, and 49.3 years, respectively.

Gonad development and vitellogenin production in zebrafish (Danio rerio) exposed to ethinylestradiol and methyltestosterone.

PubMed

Orn, Stefan; Holbech, Henrik; Madsen, Trine H; Norrgren, Leif; Petersen, Gitte I

2003-12-10

In a partial life-cycle test, the impact of 17alpha-ethinylestradiol (EE2) and 17alpha-methyltestosterone (MT) on juvenile zebrafish was evaluated by use of vitellogenin measurements and gonadal development. Exposure to EE2 (1-25 ng/l) resulted in a dose-dependent increase in vitellogenin production starting at 2 ng/l. Significant changes in sex ratios in female direction were detected at 1 ng/l, with complete sex reversal taking place after exposure to 2 ng/l. No intersex fish were observed after exposure to EE2. Exposure to MT resulted in decreased vitellogenin concentrations. Complete sex reversal was detected in all MT concentrations used (26-1000 ng/l). A large proportion of intersex fish was observed after exposure to 1000 ng MT/l. The period of gonadal sex reversal in non-exposed zebrafish was also studied. The main morphological features of the transformation of ovaries into testis were observed 4-5 weeks after hatching.

Effects of 17 α-methyltestosterone on transcriptome, gonadal histology and sex steroid hormones in rare minnow Gobiocypris rarus.

PubMed

Gao, Jiancao; Liu, Shaozhen; Zhang, Yingying; Yang, Yanping; Yuan, Cong; Chen, Shu; Wang, Zaizhao

2015-09-01

The 17α-methyltestosterone (MT), a synthetic androgen, is known for its interference effects on the endocrine system. Aiming to investigate the transcriptome profiling of gonads induced by MT and to understand the molecular mechanism by which MT causes adverse effects in fish, transcriptome profiling of gonads, gonadal histology and the sex steroid hormones in response to MT were analyzed in Gobiocypris rarus. Eight libraries, 4 from the ovary and 4 from the testis, were constructed and sequenced and then a total number of clean reads per sample ranging from 7.03 to 9.99 million were obtained. In females, a total of 191 transcripts were differentially regulated by MT, consisting of 102 up-regulated transcripts and 89 down-regulated transcripts. In males, 268 differentially expressed genes with 108 up-regulated and 160 down-regulated were detected upon MT exposure. Testosterone serves as the major sex steroid hormone content in G. rarus of both sexes. The concentrations of 17β-estradiol, testosterone and 11-ketotestosterone were significantly increased in females and decreased in males after MT exposure. Interestingly, MT caused a decreased number of vitellogenic oocytes in the ovary and spermatozoa in the testis. After MT exposure, four differentially expressed genes (ndufa4, slc1a3a, caskin-2 and rpt3) were found in G. rarus of both sexes. Overall, we suggest that MT seemed to affect genes involved in pathways related to physiological processes in the gonads of G. rarus. These processes include the electron transfer of Complex IV, endothelial cell activation, axon growth and guidance, and proteasome assembly and glutamate transport metabolic. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of tributyltin on early life-stage, reproduction, and gonadal sex differentiation in Japanese medaka (Oryzias latipes).

PubMed

Horie, Yoshifumi; Yamagishi, Takahiro; Shintaku, Yoko; Iguchi, Taisen; Tatarazako, Norihisa

2018-07-01

Tributyltin, an organotin compound, was used worldwide as an antifouling agent in aquatic environments and there has been much concern about the toxicological and ecotoxicological properties of organotin compounds. Even though it has been prohibited worldwide, tributyltin is still detected at low concentrations in aquatic environments. Here we investigated the effects of tributyltin on the early life-stage, reproduction, and gonadal sex differentiation in Japanese medaka (Oryzias latipes). In adults, exposure to tributyltin at 3.82 μg/L suppressed fecundity and fertility and increased mortality. At 10.48 μg/L all medaka died by the sixth day of exposure. Exposure to tributyltin during early life-stages induced no significant differences in mortality or embryonic development, but growth was suppressed in groups exposed to 0.13 and 0.68 μg/L. Furthermore, there was no abnormal gonadal development in Japanese medaka exposed to tributyltin. These results provide evidence of the negative effects of tributyltin on reproduction in a teleost fish. Tributyltin did not affect gonadal sex differentiation in Japanese medaka, but fecundity and fertility were suppressed, although it is not clear whether this suppression resulted from the endocrine-disrupting action of tributyltin or its toxicity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Toxic effects of male Perna viridis gonad exposed to BaP, DDT and their mixture: A metabolomic and proteomic study of the underlying mechanism.

PubMed

Song, Qinqin; Zheng, Pengfei; Qiu, Liguo; Jiang, Xiu; Zhao, Hongwei; Zhou, Hailong; Han, Qian; Diao, Xiaoping

2016-01-05

Benzo(a)pyrene and dichlorodiphenyltrichloroethane are typical persistent organic pollutants, and also the widespread environmental estrogens with known toxicity towards green mussels Perna viridis. In this study, the toxicological effects of BaP and DDT and their mixture were assessed in green mussel gonads using proteomic and metabolomic approaches. Metabolomics by NMR spectroscopy revealed that BaP did not show obvious metabolite changes in the gonad of male green mussel. DDT mainly caused some disturbance of osmotic regulation and energy metabolism by changing BCAAs, alanine, threonine, arginine, etc., unknown metabolite (3.53 ppm), glycine, homarine and ATP at different levels. However, the mixture of BaP and DDT mainly caused some disturbance in osmotic regulation and energy metabolism by differentially altering branched chain amino acids, glutamate, alanine, arginine, unknown metabolite (3.53 ppm), glycine, 4-aminobutyrate, dimethylglycine, homarine and ATP. The results suggest that DDT alone may cause most of metabolites changes in the mixture exposed male mussel gonad, and the results also show that the male P. viridis gonad was more sensitive to DDT than BaP exposures. Proteomic study showed that BaP, DDT and their mixture may have different modes of action. Proteomic responses revealed that BaP induced signal transduction, oxidative stress, spermatogenesis, etc. in the male green mussel gonad; whereas DDT exposure altered proteins that were associated with signal transduction, oxidative stress, cytoskeleton and cell structure, cellular organization, energy metabolism, etc. However, the mixture of BaP and DDT affected proteins related to cytoskeleton and cell structure, oxidative stress, cellular organization, etc. This research demonstrated that metabolomic and proteomic approaches could better elucidate the underlying mechanism of environmental pollutants gonad toxicity. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Sex Reversal and Comparative Data Undermine the W Chromosome and Support Z-linked DMRT1 as the Regulator of Gonadal Sex Differentiation in Birds.

PubMed

Hirst, Claire E; Major, Andrew T; Ayers, Katie L; Brown, Rosie J; Mariette, Mylene; Sackton, Timothy B; Smith, Craig A

2017-09-01

The exact genetic mechanism regulating avian gonadal sex differentiation has not been completely resolved. The most likely scenario involves a dosage mechanism, whereby the Z-linked DMRT1 gene triggers testis development. However, the possibility still exists that the female-specific W chromosome may harbor an ovarian determining factor. In this study, we provide evidence that the universal gene regulating gonadal sex differentiation in birds is Z-linked DMRT1 and not a W-linked (ovarian) factor. Three candidate W-linked ovarian determinants are HINTW, female-expressed transcript 1 (FET1), and female-associated factor (FAF). To test the association of these genes with ovarian differentiation in the chicken, we examined their expression following experimentally induced female-to-male sex reversal using the aromatase inhibitor fadrozole (FAD). Administration of FAD on day 3 of embryogenesis induced a significant loss of aromatase enzyme activity in female gonads and masculinization. However, expression levels of HINTW, FAF, and FET1 were unaltered after experimental masculinization. Furthermore, comparative analysis showed that FAF and FET1 expression could not be detected in zebra finch gonads. Additionally, an antibody raised against the predicted HINTW protein failed to detect it endogenously. These data do not support a universal role for these genes or for the W sex chromosome in ovarian development in birds. We found that DMRT1 (but not the recently identified Z-linked HEMGN gene) is male upregulated in embryonic zebra finch and emu gonads, as in the chicken. As chicken, zebra finch, and emu exemplify the major evolutionary clades of birds, we propose that Z-linked DMRT1, and not the W sex chromosome, regulates gonadal sex differentiation in birds. Copyright © 2017 Endocrine Society.

Kisspeptin regulates the hypothalamus-pituitary-gonad axis gene expression during sexual maturation in the cinnamon clownfish, Amphiprion melanopus.

PubMed

Kim, Na Na; Shin, Hyun Suk; Choi, Young Jae; Choi, Cheol Young

2014-02-01

Kisspeptins (Kiss) have been recognized as potent regulators of reproduction in teleosts, and Kiss is suggested to be a key regulator of the hypothalamus-pituitary-gonad axis (HPG). However, its regulatory role on reproduction in fish remains unclear. Therefore, to investigate the role of Kiss on fish reproduction, this study aimed to test differences in the hormones of the HPG axis, Kiss as neuropeptides, and sex steroids on the sexual maturation of paired cinnamon clownfish, Amphiprion melanopus, following treatment with Kiss. We investigated the actions of sex maturation hormones, including HPG axis hormones and sex steroid hormones, such as gonadotropin-releasing hormones, gonadotropin hormones (GTHs), GTH receptors, estrogen receptors, and vitellogenin in the pituitary, gonads, and liver following treatment with Kiss. The expression levels of HPG axis genes increased after the Kiss injection. In addition, the levels of plasma 17α-hydroxypregnenolone, estradiol-17β, and 11-ketotestosterone increased. These results support the hypothesis that Kiss play important roles in the regulation of the HPG axis and are most likely involved in gonadal development and sexual maturation in cinnamon clownfish. Copyright © 2013 Elsevier Inc. All rights reserved.

A General Theory of Sexual Differentiation

PubMed Central

Arnold, Arthur P.

2016-01-01

A general theory of mammalian sexual differentiation is proposed. All biological sex differences are the result of the inequality in effects of the sex chromosomes, which are the only factors that differ in XX vs. XY zygotes. This inequality leads to male-specific effects of the Y chromosome, including expression of the testis-determining gene Sry that causes differentiation of testes. Thus, Sry sets up lifelong sex differences in effects of gonadal hormones. Y genes also act outside of the gonads to cause male-specific effects. Differences in the number of X chromosomes between XX and XY cells causes sex differences in expression (1) of Xist, (2) of X genes that escape inactivation, and (2) of parentally imprinted X genes. Sex differences in phenotype are ultimately the result of multiple, independent sex-biasing factors, hormonal and sex chromosomal. These factors act in parallel and in combination to induce sex differences. They can also can offset each other to reduce sex differences. Other mechanisms, operating at the level of populations, cause groups of males to differ on average from groups of females. The theory has advantages for directing attention to inherent sex-biasing factors that operate in many tissues to cause sex differences, to cause sex-biased protection from disease, and to frame questions for further study. PMID:27870435

A general theory of sexual differentiation.

PubMed

Arnold, Arthur P

2017-01-02

A general theory of mammalian sexual differentiation is proposed. All biological sex differences are the result of the inequality in effects of the sex chromosomes, which are the only factors that differ in XX vs. XY zygotes. This inequality leads to male-specific effects of the Y chromosome, including expression of the testis-determining gene Sry that causes differentiation of testes. Thus, Sry sets up lifelong sex differences in effects of gonadal hormones. Y genes also act outside of the gonads to cause male-specific effects. Differences in the number of X chromosomes between XX and XY cells cause sex differences in expression (1) of Xist, (2) of X genes that escape inactivation, and (3) of parentally imprinted X genes. Sex differences in phenotype are ultimately the result of multiple, independent sex-biasing factors, hormonal and sex chromosomal. These factors act in parallel and in combination to induce sex differences. They also can offset each other to reduce sex differences. Other mechanisms, operating at the level of populations, cause groups of males to differ on average from groups of females. The theory frames questions for further study, and directs attention to inherent sex-biasing factors that operate in many tissues to cause sex differences, and to cause sex-biased protection from disease. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Efficient and Heritable Gene Targeting in Tilapia by CRISPR/Cas9

PubMed Central

Li, Minghui; Yang, Huihui; Zhao, Jiue; Fang, Lingling; Shi, Hongjuan; Li, Mengru; Sun, Yunlv; Zhang, Xianbo; Jiang, Dongneng; Zhou, Linyan; Wang, Deshou

2014-01-01

Studies of gene function in non-model animals have been limited by the approaches available for eliminating gene function. The CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR associated) system has recently become a powerful tool for targeted genome editing. Here, we report the use of the CRISPR/Cas9 system to disrupt selected genes, including nanos2, nanos3, dmrt1, and foxl2, with efficiencies as high as 95%. In addition, mutations in dmrt1 and foxl2 induced by CRISPR/Cas9 were efficiently transmitted through the germline to F1. Obvious phenotypes were observed in the G0 generation after mutation of germ cell or somatic cell-specific genes. For example, loss of Nanos2 and Nanos3 in XY and XX fish resulted in germ cell-deficient gonads as demonstrated by GFP labeling and Vasa staining, respectively, while masculinization of somatic cells in both XY and XX gonads was demonstrated by Dmrt1 and Cyp11b2 immunohistochemistry and by up-regulation of serum androgen levels. Our data demonstrate that targeted, heritable gene editing can be achieved in tilapia, providing a convenient and effective approach for generating loss-of-function mutants. Furthermore, our study shows the utility of the CRISPR/Cas9 system for genetic engineering in non-model species like tilapia and potentially in many other teleost species. PMID:24709635

Assessing the putative roles of X-autosome and X-Y interactions in hybrid male sterility of the Drosophila bipectinata species complex.

PubMed

Mishra, Paras Kumar; Singh, Bashisth Narayan

2007-07-01

Interspecific F1 hybrid males of the Drosophila bipectinata species complex are sterile, while females are fertile, following Haldane's rule. A backcross scheme involving a single recessive visible marker on the X chromosome has been used to assess the putative roles of X-autosome and X-Y interactions in hybrid male sterility in the D. bipectinata species complex. The results suggest that X-Y interactions are playing the major role in hybrid male sterility in the crosses D. bipectinata x D. parabipectinata and D. bipectinata x D. pseudoananassae, while X-autosome interactions are largely involved in hybrid male sterility in the crosses D. malerkotliana x D. bipectinata and D. malerkotliana x D. parabipectinata. However, by using this single marker it is not possible to rule out the involvement of autosome-autosome interactions in hybrid male sterility. These findings also lend further support to the phylogenetic relationships among 4 species of the D. bipectinata complex.

Seasonal modulation of immunity by melatonin and gonadal steroids in a short day breeder goat Capra hircus.

PubMed

Ghosh, Somenath; Singh, Amaresh K; Haldar, Chandana

2014-11-01

Role of melatonin in regulation of immunity and reproduction has never been studied in detail in goats. The aim of the present study was to explore hormonal regulation of immunity in goats with special reference to melatonin. Plasma of male and female goats (n = 18 per sex per season) was processed for hormonal (estrogen, testostrone, and melatonin) and cytokine (interleukin [IL-2], IL-6, and tumor necrosis factor α) measurements during three seasons, i.e., summer, monsoon, and winter. To assess cell-mediated immune response, percent stimulation ratio of thymocytes was recorded during three seasons. To support and establish the modulation by hormones, Western blot analysis for expressions of melatonin receptors (MT1, MT2), androgen receptor, and estrogen receptor α and estimations of marker enzymes, arylalkylamine N-acetyltransferase for melatonin and 3β-hydroxysteroid dehydrogenase activities for steroidogenesis were performed in thymus. All the hormones and cytokines were estimated by commercial kits. Biochemical, immunologic, and Western blot analyses were done by standardized protocols. We noted a significant increase in estrogen and testosterone levels (P < 0.05) in circulation during monsoon along with melatonin (P < 0.05) presenting a parallel relationship. Expressions of melatonin receptors (MT1 and MT2) in thymus of both the sexes were significantly high (P < 0.01) during winter. Estrogen receptor α expression in female thymus was significantly high during monsoon (P < 0.05). However, androgen receptor showed almost static expression pattern in male thymus during three seasons. Further, both arylalkylamineN-acetyltransferase and 3β-hydroxysteroid dehydrogenase enzyme activities were significantly high (P < 0.05; P < 0.01, respectively) during monsoon. These results suggest that there may be a functional parallelism between gonadal steroids and melatonin as melatonin is progonadotrophic in goats. Cell-mediated immune parameters (percent stimulation

Germ cells are not the primary factor for sexual fate determination in goldfish.

PubMed

Goto, Rie; Saito, Taiju; Takeda, Takahiro; Fujimoto, Takafumi; Takagi, Misae; Arai, Katsutoshi; Yamaha, Etsuto

2012-10-01

The presence of germ cells in the early gonad is important for sexual fate determination and gonadal development in vertebrates. Recent studies in zebrafish and medaka have shown that a lack of germ cells in the early gonad induces sex reversal in favor of a male phenotype. However, it is uncertain whether the gonadal somatic cells or the germ cells are predominant in determining gonadal fate in other vertebrate. Here, we investigated the role of germ cells in gonadal differentiation in goldfish, a gonochoristic species that possesses an XX-XY genetic sex determination system. The primordial germ cells (PGCs) of the fish were eliminated during embryogenesis by injection of a morpholino oligonucleotide against the dead end gene. Fish without germ cells showed two types of gonadal morphology: one with an ovarian cavity; the other with seminiferous tubules. Next, we tested whether function could be restored to these empty gonads by transplantation of a single PGC into each embryo, and also determined the gonadal sex of the resulting germline chimeras. Transplantation of a single GFP-labeled PGC successfully produced a germline chimera in 42.7% of the embryos. Some of the adult germline chimeras had a developed gonad on one side that contained donor derived germ cells, while the contralateral gonad lacked any early germ cell stages. Female germline chimeras possessed a normal ovary and a germ-cell free ovary-like structure on the contralateral side; this structure was similar to those seen in female morphants. Male germline chimeras possessed a testis and a contralateral empty testis that contained some sperm in the tubular lumens. Analysis of aromatase, foxl2 and amh expression in gonads of morphants and germline chimeras suggested that somatic transdifferentiation did not occur. The offspring of fertile germline chimeras all had the donor-derived phenotype, indicating that germline replacement had occurred and that the transplanted PGC had rescued both female and

Telomeric fusion and chromosome instability in multiple tissues of a patient with mosaic Ullrich-Turner syndrome

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

Sawyer, J.R.; North, P.E.; Hassed, S.J.

1997-04-14

We describe the cytogenetic evolution of multiple cell lines in the gonadal tissue of a 10-year-old girl with mosaic Ullrich-Turner syndrome (UTS) involving clonal telomeric associations (tas) of the Y chromosome. G-band analysis of all tissues showed at least 2 cell lines; 45,X and 46,X,tas(Y;21)(q12;p13). However, analysis of left gonadal tissue of this patient showed the evolution of 2 additional cell lines, one designated 45,X,tas(Y;21)(q12;p13),-22 and the other 46,X,tas(Y;21)(q12;p13),+tas(Y;14)(q12;p13),-22. Fluorescence in situ hybridization (FISH) analysis of interphase nuclei from uncultured gonadal tissue confirmed the findings of aneuploidy in the left gonadal tissue and extended the findings of aneuploidy to themore » tissue of the right gonad. The chromosome findings in the gonadal tissue of this patient suggest a preneoplastic karyotype relating to several distinct tumor associations. The clonal evolution of telomeric fusions indicates chromosome instability and suggests the extra copy of the Y chromosome may have resulted from a fusion-related malsegregation. In addition, the extra Y suggests low-level amplification of a putative gonadoblastoma gene, while the loss of chromosome 22 suggests the loss of heterozygosity for genes on chromosome 22. This case demonstrates the utility of the study of gonadal tissue in 45X46,XY UTS patients, and provides evidence that clonal telomeric fusions may, in rare cases, be associated with chromosomal malsegregation and with the subsequent evolution of unstable karyotypes. 27 refs., 3 figs.« less

A timecourse analysis of systemic and gonadal effects of temperature on sexual development of the red-eared slider turtle Trachemys scripta elegans.

PubMed

Czerwinski, Michael; Natarajan, Anirudh; Barske, Lindsey; Looger, Loren L; Capel, Blanche

2016-12-01

Temperature dependent sex determination (TSD) is the process by which the environmental temperature experienced during embryogenesis influences the sex of an organism, as in the red-eared slider turtle Trachemys scripta elegans. In accord with current paradigms of vertebrate sex determination, temperature is believed to exert its effects on sexual development in T. scripta entirely within the middle third of development, when the gonad is forming. However, whether temperature regulates the transcriptome in T. scripta early embryos in a manner that could influence secondary sex characteristics or establish a pro-male or pro-female environment has not been investigated. In addition, apart from a handful of candidate genes, very little is known about potential similarities between the expression cascade during TSD and the genetic cascade that drives mammalian sex determination. Here, we conducted an unbiased transcriptome-wide analysis of the effects of male- and female-promoting temperatures on the turtle embryo prior to gonad formation, and on the gonad during the temperature sensitive period. We found sexually dimorphic expression reflecting differences in steroidogenic enzymes and brain development prior to gonad formation. Within the gonad, we mapped a cascade of differential expression similar to the genetic cascade established in mammals. Using a Hidden Markov Model based clustering approach, we identified groups of genes that show heterochronic shifts between M. musculus and T. scripta. We propose a model in which multiple factors influenced by temperature accumulate during early gonadogenesis, and converge on the antagonistic regulation of aromatase to canalize sex determination near the end of the temperature sensitive window of development. Copyright © 2016 Elsevier Inc. All rights reserved.

WNT4 signaling in female gonadal development.

PubMed

Pellegrino, Miriam; Maiorino, Raffaella; Schonauer, Sergio

2010-06-01

WNT4 signaling pathways represent an important step in the multi-faceted process of mammalian gonadal differentiation and the development of internal genitalia. WNT4 protein controls the cytoplasmatic stability of specific transcriptional coactivator beta catenin during both embriogenesis and adult homeostasis. The biological significance of WNT4 consists in determining the final female reproductive system, inhibiting Wolff ducts' differentiation, male steroidogenesis and vascular cell migration. An overview of WNT4 cellular mechanisms is given in order to understand its critical role in the genesis of various human diseases such as congenital malformations and gynecological disorders like polycystic ovary syndrome (PCOS). The final discussion focusses on several possible therapeutic uses of Wnt4 both during pregnancy in order to correct the genetic loss of function of the protein and during adulthood in order to normalize fertility in PCOS-affected females planning pregnancy.

On gonads and gadflies: the estrus angle.

PubMed

Hillier, Stephen G

2017-06-01

The first sex steroid to be crystallized was the vertebrate ovarian hormone, estrone - a less potent metabolite of 17β-estradiol, which in mammals stimulates the female urge to mate (estrus). The gadfly (Greek oistros ) lent its name to the process of estrus, as an insect that bites and torments in classical Greek mythology. With the purification and crystallization of a moult-inducing steroid (ecdysone) from insects, an interesting parallel emerged between mating and moulting in lower mammals and arthropods. Ecdysterone (potent ecdysone metabolite) has anabolic effects in mammalian muscle cells that can be blocked by selective estrogen receptor antagonists. Insects utilize ecdysteroids in similar ways that vertebrates use estrogens, including stimulation of oocyte growth and maturation. Ecdysteroids also modify precopulatory insect mating behaviour, further reinforcing the gonad-gadfly/mate-moult analogy. © 2017 Society for Endocrinology.

Development of the larval amphibian growth and development ...

EPA Pesticide Factsheets

The Larval Amphibian Growth and Development Assay (LAGDA) is a Tier II test guideline being developed by the US Environmental Protection Agency under the Endocrine Disruptor Screening Program. The LAGDA was designed to evaluate effects of chronic chemical exposure on growth, thyroid-mediated amphibian metamorphosis and reproductive development. To evaluate the assay’s performance, two model chemicals targeting the hypothalamic-pituitary-gonadal (HPG) axis were tested; a weak estrogen receptor agonist, 4-tert-octylphenol (tOP), and an androgen receptor agonist, 17β-trenbolone (TB). Xenopus laevis embryos were constantly exposed in flow-through conditions to various test concentrations of tOP (nominal: 6.25, 12.5, 25, 50 μg/L) or TB (nominal: 12.5, 25, 50, 100 ng/L) and clean water controls until 8 weeks post-metamorphosis, at which time growth measurements were taken and histopathology assessments were made on gonads, reproductive ducts, liver and kidneys. There were no effects on growth in either study and no signs of overt toxicity, sex reversal or gonad dysgenesis at the concentrations tested. Exposure to tOP caused a treatment-related decrease in circulating thyroxine and an increase in thyroid follicular cell hypertrophy and hyperplasia (25, 50 μg/L). Müllerian duct development was clearly affected following exposure to both chemicals; tOP exposure caused dose-dependent maturation of oviducts in both male and female frogs, whereas TB exposure ca

Molecular and morphological differentiation of testes and ovaries in relation to the thermosensitive period of gonad development in the snapping turtle, Chelydra serpentina.

PubMed

Rhen, Turk; Fagerlie, Ruby; Schroeder, Anthony; Crossley, Dane A; Lang, Jeffrey W

2015-01-01

Ambient temperatures during embryonic development determine gonadal sex in many reptiles. The temperature sensitive period for sex determination has been defined by shifting eggs between female- and male-producing temperatures in a few species. This phase spans 20-35% of embryogenesis in most species, which makes it difficult to define the mechanisms that transduce temperature into a signal for ovarian versus testicular development. We present an extensive set of studies that define a brief period when high temperature specifies, and then determines, ovarian fate in a northern population of snapping turtles, Chelydra serpentina. We shifted embryos from male to female temperatures, or vice versa, at various stages of development. Gonads in embryos incubated at female temperatures commit to ovarian fate earlier (by stage 18) than gonads in embryos incubated at male temperatures commit to testicular fate (by stages 19-21). In double shift studies, embryos were incubated at a female temperature, exposed to a male temperature for set times, and shifted back to the original temperature, or vice versa. The time required to induce ovarian development (≤6 days at female temperatures) was much shorter than the time required to induce testicular formation (>20 days at male temperatures). Differentiation of the gonads at the histological level occurred after the sex-determining period. Nevertheless, we found that a change in temperature rapidly (within 24h) influenced expression and splicing of WT1 mRNA: the absolute abundance of WT1 mRNA, the relative abundance of +KTS versus -KTS isoforms, as well as the ratio of +KTS:-KTS isoforms was higher in gonads at a male versus a female temperature. In conclusion, ovarian fate is more readily determined than testicular fate in snapping turtle embryos. The short sex-determining period in this species (6-8% of embryogenesis) will facilitate studies of molecular mechanisms for specification and determination of gonad fate by

Duality-mediated critical amplitude ratios for the (2 + 1)-dimensional S = 1XY model

NASA Astrophysics Data System (ADS)

Nishiyama, Yoshihiro

2017-09-01

The phase transition for the (2 + 1)-dimensional spin-S = 1XY model was investigated numerically. Because of the boson-vortex duality, the spin stiffness ρs in the ordered phase and the vortex-condensate stiffness ρv in the disordered phase should have a close relationship. We employed the exact diagonalization method, which yields the excitation gap directly. As a result, we estimate the amplitude ratios ρs,v/Δ (Δ: Mott insulator gap) by means of the scaling analyses for the finite-size cluster with N ≤ 22 spins. The ratio ρs/ρv admits a quantitative measure of deviation from selfduality.

Morphometric and histopathological parameters of gonadal development in adult common carp from contaminated and reference sites in Lake Mead, Nevada

USGS Publications Warehouse

Patino, R.; Goodbred, S.L.; Draugelis-Dale, R.; Barry, C.E.; Scott, Foott J.; Wainscott, M.R.; Gross, T.S.; Covay, K.J.

2003-01-01

This study examined the hypothesis that exposure to sublethal concentrations of contaminants alters the gonadal condition of feral common carp Cyprinus carpio. Adult common carp in Lake Mead, Nevada, were collected from a contaminated site (Las Vegas Bay) that receives municipal and industrial effluent and from a reference site (Overton Arm) with a relatively low level of contamination. Fish were sampled seven times over a 1-year period extending over two separate spawning seasons. Morphometric and histopathological parameters of gonadal and germ cell development were determined. In males, the pattern of seasonal changes in the gonadosomatic index (GSI) was similar between the sites and showed no clear association with site-specific seasonal temperature profiles. However, Las Vegas Bay males had consistently lower GSI values and, on one of the sampling dates, a lower proportion of sperm relative to other germ cell stages (determined histologically). Further, Las Vegas Bay males had a higher incidence of gonadal macrophage aggregates, which are putative tissue biomarkers of contaminant exposure in fishes. In females, seasonal GSI profiles, the frequency of fish with postovulatory follicles (an index of spawning activity), and the timing of new follicle recruitment all showed differences between sites, but these differences generally matched differences in water temperature profile. Also, the peak size-frequency of full-grown follicles did not differ between sites, and estimates of fecundity for the second spawning season indicated that females from the reference site unexpectedly produced a lower number of gametes, Overall, site differences in gonadal condition were observed in carp of both sexes but they seemed to be associated with site differences in contaminant levels only in males. The apparent lack of association between contaminant level and gonadal condition in female carp from mildly mesotrophic Lake Mead may indicate a lack of contaminant effects in

Gonadal Hormone Modulation of Mu, Kappa, and Delta Opioid Antinociception in Male and Female Rats

PubMed Central

Stoffel, Erin C.; Ulibarri, Catherine M.; Folk, John E.; Rice, Kenner C.

2005-01-01

Previous studies suggest that sex differences in morphine antinociception in rodents might be attributed to the activational effects of gonadal hormones. The present study determined whether hormonal modulation of opioid antinociception in adult rats extends to opioids other than the prototypic mu agonist morphine. Male and female rats were sham-gonadectomized (sham-GDX) or gonadectomized (GDX) and replaced with no hormone, estradiol (E2, females), progesterone (P4, females), E2+P4 (females), or testosterone (males). Approximately 28 days later, nociception was evaluated on the 50°C hot plate and warm water tail withdrawal tests before and after subcutaneous administration of hydromorphone, buprenorphine, U50,488, or SNC 80. In sham-GDX (gonadally intact) rats, the mu agonists and U50,488 were less effective in females than in males in at least one nociceptive test, and the delta agonist SNC 80 was less effective in males than in females. In males, gonadectomy tended to decrease, and testosterone tended to increase antinociception produced by 3 of the 4 agonists. In females, gonadectomy and hormone treatment had more variable effects, although E2 tended to decrease mu opioid antinociception. The present results suggest that activational effects of gonadal hormones are relatively modest and somewhat inconsistent on antinociception produced by various opioid agonists in the adult rat. Perspective: This study demonstrates that reproductive hormones such as testosterone in males and estradiol in females do not consistently modulate sensitivity to the analgesic effects of opioids in the adult organism. PMID:15820914

Case of successful IVF treatment of an oligospermic male with 46,XX/46,XY chimerism.

PubMed

Laursen, R J; Alsbjerg, B; Vogel, I; Gravholt, C H; Elbaek, H; Lildballe, D L; Humaidan, P; Vestergaard, E M

2018-04-30

We present a case of an infertile male with 46,XX/46,XYchimerism fathering a child after ICSI procedure. Conventional cytogenetic analysis on chromosomes, derived from lymphocytes, using standard Q-banding procedures with a 450-550-band resolution and short-tandem-repeat analysis of 14 loci. Analysis of 20 metaphases from lymphocytes indicated that the proband was a karyotypic mosaic with an almost equal distribution between male and female cell lines. In total, 12 of 20 (60%) metaphases exhibited a normal female karyotype 46,XX, while 8 of 20 (40%) metaphases demonstrated a normal male karyotype 46,XY. No structural chromosomal abnormalities were present. Out of 14 STR loci, two loci (D18S51 and D21S11) showed four different alleles in peripheral blood, buccal mucosal cells, conjunctival mucosal cells, and seminal fluid. In three loci (D2S1338, D7S820, and vWA), three alleles were detected with quantitative differences that indicated presence of four alleles. In DNA extracted from washed semen, four alleles were detected in one locus, and three alleles were detected in three loci. This pattern is consistent with tetragametic chimerism. There were no quantitative significant differences in peak heights between maternal and paternal alleles. STR-analysis on DNA from the son confirmed paternity. We report a unique case with 46,XX/46,XY chimerism confirmed to be tetragametic, demonstrated in several tissues, with male phenotype and no genital ambiguity with oligospermia fathering a healthy child after IVF with ICSI procedure.

Defect engineering of complex semiconductor alloys: Cu2-2xMxO1-yXy

NASA Astrophysics Data System (ADS)

Lany, Stephan; Stevanovic, Vladan

2013-03-01

The electrical properties of semiconductors are generally controlled via doping, i.e., the incorporation of dilute concentrations of aliovalent impurity atoms, whereas the band structure properties (gap, effective masses, optical properties) are manipulated by alloying, i.e., the incorporation of much larger amounts of isovalent elements. Theoretical approaches usually address either doping or alloying, but rarely both problems at the same time. By combining defect supercell calculations, GW quasi-particle energy calculation, and thermodynamic modeling, we study the range of electrical and band structure properties accessible by alloying aliovalent cations (M = Mg, Zn, Cd) and isovalent anions (X = S, Se) in Cu2O. In order to extend dilute defect models to higher concentrations, we take into account the association/dissociation of defect pairs and complexes, as well as the composition dependence of the band gap and the band edge energies. Considering a composition window for the Cu2-2xMxO1-yXy alloys of 0 <= (x,y) <= 0.2, we predict a wide range of possible band gaps from 1.7 to 2.6 eV, and net doping concentrations between p = 1019 cm-3 and n = 1017cm-3, notably achieving type conversion from p- to n-type at Zn or Cd compositions around x = 0.1. This work is supported as part of the SunShot initiative by the U. S. Department of Energy, Office of Energy Efficiency and Renewable Energy under Contract No. DE-AC36-08GO28308 to NREL.

Identification of Gender-specific Transcripts by Microarray in Gonad Tissue of Larval and Juvenile Xenopus tropicalis

EPA Science Inventory

Amphibian model species Xenopus tropicalis is currently being utilized by EPA in the development of a standardized in vivo reproductive toxicity assay. Perturbations to the hypothalamic-pituitary-gonadal axis from exposure to endocrine disrupting compounds during larval develop...

Estrogenic environmental contaminants alter the mRNA abundance profiles of genes involved in gonadal differentiation of the American bullfrog

PubMed Central

Wolff, Stephanie E.; Veldhoen, Nik; Helbing, Caren C.; Ramirez, Claire A.; Malpas, Janae M.; Propper, Catherine R.

2015-01-01

Wildlife and human populations are exposed to anthropogenic mixtures of chemicals in the environment that may adversely influence normal reproductive function and development. We determined the effects of exposure to estrogenic chemicals and wastewater effluent (WWE) on developing gonads of the American bullfrog, Rana (Lithobates) catesbeiana, a species whose widespread distribution make it an ideal model for environmental monitoring for endocrine effects of chemical contaminants. Premetamorphic bullfrog tadpoles were exposed to treatment vehicle, 17β-estradiol (E2; 10−9 M) or 4-tert-octylphenol (OP; 10−9 M, 10−8 M, and 10−7 M). Additionally, gonadal differentiation was evaluated in bullfrog tadpoles from a WWE-containing site versus those from a reference location receiving no WWE. In both studies, phenotypic sex, steroidogenic factor-1 (nr5a1), and aromatase (cyp19a1) mRNA levels using quantitative real-time PCR were determined. Exposure to E2 or OP did not alter sex ratios. In controls, both nr5a1 and cyp19a1 transcript levels exhibited sexual dimorphism, with males demonstrating higher levels of nr5a1 and females greater abundance of cyp19a1. However, E2 exposure increased cyp19a1 mRNA abundance in testes and decreased levels in ovaries, eliminating the sexual dimorphism observed in controls. E2-exposed males exhibited increased nr5a1 transcript levels in the testes compared to controls, while females demonstrated no E2 effect. OP treatment had no effect on female cyp19a1 mRNA abundance, but exposure to 10−7 M OP increased testicular transcript levels. Treatment with 10−9 and 10−8 M OP, but not 10−7 M, resulted in decreased abundance of nr5a1 transcript in both ovaries and testes. Animals from the field had sexually dimorphic gonadal levels of cyp19a1, but both sexes from the WWE site exhibited elevated cyp19a1 transcript abundance compared to the reference location. Individual chemical compounds and anthropogenic wastewater effluent dispersed

Successive magnetic phase transitions in α -RuCl3 : XY-like frustrated magnet on the honeycomb lattice

NASA Astrophysics Data System (ADS)

Kubota, Yumi; Tanaka, Hidekazu; Ono, Toshio; Narumi, Yasuo; Kindo, Koichi

2015-03-01