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Sample records for adult human testis

  1. Generation of pluripotent stem cells from adult human testis.

    PubMed

    Conrad, Sabine; Renninger, Markus; Hennenlotter, Jörg; Wiesner, Tina; Just, Lothar; Bonin, Michael; Aicher, Wilhelm; Bühring, Hans-Jörg; Mattheus, Ulrich; Mack, Andreas; Wagner, Hans-Joachim; Minger, Stephen; Matzkies, Matthias; Reppel, Michael; Hescheler, Jürgen; Sievert, Karl-Dietrich; Stenzl, Arnulf; Skutella, Thomas

    2008-11-20

    Human primordial germ cells and mouse neonatal and adult germline stem cells are pluripotent and show similar properties to embryonic stem cells. Here we report the successful establishment of human adult germline stem cells derived from spermatogonial cells of adult human testis. Cellular and molecular characterization of these cells revealed many similarities to human embryonic stem cells, and the germline stem cells produced teratomas after transplantation into immunodeficient mice. The human adult germline stem cells differentiated into various types of somatic cells of all three germ layers when grown under conditions used to induce the differentiation of human embryonic stem cells. We conclude that the generation of human adult germline stem cells from testicular biopsies may provide simple and non-controversial access to individual cell-based therapy without the ethical and immunological problems associated with human embryonic stem cells.

  2. Age-associated changes in microvasculature of human adult testis.

    PubMed

    Takizawa, T; Hatakeyama, S

    1978-07-01

    Age-associated architectural changes of the human testicular microvasculature from 70 autopsy cases were stereoscopically examined with a silicone-rubber injection technique. In the testis of a young subject, the interlobular main arteries run straight. The coiling phenomena of the interlobular centripetal or centrifugal arteries, which are commonly seen in adult testis, have been so far considered as physiological transformation of the vasculature. It was confirmed that the coiling changes in the interlobular main arteries of the human testis appear as an age-dependent alteration of the vasculature closely related to the volume of the gland. The practical importance of the spirallin or coiling of arteries is that it results in a considerable reduction of blood flow. The age-related coiling of the interlobular arteries is virtually accompanied by varying degrees of collapse of the peritubular capillary networks. The reduction of blood supply to the seminiferous tubules plays an active role in promoting aging of the testis. These stereoscopical observations of age-related transfiguration of testicular microvasculature were ascertained also by histometrical examinations.

  3. Paracetamol, aspirin and indomethacin display endocrine disrupting properties in the adult human testis in vitro.

    PubMed

    Albert, O; Desdoits-Lethimonier, C; Lesné, L; Legrand, A; Guillé, F; Bensalah, K; Dejucq-Rainsford, N; Jégou, B

    2013-07-01

    Do mild analgesics affect the endocrine system of the human adult testis? Mild analgesics induce multiple endocrine disturbances in the human adult testis in vitro. Mild analgesics have recently been incriminated as potential endocrine disruptors. Studies of the effects of these widely used molecules on the androgenic status of men are limited and somewhat contradictory. This prompted us to investigate whether these compounds could alter the adult human testicular function. We therefore assessed in parallel the effects of paracetamol, aspirin and indomethacin on organo-cultured adult human testis and on the NCI-H295R steroid-producing human cell line. Adult human testis explants or NCI-H295R adrenocortical human cells were cultured with 10(-4) or 10(-5) M paracetamol, aspirin or indomethacin for 24-48 h. The effect of 10(-5) M ketoconazole, used as an anti-androgenic reference molecule, was also assessed. Testes were obtained from prostate cancer patients, who had not received any hormone therapy. The protocol was approved by the local ethics committee of Rennes, France and informed consent was given by the donors. Only testes displaying spermatogenesis, as assessed by transillumination, were used in this study. Hormone levels in the culture media were determined by radioimmunoassay (testosterone, insulin-like factor 3), Enzyme-Linked Immunosorbent Assay (inhibin B) or Enzyme Immunosorbent Assay [prostaglandin (PG) D2, and PGE2]. Tissues were observed and cells counted using classical immunohistochemical methods. The three mild analgesics caused multiple endocrine disturbances in the adult human testis. This was particularly apparent in the interstitial compartment. Effective doses were in the same range as those measured in blood plasma following standard analgesic treatment. The production of testosterone and insulin-like factor 3 by Leydig cells was altered by exposure to all these drugs. Inhibin B production by Sertoli cells was marginally affected by aspirin

  4. Stage-specific Localization and Expression of c-kit in the Adult Human Testis

    PubMed Central

    Unni, Sreepoorna K.; Modi, Deepak N.; Pathak, Shilpa G.; Dhabalia, Jayesh V.; Bhartiya, Deepa

    2009-01-01

    The c-kit receptor (KIT) and its ligand, stem cell factor (SCF), represent one of the key regulators of testicular formation, development, and function and have been extensively studied in various animal models. The present study was undertaken to characterize the pattern of localization and expression of c-kit in normal adult human testis. Immunohistochemical analysis showed that KIT is expressed in the cytoplasm of spermatogonia, acrosomal granules of spermatids, and Leydig cells. Interestingly, a rather heterogenous pattern of expression of the protein along the basement membrane was observed. Intense protein localization in spermatogonia was detected in stages I–III, whereas low expression was observed in stages IV–VI of the seminiferous epithelium, indicating that the expression of the molecule was stage specific. In situ hybridization studies revealed that the transcripts of the gene were also localized in a similar non-uniform pattern. To the best of our knowledge, such a stage-specific expression of KIT has not been reported previously in the human testis. The results of the present study may expand current knowledge about the c-kit/SCF system in human spermatogenesis. (J Histochem Cytochem 57:861–869, 2009) PMID:19435714

  5. Parallel assessment of the effects of bisphenol A and several of its analogs on the adult human testis.

    PubMed

    Desdoits-Lethimonier, C; Lesné, L; Gaudriault, P; Zalko, D; Antignac, J P; Deceuninck, Y; Platel, C; Dejucq-Rainsford, N; Mazaud-Guittot, S; Jégou, B

    2017-05-08

    Are bisphenol A (BPA) and BPA analogs (BPA-A) safe for male human reproductive function? The endocrine function of human testes explants [assessed by measuring testosterone and insulin-like factor 3 (INSL3)] was impacted by exposure of the human adult testis explants to BPA/BPA-A. The few epidemiologic studies performed suggest that bisphenols have potential endocrine disruptive properties, but they did not identify clear and direct patterns of endocrine disruption. Adult human testis explants in culture were exposed to BPA and the analogs bisphenol F (BPF), bisphenol S (BPS), bisphenol E (BPE), bisphenol B (BPB) and bisphenol A diglycidyl ether (BADGE) at 10-9-10-5M for 24 or 48 h. Human adult testes were obtained from prostate cancer patients who had no hormone therapy, or from multiorgan donors. After ex vivo exposure to the investigated bisphenols, the measured outcomes were related to histopathology (gross morphology and germ cell viability determined by anti-caspase three immunohistochemistry), and the levels of testosterone, INSL3 and inhibin B were measured using immunoassays. The levels of mRNA encoding key enzymes of bisphenol biotransformation were investigated by quantitative PCR: UGT2B15 UDP (glucuronosyltransferase two family, polypeptide B15), GUSB (glucuronidase beta), SULT1A1and 3 (sulfotransferase family 1 A member 1 and 3) and STS (steroid sulfatase). A significant dose-dependent inhibition was found between testosterone levels measured in the culture medium and concentrations of BPA (P = 0.00778 at 24 h and P = 0.0291 at 48 h), BPE (P = 0.039) and BPF (P = 0.00663). The observed BPA and BPA-A-induced inhibition of testosterone production varied according to duration of exposure and BPA/BPA-A concentrations. BPA (10-9M; P < 0.05), BPB (10-9M; P < 0.05), BPS (10-9 and 10-8 M; P < 0.05) and BADGE (10-5 M; P < 0.05) increased Leydig cell INSL3 production. By contrast, BPE dose dependently inhibited INSL3 (P = 0.0372). Conversely, Sertoli cell

  6. Testis-specific expression of the human MYCL2 gene.

    PubMed Central

    Robertson, N G; Pomponio, R J; Mutter, G L; Morton, C C

    1991-01-01

    We have characterized the expression of MYCL2, an intronless X-linked gene related to MYCL1. RNase protection analysis of a panel of human normal and tumor tissues has revealed that MYCL2 is expressed almost exclusively in human adult normal testis; much lower levels of transcript were detected in one human lung adenocarcinoma. No MYCL2 transcript was found in human testis RNA obtained from second trimester fetuses. This observation suggests a germ cell rather than somatic cell origin of the transcript and possible developmental regulation of MYCL2. Northern blot analysis of poly(A)+ RNA from adult human normal testis with an antisense riboprobe revealed a transcript of approximately 4.8-kb, which is in agreement with the size predicted from the MYCL2 nucleotide sequence. Antisense transcripts were found spanning regions of MYCL2 corresponding to all three exons of MYCL1. No sizable open reading frame was seen for the MYCL2 antisense transcripts suggesting that they may represent either regulatory sequences or an intron of a gene encoded by the complementary strand. RNase protection assays and the 5' RACE protocol (Rapid Amplification of cDNA Ends) were used to address the localization of the transcription start site of the MYCL2 sense transcript and different putative promoters and transcription regulatory elements have been identified. Images PMID:1711681

  7. Aging of the human ovary and testis.

    PubMed

    Perheentupa, Antti; Huhtaniemi, Ilpo

    2009-02-05

    Aging is associated with structural and functional alterations in all organs of the human body. The aging of gonads represents in this respect a special case, because these organs are not functional for the whole lifespan of an individual and their normal function is not indispensable for functions of the rest of the body. Ovarian function lasts for the reproductive life of a woman, i.e., from menarche until menopause. The testicular endocrine function, in contrast, begins already in utero, is interrupted between neonatal life and puberty, and continues thereafter along with spermatogenesis, with only slight decline, until old age. The aging processes of the ovary and testis are therefore very different. We describe in this review the structural and functional alterations in the human ovary and testis upon aging. Special emphasis will be given to clinically significant alterations, which in women concern the causes and consequences of the individual variability of fertility during the latter part of the reproductive age. The clinically important aspect of testicular aging entails the decline of androgen production in aging men.

  8. In Vitro Spermatogenesis in Explanted Adult Mouse Testis Tissues.

    PubMed

    Sato, Takuya; Katagiri, Kumiko; Kojima, Kazuaki; Komeya, Mitsuru; Yao, Masahiro; Ogawa, Takehiko

    2015-01-01

    Research on in vitro spermatogenesis is important for elucidating the spermatogenic mechanism. We previously developed an organ culture method which can support spermatogenesis from spermatogonial stem cells up to sperm formation using immature mouse testis tissues. In this study, we examined whether it is also applicable to mature testis tissues of adult mice. We used two lines of transgenic mice, Acrosin-GFP and Gsg2-GFP, which carry the marker GFP gene specific for meiotic and haploid cells, respectively. Testis tissue fragments of adult GFP mice, aged from 4 to 29 weeks old, which express GFP at full extension, were cultured in medium supplemented with 10% KSR or AlbuMAX. GFP expression decreased rapidly and became the lowest at 7 to 14 days of culture, but then slightly increased during the following culture period. This increase reflected de novo spermatogenesis, confirmed by BrdU labeling in spermatocytes and spermatids. We also used vitamin A-deficient mice, whose testes contain only spermatogonia. The testes of those mice at 13-21 weeks old, showing no GFP expression at explantation, gained GFP expression during culturing, and spermatogenesis was confirmed histologically. In addition, the adult testis tissues of Sl/Sld mutant mice, which lack spermatogenesis due to Kit ligand mutation, were cultured with recombinant Kit ligand to induce spermatogenesis up to haploid formation. Although the efficiency of spermatogenesis was lower than that of pup, present results showed that the organ culture method is effective for the culturing of mature adult mouse testis tissue, demonstrated by the induction of spermatogenesis from spermatogonia to haploid cells.

  9. Localization of Multidrug Resistance-Associated Proteins along the Blood-Testis Barrier in Rat, Macaque, and Human Testis

    PubMed Central

    Klein, David M.; Wright, Stephen H.

    2014-01-01

    The blood-testis barrier (BTB) prevents the entry of many drugs into seminiferous tubules, which can be beneficial for therapy not intended for the testis but may decrease drug efficacy for medications requiring entry to the testis. Previous data have shown that some of the transporters in the multidrug resistance-associated protein (MRP) family (ABCC) are expressed in the testis. By determining the subcellular localization of these transporters, their physiologic function and effect on drug disposition may be better predicted. Using immunohistochemistry (IHC), we determined the site of expression of the MRP transporters expressed in the testis, namely, MRP1, MRP4, MRP5, and MRP8, from immature and mature rats, rhesus macaques, and adult humans. We determined that in all species MRP1 was restricted to the basolateral membrane of Sertoli cells, MRP5 is located in Leydig cells, and MRP8 is located in round spermatids, whereas MRP4 showed species-specific localization. MRP4 is expressed on the basolateral membrane of Sertoli cells in human and nonhuman primates, but on the apical membrane of Sertoli cells in immature and mature rats, representing a potential caution when using rat models as a means for studying drug disposition across the BTB. These data suggest that MRP1 may limit drug disposition into seminiferous tubules, as may MRP4 in human and nonhuman primates but not in rats. These data also suggest that MRP5 and MRP8 may not have a major impact on the penetration of drugs across the BTB. PMID:24130369

  10. Identification of the human testis protein phosphatase 1 interactome.

    PubMed

    Fardilha, Margarida; Esteves, Sara L C; Korrodi-Gregório, Luís; Vintém, Ana Paula; Domingues, Sara C; Rebelo, Sandra; Morrice, Nick; Cohen, Patricia T W; da Cruz e Silva, Odete A B; da Cruz e Silva, Edgar F

    2011-11-15

    Protein phosphorylation is a critical regulatory mechanism in cellular signalling. To this end, PP1 is a major eukaryotic serine/threonine-specific phosphatase whose cellular functions, in turn, depend on complexes it forms with PP1 interacting proteins-PIPs. The importance of the testis/sperm-enriched variant, PP1γ2, in sperm motility and spermatogenesis has previously been shown. Given the key role of PIPs, it is imperative to identify the physiologically relevant PIPs in testis and sperm. Hence, we performed Yeast Two-Hybrid screens of a human testis cDNA library using as baits the different PP1 isoforms and also a proteomic approach aimed at identifying PP1γ2 binding proteins. To the best of our knowledge this is the largest data set of the human testis PP1 interactome. We report the identification of 77 proteins in human testis and 7 proteins in human sperm that bind PP1. The data obtained increased the known PP1 interactome by reporting 72 novel interactions. Confirmation of the interaction of PP1 with 5 different proteins was also further validated by co-immunoprecipitation or protein overlays. The data here presented provides important insights towards the function of these proteins and opens new possibilities for future research. In fact, such diversity in PP1 regulators makes them excellent targets for pharmacological intervention.

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

    PubMed Central

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

    2014-01-01

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

  12. Biology of the Sertoli Cell in the Fetal, Pubertal, and Adult Mammalian Testis.

    PubMed

    Chojnacka, Katarzyna; Zarzycka, Marta; Mruk, Dolores D

    A healthy man typically produces between 50 × 10(6) and 200 × 10(6) spermatozoa per day by spermatogenesis; in the absence of Sertoli cells in the male gonad, this individual would be infertile. In the adult testis, Sertoli cells are sustentacular cells that support germ cell development by secreting proteins and other important biomolecules that are essential for germ cell survival and maturation, establishing the blood-testis barrier, and facilitating spermatozoa detachment at spermiation. In the fetal testis, on the other hand, pre-Sertoli cells form the testis cords, the future seminiferous tubules. However, the role of pre-Sertoli cells in this process is much less clear than the function of Sertoli cells in the adult testis. Within this framework, we provide an overview of the biology of the fetal, pubertal, and adult Sertoli cell, highlighting relevant cell biology studies that have expanded our understanding of mammalian spermatogenesis.

  13. Human testis-specific genes are under relaxed negative selection.

    PubMed

    Pierron, Denis; Razafindrazaka, Harilanto; Rocher, Christophe; Letellier, Thierry; Grossman, Lawrence I

    2014-02-01

    Recent studies have suggested that selective forces and constraints acting on genes varied during human evolution depending on the organ in which they are expressed. To gain insight into the evolution of organ determined negative selection forces, we compared the non-synonymous SNP diversity of genes expressed in different organs. Based on a HAPMAP dataset, we determined for each SNP its frequency in 11 human populations and, in each case, predicted whether or not the change it produces is deleterious. We have shown that, for all organs under study, SNPs predicted to be deleterious are present at a significantly lower frequency than SNPs predicted to be tolerated. However, testis-specific genes contain a higher proportion of deleterious SNPs than other organs. This study shows that negative selection is acting on the whole human genome, but that the action of negative selection is relaxed on testis-specific genes. This result adds to and expands the hypothesis of a recent evolutionary change in the human male reproductive system and its behavior.

  14. INSL3 stimulates spermatogonial differentiation in testis of adult zebrafish (Danio rerio).

    PubMed

    Assis, L H C; Crespo, D; Morais, R D V S; França, L R; Bogerd, J; Schulz, R W

    2016-02-01

    INSL3 (insulin-like peptide 3) is a relaxin peptide family member expressed by Leydig cells in the vertebrate testis. In mammals, INSL3 mediates testicular descent during embryogenesis but information on its function in adults is limited. In fish, the testes remain in the body cavity, although the insl3 gene is still expressed, suggesting yet undiscovered, evolutionary older functions. Anti-Müllerian hormone (Amh), in addition to inhibiting spermatogonial differentiation and androgen release, inhibits the Fsh (follicle-stimulating hormone)-induced increase in insl3 transcript levels in zebrafish testis. Therefore, the two growth factors might have antagonistic effects. We examine human INSL3 (hINSL3) effects on zebrafish germ cell proliferation/differentiation and androgen release by using a testis tissue culture system. hINSL3 increases the proliferation of type A undifferentiated (Aund) but not of type A differentiating (Adiff) spermatogonia, while reducing the proliferation of Sertoli cells associated with proliferating Aund. Since the area occupied by Aund decreases and that of Adiff increases, we conclude that hINSL3 recruits Aund into differentiation; this is supported by the hINSL3-induced down-regulation of nanos2 transcript levels, a marker of single Aund spermatogonia in zebrafish and other vertebrates. Pulse-chase experiments with a mitosis marker also indicate that hINSL3 promotes spermatogonial differentiation. However, hINSL3 does not modulate basal or Fsh-stimulated androgen release or growth factor transcript levels, including those of amh. Thus, hINSL3 seems to recruit Aund spermatogonia into differentiation, potentially mediating an Fsh effect on spermatogenesis.

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

    PubMed

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

    2017-07-31

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

  16. Exposure to constant light during testis development increases daily sperm production in adult Wistar rats.

    PubMed

    Rocha, D C; Debeljuk, L; França, L R

    1999-06-01

    Testis histometry and daily sperm production (DSP) were evaluated in adult (160-day-old) Wistar rats exposed to constant light for the first 25 days after birth, and compared with control animals which were exposed to a 12 h-light-12 h-dark light regimen. Significantly greater (P < 0.05) numbers of Sertoli cell nucleoli and round spermatids per cross-section of seminiferous tubule were found in animals exposed to constant light. In addition, epididymis weight, DSP per testis and per gram of testis, as well as Leydig cell compartment volume, were significantly increased in treated animals. Although there was a clear trend toward an increased Sertoli cell population per testis in animals exposed to constant light, this difference was not statistically significant (P < 0.05). The number of round spermatids as expressed per Sertoli cell was the same in both groups. Surprisingly, the diameter and volume of round spermatid nucleus at stages I and VII of the cycle of seminiferous epithelium were significantly lower (P < 0.05) in treated animals. In conclusion, constant illumination during neonatal testis development increased sperm production and Leydig cell compartment volume in adult rats probably through a mechanism involving elevated follicle stimulating hormone and luteinizing hormone during the prepubertal period. To our knowledge, this is the first study showing that altering the light regimen can affect sperm production in non-seasonal breeders.

  17. Sox9 and Sox8 protect the adult testis from male-to-female genetic reprogramming and complete degeneration

    PubMed Central

    Barrionuevo, Francisco J; Hurtado, Alicia; Kim, Gwang-Jin; Real, Francisca M; Bakkali, Mohammed; Kopp, Janel L; Sander, Maike; Scherer, Gerd; Burgos, Miguel; Jiménez, Rafael

    2016-01-01

    The new concept of mammalian sex maintenance establishes that particular key genes must remain active in the differentiated gonads to avoid genetic sex reprogramming, as described in adult ovaries after Foxl2 ablation. Dmrt1 plays a similar role in postnatal testes, but the mechanism of adult testis maintenance remains mostly unknown. Sox9 and Sox8 are required for postnatal male fertility, but their role in the adult testis has not been investigated. Here we show that after ablation of Sox9 in Sertoli cells of adult, fertile Sox8-/- mice, testis-to-ovary genetic reprogramming occurs and Sertoli cells transdifferentiate into granulosa-like cells. The process of testis regression culminates in complete degeneration of the seminiferous tubules, which become acellular, empty spaces among the extant Leydig cells. DMRT1 protein only remains in non-mutant cells, showing that SOX9/8 maintain Dmrt1 expression in the adult testis. Also, Sox9/8 warrant testis integrity by controlling the expression of structural proteins and protecting Sertoli cells from early apoptosis. Concluding, this study shows that, in addition to its crucial role in testis development, Sox9, together with Sox8 and coordinately with Dmrt1, also controls adult testis maintenance. DOI: http://dx.doi.org/10.7554/eLife.15635.001 PMID:27328324

  18. IN VITRO CONAZOLE EXPOSURE INHIBITS TESTOSTERONE PRODUCTION IN ADULT AND NEONATAL RAT TESTIS

    EPA Science Inventory

    IN VITRO CONAZOLE EXPOSURE INHIBITS TESTOSTERONE PRODUCTION IN THE ADULT AND NEONATAL TESTIS
    Chad R. Blystone1, 2, David J. Dix2, and John C. Rockett2
    1Department of Environmental and Molecular Toxicology, Box 7633, NC State University, Raleigh, NC 27695, USA and 2U.S. Envi...

  19. IN VITRO CONAZOLE EXPOSURE INHIBITS TESTOSTERONE PRODUCTION IN ADULT AND NEONATAL RAT TESTIS

    EPA Science Inventory

    IN VITRO CONAZOLE EXPOSURE INHIBITS TESTOSTERONE PRODUCTION IN THE ADULT AND NEONATAL TESTIS
    Chad R. Blystone1, 2, David J. Dix2, and John C. Rockett2
    1Department of Environmental and Molecular Toxicology, Box 7633, NC State University, Raleigh, NC 27695, USA and 2U.S. Envi...

  20. Human fetal testis Leydig cell disruption by exposure to the pesticide dieldrin at low concentrations.

    PubMed

    Fowler, Paul A; Abramovich, David R; Haites, Neva E; Cash, Phillip; Groome, Nigel P; Al-Qahtani, Ahmed; Murray, Tessa J; Lea, Richard G

    2007-11-01

    Declining human reproductive health over the last 60 years has been proposed to be due to effects of environmental chemicals, especially endocrine disrupting compounds, on fetal development. We investigated whether a model pesticide, dieldrin, at concentrations within both maternal circulation and environmental ranges (1 pmol/l = 0.0004 p.p.b. = 380.9 pg/l), could disrupt the human fetal testis. Human fetal testes were collected during the second trimester, a critical period of male sexual differentiation (development and masculinization). Testis explants were cultured for 24 h in the presence and absence of LH (10-1000 IU LH/l) and dieldrin (1 pmol and 1 nmol/l). Endocrine, immunohistological and proteome characteristics of the tissues were investigated. Exposure to dieldrin reduced LH-induced testosterone secretion (P < 0.05) and tissue protein concentrations of LH receptor and steroid acute regulatory protein (P < 0.05). Dieldrin altered proteins associated with cancer, apoptosis, transcription and development. Wnt-2b was reduced 3-fold and immunolocalized to Leydig and Sertoli cells. Dieldrin also reversed some LH-induced changes in protein expression, supporting the conclusion that Leydig cell function is at risk from environmental chemicals. Our findings indicate that exposure to very low, biologically relevant, concentrations of environmental chemicals could affect the fetal human Leydig cell, reducing testosterone secretion and potentially leading to subtle dysregulation of reproductive development and adult fecundity.

  1. Ibuprofen results in alterations of human fetal testis development

    PubMed Central

    Ben Maamar, Millissia; Lesné, Laurianne; Hennig, Kristin; Desdoits-Lethimonier, Christèle; Kilcoyne, Karen R.; Coiffec, Isabelle; Rolland, Antoine D.; Chevrier, Cécile; Kristensen, David M.; Lavoué, Vincent; Antignac, Jean-Philippe; Le Bizec, Bruno; Dejucq-Rainsford, Nathalie; Mitchell, Rod T.; Mazaud-Guittot, Séverine; Jégou, Bernard

    2017-01-01

    Among pregnant women ibuprofen is one of the most frequently used pharmaceutical compounds with up to 28% reporting use. Regardless of this, it remains unknown whether ibuprofen could act as an endocrine disruptor as reported for fellow analgesics paracetamol and aspirin. To investigate this, we exposed human fetal testes (7–17 gestational weeks (GW)) to ibuprofen using ex vivo culture and xenograft systems. Ibuprofen suppressed testosterone and Leydig cell hormone INSL3 during culture of 8–9 GW fetal testes with concomitant reduction in expression of the steroidogenic enzymes CYP11A1, CYP17A1 and HSD17B3, and of INSL3. Testosterone was not suppressed in testes from fetuses younger than 8 GW, older than 10–12 GW, or in second trimester xenografted testes (14–17 GW). Ex vivo, ibuprofen also affected Sertoli cell by suppressing AMH production and mRNA expression of AMH, SOX9, DHH, and COL2A1. While PGE2 production was suppressed by ibuprofen, PGD2 production was not. Germ cell transcripts POU5F1, TFAP2C, LIN28A, ALPP and KIT were also reduced by ibuprofen. We conclude that, at concentrations relevant to human exposure and within a particular narrow ‘early window’ of sensitivity within first trimester, ibuprofen causes direct endocrine disturbances in the human fetal testis and alteration of the germ cell biology. PMID:28281692

  2. 16-Ene-steroids in the human testis.

    PubMed

    Smals, A G; Weusten, J J

    1991-01-01

    Incubation of human testicular homogenates with [4-14C]pregnenolone gave substantial amounts of an unknown metabolite within 1 min, reaching plateau values of 17-23% of total radioactivity added within 5 min. Mass spectrometry of the metabolite showed it to be identical to the boar sex pheromone precursor androsta-5, 16-diene-3 beta-ol (ADL). In cell cultures the major source of ADL and its dehydrogenated metabolite androsta-4, 16-diene-3-one (ADN) was the Leydig cell. In rat and monkey testicular homogenates 16-ene-synthetase activity, a prerequisite for the synthesis of ADL and ADN, was completely lacking, limiting the presence of 16-androstenes to boars and men. In contrast to boars, however, in the human testis no 5 alpha-reductase activity was found and consequently no 5 alpha-reduced-16-androstenes, e.g. androstenol (AL, musk like) and androstenone (AN, urine like), known sex pheromones in pigs. As both sex pheromones have been identified in urine, plasma, sweat and saliva of men and (especially hirsute) women we hypothesize that AL and AN are synthesized from ADL via ADN peripherically in tissues rich in 5 alpha-reductase, i.e. skin, axillary sweat glands and probably also the salivary glands. So far, there is some evidence that both sex pheromones may have similar functions in humans as in boars.

  3. Sertoli Cells Maintain Leydig Cell Number and Peritubular Myoid Cell Activity in the Adult Mouse Testis

    PubMed Central

    Monteiro, Ana; Milne, Laura; Cruickshanks, Lyndsey; Jeffrey, Nathan; Guillou, Florian; Freeman, Tom C.; Mitchell, Rod T.; Smith, Lee B.

    2014-01-01

    The Sertoli cells are critical regulators of testis differentiation and development. In the adult, however, their known function is restricted largely to maintenance of spermatogenesis. To determine whether the Sertoli cells regulate other aspects of adult testis biology we have used a novel transgenic mouse model in which Amh-Cre induces expression of the receptor for Diphtheria toxin (iDTR) specifically within Sertoli cells. This causes controlled, cell-specific and acute ablation of the Sertoli cell population in the adult animal following Diphtheria toxin injection. Results show that Sertoli cell ablation leads to rapid loss of all germ cell populations. In addition, adult Leydig cell numbers decline by 75% with the remaining cells concentrated around the rete and in the sub-capsular region. In the absence of Sertoli cells, peritubular myoid cell activity is reduced but the cells retain an ability to exclude immune cells from the seminiferous tubules. These data demonstrate that, in addition to support of spermatogenesis, Sertoli cells are required in the adult testis both for retention of the normal adult Leydig cell population and for support of normal peritubular myoid cell function. This has implications for our understanding of male reproductive disorders and wider androgen-related conditions affecting male health. PMID:25144714

  4. Human testis-derived embryonic stem cell-like cells are not pluripotent, but possess potential of mesenchymal progenitors.

    PubMed

    Chikhovskaya, J V; Jonker, M J; Meissner, A; Breit, T M; Repping, S; van Pelt, A M M

    2012-01-01

    Spontaneous in vitro transition of undifferentiated spermatogonia into the pluripotent cell state has been achieved using neonatal and adult mouse testis tissue. In an effort to establish an analogous source of human patient-specific pluripotent stem cells, several research groups have described the derivation of embryonic stem cell-like cells from primary cultures of human testis. These cells are characterized in all studies as growing in compact colonies, expressing pluripotency-associated markers and possessing multilineage differentiation capabilities in vitro, but only one study claimed their ability to induce teratomas. This controversy initiated a debate about the pluripotent state and origin of human testis-derived ES-like cells (htES-like cells). htES-like cell colonies were obtained from primary testicular cultures of three individuals and selectively expanded using culture conditions known to support the propagation of blastocyst-derived human embryonic stem cells (ESCs), mouse epiblast stem cells and 'naïve' human ESCs. The stem cell properties of htES-like cells were subsequently assessed by testing the expression of ESC-specific markers, differentiation abilities in vitro and in vivo, and microarray profiling. The expression of pluripotency-associated markers in htES-like cells and their differentiation abilities differed significantly from those of ESCs. Gene expression microarray analysis revealed that htES-like cells possess a transcriptome distinct from human ESCs and fibroblasts, but closely resembling the transcriptome of mesenchymal stem cells (MSCs). The similarity to MSCs was confirmed by detection of SSEA4/CD146 expressing cells within htES-like colonies and efficient in vitro differentiation toward three mesodermal lineages (adipogenic, osteogenic, chondrogenic). Taken together, these results indicate that htES-like cells, in contrast to pluripotent stem cells derived from adult mouse testis, are not pluripotent and most likely not of germ

  5. Indirect inguinal hernia sac containing testis and spermatic cord in an adult patient with cryptorchidism

    PubMed Central

    Arslan, Yusuf; Karaman, Kerem; Altintoprak, Fatih; Kahyaoglu, Zeynep; Zengin, Ismail; Uzunoglu, Mustafa Yener; Demir, Hakan

    2014-01-01

    Sliding hernias are those in which part of the sac wall is formed by a retroperitoneal organ and/or its mesentery protruding outside the abdominal wall cavity. The hernia sac may contain jejunum, ileum, vermiform appendix, Meckel's diverticulum, stomach, ovary, fallopian tube or urinary bladder. Our report features an adult case with cryptorchidism in which testis and spermatic cord constitute a component of the indirect inguinal hernia sac. PMID:24876399

  6. Indirect inguinal hernia sac containing testis and spermatic cord in an adult patient with cryptorchidism.

    PubMed

    Arslan, Yusuf; Karaman, Kerem; Altintoprak, Fatih; Kahyaoglu, Zeynep; Zengin, Ismail; Uzunoglu, Mustafa Yener; Demir, Hakan

    2014-03-07

    Sliding hernias are those in which part of the sac wall is formed by a retroperitoneal organ and/or its mesentery protruding outside the abdominal wall cavity. The hernia sac may contain jejunum, ileum, vermiform appendix, Meckel's diverticulum, stomach, ovary, fallopian tube or urinary bladder. Our report features an adult case with cryptorchidism in which testis and spermatic cord constitute a component of the indirect inguinal hernia sac.

  7. Adult metastatic yolk sac tumor descending from an intra-abdominal testis: A case report and review of the literature.

    PubMed

    Wang, Zhao; Yan, Bin; Wei, Yong-Bao; Yin, Zhuo; Zhou, Ke-Qin; Yang, Jin-Rui

    2015-12-01

    Pure yolk sac tumors are extremely rare in adults; to the best of our knowledge, <20 cases have been reported. Multiple metastases originating from a pure yolk sac testicular tumor, descending from an intra-abdominal testis, are additionally extremely rare. In the present case, a man exhibiting a 30-year history of cryptorchidism and indirect inguinal hernia, was admitted to the Department of Urology (The Second Xiangya Hospital, Changsha, China) due to a mass that had descended from the abdominal cavity 7 months previously. Elevated levels of specific serum marker (α-fetoprotein, lactate dehydrogenase and human chorionic gonadotropin) did not indicate potential testicular germ cell types prior to surgery and pathological examination. Pathological results and immunohistochemistry revealed a testicular pure yolk sac tumor subsequent to surgery. The present case report and literature review describes the typical characteristics of an adult testicular yolk sac tumor, as well as the diagnosis and management of the disease.

  8. Adult metastatic yolk sac tumor descending from an intra-abdominal testis: A case report and review of the literature

    PubMed Central

    WANG, ZHAO; YAN, BIN; WEI, YONG-BAO; YIN, ZHUO; ZHOU, KE-QIN; YANG, JIN-RUI

    2015-01-01

    Pure yolk sac tumors are extremely rare in adults; to the best of our knowledge, <20 cases have been reported. Multiple metastases originating from a pure yolk sac testicular tumor, descending from an intra-abdominal testis, are additionally extremely rare. In the present case, a man exhibiting a 30-year history of cryptorchidism and indirect inguinal hernia, was admitted to the Department of Urology (The Second Xiangya Hospital, Changsha, China) due to a mass that had descended from the abdominal cavity 7 months previously. Elevated levels of specific serum marker (α-fetoprotein, lactate dehydrogenase and human chorionic gonadotropin) did not indicate potential testicular germ cell types prior to surgery and pathological examination. Pathological results and immunohistochemistry revealed a testicular pure yolk sac tumor subsequent to surgery. The present case report and literature review describes the typical characteristics of an adult testicular yolk sac tumor, as well as the diagnosis and management of the disease. PMID:26788184

  9. Expression of CatSper family transcripts in the mouse testis during post-natal development and human ejaculated spermatozoa: relationship to sperm motility.

    PubMed

    Li, Hong-Gang; Ding, Xiao-Fang; Liao, Ai-Hua; Kong, Xiang-Bing; Xiong, Cheng-Liang

    2007-05-01

    CatSper is a unique sperm cation channel-like protein family exclusively expressed in the testis and plays important roles in sperm functions. The temporal expression profiles of CatSper1-4 mRNAs in the mouse testis during post-natal development through adulthood were investigated using real-time RT-PCR. The CatSper2 transcript was present in the testis of the 8-day-old mice, and was repressed in the adult testis after two sharp up-regulations at day 18 and 35. CatSper1 and CatSper3, 4 mRNAs were detectable in the testis of 18-day and 15-day-old mice, respectively. After sharp up-regulation at day 25 and 35, respectively, they were maximal at the adult testis stage. The differences between the temporal expression profiles of the CatSper transcripts in post-natal mouse testis development suggest different regulation to their transcription, and potentially contribute to the possibility of forming heteromeric channels among these four CatSper family members. CatSper1-3 transcripts were identified to be present in the human ejaculated spermatozoa by RT-PCR. Significantly higher levels of CatSper2 and CatSper3 mRNAs revealed by real-time RT-PCR were observed in the high-motile spermatozoa than in the low-motile fraction and suggests that CatSper2 and CatSper3 transcripts in the human ejaculated spermatozoa could be the potential targets for further study and male infertility screening.

  10. Identification and characterization of human testis derived circular RNAs and their existence in seminal plasma

    PubMed Central

    Dong, Wei-Wei; Li, Hui-Min; Qing, Xing-Rong; Huang, Dong-Hui; Li, Hong-Gang

    2016-01-01

    Circular RNAs (circRNAs) have emerged as novel molecules of interest in gene regulation as other noncoding RNAs. Though they have been explored in some species and tissues, the expression and functions of circRNAs in human reproductive systems remain unknown. Here we revealed the expression profiles of circRNAs in human testis tissue using high-throughput sequencing. The conformation of these testis-derived circRNAs in seminal plasma was also investigated, aiming to provide a non-invasive liquid biopsy surrogate for testicular biopsy. We predicted >15,000 circRNAs in human testis, with most of them (10,792; 67%) new. In all the 5,928 circRNA forming genes, 1,017 are first reported by us to generate circRNAs. Interestingly, these genes are mostly related to spermatogenesis, sperm motility, fertilization, etc. The sequence feature, chromosome location, alternative splicing and other characteristics of the circRNAs in human testis were also explored. Moreover, we found that these testis-derived circRNAs could be stably detected in seminal plasma. Most of them were probably bound with proteins in seminal plasma and were very stable at room temperature. Our work has laid the foundations to decipher regulation mechanisms of circRNAs in spermatogenesis and to develop circRNAs as novel noninvasive biomarkers for male infertile diseases. PMID:27958373

  11. Identification of androgen receptor variants in testis from humans and other vertebrates.

    PubMed

    Laurentino, S S; Pinto, P I S; Tomás, J; Cavaco, J E; Sousa, M; Barros, A; Power, D M; Canário, A V M; Socorro, S

    2013-06-01

    The androgen receptor (AR) is a ligand-activated transcription factor member of the nuclear receptor superfamily. The existence of alternatively spliced variants is well recognised for several members of this superfamily, most of them having functional importance. For example, several testicular oestrogen receptor variants have been suggested to play a role in the regulation of spermatogenesis. However, information on AR variants is mostly related to cancer and androgen insensitivity syndrome (AIS) cases. The objective of this study was to investigate the expression of AR variants in the testis from humans and other vertebrates. Four AR variants [ARΔ2(Stop) , ARΔ2(23Stop) , ARΔ3 and ARΔ4(120)] were identified in human testis. ARΔ2(Stop) and ARΔ3, with exon 2 or 3 deleted, respectively, were also expressed in human liver, lung, kidney and heart. In addition, ARΔ2(Stop) was expressed in rat and gilthead seabream testis, while an ARΔ3 was detected in African clawed frog testis. This is the first report revealing the existence of AR variants in the testis of evolutionarily distant vertebrate species and in nonpathological tissues. These data suggest the functional importance of these novel AR forms and demonstrate a complexity in AR signalling that is not exclusive of pathological conditions.

  12. Structure of human nucleosome containing the testis-specific histone variant TSH2B

    SciTech Connect

    Urahama, Takashi; Horikoshi, Naoki; Osakabe, Akihisa; Tachiwana, Hiroaki; Kurumizaka, Hitoshi

    2014-03-25

    The crystal structure of human nucleosome containing the testis-specific TSH2B variant has been determined. The TSH2B Ser85 residue does not interact with H4 in the nucleosome, and induces a local structural difference between TSH2B and H2B in nucleosomes. The human histone H2B variant TSH2B is highly expressed in testis and may function in the chromatin transition during spermatogenesis. In the present study, the crystal structure of the human testis-specific nucleosome containing TSH2B was determined at 2.8 Å resolution. A local structural difference between TSH2B and canonical H2B in nucleosomes was detected around the TSH2B-specific amino-acid residue Ser85. The TSH2B Ser85 residue does not interact with H4 in the nucleosome, but in the canonical nucleosome the H2B Asn84 residue (corresponding to the TSH2B Ser85 residue) forms water-mediated hydrogen bonds with the H4 Arg78 residue. In contrast, the other TSH2B-specific amino-acid residues did not induce any significant local structural changes in the TSH2B nucleosome. These findings may provide important information for understanding how testis-specific histone variants form nucleosomes during spermatogenesis.

  13. Sertoli Cell Number Defines and Predicts Germ and Leydig Cell Population Sizes in the Adult Mouse Testis.

    PubMed

    Rebourcet, Diane; Darbey, Annalucia; Monteiro, Ana; Soffientini, Ugo; Tsai, Yi Ting; Handel, Ian; Pitetti, Jean-Luc; Nef, Serge; Smith, Lee B; O'Shaughnessy, Peter J

    2017-09-01

    Sertoli cells regulate differentiation and development of the testis and are essential for maintaining adult testis function. To model the effects of dysregulating Sertoli cell number during development or aging, we have used acute diphtheria toxin-mediated cell ablation to reduce Sertoli cell population size. Results show that the size of the Sertoli cell population that forms during development determines the number of germ cells and Leydig cells that will be present in the adult testis. Similarly, the number of germ cells and Leydig cells that can be maintained in the adult depends directly on the size of the adult Sertoli cell population. Finally, we have used linear modeling to generate predictive models of testis cell composition during development and in the adult based on the size of the Sertoli cell population. This study shows that at all ages the size of the Sertoli cell population is predictive of resulting testicular cell composition. A reduction in Sertoli cell number/proliferation at any age will therefore lead to a proportional decrease in germ cell and Leydig cell numbers, with likely consequential effects on fertility and health.

  14. Signaling by TGF-betas in tubule cultures of adult rat testis

    PubMed Central

    Chan, Kai-Hui; Galuska, Sebastian P; Kudipudi, Pradeep Kumar; Riaz, Mohammad Assad; Loveland, Kate L; Konrad, Lutz

    2017-01-01

    Although signal transduction of transforming growth factor-betas (TGF-βs) is well characterized in individual cell types, data about TGF-β signaling in a cellular context is still scarce. In this study, we used ex vivo tubule cultures from adult rat testis to investigate TGF-β signaling. We show for the first time in testicular tubules, that TGF-βs also signal via the BMP type I receptors, with ALK2 used by TGF-β1 and ALK3 and ALK6 by TGF-β2. This signal transduction is mediated via Smad3 as well as via Smad1. In contrast, BMPs (BMP2 and BMP7) do not signal via the high-affinity type I and type II TGFβ receptors, TBR1 or TBR2. Furthermore, treatment of tubule cultures with either TGF-β1 or TGF-β2 had profound significant stimulatory effects on secretion of plasminogen activator-1 (PAI-1) through utilization of TGF-β and BMP receptors. Specific inhibitors for either TBR1 or BMP receptors yielded nearly complete inhibition of TGF-β signaling. The TBR1-TBR2 signalosome was detected with Duolink upon stimulation with either TGF-β1 or TGF-β2, predominantly in spermatogenic cells of the adult rat testis, particularly in elongated spermatids. In summary, this examination of intact rat testicular tubules demonstrated for the first time that TGF-βs signal mainly through TBR1 and TBR2 but also use BMP receptors, including for secretion of PAI-1. Whereas ALK2 participates in the TGF-β1-induced TBR1-TBR2 signalosome, ALK3 and ALK6 are involved in signaling of TGF-β2. Detection of the TBR1-TBR2 signalosome in late spermiogenic cells indicates a post-meiotic activity. PMID:28386343

  15. Effects of different kinds of essentiality on sequence evolution of human testis proteins

    PubMed Central

    Schumacher, Julia; Zischler, Hans; Herlyn, Holger

    2017-01-01

    We asked if essentiality for either fertility or viability differentially affects sequence evolution of human testis proteins. Based on murine knockout data, we classified a set of 965 proteins expressed in human seminiferous tubules into three categories: proteins essential for prepubertal survival (“lethality proteins”), associated with male sub- or infertility (“male sub-/infertility proteins”), and nonessential proteins. In our testis protein dataset, lethality genes evolved significantly slower than nonessential and male sub-/infertility genes, which is in line with other authors’ findings. Using tissue specificity, connectivity in the protein-protein interaction (PPI) network, and multifunctionality as proxies for evolutionary constraints, we found that of the three categories, proteins linked to male sub- or infertility are least constrained. Lethality proteins, on the other hand, are characterized by broad expression, many PPI partners, and high multifunctionality, all of which points to strong evolutionary constraints. We conclude that compared with lethality proteins, those linked to male sub- or infertility are nonetheless indispensable, but evolve under more relaxed constraints. Finally, adaptive evolution in response to postmating sexual selection could further accelerate evolutionary rates of male sub- or infertility proteins expressed in human testis. These findings may become useful for in silico detection of human sub-/infertility genes. PMID:28272493

  16. Identification of a novel human cancer/testis gene MAEL that is regulated by DNA methylation.

    PubMed

    Xiao, Ling; Wang, Yijun; Zhou, Yankai; Sun, Yi; Sun, Wei; Wang, Lin; Zhou, Chang; Zhou, Jianlin; Zhang, Jian

    2010-06-01

    The mouse maelstrom (MAEL) gene has been found to be expressed in male germ cells and to play a role in spermatogenesis. Here, we cloned the human MAEL gene by digital differential display and found that, among human tissues, MAEL is only expressed in the testis, but it is also expressed in various cancer cell lines. The transcription start site of the MAEL gene is 74-bp upstream of the start codon. The region from -216 to +150 is the basal promoter of the MAEL gene, and a CpG island (-295 to +148) is located in this region. Treatment with the demethylating agent 5'-Aza-2-Deoxycytidine significantly upregulated MAEL expression. These results suggest that MAEL is a novel cancer/testis-associated gene and is regulated by DNA methylation.

  17. Advantage of Guaraná (Paullinia cupana Mart.) supplementation on cadmium-induced damages in testis of adult Wistar rats.

    PubMed

    Leite, Rodrigo P; Predes, Fabrícia S; Monteiro, Juliana C; Freitas, Karine M; Wada, Ronaldo S; Dolder, Heidi

    2013-01-01

    Paullinia cupana is an Amazonian bush whose seeds have long been used in folk medicine. However, most of the therapeutic properties attributed to this plant are broad and nonspecific, although an antioxidant activity has been reported.  On the other hand, cadmium is a heavy metal known for increasing free radicals, hence resulting in cellular oxidative damages. This study was designed to evaluate whether Paullinia cupana is able to reduce cadmium-induced morphological impairment in Wistar rat testis. Adult male Wistar rats 110 days old were ip injected with cadmium (1.15 mg/kg BW [body weight]) and subsequently treated with P. cupana during 56 days.  Furthermore, groups receiving either P. cupana extract or cadmium are mentioned. After the treatment period, testis samples were subjected to histological and stereological analyses. Moderate to severe testicular impairments were shown by the animals exposed to cadmium. However, the animals supplemented with P. cupana after cadmium exposure showed a significant decrease in the proportion of damaged seminiferous tubules. Also, P. cupana supplementation was effective in maintaining the number of Leydig cells per testis in the animals exposed to cadmium. In conclusion, P. cupana supplementation was partially efficient in preventing cadmium from damaging the testis of adult Wistar rats.

  18. Expression of POTE protein in human testis detected by novel monoclonal antibodies

    SciTech Connect

    Ise, Tomoko; Das, Sudipto; Nagata, Satoshi; Maeda, Hiroshi; Lee, Yoomi; Onda, Masanori; Anver, Miriam R.; Pastan, Ira

    2008-01-25

    The POTE gene family is composed of 13 highly homologous paralogs preferentially expressed in prostate, ovary, testis, and placenta. We produced 10 monoclonal antibodies (MAbs) against three representative POTE paralogs: POTE-21, POTE-2{gamma}C, and POTE-22. One reacted with all three paralogs, six MAbs reacted with POTE-2{gamma}C and POTE-22, and three MAbs were specific to POTE-21. Epitopes of all 10 MAbs were located in the cysteine-rich repeats (CRRs) motifs located at the N-terminus of each POTE paralog. Testing the reactivity of each MAb with 12 different CRRs revealed slight differences among the antigenic determinants, which accounts for differences in cross-reactivity. Using MAbs HP8 and PG5 we were able to detect a POTE-actin fusion protein in human testis by immunoprecipitation followed by Western blotting. By immunohistochemistry we demonstrated that the POTE protein is expressed in primary spermatocytes, implying a role in spermatogenesis.

  19. Expression of POTE protein in human testis detected by novel monoclonal antibodies.

    PubMed

    Ise, Tomoko; Das, Sudipto; Nagata, Satoshi; Maeda, Hiroshi; Lee, Yoomi; Onda, Masanori; Anver, Miriam R; Bera, Tapan K; Pastan, Ira

    2008-01-25

    The POTE gene family is composed of 13 highly homologous paralogs preferentially expressed in prostate, ovary, testis, and placenta. We produced 10 monoclonal antibodies (MAbs) against three representative POTE paralogs: POTE-21, POTE-2gammaC, and POTE-22. One reacted with all three paralogs, six MAbs reacted with POTE-2gammaC and POTE-22, and three MAbs were specific to POTE-21. Epitopes of all 10 MAbs were located in the cysteine-rich repeats (CRRs) motifs located at the N-terminus of each POTE paralog. Testing the reactivity of each MAb with 12 different CRRs revealed slight differences among the antigenic determinants, which accounts for differences in cross-reactivity. Using MAbs HP8 and PG5 we were able to detect a POTE-actin fusion protein in human testis by immunoprecipitation followed by Western blotting. By immunohistochemistry we demonstrated that the POTE protein is expressed in primary spermatocytes, implying a role in spermatogenesis.

  20. Expression of POTE protein in human testis detected by novel monoclonal antibodies

    PubMed Central

    Ise, Tomoko; Das, Sudipto; Nagata, Satoshi; Maeda, Hiroshi; Lee, Yoomi; Onda, Masanori; Anver, Miriam R.; Bera, Tapan K.; Pastan, Ira

    2008-01-01

    The POTE gene family is composed of 13 highly homologous paralogs preferentially expressed in prostate, ovary, testis and placenta. We produced 10 monoclonal antibodies (MAbs) against 3 representative POTE paralogs: POTE-21, POTE-2γC and POTE-22. One reacted with all 3 paralogs, 6 MAbs reacted with POTE-2γC and POTE-22, and 3 MAbs were specific to POTE-21. Epitopes of all 10 MAbs were located in the cysteine-rich repeats (CRRs) motifs located at the N-terminus of each POTE paralog. Testing the reactivity of each MAb with 12 different CRRs revealed slight differences among the antigenic determinants, which accounts for differences in cross-reactivity. Using MAbs HP8 and PG5 we were able to detect a POTE-actin fusion protein in human testis by immunoprecipitation followed by Western blotting. By immunohistochemistry we demonstrated that the POTE protein is expressed in primary spermatocytes, implying a role in spermatogenesis. PMID:17996727

  1. Structure of human nucleosome containing the testis-specific histone variant TSH2B.

    PubMed

    Urahama, Takashi; Horikoshi, Naoki; Osakabe, Akihisa; Tachiwana, Hiroaki; Kurumizaka, Hitoshi

    2014-04-01

    The human histone H2B variant TSH2B is highly expressed in testis and may function in the chromatin transition during spermatogenesis. In the present study, the crystal structure of the human testis-specific nucleosome containing TSH2B was determined at 2.8 Å resolution. A local structural difference between TSH2B and canonical H2B in nucleosomes was detected around the TSH2B-specific amino-acid residue Ser85. The TSH2B Ser85 residue does not interact with H4 in the nucleosome, but in the canonical nucleosome the H2B Asn84 residue (corresponding to the TSH2B Ser85 residue) forms water-mediated hydrogen bonds with the H4 Arg78 residue. In contrast, the other TSH2B-specific amino-acid residues did not induce any significant local structural changes in the TSH2B nucleosome. These findings may provide important information for understanding how testis-specific histone variants form nucleosomes during spermatogenesis.

  2. Effects of Estradiol and Methoxychlor on Leydig Cell Regeneration in the Adult Rat Testis

    PubMed Central

    Chen, Bingbing; Chen, Dongxin; Jiang, Zheli; Li, Jingyang; Liu, Shiwen; Dong, Yaoyao; Yao, Wenwen; Akingbemi, Benson; Ge, Renshan; Li, Xiaokun

    2014-01-01

    The objective of the present study is to determine whether methoxychlor (MXC) exposure in adulthood affects rat Leydig cell regeneration and to compare its effects with estradiol (E2). Adult 90-day-old male Sprague-Dawley rats received ethane dimethane sulfonate (EDS) to eliminate the adult Leydig cell population. Subsequently, rats were randomly assigned to four groups and gavaged with corn oil (control), 0.25 mg/kg E2 and 10 or 100 mg/kg MXC daily from days 5 to 30 post-EDS treatment. The results showed that MXC and E2 reduced serum testosterone levels on day 58 post-EDS treatment. qPCR showed Hsd17b3 mRNA levels were downregulated 7–15 fold by E2 and MXC, indicating that development of the new population of Leydig cells was arrested at the earlier stage. This observation was supported by the results of histochemical staining, which demonstrated that Leydig cells in MXC-treated testis on day 58 post-EDS treatment were mostly progenitor Leydig cells. However, Pdgfb mRNA levels were downregulated, while Lif transcript levels were increased by MXC. In contrast, E2 did not affect gene expression for these growth factors. In conclusion, our findings indicated that both MXC and E2 delayed rat Leydig cell regeneration in the EDS-treated model, presumably acting by different mechanisms. PMID:24806340

  3. Identification and comparison of gonadal transcripts of testis and ovary of adult common carp Cyprinus carpio using suppression subtractive hybridization.

    PubMed

    Chen, Jian-Jun; Xia, Xiao-Hua; Wang, Li-Fang; Jia, Yong-Fang; Nan, Ping; Li, Li; Chang, Zhong-Jie

    2015-06-01

    The limited number of gonad-specific and gonad-related genes that have been identified in fish represents a major obstacle in the study of fish gonad development and sex differentiation. In common carp Cyprinus carpio from China's Yellow River, the ovary and testis differ in volume and weight in adult fish of the same age. Comparing sperm, egg, and somatic cell transcripts in this carp may provide insight into the mechanisms of its gonad development and sex differentiation. In the present work, gene expression patterns in the carp ovary and testis were compared using suppression subtractive hybridization. Two bidirectional subtracted complementary DNA (cDNA) libraries were analyzed in parallel using testis or ovary as testers. Eighteen nonredundant clones were identified in the male library, including 15 known cDNAs. The expression patterns of selected genes in testis and ovary were analyzed using reverse transcriptase polymerase chain reaction. Tektin-1, GAPDS, FGFIBP, IGFBP-5, and an unknown gene from the Ccmg4 clone were observed to be expressed only in testis. GSDF, BMI1b, Wt1a, and an unknown gene from the Ccme2 clone were expressed at higher levels in testis than in ovary at sexual maturity. Thirty functional expressed sequence tags (ESTs) were identified in 43 sequenced clones in the female library, including 28 known cDNAs, one uncharacterized cDNA (EST clone), and one novel sequence. Eight identified ESTs showed significant differences in expression between the testis and the ovary. ZP3C and Psmb2 were expressed exclusively in ovary, whereas the expression levels of IFIPGL-1, Setd6, ATP-6, CDC45, AIF-1, and an unknown gene from the Ccfh2 clone were more strongly expressed in ovary than in testis. In addition, the expression of ZP3C, Wt1a, and Setd6 was analyzed in male and female gonads, heart, liver, kidney, and brain. ZP3C was expressed only in ovary. Setd6 expression was significantly stronger in female tissues than that in the male, except in the liver

  4. Immunolocalisation of ghrelin and obestatin in human testis, seminal vesicles, prostate and spermatozoa.

    PubMed

    Moretti, E; Vindigni, C; Tripodi, S A; Mazzi, L; Nuti, R; Figura, N; Collodel, G

    2014-01-01

    The role of ghrelin and obestatin in male reproduction has not completely been clarified. We explored ghrelin and obestatin localisation in the male reproductive system. Polyclonal antibodies anti-ghrelin and anti-obestatin were used to detect the expression of these hormones in human testis, prostate and seminal vesicles by immunocytochemistry, while in ejaculated and swim up selected spermatozoa by immunofluorescence. Sertoli cells were positive for both peptides and Leydig cells for ghrelin; germ cells were negative for both hormones. Mild signals for ghrelin and obestatin were observed in rete testis; efferent ductules were the most immune reactive region for both peptides. Epididymis was moderately positive for ghrelin; vas deferens and seminal vesicles showed intense obestatin and moderate ghrelin labelling; prostate tissue expressed obestatin alone. Ejaculated and selected spermatozoa were positive for both peptides in different head and tail regions. This study confirms ghrelin localisation in Leydig and Sertoli cells; the finding that ghrelin is expressed in rete testis, epididymis, vas deferens and seminal vesicles is novel, as well as the localisation of obestatin in almost all tracts of the male reproductive system. This research could offer insights for stimulating other studies, particularly on the role of obestatin in sperm physiology, which is still obscure.

  5. Association of Human Development Index with global bladder, kidney, prostate and testis cancer incidence and mortality.

    PubMed

    Greiman, Alyssa K; Rosoff, James S; Prasad, Sandip M

    2017-05-08

    To describe contemporary worldwide age-standardized incidence and mortality rates for bladder, kidney, prostate and testis cancer and their association with development. We obtained gender-specific, age-standardized incidence and mortality rates for 184 countries and 16 major world regions from the GLOBOCAN 2012 database. We compared the mortality-to-incidence ratios (MIRs) at national and regional levels in males and females, and assessed the association with socio-economic development using the 2014 United Nations Human Development Index (HDI). Age-standardized incidence rates were 2.9 (bladder) to 7.4 (testis) times higher for genitourinary malignancies in more developed countries compared with less developed countries. Age-standardized mortality rates were 1.5-2.2 times higher in more vs less developed countries for prostate, bladder and kidney cancer, with no variation in mortality rates observed in testis cancer. There was a strong inverse relationship between HDI and MIR in testis (regression coefficient 1.65, R(2) = 0.78), prostate (regression coefficient -1.56, R(2) = 0.85), kidney (regression coefficient -1.34, R(2) = 0.74), and bladder cancer (regression coefficient -1.01, R(2) = 0.80). While incidence and mortality rates for genitourinary cancers vary widely throughout the world, the MIR is highest in less developed countries for all four major genitourinary malignancies. Further research is needed to understand whether differences in comorbidities, exposures, time to diagnosis, access to healthcare, diagnostic techniques or treatment options explain the observed inequalities in genitourinary cancer outcomes. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

  6. Cancer/testis antigens are novel targets of immunotherapy for adult T-cell leukemia/lymphoma.

    PubMed

    Nishikawa, Hiroyoshi; Maeda, Yuka; Ishida, Takashi; Gnjatic, Sacha; Sato, Eiichi; Mori, Fumiko; Sugiyama, Daisuke; Ito, Asahi; Fukumori, Yasuo; Utsunomiya, Atae; Inagaki, Hiroshi; Old, Lloyd J; Ueda, Ryuzo; Sakaguchi, Shimon

    2012-03-29

    Adult T-cell leukemia/lymphoma (ATLL) is an intractable hematologic malignancy caused by human T-lymphotropic virus type 1 (HTLV-1), which infects approximately 20 million people worldwide. Here, we have explored the possible expression of cancer/testis (CT) antigens by ATLL cells, as CT antigens are widely recognized as ideal targets of cancer immunotherapy against solid tumors. A high percentage (87.7%) of ATLL cases (n = 57) expressed CT antigens at the mRNA level: NY-ESO-1 (61.4%), MAGE-A3 (31.6%), and MAGE-A4 (61.4%). CT antigen expression was confirmed by immunohistochemistry. This contrasts with other types of lymphoma or leukemia, which scarcely express these CT antigens. Humoral immune responses, particularly against NY-ESO-1, were detected in 11.6% (5 of 43) and NY-ESO-1-specific CD8(+) T-cell responses were observed in 55.6% (5 of 9) of ATLL patients. NY-ESO-1-specific CD8(+) T cells recognized autologous ATLL cells and produced effector cytokines. Thus, ATLL cells characteristically express CT antigens and therefore vaccination with CT antigens can be an effective immunotherapy of ATLL.

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

    PubMed

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

    2014-12-15

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

  8. The Jak-STAT target Chinmo prevents sex transformation of adult stem cells in the Drosophila testis niche

    PubMed Central

    Ma, Qing; Wawersik, Matthew; Matunis, Erika L.

    2014-01-01

    Local signals maintain adult stem cells in many tissues. Whether the sexual identity of adult stem cells must also be maintained was not known. In the adult Drosophila testis niche, local Jak-STAT signaling promotes somatic cyst stem cell (CySC) renewal through several effectors, including the putative transcription factor Chronologically inappropriate morphogenesis (Chinmo). Here, we find that Chinmo also prevents feminization of CySCs. Chinmo promotes expression of the canonical male sex determination factor DoublesexM (DsxM) within CySCs and their progeny, and ectopic expression of DsxM in the CySC lineage partially rescues the chinmo sex transformation phenotype, placing Chinmo upstream of DsxM. The Dsx homologue DMRT1 prevents the male-to female conversion of differentiated somatic cells in the adult mammalian testis, but its regulation is not well understood. Our work indicates that sex maintenance occurs in adult somatic stem cells, and that this highly conserved process is governed by effectors of niche signals. PMID:25453558

  9. Methoxychlor induces apoptosis via mitochondria- and FasL-mediated pathways in adult rat testis.

    PubMed

    Vaithinathan, S; Saradha, B; Mathur, P P

    2010-04-29

    In the past few years, there has been much concern about the adverse health effects of environmental contaminants in general and organochlorine in particular. Studies have shown the repro-toxic effects of long-term exposure to methoxychlor, a member of the organochlorine family. However, the insight into the mechanisms of gonadal toxicity induced by methoxychlor is not well known. In the present study we sought to elucidate the mechanism(s) underpinning the gonadal effects within hours of exposure to methoxychlor. Experimental rats were divided into six groups of four each. Animals were orally administered with a single dose of methoxychlor (50mg/kg body weight) and killed at 0, 3, 6, 12, 24, and 72h post-treatment. The levels and time-course of induction of apoptosis-related proteins like cytochorome C, caspase 3 and procaspase 9, Fas-FasL and NF-kappaB were determined to assess sequential induction of apoptosis in the rat testis. DNA damage was assessed by TUNEL assay and flowcytometry. Administration of methoxychlor resulted in a significant increase in the levels of cytosolic cytochrome c and procaspase 9 as early as 6h following exposure. Time-dependent elevations in the levels of Fas, FasL, pro- and cleaved caspase 3 were observed. The DNA damage was measured and showed time-dependent increase in the TUNEL positive cells, and also by flowcytometry of testicular cells. The study demonstrates induction of testicular apoptosis in adult rats following exposure to a single dose of methoxychlor. 2010 Elsevier Ireland Ltd. All rights reserved.

  10. Pseudogenization of testis-specific Lfg5 predates human/Neanderthal divergence.

    PubMed

    Mariotti, Marco; Smith, Temple F; Sudmant, Peter H; Goldberger, Gabriel

    2014-05-01

    Recent reviews discussed the critical roles of apoptosis in human spermatogenesis and infertility. These reviews highlight the FasL-induced caspase cascade in apoptosis lending importance to our discovery of the pseudogene status of the Lfg5 gene in modern humans, Neanderthal and the Denisovan. This gene is a member of the ancient and highly conserved apoptosis Lifeguard family. This pseudogenization is the result of a premature stop codon at the 3'-end of exon 8 not found in any other ortholog. With the current exception of the domesticated bovine and buffalo, Lfg5's expression in mammals is testis-specific. A full analysis of this gene, its phylogenetic context and its recent hominin changes suggest its inactivation was likely under selection in human evolution.

  11. Identity of M2A (D2-40) antigen and gp36 (Aggrus, T1A-2, podoplanin) in human developing testis, testicular carcinoma in situ and germ-cell tumours.

    PubMed

    Sonne, Si Brask; Herlihy, Amy S; Hoei-Hansen, Christina E; Nielsen, John E; Almstrup, Kristian; Skakkebaek, Niels E; Marks, Alexander; Leffers, Henrik; Rajpert-De Meyts, Ewa

    2006-08-01

    Testicular germ-cell tumours of young adults are derived from a pre-invasive intratubular lesion, carcinoma in situ (CIS). In a recent genome-wide gene expression screening using cDNA microarrays, we found PDPN over-expressed in CIS compared to normal adult testis. PDPN encodes podoplanin (Aggrus, human gp36, T1A-2), a transmembrane glycoprotein expressed in lymphatic endothelium and various solid tumours. To examine a potential role for PDPN in testicular neoplasms and during testicular development, we investigated its expression pattern during the development of human testis and in a series of testicular CIS, gonadoblastoma and overt germ-cell tumours. We established by RT-PCR and by immunohistochemistry with a gp36 antibody that PDPN mRNA and the protein product were expressed in testes with germ-cell neoplasms but not in the normal adult testis. We also found gp36 expression in early foetal gonocytes and immature Sertoli cells, similar to the expression pattern of M2A antigen, a previously identified marker for CIS and seminoma. This reinforced our previous proposal that M2A (D2-40) antigen was identical to gp36 (podoplanin, Aggrus, T1A-2). Our findings also suggest that podoplanin has a function in developing testis, most likely at the level of cell-cell interactions among pre-meiotic germ cells and immature Sertoli cells.

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

    PubMed Central

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

    2007-01-01

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

  13. The Histone Variant His2Av is Required for Adult Stem Cell Maintenance in the Drosophila Testis

    PubMed Central

    Fuller, Margaret T.

    2013-01-01

    Many tissues are sustained by adult stem cells, which replace lost cells by differentiation and maintain their own population through self-renewal. The mechanisms through which adult stem cells maintain their identity are thus important for tissue homeostasis and repair throughout life. Here, we show that a histone variant, His2Av, is required cell autonomously for maintenance of germline and cyst stem cells in the Drosophila testis. The ATP-dependent chromatin-remodeling factor Domino is also required in this tissue for adult stem cell maintenance possibly by regulating the incorporation of His2Av into chromatin. Interestingly, although expression of His2Av was ubiquitous, its function was dispensable for germline and cyst cell differentiation, suggesting a specific role for this non-canonical histone in maintaining the stem cell state in these lineages. PMID:24244183

  14. Epitopes of human testis-specific lactate dehydrogenase deduced from a cDNA sequence

    SciTech Connect

    Millan, J.L.; Driscoll, C.E.; LeVan, K.M.; Goldberg, E.

    1987-08-01

    The sequence and structure of human testis-specific L-lactate dehydrogenase (LDHC/sub 4/, LDHX; (L)-lactate:NAD/sup +/ oxidoreductase, EC 1.1.1.27) has been derived from analysis of a complementary DNA (cDNA) clone comprising the complete protein coding region of the enzyme. From the deduced amino acid sequence, human LDHC/sub 4/ is as different from rodent LDHC/sub 4/ (73% homology) as it is from human LDHA/sub 4/ (76% homology) and porcine LDHB/sub 4/ (68% homology). Subunit homologies are consistent with the conclusion that the LDHC gene arose by at least two independent duplication events. Furthermore, the lower degree of homology between mouse and human LDHC/sub 4/ and the appearance of this isozyme late in evolution suggests a higher rate of mutation in the mammalian LDHC genes than in the LDHA and -B genes. Comparison of exposed amino acid residues of discrete anti-genic determinants of mouse and human LDHC/sub 4/ reveals significant differences. Knowledge of the human LDHC/sub 4/ sequence will help design human-specific peptides useful in the development of a contraceptive vaccine.

  15. MicroRNA (miRNA) cloning analysis reveals sex differences in miRNA expression profiles between adult mouse testis and ovary.

    PubMed

    Mishima, Takuya; Takizawa, Takami; Luo, Shan-Shun; Ishibashi, Osamu; Kawahigashi, Yutaka; Mizuguchi, Yoshiaki; Ishikawa, Tomoko; Mori, Miki; Kanda, Tomohiro; Goto, Tadashi; Takizawa, Toshihiro

    2008-12-01

    MicroRNAs (miRNAs) are endogenous non-coding small RNAs that can regulate the expression of complementary mRNA targets. Identifying tissue-specific miRNAs is the first step toward understanding the biological functions of miRNAs, which include the regulation of tissue differentiation and the maintenance of tissue identity. In this study, we performed small RNA library sequencing in adult mouse testis and ovary to reveal their characteristic organ- and gender-specific profiles and to elucidate the characteristics of the miRNAs expressed in the reproductive system. We obtained 10,852 and 11 744 small RNA clones from mouse testis and ovary respectively (greater than 10,000 clones per organ), which included 6630 (159 genes) and 10,192 (154 genes) known miRNAs. A high level of efficiency of miRNA library sequencing was achieved: 61% (6630 miRNA clones/10,852 small RNA clones) and 87% (10,192/11,744) for adult mouse testis and ovary respectively. We obtained characteristic miRNA signatures in testis and ovary; 55 miRNAs were detected highly, exclusively, or predominantly in adult mouse testis and ovary, and discovered two novel miRNAs. Male-biased expression of miRNAs occurred on the X-chromosome. Our data provide important information on sex differences in miRNA expression that should facilitate studies of the reproductive organ-specific roles of miRNAs.

  16. Prolonged exposure to acetaminophen reduces testosterone production by the human fetal testis in a xenograft model

    PubMed Central

    Anderson, Richard A.; Johnston, Zoe C.; Chetty, Tarini; Smith, Lee B.; Mckinnell, Chris; Dean, Afshan; Homer, Natalie Z.; Jorgensen, Anne; Camacho-Moll, Maria-Elena; Sharpe, Richard M.; Mitchell, Rod T.

    2016-01-01

    Most common male reproductive disorders are linked to lower testosterone exposure in fetal life, although the factors responsible for suppressing fetal testosterone remain largely unknown. Protracted use of acetaminophen during pregnancy is associated with increased risk of cryptorchidism in sons, but effects on fetal testosterone production have not been demonstrated. We used a validated xenograft model to expose human fetal testes to clinically relevant doses and regimens of acetaminophen. Exposure to a therapeutic dose of acetaminophen for 7 days significantly reduced plasma testosterone (45% reduction; p=0.025) and seminal vesicle weight (a biomarker of androgen exposure; 18% reduction; p=0.005) in castrate host mice bearing human fetal testis xenografts, whereas acetaminophen exposure for just 1 day did not alter either parameter. Plasma acetaminophen concentrations (at 1 hour after the final dose) in exposed host mice were substantially below those reported in humans after a therapeutic oral dose. Subsequent in utero exposure studies in rats indicated that the acetaminophen-induced reduction in testosterone likely results from reduced expression of key steroidogenic enzymes (Cyp11a1, Cyp17a1). Our results suggest that protracted use of acetaminophen (1 week) may suppress fetal testosterone production, which could have adverse consequences. Further studies are required to establish the dose-response and treatment-duration relationships to delineate the maximum dose and treatment period without this adverse effect. PMID:25995226

  17. Osteocalcin regulates murine and human fertility through a pancreas-bone-testis axis

    PubMed Central

    Oury, Franck; Ferron, Mathieu; Huizhen, Wang; Confavreux, Cyrille; Xu, Lin; Lacombe, Julie; Srinivas, Prashanth; Chamouni, Alexandre; Lugani, Francesca; Lejeune, Herve; Kumar, T. Rajendra; Plotton, Ingrid; Karsenty, Gerard

    2013-01-01

    The osteoblast-derived hormone osteocalcin promotes testosterone biosynthesis in the mouse testis by binding to GPRC6A in Leydig cells. Interestingly, Osteocalcin-deficient mice exhibit increased levels of luteinizing hormone (LH), a pituitary hormone that regulates sex steroid synthesis in the testes. These observations raise the question of whether LH regulates osteocalcin’s reproductive effects. Additionally, there is growing evidence that osteocalcin levels are a reliable marker of insulin secretion and sensitivity and circulating levels of testosterone in humans, but the endocrine function of osteocalcin is unclear. Using mouse models, we found that osteocalcin and LH act in 2 parallel pathways and that osteocalcin-stimulated testosterone synthesis is positively regulated by bone resorption and insulin signaling in osteoblasts. To determine the importance of osteocalcin in humans, we analyzed a cohort of patients with primary testicular failure and identified 2 individuals harboring the same heterozygous missense variant in one of the transmembrane domains of GPRC6A, which prevented the receptor from localizing to the cell membrane. This study uncovers the existence of a second endocrine axis that is necessary for optimal male fertility in the mouse and suggests that osteocalcin modulates reproductive function in humans. PMID:23728177

  18. Inducible expression of cancer-testis antigens in human prostate cancer

    PubMed Central

    Heninger, Erika; Krueger, Timothy E.G.; Thiede, Stephanie M.; Sperger, Jamie M.; Byers, Brianna L.; Kircher, Madison R.; Kosoff, David; Yang, Bing; Jarrard, David F.; McNeel, Douglas G.; Lang, Joshua M.

    2016-01-01

    Immune tolerance to self-antigens can limit robust anti-tumor immune responses in the use of tumor vaccines. Expression of novel tumor associated antigens can improve immune recognition and lysis of tumor cells. The cancer-testis antigen (CTA) family of proteins has been hypothesized to be an ideal class of antigens due to tumor-restricted expression, a subset of which have been found to induce antibody responses in patients with prostate disease. We demonstrate that CTA expression is highly inducible in five different Prostate Cancer (PC) cell lines using a hypomethylating agent 5-Aza-2′-deoxycytidine (5AZA) and/or a histone deacetylase inhibitor LBH589. These CTAs include NY-ESO1, multiple members of the MAGE and SSX families and NY-SAR35. A subset of CTAs is synergistically induced by the combination of 5AZA and LBH589. We developed an ex vivo organ culture using human PC biopsies for ex vivo drug treatments to evaluate these agents in clinical samples. These assays found significant induction of SSX2 in 9/9 distinct patient samples and NY-SAR35 in 7/9 samples. Further, we identify expression of SSX2 in circulating tumor cells (CTC) from patients with advanced PC. These results indicate that epigenetic modifying agents can induce expression of a broad range of neoantigens in human PC and may serve as a useful adjunctive therapy with novel tumor vaccines and checkpoint inhibitors. PMID:27769045

  19. IN VITRO CONAZOLE EXPOSURE INHIBITS TESTOSTERONE PRODUCTION IN THE ADULT AND NEONATAL RAT TESTIS THROUGH THE INHIBITION OF CYP17 ACTIVITY

    EPA Science Inventory

    IN VITRO CONAZOLE EXPOSURE INHIBITS TESTOSTERONE PRODUCTION IN THE ADULT AND NEONATAL RAT TESTIS THROUGH THE INHIBITION OF CYP17 ACTIVITY

    Chad R. Blystone1, David J. Dix2, and John C. Rockett2
    1Department of Environmental and Molecular Toxicology, NC State University, R...

  20. IN VITRO CONAZOLE EXPOSURE INHIBITS TESTOSTERONE PRODUCTION IN THE ADULT AND NEONATAL RAT TESTIS THROUGH THE INHIBITION OF CYP17 ACTIVITY

    EPA Science Inventory

    IN VITRO CONAZOLE EXPOSURE INHIBITS TESTOSTERONE PRODUCTION IN THE ADULT AND NEONATAL RAT TESTIS THROUGH THE INHIBITION OF CYP17 ACTIVITY

    Chad R. Blystone1, David J. Dix2, and John C. Rockett2
    1Department of Environmental and Molecular Toxicology, NC State University, R...

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

    PubMed

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

    2017-10-01

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

  2. Expression of c-Kit receptor mRNA and protein in the developing, adult and irradiated rodent testis.

    PubMed

    Prabhu, Sridurga Mithra; Meistrich, Marvin L; McLaughlin, Eileen A; Roman, Shaun D; Warne, Sam; Mendis, Sirisha; Itman, Catherine; Loveland, Kate Lakoski

    2006-03-01

    Germ cell proliferation, migration and survival during all stages of spermatogenesis are affected by stem cell factor signalling through the c-Kit receptor, the expression and function of which are vital for normal male reproductive function. The present study comprehensively describes the c-Kit mRNA and protein cellular expression profiles in germ cells of the postnatal and adult rodent testis, revealing their significant elevation in synthesis at the onset of spermatogenesis. Real-time PCR analysis for both mice and rats matched the cellular mRNA expression profile where examined. Localization studies in normal mouse testes indicated that both c-Kit mRNA and protein are first detectable in differentiating spermatogonia. In addition, all spermatogonia isolated from 8-day-old mice displayed detectable c-Kit mRNA, but 30-50% of these lacked protein expression. The c-Kit mRNA and protein profile in normal rat testes indicated expression in gonocytes, in addition to differentiating spermatogonia. However, in the irradiated adult rat testes, in which undifferentiated spermatogonia are the only germ cell type, mRNA was also detected in the absence of protein. This persisted at 3 days and 1 and 2 weeks following treatment with gonadotrophin-releasing hormone (GnRH) antagonist to stimulate spermatogenesis recovery. By 4 weeks of GnRH antagonist treatment, accompanying the emergence of differentiating spermatogonia, both mRNA and protein were detected. Based on these observations, we propose that c-Kit mRNA and protein synthesis are regulated separately, possibly by influences linked to testis maturation and circulating hormone levels.

  3. Intratubular germ cell neoplasia of the human testis: heterogeneous protein expression and relation to invasive potential.

    PubMed

    Mitchell, Rod T; E Camacho-Moll, Maria; Macdonald, Joni; Anderson, Richard A; Kelnar, Christopher J H; O'Donnell, Marie; Sharpe, Richard M; Smith, Lee B; Grigor, Ken M; Wallace, W Hamish B; Stoop, Hans; Wolffenbuttel, Katja P; Donat, Roland; Saunders, Philippa Tk; Looijenga, Leendert Hj

    2014-09-01

    Testicular germ cell cancer develops from premalignant intratubular germ cell neoplasia, unclassified cells that are believed to arise from failure of normal maturation of fetal germ cells from gonocytes (OCT4(+)/MAGEA4(-)) into pre-spermatogonia (OCT4(-)/MAGEA4(+)). Intratubular germ cell neoplasia cell subpopulations based on stage of germ cell differentiation have been described, however the importance of these subpopulations in terms of invasive potential has not been reported. We hypothesized that cells expressing an immature (OCT4(+)/MAGEA4(-)) germ cell profile would exhibit an increased proliferation rate compared with those with a mature profile (OCT4(+)/MAGEA4(+)). Therefore, we performed triple immunofluorescence and stereology to quantify the different intratubular germ cell neoplasia cell subpopulations, based on expression of germ cell (OCT4, PLAP, AP2γ, MAGEA4, VASA) and proliferation (Ki67) markers, in testis sections from patients with preinvasive disease, seminoma, and non-seminoma. We compared these subpopulations with normal human fetal testis and with seminoma cells. Heterogeneity of protein expression was demonstrated in intratubular germ cell neoplasia cells with respect to gonocyte and spermatogonial markers. It included an embryonic/fetal germ cell subpopulation lacking expression of the definitive intratubular germ cell neoplasia marker OCT4, that did not correspond to a physiological (fetal) germ cell subpopulation. OCT4(+)/MAGEA4(-) cells showed a significantly increased rate of proliferation compared with the OCT4(+)/MAGEA4(+) population (12.8 versus 3.4%, P<0.0001) irrespective of histological tumor type, reflected in the predominance of OCT4(+)/MAGEA4(-) cells in the invasive tumor component. Surprisingly, OCT4(+)/MAGEA4(-) cells in patients with preinvasive disease showed significantly higher proliferation compared to those with seminoma or non-seminoma (18.1 versus 10.2 versus 7.2%, P<0.05, respectively). In conclusion, this study

  4. Testis cancer.

    PubMed

    Sokoloff, Mitchell H; Joyce, Geoffrey F; Wise, Matthew

    2007-06-01

    We quantified the burden of testis cancer in the United States by identifying trends in its incidence, its treatment and the use of health care resources to estimate the economic impact of the disease. The analytical methods used to generate these results were described previously. The overall incidence of testis cancer in the United States increased 46% between 1975 and 2001. During the same period the ratio of seminoma to nonseminoma increased and there were fewer men presenting with stage II and III tumors. Survival rates increased successively, attaining the current level of 95.9%. Treatment patterns changed and active surveillance increased as a primary treatment modality. Overall hospitalization rates for men with testis cancer decreased from 1.8/100,000 in 1994 and 1.4/100,000 in 2000. Care for white men shifted to the outpatient setting, which did not occur for black men. The estimated annual expenditure for testis cancer for privately insured individuals between ages 18 and 54 years was $6,236. National estimates of annual medical expenditures placed the total cost of treatment at $21.8 million in 2000, representing an increase of 10% over the total in 1994. Of men with testis cancer 16% missed work for treatment of the disease with an average of 8.4 total hours of work missed. The cost of testis cancer is estimated at almost $21.8 million annually. It appears to be increasing with time despite a shift to active surveillance treatments and less hospitalization.

  5. Aquaporins in the human testis and spermatozoa - identification, involvement in sperm volume regulation and clinical relevance.

    PubMed

    Yeung, C H; Callies, C; Tüttelmann, F; Kliesch, S; Cooper, T G

    2010-08-01

    Despite the high water-permeability of human spermatozoa, little is known about the identity and the role of aquaporins (AQP) in them or germ cells. Using ejaculates from donors, sperm AQPs were identified by western blotting followed by the analysis of mRNA with RT-PCR. Protein expression in the testis and spermatozoa was localized by immunocytochemistry. Inhibitors were used to investigate the involvement of aquaporins in water transport when ejaculated spermatozoa were swollen in medium mimicking uterine hypo-osmolality by quinine that blocks volume regulation. Sperm AQP7 and AQP8 in 39 infertile patients and 11 healthy donors were quantified by flow cytometry. AQP1 was absent from spermatozoa. Sperm and testicular AQP7-9 had nucleotide sequences identical to those of somatic cells but AQP8 mRNA also showed shorter variants. AQP7 was expressed abundantly by round and elongated spermatids and ejaculated spermatozoa, AQP8 by all germ cells and spermatozoa, and AQP9 rarely by spermatocytes or Sertoli cells. Protein bands showed specificity by western blotting for AQP7 and AQP8 but not AQP9. The absence of sperm AQP9 was further suggested by the ineffectiveness of its inhibitor phloretin in blocking quinine-induced swelling, but HgCl(2,) which inhibits AQP8, was effective. Sperm AQP7 expression was correlated with progressive motility and was lower in patients than in donors. Sperm AQP8 expression was inversely correlated with the extent of sperm coiling, which is a swelling phenomenon, but showed no difference between patients and donors. In conclusion, AQP7 and AQP8 were identified in human spermatozoa and could play a role in glycerol metabolism and water transport respectively.

  6. Effect of extract of Hibiscus on the ultrastructure of the testis in adult mice.

    PubMed

    Mahmoud, Yomna Ibrahim

    2012-07-01

    Hibiscus sabdariffa extract is a popular beverage in many tropical and sub-tropical countries. Although, Hibiscus tea is known for its medicinal effects for thousands of years, scientific evidence of its systemic safety is very limited. The current study aimed to assess the potential adverse effects of H. sabdariffa extract on sperm morphology and testicular ultrastructure of albino mice. Thirty adult male albino mice were divided into three equal groups and were given: (a) distilled water, (b) cold Hibiscus aqueous extract, and (c) boiled Hibiscus aqueous extract. Hibiscus extract was administered orally daily for 4 weeks in a dose of 200 mg/kg body weight/mouse. Twenty-four hours after the last treatment, mice were decapitated and the testes and epididymides were excised and processed for transmission electron microscopy to assess ultrastructural and sperm abnormalities. The results clearly demonstrate that aqueous extracts from dried calyx of H. sabdariffa, either cold or boiled, alter normal sperm morphology and testicular ultrastructure and adversely influence the male reproductive fertility in albino mice. The current data suggest that Hibiscus extract should be consumed with caution, and reasonable estimates of the human risk associated with its consumption should be provided. Copyright © 2011 Elsevier GmbH. All rights reserved.

  7. The Effect of a Unilateral Orchiectomy before Gonadotoxic Treatment on the Contralateral Testis in Adult and Prepubertal Rats

    PubMed Central

    Rombaut, Charlotte; Faes, Katrien; Goossens, Ellen

    2016-01-01

    Purpose Previous studies have shown that the removal of one testis leads to a compensatory mechanism in the contralateral one, but this was species and age dependent. The aim of this study was to check whether this compensation would still occur after the combination of a unilateral orchiectomy and gonadotoxic treatment, since this resembles the clinical situation of patients who have to undergo highly toxic cancer treatment and therefore choose to cryopreserve a testicular biopsy for fertility restoration purposes. Materials & Methods Sprague Dawley rats underwent either unilateral orchiectomy, gonadotoxic busulfan treatment, the combination of both or served as fertile control. A comparison of the compensatory effects was made between adult and prepubertal treated rats. Mating experiments were performed, testosterone levels were followed-up, testicular weight was recorded and histology was analysed. Results Adult treated rats were able to restore fertility spontaneously in all treatment groups. On the other hand, 30% of the rats that underwent a unilateral orchiectomy and gonadotoxic treatment at prepubertal age showed hampered spermatogenesis, low testosterone levels, decreased testicular weights and were not able to reproduce. Conclusion This study emphasizes the need of fertility preservation strategies in prepubertal patients before gonadotoxic interventions. PMID:27768736

  8. 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

  9. Permeability to lanthanum of blood testis barrier in human germinal aplasia.

    PubMed

    Camatini, M; Franchi, E; Decurtis, I

    1981-07-01

    The permeability of Sertoli tight junctions to lanthanum administrated during fixation is demonstrated in biopsies of patients with partial germinal aplasia. In freeze-fracture replicas the number of fibrils is not significantly different from the data obtained in normal testis. Thus, in these pathological conditions junctional permeability is not related solely to the complexity of the network revealed by freeze-fracture.

  10. Studies of the human testis. VII. Conversion of pregnenolone to progesterone.

    PubMed

    Fan, D F; Troen, P

    1975-09-01

    Delta5-3beta-Hydroxysteroid dehydrogenase (EC.1.1.1.145) and steroid delta-isomerase (EC.5.3.3.1) were extracted from frozen human testicular tissue and co-precipitated by addition of ammonium sulfate. The activities of both enzymes were localized in the 0-40% (NH4)2SO4 fraction. The enzyme preparation catalyzed conversion of pregnenolone, 17alpha-hydroxypregnenolone, dehydroepiandrosterone, and androstenediol to the corresponding delta4-3-oxosteroid. Since isomerization appeared not to be the rate-limiting step of the overall reaction, measurement of activity of delta5-3beta-hydroxysteroid dehydrogenase was related to the amount of delta4-3-oxosteroid produced from the corresponding delta5-3beta-hydroxysteroid. Delta5-3beta-Hydroxysteroid dehydrogenase required NAD for maximal activity. The Michaelis constants (Km) for NAD were 50 muM, 33 muM and 14 muM, respectively for the dehydrogenation of pregnenolone, 17alpha-hydroxypregnenolone, androstenediol and dehydroepiandrosterone. Km values for each substrate were: pregnenolone 10 muM, 17alpha-hydroxypregnenolone and dehydroepiandrosterone 2.5 muM and androstenediol 3.0 muM. Human testicular delta5-3beta-hydroxysteroid dehydrogenase was inhibited by most of the steroids procued by the testis. The following steroids acted as competitive inhibitors with pregnenolone: 17alpha-hydroxypregenolone (Ki = 1.3 muM), androstenediol (Ki = 2.4 muM), dehydroepiandrosterone (Ki = 0.74 muM), 20alpha-dihydroprogesterone (Ki = 1.1 muM) estrone (Ki = 0.33 muM) and estradiol-17beta (Ki = 0.87 muM). 17alpha-Hydroxyprogesterone, testosterone and androstenedione showed mixed-type inhibition of the enzyme for pregnenolone. Progesterone and NADH were noncompetitive inhibitors of the enzyme for pregnenolone. Ki values, with respect to prenenolone, were 7.4 muM for progesterone and 150 muM for NADH. NADH, however, acted competitively with NAD and Ki value was 30 muM.

  11. Zika virus infects human Sertoli cells and modulates the integrity of the in vitro blood-testis barrier model.

    PubMed

    Siemann, David N; Strange, Daniel P; Maharaj, Payal N; Shi, Pei-Yong; Verma, Saguna

    2017-09-06

    Confirmed reports of ZIKV in human seminal fluid for months after the clearance of viremia suggest the ability of ZIKV to establish persistent infection in the seminiferous tubules, an immune privileged site in the testis protected by the blood-testis barrier, also called the Sertoli cell barrier (SCB). However, cellular targets of ZIKV in human testis and mechanisms by which the virus enters seminiferous tubules remain unclear. We demonstrate that primary human SCs were highly susceptible to ZIKV as compared to the closely related dengue virus and induced expression of IFN-α, key cytokines and cell-adhesion molecules (VCAM-1 and ICAM-1). Further, using an in vitro SCB model, we show ZIKV was released on the adluminal side of the SCB model with higher efficiency than the blood-brain barrier. ZIKV-infected SCs exhibited enhanced adhesion of leukocytes that correlated with decrease in the SCB integrity. ZIKV infection did not affect the expression of tight and adherens junction proteins such as ZO-1, claudin and JAM-A, however exposure of SCs with inflammatory mediators derived from ZIKV-infected macrophages led to the degradation of ZO-1 protein that correlated with increased SCB permeability. Taken together, our data suggest that infection of SCs may be one of the crucial steps by which ZIKV gains access to the site of spermatozoa development and identify SCs as a therapeutic target to clear testicular infections. The SCB model opens up opportunities to assess interactions of SCs with other testicular cells and test the ability of anti-ZIKV drugs to cross the barrier.IMPORTANCE Recent outbreaks of ZIKV, a neglected mosquito-borne flavivirus, have identified sexual transmission as a new route of disease spread, not reported for other flaviviruses. To be able to sexually transmit for months after clearance of the viremia, ZIKV must establish infection in the seminiferous tubules, a site for spermatozoa development. However, little is known about the cell types that

  12. Differential expression analysis of Paralichthys olivaceus microRNAs in adult ovary and testis by deep sequencing.

    PubMed

    Gu, Yifeng; Zhang, Lei; Chen, Xiaowu

    2014-08-01

    MicroRNAs (miRNAs) play an important role in gonadal development and differentiation in fish. However, understanding of the mechanism of this process is hindered by our poor knowledge of miRNA expression patterns in fish gonads. In this study, miRNA libraries derived from adult gonads of Paralichthys olivaceus were generated by using next-generation sequencing (NGS) technology. Bioinformatics analysis was performed to distinguish mature miRNA sequences from two classes of small RNAs represented in the sequencing data. A total of 141 mature miRNAs were identified, in which 21 miRNAs were found in P. olivaceus for the first time. Variance and preference of miRNAs expression were concluded from the deep sequencing reads. Some miRNAs, such as pol-miR-143, pol-miR-26a and pol-let-7a were found with quite high expression levels in both gonads, while some exhibited a clear sex-biased expression in different gonad. Approximate 20.0% and 13.1% of the isolated miRNAs were preferentially expressed in the testis (FC<0.5) or ovary (FC>2), respectively. The identification and the preliminary analysis of the sex-biased expression of miRNAs in P. olivaceus gonads in our work by using NGS will provide us a basic catalog of miRNAs to facilitate future improvement and exploitation of sexual regulatory mechanisms in P. olivaceus. Copyright © 2014. Published by Elsevier Inc.

  13. Estrogenic Exposure Alters the Spermatogonial Stem Cells in the Developing Testis, Permanently Reducing Crossover Levels in the Adult

    PubMed Central

    Vrooman, Lisa A.; Oatley, Jon M.; Griswold, Jodi E.; Hassold, Terry J.; Hunt, Patricia A.

    2015-01-01

    Bisphenol A (BPA) and other endocrine disrupting chemicals have been reported to induce negative effects on a wide range of physiological processes, including reproduction. In the female, BPA exposure increases meiotic errors, resulting in the production of chromosomally abnormal eggs. Although numerous studies have reported that estrogenic exposures negatively impact spermatogenesis, a direct link between exposures and meiotic errors in males has not been evaluated. To test the effect of estrogenic chemicals on meiotic chromosome dynamics, we exposed male mice to either BPA or to the strong synthetic estrogen, ethinyl estradiol during neonatal development when the first cells initiate meiosis. Although chromosome pairing and synapsis were unperturbed, exposed outbred CD-1 and inbred C3H/HeJ males had significantly reduced levels of crossovers, or meiotic recombination (as defined by the number of MLH1 foci in pachytene cells) by comparison with placebo. Unexpectedly, the effect was not limited to cells exposed at the time of meiotic entry but was evident in all subsequent waves of meiosis. To determine if the meiotic effects induced by estrogen result from changes to the soma or germline of the testis, we transplanted spermatogonial stem cells from exposed males into the testes of unexposed males. Reduced recombination was evident in meiocytes derived from colonies of transplanted cells. Taken together, our results suggest that brief exogenous estrogenic exposure causes subtle changes to the stem cell pool that result in permanent alterations in spermatogenesis (i.e., reduced recombination in descendent meiocytes) in the adult male. PMID:25615633

  14. Cellular and intracellular distribution of growth hormone in the adult chicken testis.

    PubMed

    Martínez-Moreno, C G; Palma, L; Carranza, M; Harvey, S; Arámburo, C; Luna, M

    2011-07-01

    Endocrine actions of growth hormone (GH) have been implicated during the development of adult testicular function in several mammalian species, and recently intracrine, autocrine, and paracrine effects have been proposed for locally expressed GH. Previous reports have shown the distribution of GH mRNA and the molecular heterogeneity of GH protein in both adult chicken testes and vas deferens. This study provides evidence of the presence and distribution of GH and its receptor (GHR) during all stages of spermatogenesis in adult chicken testes. This hormone and its receptor are not restricted to the cytoplasm; they are also found in the nuclei of spermatogonia, spermatocytes, and spermatids. The pattern of GH isoforms was characterized in the different, isolated germ cell subpopulations, and the major molecular variant in all subpopulations was 17 kDa GH, as reported in other chicken extra-pituitary tissues. Another molecular variant, the 29 kDa moiety, was found mainly in the enriched spermatocyte population, suggesting that it acts at specific developmental stages. The co-localization of GH with the proliferative cell nuclear antigen PCNA (a DNA replication marker present in spermatogonial cells) was demonstrated by immunohistochemistry. These results show for the first time that GH and GHR are present in the nuclei of adult chicken germinal cells, and suggest that GH could participate in proliferation and differentiation during the complex process of spermatogenesis.

  15. Effect of mono-(2-ethylhexyl) phthalate on human and mouse fetal testis: In vitro and in vivo approaches

    SciTech Connect

    Muczynski, V.; Cravedi, J.P.; Lehraiki, A.; Levacher, C.; Moison, D.; Lecureuil, C.; Messiaen, S.; Perdu, E.; Frydman, R.; Habert, R.; and others

    2012-05-15

    The present study was conducted to determine whether exposure to the mono-(2-ethylhexyl) phthalate (MEHP) represents a genuine threat to male human reproductive function. To this aim, we investigated the effects on human male fetal germ cells of a 10{sup −5} M exposure. This dose is slightly above the mean concentrations found in human fetal cord blood samples by biomonitoring studies. The in vitro experimental approach was further validated for phthalate toxicity assessment by comparing the effects of in vitro and in vivo exposure in mouse testes. Human fetal testes were recovered during the first trimester (7–12 weeks) of gestation and cultured in the presence or not of 10{sup −5} M MEHP for three days. Apoptosis was quantified by measuring the percentage of Caspase-3 positive germ cells. The concentration of phthalate reaching the fetal gonads was determined by radioactivity measurements, after incubations with {sup 14}C-MEHP. A 10{sup −5} M exposure significantly increased the rate of apoptosis in human male fetal germ cells. The intratesticular MEHP concentration measured corresponded to the concentration added in vitro to the culture medium. Furthermore, a comparable effect on germ cell apoptosis in mouse fetal testes was induced both in vitro and in vivo. This study suggests that this 10{sup −5} M exposure is sufficient to induce changes to the in vivo development of the human fetal male germ cells. -- Highlights: ► 10{sup −5} M of MEHP impairs germ cell development in the human fetal testis. ► Organotypic culture is a suitable approach to investigate phthalate effects in human. ► MEHP is not metabolized in the human fetal testis. ► In mice, MEHP triggers similar effects both in vivo and in vitro.

  16. [Unclassified sex cord testis tumor].

    PubMed

    Grenha, Vânia; Serra, Paula; Coelho, Hugo; Retroz, Edson; Temido, Paulo; Mota, Alfredo

    2014-01-01

    Unclassified sex cord testis tumor is an extremely rare tumor, especially in the adult. It is characterized histologically for a nonspecific combination of testis stromal and epithelial elements, with varying degree of differentiation. Treatment usually consists of radical orchiectomy followed by clinical and imaging surveillance. The available literature about this pathology relies almost exclusively on clinical cases. It's our aim to describe the case of a 37 years old man with an unclassified sex cord testis tumor, the first case described in Portugal, and to review the literature about this issue.

  17. In Utero Exposure to Di-(2-Ethylhexyl) Phthalate Decreases Mineralocorticoid Receptor Expression in the Adult Testis

    PubMed Central

    Martinez-Arguelles, D. B.; Culty, M.; Zirkin, B. R.; Papadopoulos, V.

    2009-01-01

    In utero exposure to di-(2-ethylhexyl) phthalate (DEHP) has been shown to result in decreased androgen formation by fetal and adult rat testes. In the fetus, decreased androgen is accompanied by the reduced expression of steroidogenic enzymes. The mechanism by which in utero exposure results in reduced androgen formation in the adult, however, is unknown. We hypothesized that deregulation of the nuclear steroid receptors might explain the effects of in utero DEHP exposure on adult testosterone production. To test this hypothesis, pregnant Sprague Dawley dams were gavaged with 100–950 mg DEHP per kilogram per day from gestational d 14–19, and testes were collected at gestational d 20 and postnatal days (PND) 3, 21, and 60. Among the nuclear receptors studied, the mineralocorticoid receptor (MR) mRNA and protein levels were reduced in PND60 interstitial Leydig cells, accompanied by reduced mRNA expression of MR-regulated genes. Methylation-sensitive PCR showed effects on the nuclear receptor subfamilies NR3A and -3C, but only MR was affected at PND60. Pyrosequencing of two CpG islands within the MR gene promoter revealed a loss of methylation in DEHP-treated animals that was correlated with reduced MR. Because MR activation is known to stimulate Leydig cell testosterone formation, and MR inhibition to be repressive, our results are consistent with the hypothesis that in utero exposure to DEHP leads to MR dysfunction and thus to depressed testosterone production in the adult. We suggest that decreased MR, possibly epigenetically mediated, is a novel mechanism by which phthalates may affect diverse functions later in life. PMID:19819939

  18. Human Metapneumovirus in Adults

    PubMed Central

    Haas, Lenneke E. M.; Thijsen, Steven F. T.; van Elden, Leontine; Heemstra, Karen A.

    2013-01-01

    Human metapneumovirus (HMPV) is a relative newly described virus. It was first isolated in 2001 and currently appears to be one of the most significant and common human viral infections. Retrospective serologic studies demonstrated the presence of HMPV antibodies in humans more than 50 years earlier. Although the virus was primarily known as causative agent of respiratory tract infections in children, HMPV is an important cause of respiratory infections in adults as well. Almost all children are infected by HMPV below the age of five; the repeated infections throughout life indicate transient immunity. HMPV infections usually are mild and self-limiting, but in the frail elderly and the immunocompromised patients, the clinical course can be complicated. Since culturing the virus is relatively difficult, diagnosis is mostly based on a nucleic acid amplification test, such as reverse transcriptase polymerase chain reaction. To date, no vaccine is available and treatment is supportive. However, ongoing research shows encouraging results. The aim of this paper is to review the current literature concerning HMPV infections in adults, and discuss recent development in treatment and vaccination. PMID:23299785

  19. Seasonal changes of testis volume and sperm quality in adult fallow deer (Dama dama) and their relationship to the antler cycle.

    PubMed

    Gosch, B; Fischer, K

    1989-01-01

    Four adult male fallow deer were investigated for 1-4 consecutive years to study the relationships between annual changes in testis volume, sperm quality and antler status. Testicular volume started to increase in July/August, peaked just before the rut, declined until December to 50% of maximum, persisted at this level up to February/March and reached minimal volume after antler casting in late April. There was no apparent age effect on the seasonality of testis size fluctuations. Velvet shedding and antler casting occurred at about 80% and 25%, respectively, of maximal testis volume. Spermatozoa had the same general appearance as those of related ruminants. Viable spermatozoa appeared between August and early May which corresponds almost exactly to the time when fallow deer are in hard antler. From September to March sperm quality would fulfil artificial insemination standards for cattle semen. In June and the first half of July 14 out of 15 ejaculates were devoid of any sperm cells. There were no indications of a secondary seasonal peak in values monitored.

  20. 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

    What are the effects of experimentally manipulating meiosis signalling by addition of retinoic acid (RA) in cultured human fetal gonads? RA-treatment accelerated meiotic entry in cultured fetal ovary samples, while addition of RA resulted in a dysgenetic gonadal phenotype in fetal testis cultures. One of the first manifestations of sex differentiation is the initiation of meiosis in fetal ovaries. In contrast, meiotic entry is actively prevented in the fetal testis at this developmental time-point. It has previously been shown that RA-treatment mediates initiation of meiosis in human fetal ovary ex vivo. This was a controlled ex vivo study of human fetal gonads treated with RA in 'hanging-drop' tissue cultures. The applied experimental set-up preserves germ cell-somatic niche interactions and the investigated outcomes included tissue integrity and morphology, cell proliferation and survival and the expression of markers of meiosis and sex differentiation. Tissue from 24 first trimester human fetuses was included in this study, all from elective terminations at gestational week (GW) 7-12. Gonads were cultured for 2 weeks with and without addition of 1 µM RA. Samples were subsequently formalin-fixed and investigated by immunohistochemistry and cell counting. Proteins investigated and quantified included; octamer-binding transcription factor 4 (OCT4), transcription factor AP-2 gamma (AP2γ) (embryonic germ cell markers), SRY (sex determining region Y)-box 9 (SOX9), anti-Müllerian hormone (AMH) (immature Sertoli cell markers), COUP transcription factor 2 (COUP-TFII) (marker of interstitial cells), forkhead box L2 (FOXL2) (granulosa cell marker), H2A histone family, member X (γH2AX) (meiosis marker), doublesex and mab-3 related transcription factor 1 (DMRT1) (meiosis regulator), cleaved poly ADP ribose polymerase (PARP), cleaved Caspase 3 (apoptosis markers) and Ki-67 antigen (Ki-67) (proliferation marker). Also, proliferation was determined using a 5'-bromo-2

  1. Analysis of SOX2 expression in developing human testis and germ cell neoplasia.

    PubMed

    Sonne, Si B; Perrett, Rebecca M; Nielsen, John E; Baxter, Melissa A; Kristensen, David M; Leffers, Henrik; Hanley, Neil A; Rajpert-De-Meyts, Ewa

    2010-01-01

    The transcriptional regulators of pluripotency, POU5F1 (OCT4), NANOG and SOX2, are highly expressed in embryonal carcinoma (EC). In contrast to OCT4 and NANOG, SOX2 has not been demonstrated in the early human germ cell lineage or carcinoma in situ (CIS), the precursor for testicular germ cell tumours (TGCTs). Here, we have analysed SOX2 expression in CIS and overt TGCTs, as well as normal second and third trimester fetal, prepubertal and adult testes by in situ hybridisation and immunohistochemistry using three different antibodies. In contrast to earlier studies, we detected SOX2 mRNA in most CIS cells. We also detected speckled nuclear SOX2 immunoreactivity in CIS cells with one primary antibody, which was not apparent with other primary antibodies. The results demonstrate SOX2 gene expression in CIS for the first time and raise the possibility of post-transcriptional regulation, most likely sumoylation as a mechanism for limiting SOX2 action in these cells.

  2. Mammalian Testis-determining Factor SRY and the Enigma of Inherited Human Sex Reversal

    PubMed Central

    Phillips, Nelson B.; Racca, Joseph; Chen, Yen-Shan; Singh, Rupinder; Jancso-Radek, Agnes; Radek, James T.; Wickramasinghe, Nalinda P.; Haas, Elisha; Weiss, Michael A.

    2011-01-01

    Mammalian testis-determining factor SRY contains a high mobility group box, a conserved eukaryotic motif of DNA bending. Mutations in SRY cause XY gonadal dysgenesis and somatic sex reversal. Although such mutations usually arise de novo in spermatogenesis, some are inherited and so specify male development in one genetic background (the father) but not another (the daughter). Here, we describe the biophysical properties of a representative inherited mutation, V60L, within the minor wing of the L-shaped domain (box position 5). Although the stability and DNA binding properties of the mutant domain are similar to those of wild type, studies of SRY-induced DNA bending by subnanosecond time-resolved fluorescence resonance energy transfer (FRET) revealed enhanced conformational fluctuations leading to long range variation in bend angle. 1H NMR studies of the variant protein-DNA complex demonstrated only local perturbations near the mutation site. Because the minor wing of SRY folds on DNA binding, the inherited mutation presumably hinders induced fit. Stopped-flow FRET studies indicated that such frustrated packing leads to accelerated dissociation of the bent complex. Studies of SRY-directed transcriptional regulation in an embryonic gonadal cell line demonstrated partial activation of downstream target Sox9. Our results have demonstrated a nonlocal coupling between DNA-directed protein folding and protein-directed DNA bending. Perturbation of this coupling is associated with a genetic switch poised at the threshold of activity. PMID:21849498

  3. Photoperiodic regulation of melatonin membrane receptor (MT1R) expression and steroidogenesis in testis of adult golden hamster, Mesocricetus auratus.

    PubMed

    Mukherjee, Arun; Haldar, Chandana

    2014-11-01

    Photoperiodic modulation of melatonin membrane receptor (MT1R) expression in testis has never been reported for any seasonal breeder. Thus, the aim of the present study was to investigate the expression dynamics of MT1R in testis and its interaction with testicular steroidogenesis in a long-day breeder, Mesocricetus auratus. Hamsters were exposed to different photoperiodic conditions i.e. critical- (CP; 12.5L:11.5D); short-day- (SD; 8L:16D) and long-day- (LD; 16L:8D) for 10 weeks wherein testicular steroidogenesis, local melatonin synthesis and the expression of MT1R were analyzed. SD induced melatonin suppressed testicular steroidogenesis as evident from regressed testicular histoarchitecture, decreased expression of AR, StAR, LH-R, P₄₅₀SCC and enzyme activities of 3β- and 17β-HSD. Differential photoperiodic regulation of MT1R expression in testis suggests its involvement in photoperiodic signal transduction for seasonal adjustment of reproduction. Increased S-NAT (Serotonin N-acetyl transferase) activity and local testicular melatonin under SD condition suggest an inhibitory effect of the local melatonergic system on testicular steroidogenesis. Completely opposite responses were recorded for all the parameters analyzed when hamsters were exposed to CP or LD conditions. In conclusion, we may suggest that photoperiod via regulating circulatory and local melatonin level as well as MT1R expression in testes fine tunes the steroidogenesis and thereby, the reproductive status of male golden hamster.

  4. Human and mouse ZFY genes produce a conserved testis-specific transcript encoding a zinc finger protein with a short acidic domain and modified transactivation potential.

    PubMed

    Decarpentrie, Fanny; Vernet, Nadège; Mahadevaiah, Shantha K; Longepied, Guy; Streichemberger, Eric; Aknin-Seifer, Isabelle; Ojarikre, Obah A; Burgoyne, Paul S; Metzler-Guillemain, Catherine; Mitchell, Michael J

    2012-06-15

    Mammalian ZFY genes are located on the Y chromosome, and code putative transcription factors with 12-13 zinc fingers preceded by a large acidic (activating) domain. In mice, there are two genes, Zfy1 and Zfy2, which are expressed mainly in the testis. Their transcription increases in germ cells as they enter meiosis, both are silenced by meiotic sex chromosome inactivation (MSCI) during pachytene, and Zfy2 is strongly reactivated later in spermatids. Recently, we have shown that mouse Zfy2, but not Zfy1, is involved in triggering the apoptotic elimination of specific types of sex chromosomally aberrant spermatocytes. In humans, there is a single widely transcribed ZFY gene, and there is no evidence for a specific role in the testis. Here, we characterize ZFY transcription during spermatogenesis in mice and humans. In mice, we define a variety of Zfy transcripts, among which is a Zfy2 transcript that predominates in spermatids, and a Zfy1 transcript, lacking an exon encoding approximately half of the acidic domain, which predominates prior to MSCI. In humans, we have identified a major testis-specific ZFY transcript that encodes a protein with the same short acidic domain. This represents the first evidence that ZFY has a conserved function during human spermatogenesis. We further show that, in contrast to the full acidic domain, the short domain does not activate transcription in yeast, and we hypothesize that this explains the functional difference observed between Zfy1 and Zfy2 during mouse meiosis.

  5. Molecular characterization of a slowly gating human hyperpolarization-activated channel predominantly expressed in thalamus, heart, and testis

    PubMed Central

    Seifert, Reinhard; Scholten, Alexander; Gauss, Renate; Mincheva, Antoaneta; Lichter, Peter; Kaupp, U. Benjamin

    1999-01-01

    Rhythmic activity of neurons and heart cells is endowed by pacemaker channels that are activated by hyperpolarization and directly regulated by cyclic nucleotides (termed HCN channels). These channels constitute a multigene family, and it is assumed that the properties of each member are adjusted to fit its particular function in the cell in which it resides. Here we report the molecular and functional characterization of a human subtype hHCN4. hHCN4 transcripts are expressed in heart, brain, and testis. Within the brain, the thalamus is the predominant area of hHCN4 expression. Heterologous expression of hHCN4 produces channels of unusually slow kinetics of activation and inactivation. The mean potential of half-maximal activation (V1/2) was −75.2 mV. cAMP shifted V1/2 by 11 mV to more positive values. The hHCN4 gene was mapped to chromosome band 15q24–q25. The characteristic expression pattern and the sluggish gating suggest that hHCN4 controls the rhythmic activity in both thalamocortical neurons and pacemaker cells of the heart. PMID:10430953

  6. Arts & Humanities in Adult Education.

    ERIC Educational Resources Information Center

    Word's Worth: A Quarterly Newsletter of the Lifelong Learning Network, 1998

    1998-01-01

    This issue of a quarterly newsletter on lifelong learning focuses on the theme of the arts and humanities in adult literacy education. The following articles are included: (1) "In Defense of a Practical Education" (Earl Shorris); (2) "From the Program Director" (Elizabeth Bryant McCrary); (3) "Vermont Council on the Humanities: Book Discussion…

  7. Stage and region-specific localization of lipocalin-type prostaglandin D synthase in the adult murine testis and epididymis.

    PubMed

    Gerena, R L; Eguchi, N; Urade, Y; Killian, G J

    2000-01-01

    Lipocalin-type prostaglandin D synthase in semen has been associated with male fertility, although this relationship is not well defined. To gain insight into potential mechanisms, the objective of the present study was to immunocytochemically localize lipocalin-type prostaglandin D synthase within the testis, efferent ducts, and 4 segments of mouse epididymis. In the testis, immunoperoxidase staining was localized within the Sertoli cells only at stages VI-VIII of the spermatogenic cycle, which is just prior to spermiation. Intense staining was also evident throughout the interstitial tissue, including Leydig cells. The entire epithelium of the efferent ducts, including ciliated and nonciliated cells, was immunoreactive. A distinct pattern of immunostaining for lipocalin-type prostaglandin D synthase was observed in different regions of epididymis, suggesting a possible role in sperm maturation. Staining for lipocalin-type prostaglandin D synthase was strikingly absent in the initial segment. In caput epididymidis, staining was evident throughout the cell cytoplasm of principal cells with some cells more intensely stained than adjacent ones. In the corpus region, overall staining intensity decreased and appeared to be concentrated in the apical region of principal cells, but some cells were completely unreactive. Reaction product in the cauda region was heavily concentrated on microvilli and within the epididymal lumen. In all epididymal regions, expression of lipocalin-type prostaglandin D synthase was specific to epithelial principal cells; no immunoreactivity was apparent in other cell types. The specific localization of lipocalin-type prostaglandin D synthase within the testicular interstitial tissue, Sertoli cells, and principal cells of caput epididymidis strongly suggests that this protein plays an integral role in both the development and maturation of sperm.

  8. Effects of Arctium lappa on Cadmium-Induced Damage to the Testis and Epididymis of Adult Wistar Rats.

    PubMed

    Predes, Fabricia de Souza; Diamante, M A S; Foglio, M A; Dolder, H

    2016-10-01

    The protective role of Arctium lappa (AL) on the testes of rats acutely exposed to cadmium (Cd) was tested. The rats were randomly divided into a control group (C-group) and three major experimental groups, which were further subdivided into minor groups (n = 6) according to the experimental period (7 or 56 days). The C-group was subdivided into C-7 and C-56 [receiving a single saline solution, intraperitoneal (i.p.), on the first day]; the AL-group, AL-7, and AL-56, received AL extract (300 mg/kg/daily); the Cd group, Cd-7 and Cd-56, received a single i.p. dose of CdCl2 (1.2 mg/kg body weight (BW)) on the first day; the CdAL group, CdAL-7 and CdAL-56, received the same Cd dose, followed by AL extract. Water or AL extract was administered daily by gavage. After either 7 or 56 days, the testis and accessory glands were removed after whole-body perfusion. Exposure to Cd and CdAL decreased the weight of the testis and epididymis, the gonadosomatic index, seminiferous tubular (ST) diameter, and ST volumetric proportion, and increased the volumetric proportion of interstitium after 56 days. In the epididymis caput, the tubular volumetric proportion decreased along with an increase of interstitial volumetric proportion and epithelium height after 56 days. The alterations observed were less severe only after 7 days. A progressive testicular damage resulted mainly in tubules lined only by Sertoli cells. The sperm number and cell debris decreased in the epididymis. We demonstrated that the testicular damage induced by single acute i.p. exposure to Cd occurred despite the daily oral intake of AL extract.

  9. Enhancer of polycomb coordinates multiple signaling pathways to promote both cyst and germline stem cell differentiation in the Drosophila adult testis.

    PubMed

    Feng, Lijuan; Shi, Zhen; Chen, Xin

    2017-02-01

    Stem cells reside in a particular microenvironment known as a niche. The interaction between extrinsic cues originating from the niche and intrinsic factors in stem cells determines their identity and activity. Maintenance of stem cell identity and stem cell self-renewal are known to be controlled by chromatin factors. Herein, we use the Drosophila adult testis which has two adult stem cell lineages, the germline stem cell (GSC) lineage and the cyst stem cell (CySC) lineage, to study how chromatin factors regulate stem cell differentiation. We find that the chromatin factor Enhancer of Polycomb [E(Pc)] acts in the CySC lineage to negatively control transcription of genes associated with multiple signaling pathways, including JAK-STAT and EGF, to promote cellular differentiation in the CySC lineage. E(Pc) also has a non-cell-autonomous role in regulating GSC lineage differentiation. When E(Pc) is specifically inactivated in the CySC lineage, defects occur in both germ cell differentiation and maintenance of germline identity. Furthermore, compromising Tip60 histone acetyltransferase activity in the CySC lineage recapitulates loss-of-function phenotypes of E(Pc), suggesting that Tip60 and E(Pc) act together, consistent with published biochemical data. In summary, our results demonstrate that E(Pc) plays a central role in coordinating differentiation between the two adult stem cell lineages in Drosophila testes.

  10. Enhancer of polycomb coordinates multiple signaling pathways to promote both cyst and germline stem cell differentiation in the Drosophila adult testis

    PubMed Central

    Feng, Lijuan; Shi, Zhen; Chen, Xin

    2017-01-01

    Stem cells reside in a particular microenvironment known as a niche. The interaction between extrinsic cues originating from the niche and intrinsic factors in stem cells determines their identity and activity. Maintenance of stem cell identity and stem cell self-renewal are known to be controlled by chromatin factors. Herein, we use the Drosophila adult testis which has two adult stem cell lineages, the germline stem cell (GSC) lineage and the cyst stem cell (CySC) lineage, to study how chromatin factors regulate stem cell differentiation. We find that the chromatin factor Enhancer of Polycomb [E(Pc)] acts in the CySC lineage to negatively control transcription of genes associated with multiple signaling pathways, including JAK-STAT and EGF, to promote cellular differentiation in the CySC lineage. E(Pc) also has a non-cell-autonomous role in regulating GSC lineage differentiation. When E(Pc) is specifically inactivated in the CySC lineage, defects occur in both germ cell differentiation and maintenance of germline identity. Furthermore, compromising Tip60 histone acetyltransferase activity in the CySC lineage recapitulates loss-of-function phenotypes of E(Pc), suggesting that Tip60 and E(Pc) act together, consistent with published biochemical data. In summary, our results demonstrate that E(Pc) plays a central role in coordinating differentiation between the two adult stem cell lineages in Drosophila testes. PMID:28196077

  11. [Transverse ectopic testis].

    PubMed

    Jouini, Riadh; Lefi, Mounir; Sami, Chelly; Manef, Gesmi; Mohsen, Belguith; Nouri, Abdellatif

    2002-09-01

    Transverse ectopic testis (TET) is a rare form of ectopic testis. The authors report the case of a 2-month-old infant presenting with right inguinoscrotal hernia and ectopic left testis with an impalpable testis. Opening of the hernia sac revealed two testes with two distally fused vasa deferentes. The contralateral testis was easily descended by translocation through the other inguinal canal. A favourable result was obtained with two testes situated in a normal position. In the light of this case, the authors emphasize the clinical and therapeutic features of this anomaly.

  12. Inhibition of in vitro human chorionic gonadotropin-stimulated testosterone production in testis and of ovulation in the rat by charcoal-treated rat testicular extract

    SciTech Connect

    de Bellabarba, G.A.; Bishop, W.; Rojas, F.J.

    1984-01-16

    Previously, the authors described the presence of a factor obtained from rat testis that was found to inhibit human chorionic gonadotropin (hCG) binding to gonadal receptors. In the present study, similarly prepared testicular extract was tested for its effects on in vitro hCG-stimulated testosterone production by isolated testis interstitial cells and for its effect on spontaneous ovulation in the rat. Incubation of interstitial cells with charcoal-treated extract significantly inhibited the steroidogenic response to hCG in a dose-related manner. This inhibition was also apparent after heating the extract for 10 min at 100/sup 0/C. A single i.p. injection of testicular extract inhibited spontaneous ovulation in the rat. This effect was also observed after heating the extract for 10 min at 100/sup 0/C. It is concluded that the aqueous testicular extract contains a factor able to antagonize the physiological events mediated by luteinizing hormone (LH)/hCG, and that this factor is consistent with the presence of an LH/hCG-binding inhibitory activity in rat testis.

  13. Identification of new TSGA10 transcript variants in human testis with conserved regulatory RNA elements in 5'untranslated region and distinct expression in breast cancer.

    PubMed

    Salehipour, Pouya; Nematzadeh, Mahsa; Mobasheri, Maryam Beigom; Afsharpad, Mandana; Mansouri, Kamran; Modarressi, Mohammad Hossein

    2017-09-01

    Testis specific gene antigen 10 (TSGA10) is a cancer testis antigen involved in the process of spermatogenesis. TSGA10 could also play an important role in the inhibition of angiogenesis by preventing nuclear localization of HIF-1α. Although it has been shown that TSGA10 messenger RNA (mRNA) is mainly expressed in testis and some tumors, the transcription pattern and regulatory mechanisms of this gene remain largely unknown. Here, we report that human TSGA10 comprises at least 22 exons and generates four different transcript variants. It was identified that using two distinct promoters and splicing of exons 4 and 7 produced these transcript variants, which have the same coding sequence, but the sequence of 5'untanslated region (5'UTR) is different between them. This is significant because conserved regulatory RNA elements like upstream open reading frame (uORF) and putative internal ribosome entry site (IRES) were found in this region which have different combinations in each transcript variant and it may influence translational efficiency of them in normal or unusual environmental conditions like hypoxia. To indicate the transcription pattern of TSGA10 in breast cancer, expression of identified transcript variants was analyzed in 62 breast cancer samples. We found that TSGA10 tends to express variants with shorter 5'UTR and fewer uORF elements in breast cancer tissues. Our study demonstrates for the first time the expression of different TSGA10 transcript variants in testis and breast cancer tissues and provides a first clue to a role of TSGA10 5'UTR in regulation of translation in unusual environmental conditions like hypoxia. Copyright © 2017. Published by Elsevier B.V.

  14. Assuring safety without animal testing: the case for the human testis in vitro.

    PubMed

    Chapin, Robert E; Boekelheide, Kim; Cortvrindt, Rita; van Duursen, Majorie B M; Gant, Tim; Jegou, Bernard; Marczylo, Emma; van Pelt, Ans M M; Post, Janine N; Roelofs, Maarke J E; Schlatt, Stefan; Teerds, Katja J; Toppari, Jorma; Piersma, Aldert H

    2013-08-01

    From 15 to 17 June 2011, a dedicated workshop was held on the subject of in vitro models for mammalian spermatogenesis and their applications in toxicological hazard and risk assessment. The workshop was sponsored by the Dutch ASAT initiative (Assuring Safety without Animal Testing), which aims at promoting innovative approaches toward toxicological hazard and risk assessment on the basis of human and in vitro data, and replacement of animal studies. Participants addressed the state of the art regarding human and animal evidence for compound mediated testicular toxicity, reviewed existing alternative assay models, and brainstormed about future approaches, specifically considering tissue engineering. The workshop recognized the specific complexity of testicular function exemplified by dedicated cell types with distinct functionalities, as well as different cell compartments in terms of microenvironment and extracellular matrix components. This complexity hampers quick results in the realm of alternative models. Nevertheless, progress has been achieved in recent years, and innovative approaches in tissue engineering may open new avenues for mimicking testicular function in vitro. Although feasible, significant investment is deemed essential to be able to bring new ideas into practice in the laboratory. For the advancement of in vitro testicular toxicity testing, one of the most sensitive end points in regulatory reproductive toxicity testing, such an investment is highly desirable. Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  15. Intratubular trophoblasts in the contralateral testis caused elevation of serum human chorionic gonadotropin following complete remission of stage II testicular tumor: a case report.

    PubMed

    Nitta, Satoshi; Kawai, Koji; Onozawa, Mizuki; Ando, Satoshi; Miyazaki, Jun; Nagata, Chigusa; Noguchi, Masayuki; Yamasaki, Kazumitsu; Uchida, Katsunori; Iwamoto, Teruaki; Nishiyama, Hiroyuki

    2013-01-01

    We report the case of a 22-year-old male who had a history of metastatic right testicular tumor successfully treated with chemotherapy and surgery. Twenty-one months after the initial treatment, the serum human chorionic gonadotropin started to increase gradually, but whole body imaging including the left testis revealed no abnormal finding except testicular microlithiasis. A biopsy of the left testis revealed intratubular germ cell neoplasia, unclassified type. After the human chorionic gonadotropin level reached 6.6 mIU/ml, he underwent left high orchiectomy. Histology demonstrated a small malignant germ cell tumor as well as intratubular germ cell neoplasia, unclassified type, both of which were negative for human chorionic gonadotropin staining. Besides these lesions, there were tiny foci of human chorionic gonadotropin-immunoreactive intratubular trophoblasts. Serum human chorionic gonadotropin normalized immediately after the orchiectomy, and he had no sign of recurrence at 6 months. The present case will provide new insight into the diagnosis of testicular tumor recurrence with isolated elevation of a serum tumor marker.

  16. Modulation of K+ conductances by Ca2+ and human chorionic gonadotrophin in Leydig cells from mature rat testis.

    PubMed Central

    Desaphy, J F; Rogier, C; Joffre, M

    1996-01-01

    1. Although the control of steroidogenic activity of the Leydig cell by the peptides luteinizing hormone (LH) and human chorionic gonadotrophin (hCG) is clearly mediated by cAMP, the extent to which Ca2+ controls the Leydig cell function is less well defined. In the present study, the whole-cell configuration of the patch-clamp technique was used to investigate the modulation of potassium conductances by calcium and hCG, in the Leydig cells from mature rat testis. 2. In symmetrical glutamate solutions, depolarizations elicited outwardly rectifying currents, which were mainly carried by potassium and were blocked by tetraethylammonium and 4-aminopyridine. For values of [Ca2+]i below 10(-8) M, transient currents of low amplitudes, insensitive to charybdotoxin (CTX) and iberiotoxin (IBTX), were activated above -40 mV. For [Ca2+]i values of 10(-7) M and above, noisy currents with slow activation kinetics were activated above 0 mV. These currents were sustained and were sensitive to CTX and IBTX. 3. Both current types were modulated by intracellular calcium. Ionomycin and a [Ca2+]i elevation in the range from 10(-9) to 10(-7) M, both inhibited the CTX-insensitive currents, whereas a rise in the calcium concentration above 10(-7) M increased the amplitude and shifted the threshold of activation of the CTX-sensitive currents to less positive levels. 4. hCG (1-50 i.u. ml-1), in conditions where the chloride currents were strongly inhibited by 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulphonic acid (SITS), induced a partial inhibition of the CTX-insensitive currents but was unable to increase the CTX-sensitive currents. 5. No voltage-sensitive calcium current was recorded in control or hCG-stimulated cells. 6. The results indicate that hCG inhibits one kind of Ca(2+)-modulated channel, perhaps as a result of a moderate [Ca2+]i rise, but is unable to increase the intracellular Ca2+ concentration to the range in which large conductance Ca(2+)-dependent channels are

  17. Modulation of K+ conductances by Ca2+ and human chorionic gonadotrophin in Leydig cells from mature rat testis.

    PubMed

    Desaphy, J F; Rogier, C; Joffre, M

    1996-08-15

    1. Although the control of steroidogenic activity of the Leydig cell by the peptides luteinizing hormone (LH) and human chorionic gonadotrophin (hCG) is clearly mediated by cAMP, the extent to which Ca2+ controls the Leydig cell function is less well defined. In the present study, the whole-cell configuration of the patch-clamp technique was used to investigate the modulation of potassium conductances by calcium and hCG, in the Leydig cells from mature rat testis. 2. In symmetrical glutamate solutions, depolarizations elicited outwardly rectifying currents, which were mainly carried by potassium and were blocked by tetraethylammonium and 4-aminopyridine. For values of [Ca2+]i below 10(-8) M, transient currents of low amplitudes, insensitive to charybdotoxin (CTX) and iberiotoxin (IBTX), were activated above -40 mV. For [Ca2+]i values of 10(-7) M and above, noisy currents with slow activation kinetics were activated above 0 mV. These currents were sustained and were sensitive to CTX and IBTX. 3. Both current types were modulated by intracellular calcium. Ionomycin and a [Ca2+]i elevation in the range from 10(-9) to 10(-7) M, both inhibited the CTX-insensitive currents, whereas a rise in the calcium concentration above 10(-7) M increased the amplitude and shifted the threshold of activation of the CTX-sensitive currents to less positive levels. 4. hCG (1-50 i.u. ml-1), in conditions where the chloride currents were strongly inhibited by 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulphonic acid (SITS), induced a partial inhibition of the CTX-insensitive currents but was unable to increase the CTX-sensitive currents. 5. No voltage-sensitive calcium current was recorded in control or hCG-stimulated cells. 6. The results indicate that hCG inhibits one kind of Ca(2+)-modulated channel, perhaps as a result of a moderate [Ca2+]i rise, but is unable to increase the intracellular Ca2+ concentration to the range in which large conductance Ca(2+)-dependent channels are

  18. Insulin-like and testis ecdysiotropin neuropeptides are regulated by the circadian timing system in the brain during larval-adult development in the insect Rhodnius prolixus (Hemiptera).

    PubMed

    Vafopoulou, Xanthe; Steel, Colin G H

    2012-11-01

    Insulin-like peptides (ILPs) regulate numerous functions in insects including growth, development, carbohydrate metabolism and female reproduction. This paper reports the immunohistochemical localization of ILPs in brain neurons of Rhodnius prolixus and their intimate associations with the brain circadian clock system. In larvae, three groups of neurons in the protocerebrum are ILP-positive, and testis ecdysiotropin (TE) is co-localized in two of them. During adult development, the number of ILP groups increased to four. A blood meal initiates transport and release of ILPs, indicating that release is nutrient dependent. Both production and axonal transport of ILPs continue during adult development with clear cytological evidence of a daily rhythm that closely correlates with the daily rhythm of ILPs release from brains in vitro. The same phenomena were observed with TE previously. Double labeling for ILPs and pigment dispersing factor (PDF) (contained in the brain lateral clock cells, LNs) revealed intimate associations between axons of the ILP/TE cells and PDF-positive axons in both central brain and retrocerebral complex, revealing potential neuronal pathways for circadian regulation of ILPs and TE. Similar close associations were found previously between LN axons and axons of the brain neurons producing the neuropeptide prothoracicotropic hormone. Thus, the brain clock system controls rhythmicity in multiple brain neurohormones. It is suggested that rhythms in circulating ILPs and TE act in concert with known rhythms of circulating ecdysteroids in both larvae and adults to orchestrate the timing of cellular responses in diverse tissues of the animal, thereby generating internal temporal order within it.

  19. Protective effect of Guaraná (Paullinia cupana var. sorbilis) pre-treatment on cadmium-induced damages in adult Wistar testis.

    PubMed

    Leite, Rodrigo Paula; Wada, Ronaldo Seichi; Monteiro, Juliana Castro; Predes, Fabrícia Souza; Dolder, Heidi

    2011-06-01

    Guaraná (Paullinia cupana) is an Amazonian plant. Its antioxidant potential was demonstrated to be due to the high polyphenol concentration. On the other hand, one of the mechanisms underlying cadmium-induced cellular damage is free radical mediated, resulting in increased oxidative processes. This study investigated P. cupana's potential to attenuate cadmium-induced damages in Wistar rat testis. Adult male Wistar rats were either pre-treated with 2 mg/g body weight (BW) of powdered P. cupana seed during 56 days and/or injected with cadmium chloride at a dose of 1.15 mg/kg BW. After cadmium exposition (48 h), testes samples were evaluated by histological and stereological analyses. Both groups exposed to cadmium presented evident morphological alterations relative to control animals. A few rodents showed massive cell death in the seminiferous epithelium and intertubular space, indicating that some animals are more sensitive to cadmium. Despite the alterations observed in both groups, pre-treatment with P. cupana was effective in attenuating morphological changes in Leydig cells, as well as reducing inflammatory response, relative to animals exclusively exposed to the metal. Animals treated only with P. cupana presented a significant increase in plasma testosterone levels and a significant increase in volumetric proportions of seminiferous tubules, which are indicative of spermatogenic stimulation.

  20. The Impact of Long-Term Exposure to Space Environment on Adult Mammalian Organisms: A Study on Mouse Thyroid and Testis

    PubMed Central

    Masini, Maria Angela; Albi, Elisabetta; Barmo, Cristina; Bonfiglio, Tommaso; Bruni, Lara; Canesi, Laura; Cataldi, Samuela; Curcio, Francesco; D'Amora, Marta; Ferri, Ivana; Goto, Katsumasa; Kawano, Fuminori; Lazzarini, Remo; Loreti, Elisabetta; Nakai, Naoya; Ohira, Takashi; Ohira, Yoshinobu; Palmero, Silvio; Prato, Paola; Ricci, Franco; Scarabelli, Linda; Shibaguchi, Tsubasa; Spelat, Renza; Strollo, Felice; Ambesi-Impiombato, Francesco Saverio

    2012-01-01

    Hormonal changes in humans during spaceflight have been demonstrated but the underlying mechanisms are still unknown. To clarify this point thyroid and testis/epididymis, both regulated by anterior pituitary gland, have been analyzed on long-term space-exposed male C57BL/10 mice, either wild type or pleiotrophin transgenic, overexpressing osteoblast stimulating factor-1. Glands were submitted to morphological and functional analysis. In thyroids, volumetric ratios between thyrocytes and colloid were measured. cAMP production in 10−7M and 10−8M thyrotropin-treated samples was studied. Thyrotropin receptor and caveolin-1 were quantitized by immunoblotting and localized by immunofluorescence. In space-exposed animals, both basal and thyrotropin-stimulated cAMP production were always higher. Also, the structure of thyroid follicles appeared more organized, while thyrotropin receptor and caveolin-1 were overexpressed. Unlike the control samples, in the space samples thyrotropin receptor and caveolin-1 were both observed at the intracellular junctions, suggesting their interaction in specific cell membrane microdomains. In testes, immunofluorescent reaction for 3β- steroid dehydrogenase was performed and the relative expressions of hormone receptors and interleukin-1β were quantified by RT-PCR. Epididymal sperm number was counted. In space-exposed animals, the presence of 3β and 17β steroid dehydrogenase was reduced. Also, the expression of androgen and follicle stimulating hormone receptors increased while lutenizing hormone receptor levels were not affected. The interleukin 1 β expression was upregulated. The tubular architecture was altered and the sperm cell number was significantly reduced in spaceflight mouse epididymis (approx. −90% vs. laboratory and ground controls), indicating that the space environment may lead to degenerative changes in seminiferous tubules. Space-induced changes of structure and function of thyroid and testis/epididymis could be

  1. The impact of long-term exposure to space environment on adult mammalian organisms: a study on mouse thyroid and testis.

    PubMed

    Masini, Maria Angela; Albi, Elisabetta; Barmo, Cristina; Bonfiglio, Tommaso; Bruni, Lara; Canesi, Laura; Cataldi, Samuela; Curcio, Francesco; D'Amora, Marta; Ferri, Ivana; Goto, Katsumasa; Kawano, Fuminori; Lazzarini, Remo; Loreti, Elisabetta; Nakai, Naoya; Ohira, Takashi; Ohira, Yoshinobu; Palmero, Silvio; Prato, Paola; Ricci, Franco; Scarabelli, Linda; Shibaguchi, Tsubasa; Spelat, Renza; Strollo, Felice; Ambesi-Impiombato, Francesco Saverio

    2012-01-01

    Hormonal changes in humans during spaceflight have been demonstrated but the underlying mechanisms are still unknown. To clarify this point thyroid and testis/epididymis, both regulated by anterior pituitary gland, have been analyzed on long-term space-exposed male C57BL/10 mice, either wild type or pleiotrophin transgenic, overexpressing osteoblast stimulating factor-1. Glands were submitted to morphological and functional analysis.In thyroids, volumetric ratios between thyrocytes and colloid were measured. cAMP production in 10(-7)M and 10(-8)M thyrotropin-treated samples was studied. Thyrotropin receptor and caveolin-1 were quantitized by immunoblotting and localized by immunofluorescence. In space-exposed animals, both basal and thyrotropin-stimulated cAMP production were always higher. Also, the structure of thyroid follicles appeared more organized, while thyrotropin receptor and caveolin-1 were overexpressed. Unlike the control samples, in the space samples thyrotropin receptor and caveolin-1 were both observed at the intracellular junctions, suggesting their interaction in specific cell membrane microdomains.In testes, immunofluorescent reaction for 3β- steroid dehydrogenase was performed and the relative expressions of hormone receptors and interleukin-1β were quantified by RT-PCR. Epididymal sperm number was counted. In space-exposed animals, the presence of 3β and 17β steroid dehydrogenase was reduced. Also, the expression of androgen and follicle stimulating hormone receptors increased while lutenizing hormone receptor levels were not affected. The interleukin 1 β expression was upregulated. The tubular architecture was altered and the sperm cell number was significantly reduced in spaceflight mouse epididymis (approx. -90% vs. laboratory and ground controls), indicating that the space environment may lead to degenerative changes in seminiferous tubules.Space-induced changes of structure and function of thyroid and testis/epididymis could be

  2. Deep Coverage Proteomics Identifies More Low-Abundance Missing Proteins in Human Testis Tissue with Q-Exactive HF Mass Spectrometer.

    PubMed

    Wei, Wei; Luo, Weijia; Wu, Feilin; Peng, Xuehui; Zhang, Yao; Zhang, Manli; Zhao, Yan; Su, Na; Qi, YingZi; Chen, Lingsheng; Zhang, Yangjun; Wen, Bo; He, Fuchu; Xu, Ping

    2016-11-04

    Since 2012, missing proteins (MPs) investigation has been one of the critical missions of Chromosome-Centric Human Proteome Project (C-HPP) through various biochemical strategies. On the basis of our previous testis MPs study, faster scanning and higher resolution mass-spectrometry-based proteomics might be conducive to MPs exploration, especially for low-abundance proteins. In this study, Q-Exactive HF (HF) was used to survey proteins from the same testis tissues separated by two separating methods (tricine- and glycine-SDS-PAGE), as previously described. A total of 8526 proteins were identified, of which more low-abundance proteins were uniquely detected in HF data but not in our previous LTQ Orbitrap Velos (Velos) reanalysis data. Further transcriptomics analysis showed that these uniquely identified proteins by HF also had lower expression at the mRNA level. Of the 81 total identified MPs, 74 and 39 proteins were listed as MPs in HF and Velos data sets, respectively. Among the above MPs, 47 proteins (43 neXtProt PE2 and 4 PE3) were ranked as confirmed MPs after verifying with the stringent spectra match and isobaric and single amino acid variants filtering. Functional investigation of these 47 MPs revealed that 11 MPs were testis-specific proteins and 7 MPs were involved in spermatogenesis process. Therefore, we concluded that higher scanning speed and resolution of HF might be factors for improving the low-abundance MP identification in future C-HPP studies. All mass-spectrometry data from this study have been deposited in the ProteomeXchange with identifier PXD004092.

  3. Serotonergic innervation of the rat testis.

    PubMed

    Campos, M B; Vitale, M L; Calandra, R S; Chiocchio, S R

    1990-03-01

    The presence of 5-hydroxytryptamine (5-HT) was determined by h.p.l.c. in perchloric extracts of each isolated compartment of the adult rat testis. The testicular capsule, interstitial cells and interstitial fluid contained 5-HT, but 5-HT was not detected in the tubular compartment. In a group of adult rats, one testis was unilaterally denervated, and the contralateral testis used as control. The superior spermatic nerve, arising from the renal plexus, was excised and 1 week after surgery 5-HT content was measured in the capsule and interstitial fluid of both testes. Denervation caused a significant fall (34%) in 5-HT content. These results indicate that at least part of the testicular 5-HT derives from a serotonergic innervation of the gonad.

  4. Murine Asb-17 expression during mouse testis development and spermatogenesis.

    PubMed

    Kim, Kye-Seong; Kim, Myung-Sun; Kim, Soo-Kyung; Baek, Kwang-Hyun

    2004-05-01

    In this study we isolated a murine mAsb-17 from mouse testis by RT-PCR using primers designed based on the sequences from the GenBank database. The sequence analysis showed that mAsb-17 encodes a 295 amino acid polypeptide with a molecular weight of approximately 34 kDa containing two ankyrin repeats and one SOCS box. The amino acid sequence of mASB-17 showed 87.5%, 98.3% and 92.9% identity with that of human, rat and dog, respectively. Interestingly, northern blot analysis showed that mAsb-17 was expressed only in the testis. The expression analysis by RT-PCR for mAsb-17 in mouse indicates that mAsb-17 is expressed from the fourth week after birth to adult, with the highest expression in round spermatids. Both northern blot and RT-PCR analyses suggest that mASB-17 may play essential roles in testis development and spermatogenesis.

  5. Management of the undescended testis

    PubMed Central

    Klauber, George T.

    1973-01-01

    Surgical correction of the undescended testis is frequently postponed beyond the optimal time, namely, 6 years of age. An accurate diagnosis of undescended testis may be made during the first year of life. Complications and mistakes arising from misdiagnosis of undescended testis and retracted testis may, therefore, be prevented by recording findings. The purpose of this article is to present the arguments in favour of early diagnosis and operative treatment of undescended testis, and to correct possible misconceptions. PMID:4145116

  6. Binding of /sup 125/I-hCG to rainbow trout (Salmo gairdneri) testis in vitro. [Human Chorionic Gonadotropin

    SciTech Connect

    Schlaghecke, R.

    1983-02-01

    Homogenates of maturing rainbow trout testes show specific binding sites for /sup 125/I-labeled hCG (. /sup 125/I-labeled hCG). The binding is competitively inhibited by unlabeled hCG and by a hypophyseal extract of rainbow trout. It could be demonstrated that the tissue /sup 125/I-hCG binding specificity is restricted to the gonadal preparation. The trout testis was characterized by determining affinity and capacity from Scatchard plot analysis giving a high constant of dissociation Kd 3.65 x 10(-10)/M and a low binding capacity of 0.88 x 10(-15) M/mg tissue. The test system is markedly dependent on temperature, incubation-time, and pH. The maximum binding was found at 37 degrees during 2 hr of incubation in a buffer of pH 7.5.

  7. Cryptorchid testis with torsion: Inguinoscrotal whirlpool sign

    PubMed Central

    Indiran, Venkatraman

    2016-01-01

    Non contrast helical computed tomography (CT) study of the abdomen is frequently performed in evaluation of suspected ureteric colic. We present CT images of a young adult male patient who had torsion of an undescended, non-neoplastic testis and describe the “Inguinoscrotal whirlpool sign on CT”. PMID:27555688

  8. Sry, more than testis determination?

    PubMed

    Turner, Monte E; Ely, Daniel; Prokop, Jeremy; Milsted, Amy

    2011-09-01

    The Sry locus on the mammalian Y chromosome is the developmental switch responsible for testis determination. Inconsistent with this important function, the Sry locus is transcribed in adult males at times and in tissues not involved with testis determination. Sry is expressed in multiple tissues of the peripheral and central nervous system. Sry is derived from Sox3 and is similar to other SOXB family loci. The SOXB loci are responsible for nervous system development. Sry has been demonstrated to modulate the catecholamine pathway, so it should have functional consequences in the central and peripheral nervous system. The nervous system expression and potential function are consistent with Sry as a SOXB family member. In mammals, Sox3 is X-linked and undergoes dosage compensation in females. The expression of Sry in adult males allows for a type of sexual differentiation independent of circulating gonadal hormones. A quantitative difference in Sox3 plus Sry expression in males vs. females could drive changes in the transcriptome of these cells, differentiating male and female cells. Sry expression and its transcriptional effects should be considered when investigating sexual dimorphic phenotypes.

  9. Expression of DMRT1 in the mammalian ovary and testis--from marsupials to mice.

    PubMed

    Pask, A J; Behringer, R R; Renfree, M B

    2003-01-01

    Doublesex and mab3 related transcript (DMRT1) was identified as a candidate gene for human 9p24.3 associated sex reversal. DMRT1 orthologues have highly conserved roles in sexual differentiation from flies and worms to humans. A DMRT1 orthologue was isolated from a marsupial, the tammar wallaby Macropus eugenii. The wallaby gene is highly conserved with other vertebrate DMRT1 genes, especially within the P/S and DM domains. It is expressed in the differentiating testis from the late fetus, during pouch life and in the adult. As in eutherian mammals, DMRT1 protein was localized in the germ cells and the Sertoli cells of the testis, but in addition it was detected in the Leydig cells, peri-tubular myoid cells and within the acrosome of the sperm heads. DMRT1 protein was also detected in the fetal and adult ovary pre-granulosa, granulosa and germ cells. Similarly, we also detected DMRT1 in the granulosa cells of all developing follicles in the adult mouse ovary. This is the first report of DMRT1 expression in the adult mammalian ovary, and suggests a wider role for this gene in mammals, in both the testis and ovarian function.

  10. [A case of giant obsolete hydrocele testis].

    PubMed

    Numa, H; Sakamoto, S; Itoh, H; Kusuyama, H; Hiraga, S; Okada, K

    1987-09-01

    A 58-year-old man visited the urological clinic in Prefectural Tohkamachi Hospital with complaint of swelling of bilateral scrotal contents. He had no history of fever, pain or difficulty of urination. Physical examination revealed a giant mass of adult-head size in right scrotum and left inguinal hernia of fist growth. Surgical extirpation of the right scrotal mass and left inguinal herniorrhaphy was performed and the mass was diagnosed as obsolete hydrocele testis and weighed 1,600 g. The excised hydrocele sac showed marked thickening and dark brown pus amounted to about 1,400 ml, which was negative in bacterial culture. Histological examination revealed partial deposits of cholesterol and calcification in tunica vaginalis with extremely atrophic testis and destructive spermatogenesis. The findings suggested the existence of long-term infection in hydrocele testis. The etiology and pathogenesis of this disease is discussed.

  11. Testis tumor associated to microlithiasis

    PubMed Central

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

    2013-01-01

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

  12. Enhancement of mouse germ cell-associated genes expression by injection of human umbilical cord mesenchymal stem cells into the testis of chemical-induced azoospermic mice.

    PubMed

    Yang, Rui-Feng; Liu, Tai-Hua; Zhao, Kai; Xiong, Cheng-Liang

    2014-01-01

    Various methods are currently under investigation to preserve fertility in males treated with high-dose chemotherapy and radiation for malignant and nonmalignant disorders. Human umbilical cord mesenchymal stem cells (HUC-MSCs), which possess potent immunosuppressive function and secrete various cytokines and growth factors, have the potential clinical applications. As a potential alternative, we investigate whether injection of HUC-MSCs into the interstitial compartment of the testes to promote spermatogenic regeneration efficiently. HUC-MSCs were isolated from different sources of umbilical cords and injected into the interstitial space of one testis from 10 busulfan-treated mice (saline and HEK293 cells injections were performed in a separate set of mice) and the other testis remained uninjected. Three weeks after MSCs injection, Relative quantitative reverse transcription polymerase chain reaction was used to identify the expression of 10 of germ cell associated, which are all related to meiosis, demonstrated higher levels of spermatogenic gene expression (2-8 fold) in HUC-MSCs injected testes compared to the contralateral uninjected testes (five mice). Protein levels for germ cell-specific genes, miwi, vasa and synaptonemal complex protein (Scp3) were also higher in MSC-treated testes compared to injected controls 3 weeks after treatment. However, no different expression was detected in saline water and HEK293 cells injection control group. We have demonstrated HUC-MSCs could affect mouse germ cell-specific genes expression. The results also provide a possibility that the transplanted HUC-MSCs may promote the recovery of spermatogenesis. This study provides further evidence for preclinical therapeutic effects of HUC-MSCs, and explores a new approach to the treatment of azoospermia.

  13. Human adult deglutition during sleep.

    PubMed

    Sato, Kiminori; Nakashima, Tadashi

    2006-05-01

    Clearance of the pharynx by deglutition is important in protecting the airway. The pattern of deglutition during sleep was investigated. Deglutition during sleep was examined in 8 normal human adults via time-matched recordings of polysomnography and surface electromyography (EMG) of the thyrohyoid and suprahyoid muscles. During sleep, deglutition was episodic, and was absent for long periods. The mean number of swallows per hour (+/-SD) during the total sleep time was 2.9 +/- 1.3. The mean period of the longest absence of deglutition was 50.6 +/- 10.2 minutes. Most deglutition occurred in association with spontaneous electroencephalographic arousal in rapid eye movement (REM) sleep and non-REM sleep. Deglutition was related to sleep stage. The mean number of swallows per hour was 7.2 +/- 3.5 during stage 1 sleep and 2.0 +/- 0.7 during stage 2 sleep. There was little deglutition during stages 3 and 4. The deeper the sleep stage became, the lower the mean deglutition frequency became. The mean number of swallows per hour was 2.7 +/- 2.2 during REM sleep. The EMG amplitude dropped to the lowest level of recording and hypotonic EMG activity increased during REM sleep. Deglutition, a vital function, is infrequent during sleep.

  14. Dynamics of hippocampal neurogenesis in adult humans

    PubMed Central

    Alkass, Kanar; Bernard, Samuel; Salehpour, Mehran; Huttner, Hagen B.; Boström, Emil; Westerlund, Isabelle; Vial, Celine; Buchholz, Bruce A.; Possnert, Göran; Mash, Deborah C.; Druid, Henrik; Frisén, Jonas

    2015-01-01

    Adult-born hippocampal neurons are important for cognitive plasticity in rodents. There is evidence for hippocampal neurogenesis in adult humans, although whether its extent is sufficient to have functional significance has been questioned. We have assessed the generation of hippocampal cells in humans by measuring the concentration of nuclear bomb test-derived 14C in genomic DNA and we present an integrated model of the cell turnover dynamics. We found that a large subpopulation of hippocampal neurons, constituting one third of the neurons, is subject to exchange. In adult humans, 700 new neurons are added per day, corresponding to an annual turnover of 1.75% of the neurons within the renewing fraction, with a modest decline during aging. We conclude that neurons are generated throughout adulthood and that the rates are comparable in middle aged humans and mice, suggesting that adult hippocampal neurogenesis may contribute to human brain function. PMID:23746839

  15. An unusual 'appendix' testis.

    PubMed

    Wilson-Storey, D; Nour, S

    1989-12-01

    A six-week-old infant was seen with bilateral inguinal herniae. It was noted that the position of the right testis within the scrotum varied with the degree of inguinal herniation. At exploration the appendix was found lying within the patent processus vaginalis with its tip firmly adherent to the upper pole of the right testis. Appendicectomy was performed through the same incision. This unusual finding should be considered by the clinician if presented with a child with easily reducible inguinal herniae and a fluctuating testicular position.

  16. Functional changes in mRNA expression and alternative pre-mRNA splicing associated with the effects of nutrition on apoptosis and spermatogenesis in the adult testis.

    PubMed

    Guan, Yongjuan; Liang, Guanxiang; Martin, Graeme B; Guan, Le Luo

    2017-01-10

    The effects of nutrition on testis mass in the sexually mature male have long been known, however, the cellular and molecular processes of the testis response to nutrition was not fully understood. We tested whether the defects in spermatogenesis and increases in germ cell apoptosis in the testis that are induced by under-nutrition are associated with changes in mRNA expression and pre-mRNA alternative splicing using groups of 8 male sheep fed for a 10% increase or 10% decrease in body mass over 65 days. We identified 2,243 mRNAs, including TP53 and Claudin 11, that were differentially expressed in testis from underfed and well-fed sheep (FDR < 0.1), and found that their expression changed in parallel with variations in germ cell numbers, testis size, and spermatogenesis. Furthermore, pairs of 269 mRNAs and 48 miRNAs were identified on the basis of target prediction. The regulatory effect of miRNAs on mRNA expression, in combination with functional analysis, suggests that these miRNAs are involved in abnormal reproductive morphology, apoptosis and male infertility. Nutrition did not affect the total number of alternative splicing events, but affected 206 alternative splicing events. A total of 159 genes, including CREM, SPATA6, and DDX4, were differentially spliced between dietary treatments, with functions related to RNA splicing and spermatogenesis. In addition, three gene modules were positively correlated with spermatogenesis-related phenotypic traits and negatively related to apoptosis-related phenotypic traits. Among these gene modules, seven (CFLAR, PTPRC, F2R, MAP3K1, EPHA7, APP, BCAP31) were also differentially expressed between nutritional treatments, indicating their potential as markers of spermatogenesis or apoptosis. Our findings on significant changes in mRNAs and pre-mRNA alternative splicing under-nutrition suggest that they may partly explain the disruption of spermatogenesis and the increase germ cell apoptosis. However, more research is

  17. Germ cell dynamics in the testis of the postnatal common marmoset monkey (Callithrix jacchus).

    PubMed

    Albert, S; Ehmcke, J; Wistuba, J; Eildermann, K; Behr, R; Schlatt, S; Gromoll, J

    2010-11-01

    The seminiferous epithelium in the nonhuman primate Callithrix jacchus is similarly organized to man. This monkey has therefore been used as a preclinical model for spermatogenesis and testicular stem cell physiology. However, little is known about the developmental dynamics of germ cells in the postnatal primate testis. In this study, we analyzed testes of newborn, 8-week-old, and adult marmosets employing immunohistochemistry using pluripotent stem cell and germ cell markers DDX4 (VASA), POU5F1 (OCT3/4), and TFAP2C (AP-2γ). Stereological and morphometric techniques were applied for quantitative analysis of germ cell populations and testicular histological changes. Quantitative RT-PCR (qRT-PCR) of testicular mRNA was applied using 16 marker genes establishing the corresponding profiles during postnatal testicular development. Testis size increased during the first 8 weeks of life with the main driver being longitudinal outgrowth of seminiferous cords. The number of DDX4-positive cells per testis doubled between birth and 8 weeks of age whereas TFAP2C- and POU5F1-positive cells remained unchanged. This increase in DDX4-expressing cells indicates dynamic growth of the differentiated A-spermatogonial population. The presence of cells expressing POU5F1 and TFAP2C after 8 weeks reveals the persistence of less differentiated germ cells. The mRNA and protein profiles determined by qRT-PCR and western blot in newborn, 8-week-old, and adult marmosets corroborated the immunohistochemical findings. In conclusion, we demonstrated the presence of distinct spermatogonial subpopulations in the primate testis exhibiting different dynamics during early testicular development. Our study demonstrates the suitability of the marmoset testis as a model for human testicular development.

  18. Photoperiodic modulation of thyroid hormone receptor (TR-α), deiodinase-2 (Dio-2) and glucose transporters (GLUT 1 and GLUT 4) expression in testis of adult golden hamster, Mesocricetus auratus.

    PubMed

    Verma, Rakesh; Haldar, Chandana

    2016-12-01

    Phenomenon of seasonal reproduction is being regulated by changes in day length or photoperiod. The molecular mechanism underlying the event of photoperiodic regulation of testis and thyroid functions along with glucose uptake transporters has never been reported for golden hamster, M. auratus. The present study was performed to investigate the effect of photoperiod on the expression of key thyroid hormone receptor (TR-α), deiodinase-2 (Dio-2) and glucose uptake transporters (GLUT-1 & GLUT-4) in testicular germ cell and Leydig cells, and its correlation with the testicular androgen receptor (AR), germ cell proliferation factor (PCNA) and cell survival factor (Bcl-2) in testis of adult golden hamster, Mesocricetus auratus. Hamsters were exposed to different photoperiodic regimes i.e. critical photoperiod (CP), short day (SD) and long day (LD) for 10weeks. LD induces upregulation of thyroidal and gonadal activity as evident by active thyroid gland and testicular histoarchitecture, peripheral total thyroid (tT3, tT4) and testosterone hormone profiles when compared with SD exposed hamsters. Further, LD increased the expression of testicular TR-α, Dio-2, GLUT-1, GLUT-4 along with testicular AR and glucose content thereby enhancing germ cell proliferation and survival as reflected by increased PCNA and Bcl-2 expression when compared to SD exposed hamsters. Thus, it can be suggested that testicular thyroid hormone status is being regulated by photoperiod and is possibly involved in seasonal adaptation to reproductive phenomenon of golden hamster.

  19. Electroporation of the Testis

    NASA Astrophysics Data System (ADS)

    Yomogida, Kentaro

    The mature mammalian testis is a marvelous organ that produces numerous sperm cells during its reproductive phase. This biologically significant process consists of three steps: stem cell self-renewal and differentiation, meiosis and genetic recombination, and haploid cell morphogenesis into sperm (Russell et al., 1990). The first step provides a good model for investigating the molecular mechanism of stem cell regulation. Currently, the mechanism underlying sperm cell production is a very exciting topic in regenerative medicine (Lensch et al. 2007; Okita et al., 2007). The spermatogonial stem cell system has several advantages, including the easy histological identification of stem cells (Russell et al., 1990), a clear relationship between stem cells and the supporting Sertoli cells, which provide a stem cell niche (Tadokoro et al., 2002; Yomogida et al., 2003), and a transplantation assay for stem cell activity (Oatley & Brinster, 2006). Although germline stem (GS) cells derived from the gonocytes in newborn testis constitute a suitable in vitro system for investigating the properties of spermatogonial stem cells (Kanatsu-Shinohara et al., 2003, 2004), studies using living mammalian testes continue to provide information regarding the roles of the stem cell niche. In vivo electroporation of the supporting cells in the testis will expand our ability to study it.

  20. Germ cell apoptosis after treatment of cryptorchidism with human chorionic gonadotropin is associated with impaired reproductive function in the adult.

    PubMed Central

    Dunkel, L; Taskinen, S; Hovatta, O; Tilly, J L; Wikström, S

    1997-01-01

    Cryptorchidism results in impaired fertility. Reduced numbers of testicular germ cells can be shown histologically during the first years of life. The process causing germ cell loss in cryptorchid prepubertal boys is unknown, but it could be the result of a form of programmed cell death known as apoptosis. 25 adult men with a history of surgically treated cryptorchidism were studied, 15 of whom had received an unsuccessful human chorionic gonadotropin (hCG) therapy before orchidopexy. Apoptotic DNA fragmentation was assayed in testis biopsies taken during orchidopexy by end-labeling, both in extracted DNA and histochemically in situ. Only a few scattered apoptotic spermatogonias were seen by end-labeling of biopsies from patients not treated with hCG, whereas more extensive labeling of spermatogonia was seen after hCG treatment. As estimated by gel electrophoresis, the amount of low molecular weight DNA was 4.3-fold higher in the hCG-treated group when compared with the level in scrotal testis of non-hCG-treated patients (P < 0.001). About 20 yr after the biopsy, the low molecular weight DNA fragmentation correlated negatively with the testis volume (r = -0.84; P < 0.001) and positively with serum FSH levels (r = 0.73; P < 0.001). Findings in the semen analysis were similar between the groups. Apoptotic loss of spermatogonia after hCG treatment of cryptorchidism warrants reevaluation of the safety of this treatment. PMID:9410913

  1. Testis Transcriptome Modulation in Klinefelter Patients with Hypospermatogenesis

    PubMed Central

    D’Aurora, Marco; Ferlin, Alberto; Garolla, Andrea; Franchi, Sara; D’Onofrio, Laura; Trubiani, Oriana; Palka, Giandomenico; Foresta, Carlo; Stuppia, Liborio; Gatta, Valentina

    2017-01-01

    The main genetic cause of male infertility is represented by the Klinefelter Syndrome (KS), a condition accounting for 3% of all cases of infertility and up to15% of cases of azoospermia. KS is generally characterized by azoospermia; approximately 10% of cases have severe oligozoospermia. Among these, the 30–40% of patients show hypospermatogenesis. The mechanisms leading to adult testis dysfunctions are not completely understood. A microarray transcriptome analysis was performed on testis biopsies obtained from three KS patients with hypospermatogenesis and three control subjects. KS testis showed a differential up- and down-regulation of 303 and 747 transcripts, respectively, as compared to controls. The majority of down-regulated transcripts were involved in spermiogenesis failure and testis morphological defects, whereas up-regulated genes were responsible for testis apoptotic processes. Functional analysis of the transcriptionally altered genes indicated a deregulation in cell death, germ cell function and morphology as well as blood-testis-barrier maintenance and Leydig cells activity. These data support a complex scenario in which spermatogenic impairment is the result of functional and morphological alterations in both germinal and somatic components of KS testis. These findings could represent the basis for evaluating new markers of KS spermatogenesis and potential targets of therapeutic intervention to preserve residual spermatogenesis. PMID:28361989

  2. The human testis determining factor SRY localizes in midbrain dopamine neurons and regulates multiple components of catecholamine synthesis and metabolism

    PubMed Central

    Czech, Daniel P.; Lee, Joohyung; Sim, Helena; Parish, Clare L.; Vilain, Eric; Harley, Vincent R.

    2012-01-01

    The male sex is determined by the sex determining region on the Y chromosome (SRY) transcription factor. The unexpected action of SRY in the control of voluntary movement in male rodents suggests a role in regulation of dopamine transmission and dopamine-related disorders with sex bias such as Parkinson’s disease. We investigated SRY expression in the human brain and function in vitro. SRY immunoreactivity was detected in the human male, but not female, substantia nigra pars compacta (SNc) within a sub-population of tyrosine hydroxylase (TH) positive neurons. SRY protein also co-localised with TH positive neurons in the ventral tegmental area and GAD-positive neurons in the substantia nigra pars reticulate (SNr). Retinoic acid-induced differentiation of precursor NT2 cells into dopaminergic cells (NT2N) increased expression of TH, NURR1, D2R and SRY. In the human neuroblastoma cell line, M17, SRY knockdown resulted in a reduction in TH, DDC, DBH and MAO-A expression; enzymes which control dopamine synthesis and metabolism. Conversely, SRY overexpression increased TH, DDC, DBH, D2R and MAO-A levels, which was accompanied by increased extracellular dopamine levels. A luciferase assay demonstrated that SRY activated a 4.6 kb 5′ upstream regulatory region of the human TH promoter/nigral enhancer. Combined, these results suggest that SRY may play a role as a positive regulator of catecholamine synthesis and metabolism in the human male midbrain. Given the limitations of human tissue analysis, further studies are required to provide a definitive answer on SRY expression in human brain regions. PMID:22568433

  3. Asymmetrical size and functionality of the pampas deer (Ozotoceros bezoarticus) testes: Right testis is bigger but left testis is more efficient in spermatogenesis.

    PubMed

    Ungerfeld, Rodolfo; Villagrán, Matías; Lacuesta, Lorena; Vazquez, Noelia; Pérez, William

    2017-09-07

    Information about gonadal asymmetries in ruminants is very scarce. In this work, we performed three complementary studies to compare characteristics of both testes: (i) weight and size of offspring and adult dead males; (ii) the tissue:fluid relationship determined by ultrasound scanning; and (iii) the spermatogenic status using fine needle aspiration cytology. The right testis was heavier than the left one in both offspring and adult animals and had greater width and volume in adult males than the left one. The ultrasound pixel intensity was similar in both testes. The right testis tended to have more spermatogonia (p = .06) and had a greater percentage of early spermatids (p = .004) than the left testis. On the other hand, the left testis had a greater percentage of spermatozoa (p = .05). The left testis had a greater spermatozoa/spermatogonia ratio (p = .02) and tended to have more spermatozoa/Sertoli cells ratio (p = .07). The spermatogenic index tended to be greater in the left than in the right testis (p = .06). Overall, we concluded that the right testis of pampas deer males is bigger but according to the cytology, it seems to be less spermatogenically effective than the left one, but these differences are not explained by different tissue:fluid ratio in each testis. Although differences were greater in adults than in offspring, asymmetry was observed even in just born offspring. © 2017 Blackwell Verlag GmbH.

  4. Structure-function relationships in human testis-determining factor SRY: an aromatic buttress underlies the specific DNA-bending surface of a high mobility group (HMG) box.

    PubMed

    Racca, Joseph D; Chen, Yen-Shan; Maloy, James D; Wickramasinghe, Nalinda; Phillips, Nelson B; Weiss, Michael A

    2014-11-21

    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.

  5. Cancer testis antigen expression in testicular germ cell tumorigenesis.

    PubMed

    Bode, Peter K; Thielken, Andrea; Brandt, Simone; Barghorn, André; Lohe, Bernd; Knuth, Alexander; Moch, Holger

    2014-06-01

    Cancer testis antigens are encoded by germ line-associated genes that are present in normal germ cells of testis and ovary but not in differentiated tissues. Their expression in various human cancer types has been interpreted as 're-expression' or as intratumoral progenitor cell signature. Cancer testis antigen expression patterns have not yet been studied in germ cell tumorigenesis with specific emphasis on intratubular germ cell neoplasia unclassified as a precursor lesion for testicular germ cell tumors. Immunohistochemistry was used to study MAGEA3, MAGEA4, MAGEC1, GAGE1 and CTAG1B expression in 325 primary testicular germ cell tumors, including 94 mixed germ cell tumors. Seminomatous and non-seminomatous components were separately arranged and evaluated on tissue microarrays. Spermatogonia in the normal testis were positive, whereas intratubular germ cell neoplasia unclassified was negative for all five CT antigens. Cancer testis antigen expression was only found in 3% (CTAG1B), 10% (GAGE1, MAGEA4), 33% (MAGEA3) and 40% (MAGEC1) of classic seminoma but not in non-seminomatous testicular germ cell tumors. In contrast, all spermatocytic seminomas were positive for cancer testis antigens. These data are consistent with a different cell origin in spermatocytic seminoma compared with classic seminoma and support a progression model with loss of cancer testis antigens in early tumorigenesis of testicular germ cell tumors and later re-expression in a subset of seminomas.

  6. Ultrastructure of Spermatogenesis in the Testis of Paragonimus heterotremus

    PubMed Central

    Uabundit, Nongnut; Kanla, Pipatphong; Puthiwat, Phongphithak; Arunyanart, Channarong; Chaiciwamongkol, Kowit; Maleewong, Wanchai; Intapan, Pewpan M.; Iamsaard, Sitthichai

    2013-01-01

    Lung fluke, Paragonimus heterotremus, is a flatworm causing pulmonary paragonimiasis in cats, dogs, and humans in Southeast Asia. We examined the ultrastructure of the testis of adult P. heterotremus with special attention to spermatogenesis and spermiogenesis using scanning and transmission electron microscopy. The full sequence of spermatogenesis and spermiogenesis, from the capsular basal lamina to the luminal surface, was demonstrated. The sequence comprises spermatogonia, spermatocytes with obvious nuclear synaptonemal complexes, spermatids, and eventual spermatozoa. Moreover, full steps of spermatid differentiation were shown which consisted of 1) early stage, 2) differentiation stage representing the flagella, intercentriolar body, basal body, striated rootlets, and electron dense nucleus of thread-like lamellar configuration, and 3) growing spermatid flagella. Detailed ultrastructure of 2 different types of spermatozoa was also shown in this study. PMID:24516272

  7. Ultrastructure of spermatogenesis in the testis of Paragonimus heterotremus.

    PubMed

    Uabundit, Nongnut; Kanla, Pipatphong; Puthiwat, Phongphithak; Arunyanart, Channarong; Chaiciwamongkol, Kowit; Maleewong, Wanchai; Intapan, Pewpan M; Iamsaard, Sitthichai; Hipkaeo, Wiphawi

    2013-12-01

    Lung fluke, Paragonimus heterotremus, is a flatworm causing pulmonary paragonimiasis in cats, dogs, and humans in Southeast Asia. We examined the ultrastructure of the testis of adult P. heterotremus with special attention to spermatogenesis and spermiogenesis using scanning and transmission electron microscopy. The full sequence of spermatogenesis and spermiogenesis, from the capsular basal lamina to the luminal surface, was demonstrated. The sequence comprises spermatogonia, spermatocytes with obvious nuclear synaptonemal complexes, spermatids, and eventual spermatozoa. Moreover, full steps of spermatid differentiation were shown which consisted of 1) early stage, 2) differentiation stage representing the flagella, intercentriolar body, basal body, striated rootlets, and electron dense nucleus of thread-like lamellar configuration, and 3) growing spermatid flagella. Detailed ultrastructure of 2 different types of spermatozoa was also shown in this study.

  8. Quantitative proteomic analysis of human testis reveals system-wide molecular and cellular pathways associated with non-obstructive azoospermia.

    PubMed

    Alikhani, Mehdi; Mirzaei, Mehdi; Sabbaghian, Marjan; Parsamatin, Pouria; Karamzadeh, Razieh; Adib, Samane; Sodeifi, Niloofar; Gilani, Mohammad Ali Sadighi; Zabet-Moghaddam, Masoud; Parker, Lindsay; Wu, Yunqi; Gupta, Vivek; Haynes, Paul A; Gourabi, Hamid; Baharvand, Hossein; Salekdeh, Ghasem Hosseini

    2017-02-15

    Male infertility accounts for half of the infertility problems experienced by couples. Azoospermia, having no measurable level of sperm in seminal fluid, is one of the known conditions resulting in male infertility. In order to elucidate the complex molecular mechanisms causing male azoospermia, label-free quantitative shotgun proteomics was carried out on testicular tissue specimens from patients with obstructive azoospermia and non-obstructive azoospermia, including maturation arrest (MA) and Sertoli cell only syndrome (SCOS). The abundance of 520 proteins was significantly changed across three groups of samples. We were able to identify several functional biological pathways enriched in azoospermia samples and confirm selected differentially abundant proteins, using multiple histological methods. The results revealed that cell cycle and proteolysis, and RNA splicing were the most significant biological processes impaired by the substantial suppression of proteins related to the aforementioned categories in SCOS tissues. In the MA patient testes, generation of precursor metabolites and energy as well as oxidation-reduction were the most significantly altered processes. Novel candidate proteins identified in this study include key transcription factors, many of which have not previously been shown to be associated with azoospermia. Our findings can provide substantial insights into the molecular regulation of spermatogenesis and human reproduction.

  9. Angiogenic properties of adult human thymus fat.

    PubMed

    Salas, Julián; Montiel, Mercedes; Jiménez, Eugenio; Valenzuela, Miguel; Valderrama, José Francisco; Castillo, Rafael; González, Sergio; El Bekay, Rajaa

    2009-11-01

    The endogenous proangiogenic properties of adipose tissue are well recognized. Although the adult human thymus has long been known to degenerate into fat tissue, it has never been considered as a potential source of angiogenic factors. We have investigated the expression of diverse angiogenic factors, including vascular endothelial growth factor A and B, angiopoietin 1, and tyrosine-protein kinase receptor-2 (an angiopoietin receptor), and then analyzed their physiological role on endothelial cell migration and proliferation, two relevant events in angiogenesis. The detection of the gene and protein expression of the various proteins has been performed by immunohistochemistry, Western blotting, and quantitative real-time polymerase chain reaction. We show, for the first time, that adult thymus fat produces a variety of angiogenic factors and induces the proliferation and migration of human umbilical cord endothelial cells. Based on these findings, we suggest that this fat has a potential angiogenic function that might affect thymic function and ongoing adipogenesis within the thymus.

  10. Laparoscopy for the nonpalpable testis.

    PubMed

    Holcomb, G W; Brock, J W; Neblett, W W; Pietsch, J B; Morgan, W M

    1994-02-01

    Between 1988 and 1992, 287 infants and children have been evaluated for an undescended testis. In 35, the testis was not palpable. These 35 patients ranged in age between 10 months and 14 years, with a mean of 44 months and a median of 15 months. Thirteen patients had a nonpalpable right testis, 18 had a nonpalpable left testis, and four had bilateral nonpalpable testes. Diagnostic laparoscopy was performed in these 35 boys with a nonpalpable testis to allow a planned approach to management of this condition. In 11 children, a testis was visualized. The testis was in an inguinal hernia sac in seven, and single stage conventional orchiopexy was performed. In four children an intra-abdominal testis was seen, and three infants underwent laparoscopic clip ligation of the testicular vessels. One teenager underwent orchiectomy. In 21 of the remaining 24 boys, small, attenuated testicular vessels were noted to pass into the inguinal canal and inguinal exploration was required. A small testicular remnant was excised in 15 patients, but orchiopexy was possible in six boys. Diagnostic laparoscopy takes 7 to 10 minutes and enables the surgeon to develop a planned approach to this condition. With the information gathered at laparoscopy, the surgeon is best able to decide if an inguinal exploration is necessary or if a single-stage orchiopexy is possible. If a two-stage orchiopexy is required for an intra-abdominal testis, then clip ligation of the testicular vessels can be performed laparoscopically as the first stage, followed by Fowler-Stephens orchiopexy 6 to 9 months later.

  11. Capillary haemangioma of the testis

    PubMed Central

    Mazal, P; Kratzik, C; Kain, R; Susani, M

    2000-01-01

    A case of testicular capillary haemangioma is reported and the importance of intraoperative examination of this very rare lesion emphasised. Capillary haemangioma of the testis can be similar to malignant testicular tumours on clinical presentation, as well as on ultrasonography and magnetic resonance imaging, and therefore should be included in the intraoperative differential diagnosis. Because of the benign nature of this lesion, conservative surgical treatment by means of tumour enucleation with preservation of the testis is possible, if intraoperative examination of frozen sections of representative tissue can be performed. Key Words: testis • haemangioma PMID:11002773

  12. Molecular cloning and characterization of chemokine-like factor super family member 1 (CKLFSF1), a novel human gene with at least 23 alternative splicing isoforms in testis tissue.

    PubMed

    Wang, Lu; Wu, Chunxiao; Zheng, Ying; Qiu, Xiaoyan; Wang, Li; Fan, Hui; Han, Wenling; Lv, Bingfeng; Wang, Ying; Zhu, Xiaohui; Xu, Mingxu; Ding, Peiguo; Cheng, Shanhong; Zhang, Yingmei; Song, Quansheng; Ma, Dalong

    2004-08-01

    Chemokine-like factor (CKLF) was isolated from PHA-stimulated U937 cells. It is composed of 152 amino acids and located on chromosome 16q22. Utilizing bioinformatics, based on CKLF cDNA and protein sequences, in combination with experimental validation, we identified a novel gene designated chemokine-like factor super family member 1 (CKLFSF1). CKLFSF1 maps on chromosome 16q22, and the full-length gene comprises of seven exons and six introns. Using RACE-PCR, we identified two potential alternative transcription start sites, 1A and 1B. Northern blot and RT-PCR analysis demonstrated that CKLFSF1 is predominantly expressed in human testis tissue, with only lower levels of expression in many other human tissues. RT-PCR and cDNA sequencing identified 23 alternatively spliced isoforms of CKLFSF1 in the testis tissue, which encode protein variants ranging from 36 to 169 amino acids in length. Immunohistochemistry analysis demonstrated that CKLFSF1 proteins are highly expressed in spermatocyte and in tissue fluid of human testes tissue. In light of these findings, we propose that CKLFSF1 may play an important role in spermatogenesis or testicular development.

  13. A newborn with antenatal testis tortion

    PubMed Central

    Çelik, Fatma Çakmak; Aygün, Canan; Ayçiçek, Tuğba; Aykanat, Mustafa Alper; Ayyıldız, Suat

    2014-01-01

    Testis tortion in the newborn (especially antenatal testis tortion) is observed very rarely and constitutes 10-12% of childhood testis tortions. In testis tortion, firm and painless testicular tissue is palpated on physical examination. Doppler ultrasonography is a sensitive method in the diagnosis. In cases of neonatal testis tortion, the testis can be saved with appropriate surgical exploration in only 0–5% of the cases. Here, a newborn with antenatal testis tortion who underwent orchiectomy in the first day of life was presented. PMID:26078672

  14. Uniquely hominid features of adult human astrocytes.

    PubMed

    Oberheim, Nancy Ann; Takano, Takahiro; Han, Xiaoning; He, Wei; Lin, Jane H C; Wang, Fushun; Xu, Qiwu; Wyatt, Jeffrey D; Pilcher, Webster; Ojemann, Jeffrey G; Ransom, Bruce R; Goldman, Steven A; Nedergaard, Maiken

    2009-03-11

    Defining the microanatomic differences between the human brain and that of other mammals is key to understanding its unique computational power. Although much effort has been devoted to comparative studies of neurons, astrocytes have received far less attention. We report here that protoplasmic astrocytes in human neocortex are 2.6-fold larger in diameter and extend 10-fold more GFAP (glial fibrillary acidic protein)-positive primary processes than their rodent counterparts. In cortical slices prepared from acutely resected surgical tissue, protoplasmic astrocytes propagate Ca(2+) waves with a speed of 36 microm/s, approximately fourfold faster than rodent. Human astrocytes also transiently increase cystosolic Ca(2+) in response to glutamatergic and purinergic receptor agonists. The human neocortex also harbors several anatomically defined subclasses of astrocytes not represented in rodents. These include a population of astrocytes that reside in layers 5-6 and extend long fibers characterized by regularly spaced varicosities. Another specialized type of astrocyte, the interlaminar astrocyte, abundantly populates the superficial cortical layers and extends long processes without varicosities to cortical layers 3 and 4. Human fibrous astrocytes resemble their rodent counterpart but are larger in diameter. Thus, human cortical astrocytes are both larger, and structurally both more complex and more diverse, than those of rodents. On this basis, we posit that this astrocytic complexity has permitted the increased functional competence of the adult human brain.

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

    PubMed

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

    2017-09-22

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

  16. Ectopic testis: a rare case.

    PubMed

    Ebrahimi, Ali

    2010-01-01

    Congenital undescending testis is a common anomaly of testis, but we had a rare case of ectopic testis. A 15-month-old infant was operated emergently because of left incarcerate inguinal hernia. Intraoperative exploration of hernial sac revealed two ectopic testes with one spermatic cord proximally but in the middle divided to two spermatic cords in a 8 shape. There was an important point about vas deferens as it was single proximal to the chord, but divided into two in the middle of the chord. Vessels showed a similar condition about. We released both testes and brought down both of them into scrotum. This is a rare case of ectopic testis transectopia with partially common vas and vessels.

  17. Thyroid Hormone and Leptin in the Testis

    PubMed Central

    Ramos, Cristiane Fonte; Zamoner, Ariane

    2014-01-01

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

  18. The effect of experimental cryptorchidism on the phosphorus NMR spectrum of the rat testis.

    PubMed

    van der Grond, J; Dijkstra, G; van Echteld, C J

    1994-06-01

    Magnetic resonance (MR) spectroscopy of the cryptorchid rat testis was used to test whether changes in the MR spectra of the rat testis might be a more sensitive indicator of changes in the metabolic status of germ cells in the testis rather than simply the cell types present. Testes of adult Wistar rats before and during 42 days of experimental cryptorchidism were investigated by in-vivo 31P MR spectroscopy. Results were compared to MR studies of the synchronized developing testis. The testicular phosphomonoester/ATP (PM/ATP) ratio was dependent only on the cell types present, and showed the same characteristics for each cell type present in the degenerating testis as in the developing testis. The testicular phosphodiester/ATP (PD/ATP) ratio decreased rapidly when the number of round and elongated spermatids was reduced. Similar effects, although less pronounced, were seen in the developing testis. The pH decreased rapidly after cryptorchidism, and was related inversely to the PM/ATP ratio, which was also observed in the developing testis. This study demonstrates that MR spectroscopy monitors the cell types present in the rat testis rather than its metabolic status.

  19. The vitamin D receptor localization and mRNA expression in ram testis and epididymis.

    PubMed

    Jin, Hui; Huang, Yang; Jin, Guang; Xue, Yanrong; Qin, Xiaowei; Yao, Xiaolei; Yue, Wenbing

    2015-02-01

    The objectives of present study were to investigate the presence of vitamin D receptor (VDR) in testis and epididymis of ram by polymerase chain reaction (PCR), to locate VDR in testis and epididymis by immunohistochemistry and to compare difference of VDR expression between testis and epididymis before and after sexual maturation by Real time-PCR and Western blot. The results showed that VDR exists in the testis and epididymis of ram while VDR protein in testis and epididymis was localized in Leydig cells, spermatogonial stem cells, spermatocytes, Sertoli cells and principal cells. For the adult ram, the amounts of VDR mRNA and VDR protein were less (p < 0.01) in testis than compared with caput, corpus and cauda epididymis. For prepubertal ram, the result showed the same trend (p < 0.01). However, the expression levels of VDR mRNA and VDR protein in caput, corpus, cauda epididymis and testis showed no significant difference (p > 0.05) between adult and prepubertal. In conclusion, VDR exists in testis and epididymis of ram, suggesting 1α,25-(OH)(2)VD(3) may play a role in ram reproduction.

  20. A novel cancer/testis antigen KP-OVA-52 identified by SEREX in human ovarian cancer is regulated by DNA methylation

    PubMed Central

    KIM, KANG-MI; SONG, MYUNG-HA; KIM, MIN-JU; DAUDI, SAYEEMA; MILIOTTO, ANTHONY; OLD, LLOYD; ODUNSI, KUNLE; LEE, SANG-YULL

    2012-01-01

    SEREX has proven to be a powerful method that takes advantage of the presence of spontaneous humoral immune response in some cancer patients. In this study, immunoscreening of normal testis and two ovarian cancer cell line cDNA expression libraries with sera from ovarian cancer patients led to the isolation of 75 independent antigens, designated KP-OVA-1 through KP-OVA-75. Of these, RT-PCR showed KP-OVA-52 to be expressed strongly in normal testis, in ovarian cancer cell lines (3/9) and in ovarian cancer tissues (1/17). The expression of KP-OVA-52 in cancer cells is also induced by the demethylating agent 5-aza-2′-deoxycytidine (ADC). To test immunogenicity, we used the Serum Antibody Detection Assay (SADA) to analyze anti-IgG antibodies against the 75 antigens that were initially isolated by SEREX. Four of the 75 antigens (KP-OVA-25, KP-OVA-35, KP-OVA-68 and KP-OVA-73) reacted exclusively with sera from cancer patients. However, KP-OVA-52 reacted with 1 of 20 ovarian cancer sera. These data suggest that the KP-OVA-52 can be considered a novel CT antigen that is regulated by DNA methylation. PMID:22684412

  1. Cytochrome P450c17 (steroid 17. cap alpha. -hydroxylase/17,20 lyase): cloning of human adrenal and testis cDNAs indicates the same gene is expressed in both tissues

    SciTech Connect

    Chung, B.; Picado-Leonard, J.; Haniu, M.; Bienkowski, M.; Hall, P.F.; Shively, J.E.; Miller, W.L.

    1987-01-01

    P450c17 is the single enzyme mediating both 17..cap alpha..-hydroxylase (steroid 17..cap alpha..-monooxygenase, EC 1.14.99.9) and 17,20 lyase activities in the synthesis of steroid hormones. It has been suggested that different P450c17 isozymes mediate these activities in the adrenal gland and testis. The authors sequenced 423 of the 509 amino acids (83%) of the porcine adrenal enzyme; based on this partial sequence, a 128-fold degenerate 17-mer was synthesized and used to screen a porcine adrenal cDNA library. This yielded a 380-base cloned cDNA, which in turn was used to isolate several human adrenal cDNAs. The longest of these, lambda hac 17-2, is 1754 base pairs long and includes the full-length coding region, the complete 3'-untranslated region, and 41 bases of the 5'-untranslated region. This cDNA encodes a protein of 508 amino acids having a predicted molecular weight of 57,379.82. High-stringency screening of a human testicular cDNA library yielded a partial clone containing 1303 identical bases. RNA gel blots and nuclease S1-protection experiments confirm that the adrenal and testicular P450c17 mRNAs are indistinguishable. These data indicate that the testis possesses a P450c17 identical to that in the adrenal. The human amino acid sequence is 66.7% homologous to the corresponding regions of the porcine sequence, and the human cDNA and amino acid sequences are 80.1 and 70.3% homologous, respectively, to bovine adrenal P450c17 cDNA. Both comparisons indicate that a central region comprising amino acid residues 160-268 is hypervariable among these species of P450c17.

  2. Short-term antiandrogen flutamide treatment causes structural alterations in somatic cells associated with premature detachment of spermatids in the testis of pubertal and adult guinea pigs.

    PubMed

    Maschio, L R; Cordeiro, R S; Taboga, S R; Góes, R M

    2010-06-01

    In spite of widespread application of flutamide in the endocrine therapies of young and adult patients, the side effects of this antiandrogen on spermatogenesis and germ-cell morphology remain unclear. This study evaluates the short-term androgen blockage effect induced by the administration of flutamide to the testes of pubertal (30-day old) and adult (65- and 135-day old) guinea pigs, with an emphasis on ultrastructural alterations of main cell types. The testes removed after 10 days of treatment with either a non-steroidal antiandrogen, flutamide (10 mg/kg of body weight) or a pharmacological vehicle alone were processed for histological, quantitative and ultrastructural analysis. In pubertal animals, flutamide androgenic blockage induces spermatogonial differentiation and accelerates testes maturation, causing degeneration and detachment of primary spermatocytes and round spermatids, which are subsequently found in great quantities in the epididymis caput. In post-pubertal and adult guinea pigs, in addition to causing germ-cell degeneration, especially in primary spermatocytes, and leading to the premature detachment of spherical spermatids, the antiandrogen treatment increased the relative volume of Leydig cells. In addition, ultrastructural evaluation indicated that irrespective of age antiandrogen treatment causes an increase in frequency of organelles involved with steroid hormone synthesis in the Leydig cells and a dramatic accumulation of myelin figures in their cytoplasm and, to a larger degree, in Sertoli cells. In conclusion, the transient exposition of the guinea pigs to flutamide, at all postnatal ages causes some degenerative lesions including severe premature detachment of spermatids and accumulation of myelin bodies in Leydig and Sertoli cells, compromising, at least temporarily, the spermatogenesis.

  3. In vivo microinjection and electroporation of mouse testis.

    PubMed

    Michaelis, Marten; Sobczak, Alexander; Weitzel, Joachim M

    2014-08-23

    This video and article contribution gives a comprehensive description of microinjection and electroporation of mouse testis in vivo. This particular transfection technique for testicular mouse cells allows the study of unique processes in spermatogenesis. The following protocol focuses on transfection of testicular mouse cells with plasmid constructs. Specifically, we used the reporter vector pEGFP-C1, which expresses enhanced green fluorescent protein (eGFP) and also the pDsRed2-N1 vector expressing red fluorescent protein (DsRed2). Both encoded reporter genes were under the control of the human cytomegalovirus immediate-early promoter (CMV). For performing gene transfer into mouse testes, the reporter plasmid constructs are injected into testes of living mice. To that end, the testis of an anaesthetized animal is exposed and the site of microinjection is prepared. Our preferred place of injection is the efferent duct, with the ultimately connected rete testis as the anatomical transport route of the spermatozoa between the testis and the epididymis. In this way, the filling of the seminiferous tubules after microinjection is excellently managed and controlled due to the use of stained DNA solutions. After observing a sufficient filling of the testis by its colored tubule structure, the organ is electroporated. This enables the transfer of the DNA solution into the testicular cells. Following 3 days of incubation, the testis is removed and investigated under the microscope for green or red fluorescence, illustrating transfection success. Generally, this protocol can be employed for delivering DNA- or RNA- constructs into living mouse testis in order to (over)express or knock down genes, facilitating in vivo gene function analysis. Furthermore, it is suitable for studying reporter constructs or putative gene regulatory elements. Thus, the main advantages of the electroporation technique are fast performance in combination with low effort as well as the moderate

  4. Latent inhibition in human adults without masking.

    PubMed

    Escobar, Martha; Arcediano, Francisco; Miller, Ralph R

    2003-09-01

    Latent inhibition refers to attenuated responding to Cue X observed when the X-outcome pairings are preceded by X-alone presentations. It has proven difficult to obtain in human adults unless the preexposure (X-alone) presentations are embedded within a masking (i.e., distracting) task. The authors hypothesized that the difficulty in obtaining latent inhibition with unmasked tasks is related to the usual training procedures, in which the preexposure and conditioning experiences are separated by a set of instructions. Experiment 1 reports latent inhibition without masking in a task in which preexposure and conditioning occur without interruption. Experiments 2 and 3 demonstrate that this attenuation in responding to target Cue X does not pass a summation test for conditioned inhibition and is context specific, thereby confirming that it is latent inhibition. Experiments 3 and 4 confirm that introducing instructions between preexposure and conditioning disrupts latent inhibition.

  5. Immunophysiology and pathology of inflammation in the testis and epididymis.

    PubMed

    Hedger, Mark P

    2011-01-01

    The ability of spermatogenic cells to evade the host immune system and the ability of systemic inflammation to inhibit male reproductive function represent two of the most intriguing conundrums of male reproduction. Clearly, an understanding of the underlying immunology of the male reproductive tract is crucial to resolving these superficially incompatible observations. One important consideration must be the very different immunological environments of the testis, where sperm develop, and the epididymis, where sperm mature and are stored. Compared with the elaborate blood-testis barrier, the tight junctions of the epididymis are much less effective. Unlike the seminiferous epithelium, immune cells are commonly observed within the epithelium, and can even be found within the lumen, of the epididymis. Crucially, there is little evidence for extended allograft survival (immune privilege) in the epididymis, as it exists in the testis, and the epididymis is much more susceptible to loss of immune tolerance. Moreover, the incidence of epididymitis is considerably greater than that of orchitis in humans, and susceptibility to sperm antibody formation after damage to the epididymis or vas deferens increases with increasing distance of the damage from the testis. Although we still know relatively little about testicular immunity, we know less about the interactions between the epididymis and the immune system. Given that the epididymis appears to be more susceptible to inflammation and immune reactions than the testis, and thereby represents the weaker link in protecting developing sperm from the immune system, it is probably time this imbalance in knowledge was addressed.

  6. Astrocitary niches in human adult medulla oblongata.

    PubMed

    Rusu, Mugurel Constantin; Dermengiu, Dan; Loreto, Carla; Motoc, Andrei Gheorghe Marius; Pop, Elena

    2013-04-01

    Astrocytes are considered as neuromodulators of the CNS. Whereas experimental studies on astrocitary functions are gaining importance, the anatomy of the astrocitary niches in the human CNS has been overlooked. The study was performed on the brainstem of 10 adult cadavers. We aimed to determine astrocitary niches in the human medulla oblongata using immunohistochemical labeling with vimentin and also CD34 immunostaining to accurately diagnose associated microvessels. Niches rich in astrocytes were identified as follows: (a) the superficial layer of astrocytes, ventral and ventrolateral, in the rostral medulla oblongata; (b) the median raphe; (c) medullary nuclei: arcuate nucleus, area postrema, nucleus of the solitary tract; (d) the subependymal zone (SEZ, caudal medulla) and subventricular zone (SVZ, rostral medulla). Astrocytes were scarce in the ventrolateral medulla, and mostly present within the pyramidal tract and the olivary nucleus. Apart from the SEZ and SVZ, the brainstem niches of astrocytes mostly overlap those regions known to perform roles as central respiratory chemoreceptors. The astrocytes of the SEZ and SVZ, which are known as stem cell niches, are related to an increased microvascular density.

  7. Mouse A-myb encodes a trans-activator and is expressed in mitotically active cells of the developing central nervous system, adult testis and B lymphocytes.

    PubMed Central

    Trauth, K; Mutschler, B; Jenkins, N A; Gilbert, D J; Copeland, N G; Klempnauer, K H

    1994-01-01

    C-myb encodes a transcriptional activator that is essential for the development of the hematopoietic system but appears to lack major roles in non-hematopoietic cells. The identification of two conserved myb-related genes, designated A-myb and B-myb, has raised the possibility that these genes are functional equivalents of c-myb in non-hematopoietic cells. Here, we report the isolation and preliminary characterization of the mouse A-myb gene. Mouse A-myb maps to the proximal region of chromosome 1 and encodes a transcriptional activator with properties similar to those of the c-myb and v-myb proteins. During embryo-genesis A-myb is predominantly expressed in several regions of the developing central nervous system (CNS) and the urogenital ridge. Expression in the CNS is confined to the neural tube, the hindbrain, the neural retina and the olfactory epithelium, and coincides with the presence of proliferating immature neuronal precursor cells. In the adult mouse, A-myb is expressed during the early stages of sperm cell differentiation and in B lymphocytes located in germinal centers of the spleen. Taken together, these results suggest a role for A-myb in the proliferation and/or differentiation of neurogenic, spermatogenic and B-lymphoid cells. Images PMID:7813437

  8. Have you got any cholesterol? Adults' views of human nutrition

    NASA Astrophysics Data System (ADS)

    Schibeci, Renato; Wong, Khoon Yoong

    1994-12-01

    The general aim of our human nutrition project is to develop a health education model grounded in ‘everyday’ or ‘situated’ cognition (Hennessey, 1993). In 1993, we began pilot work to document adult understanding of human nutrition. We used a HyperCard stack as the basis for a series of interviews with 50 adults (25 university students, and 25 adults from offcampus). The interviews were transcribed and analysed using the NUDIST computer program. A summary of the views of these 50 adults on selected aspects of human nutrition is presented in this paper.

  9. Adult Education & Human Resource Development: Overlapping and Disparate Fields

    ERIC Educational Resources Information Center

    Watkins, Karen E.; Marsick, Victoria J.

    2014-01-01

    Adult education and human resource development as fields of practice and study share some roots in common but have grown in different directions in their histories. Adult education's roots focused initially on citizenship for a democratic society, whereas human resource development's roots are in performance at work. While they have…

  10. Adult Education & Human Resource Development: Overlapping and Disparate Fields

    ERIC Educational Resources Information Center

    Watkins, Karen E.; Marsick, Victoria J.

    2014-01-01

    Adult education and human resource development as fields of practice and study share some roots in common but have grown in different directions in their histories. Adult education's roots focused initially on citizenship for a democratic society, whereas human resource development's roots are in performance at work. While they have…

  11. Encephalitis-Associated Human Metapneumovirus Pneumonia in Adult, Australia

    PubMed Central

    Mateevici, Cristina; Lin, Belinda; Chandra, Ronil V.; Chong, Victor H.T.

    2015-01-01

    Human metapneumovirus pneumonia, most commonly found in children, was diagnosed in an adult with encephalitis. This case suggests that testing for human metapneumovirus RNA in nasopharyngeal aspirate and cerebrospinal fluid samples should be considered in adults with encephalitis who have a preceding respiratory infection, PMID:26488420

  12. Allelotyping analysis suggesting a consecutive progression from intratubular germ cell neoplasia to seminoma and then to embryonal carcinoma of the adult testis.

    PubMed

    Miyai, Kosuke; Yamamoto, Sohei; Iwaya, Keiichi; Asano, Tomohiko; Tamai, Seiichi; Tsuda, Hitoshi; Matsubara, Osamu

    2013-10-01

    Among adult testicular germ cell tumors, the pathogenesis of embryonal carcinoma remains a matter of debate. Some studies suggest a single consecutive progression from intratubular germ cell neoplasia, unclassified (IGCNU), to seminoma and then to embryonal carcinoma; others suggest that seminoma and embryonal carcinoma derive independently from IGCNU. This allelotyping study aimed to clarify the genetic relationship between embryonal carcinoma components and coexisting seminoma and/or IGCNU components. From a cohort of 18 patients with embryonal carcinoma, 11 coexisting seminoma components and 14 coexisting IGCNUs were identified. DNA isolated from each laser-microdissected tissue was subjected to polymerase chain reaction and loss of heterozygosity (LOH) analysis, using 20 polymorphic markers located on 12 chromosome arms (3q, 5q, 6p, 9p, 10q, 11p, 12p, 12q, 13q, 17p, 17q, and 18q). The concordance rate for allelic patterns was 82% between IGCNU and the coexisting seminoma components, 71% between IGCNU and the coexisting embryonal carcinoma components, and 80% between seminoma components and the coexisting embryonal carcinoma components. Estimation of probability indicated that these events were very unlikely to have occurred by chance. The total frequency of LOH increased progressively from IGCNU to seminoma and then to embryonal carcinoma, with statistically significant differences. In 7 cases with 3 histologic components, 28 chromosomal loci that showed LOH in the seminoma and embryonal carcinoma components were identified, and 15 (54%) retained heterozygosity in the coexisting IGCNUs. These findings suggest that a consecutive progression from IGCNU to seminoma, and ultimately, to embryonal carcinoma mainly occurred in the testicular germ cell tumor cases. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Metastatic Granulosa Cell Tumor of the Testis: Clinical Presentation and Management

    PubMed Central

    Han, Min; Figenshau, Robert S.

    2016-01-01

    Granulosa cell tumors (GCTs) of the testis are rare sex cord-stromal tumors that are present in both juvenile and adult subtypes. While most adult GCTs are benign, those that present with distant metastases manifest a grave prognosis. Treatments for aggressive GCTs are not well established. Options that have been employed in previous cases include retroperitoneal lymph node dissection (RPLND), radiation, chemotherapy, or a combination thereof. We describe the case of a 57-year-old man who presented with a painless left testicular mass and painful gynecomastia. Serum tumor markers (alpha fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase) and computed tomography of the chest and abdomen were negative. The patient underwent left radical orchiectomy. Immunohistochemical staining was consistent with a testicular GCT. He underwent a left-template laparoscopic RPLND which revealed 2/19 positive lymph nodes. Final pathological stage was IIA. He remains free of disease 32 months after surgery. PMID:27293952

  14. Adult human brain cell culture for neuroscience research.

    PubMed

    Gibbons, Hannah M; Dragunow, Mike

    2010-06-01

    Studies of the brain have progressed enormously through the use of in vivo and in vitro non-human models. However, it is unlikely such studies alone will unravel the complexities of the human brain and so far no neuroprotective treatment developed in animals has worked in humans. In this review we discuss the use of adult human brain cell culture methods in brain research to unravel the biology of the normal and diseased human brain. The advantages of using adult human brain cells as tools to study human brain function from both historical and future perspectives are discussed. In particular, studies using dissociated cultures of adult human microglia, astrocytes, oligodendrocytes and neurons are described and the applications of these types of study are evaluated. Alternative sources of human brain cells such as adult neural stem cells, induced pluripotent stem cells and slice cultures of adult human brain tissue are also reviewed. These adult human brain cell culture methods could benefit basic research and more importantly, facilitate the translation of basic neuroscience research to the clinic for the treatment of brain disorders.

  15. Attracting Adult Learners to Humanities Courses. Final Report.

    ERIC Educational Resources Information Center

    American Association of Community and Junior Colleges, Washington, DC.

    A round table discussion among community college presidents and humanities faculty on how to encourage adults to enroll in humanities courses resulted in eleven recommendations. These included experimentation in how to access community interests in humanities courses, the integration of humanities with occupational training to help people deal…

  16. The dynamics of adult neurogenesis in human hippocampus

    PubMed Central

    Ihunwo, Amadi O.; Tembo, Lackson H.; Dzamalala, Charles

    2016-01-01

    The phenomenon of adult neurogenesis is now an accepted occurrence in mammals and also in humans. At least two discrete places house stem cells for generation of neurons in adult brain. These are olfactory system and the hippocampus. In animals, newly generated neurons have been directly or indirectly demonstrated to generate a significant amount of new neurons to have a functional role. However, the data in humans on the extent of this process is still scanty and such as difficult to comprehend its functional role in humans. This paper explores the available data on as extent of adult hippocampal neurogenesis in humans and makes comparison to animal data. PMID:28197172

  17. Mammalian testis-determining factor SRY and the enigma of inherited human sex reversal: frustrated induced fit in a bent protein-DNA complex.

    PubMed

    Phillips, Nelson B; Racca, Joseph; Chen, Yen-Shan; Singh, Rupinder; Jancso-Radek, Agnes; Radek, James T; Wickramasinghe, Nalinda P; Haas, Elisha; Weiss, Michael A

    2011-10-21

    Mammalian testis-determining factor SRY contains a high mobility group box, a conserved eukaryotic motif of DNA bending. Mutations in SRY cause XY gonadal dysgenesis and somatic sex reversal. Although such mutations usually arise de novo in spermatogenesis, some are inherited and so specify male development in one genetic background (the father) but not another (the daughter). Here, we describe the biophysical properties of a representative inherited mutation, V60L, within the minor wing of the L-shaped domain (box position 5). Although the stability and DNA binding properties of the mutant domain are similar to those of wild type, studies of SRY-induced DNA bending by subnanosecond time-resolved fluorescence resonance energy transfer (FRET) revealed enhanced conformational fluctuations leading to long range variation in bend angle. (1)H NMR studies of the variant protein-DNA complex demonstrated only local perturbations near the mutation site. Because the minor wing of SRY folds on DNA binding, the inherited mutation presumably hinders induced fit. Stopped-flow FRET studies indicated that such frustrated packing leads to accelerated dissociation of the bent complex. Studies of SRY-directed transcriptional regulation in an embryonic gonadal cell line demonstrated partial activation of downstream target Sox9. Our results have demonstrated a nonlocal coupling between DNA-directed protein folding and protein-directed DNA bending. Perturbation of this coupling is associated with a genetic switch poised at the threshold of activity.

  18. Adult Human Neurogenesis: From Microscopy to Magnetic Resonance Imaging

    PubMed Central

    Sierra, Amanda; Encinas, Juan M.; Maletic-Savatic, Mirjana

    2011-01-01

    Neural stem cells reside in well-defined areas of the adult human brain and are capable of generating new neurons throughout the life span. In rodents, it is well established that the new born neurons are involved in olfaction as well as in certain forms of memory and learning. In humans, the functional relevance of adult human neurogenesis is being investigated, in particular its implication in the etiopathology of a variety of brain disorders. Adult neurogenesis in the human brain was discovered by utilizing methodologies directly imported from the rodent research, such as immunohistological detection of proliferation and cell-type specific biomarkers in postmortem or biopsy tissue. However, in the vast majority of cases, these methods do not support longitudinal studies; thus, the capacity of the putative stem cells to form new neurons under different disease conditions cannot be tested. More recently, new technologies have been specifically developed for the detection and quantification of neural stem cells in the living human brain. These technologies rely on the use of magnetic resonance imaging, available in hospitals worldwide. Although they require further validation in rodents and primates, these new methods hold the potential to test the contribution of adult human neurogenesis to brain function in both health and disease. This review reports on the current knowledge on adult human neurogenesis. We first review the different methods available to assess human neurogenesis, both ex vivo and in vivo and then appraise the changes of adult neurogenesis in human diseases. PMID:21519376

  19. Adult human neurogenesis: from microscopy to magnetic resonance imaging.

    PubMed

    Sierra, Amanda; Encinas, Juan M; Maletic-Savatic, Mirjana

    2011-01-01

    Neural stem cells reside in well-defined areas of the adult human brain and are capable of generating new neurons throughout the life span. In rodents, it is well established that the new born neurons are involved in olfaction as well as in certain forms of memory and learning. In humans, the functional relevance of adult human neurogenesis is being investigated, in particular its implication in the etiopathology of a variety of brain disorders. Adult neurogenesis in the human brain was discovered by utilizing methodologies directly imported from the rodent research, such as immunohistological detection of proliferation and cell-type specific biomarkers in postmortem or biopsy tissue. However, in the vast majority of cases, these methods do not support longitudinal studies; thus, the capacity of the putative stem cells to form new neurons under different disease conditions cannot be tested. More recently, new technologies have been specifically developed for the detection and quantification of neural stem cells in the living human brain. These technologies rely on the use of magnetic resonance imaging, available in hospitals worldwide. Although they require further validation in rodents and primates, these new methods hold the potential to test the contribution of adult human neurogenesis to brain function in both health and disease. This review reports on the current knowledge on adult human neurogenesis. We first review the different methods available to assess human neurogenesis, both ex vivo and in vivo and then appraise the changes of adult neurogenesis in human diseases.

  20. 0610009K11Rik, a testis-specific and germ cell nuclear receptor-interacting protein

    SciTech Connect

    Zhang Heng; Denhard, Leslie A.; Zhou Huaxin; Liu Lanhsin; Lan Zijian

    2008-02-22

    Using an in silico approach, a putative nuclear receptor-interacting protein 0610009K11Rik was identified in mouse testis. We named this gene testis-specific nuclear receptor-interacting protein-1 (Tnrip-1). Tnrip-1 was predominantly expressed in the testis of adult mouse tissues. Expression of Tnrip-1 in the testis was regulated during postnatal development, with robust expression in 14-day-old or older testes. In situ hybridization analyses showed that Tnrip-1 is highly expressed in pachytene spermatocytes and spermatids. Consistent with its mRNA expression, Tnrip-1 protein was detected in adult mouse testes. Immunohistochemical studies showed that Tnrip-1 is a nuclear protein and mainly expressed in pachytene spermatocytes and round spermatids. Moreover, co-immunoprecipitation analyses showed that endogenous Tnrip-1 protein can interact with germ cell nuclear receptor (GCNF) in adult mouse testes. Our results suggest that Tnrip-1 is a testis-specific and GCNF-interacting protein which may be involved in the modulation of GCNF-mediated gene transcription in spermatogenic cells within the testis.

  1. The Type 3 Deiodinase Is a Critical Determinant of Appropriate Thyroid Hormone Action in the Developing Testis

    PubMed Central

    Martinez, M. Elena; Karaczyn, Aldona; Stohn, J. Patrizia; Donnelly, William T.; Croteau, Walburga; Peeters, Robin P.; Galton, Valerie A.; Forrest, Douglas; St. Germain, Donald

    2016-01-01

    Timely and appropriate levels of thyroid hormone (TH) signaling are necessary to ensure normal developmental outcomes in many tissues. Studies using pharmacological models of altered TH status have revealed an influence of these hormones on testis development and size, but little is known about the role of endogenous determinants of TH action in the developing male gonads. Using a genetic approach, we demonstrate that the type 3 deiodinase (D3), which inactivates TH and protects developing tissues from undue TH action, is a key factor. D3 is highly expressed in the developing testis, and D3-deficient (D3KO) mice exhibit thyrotoxicosis and cell proliferation arrest in the neonatal testis, resulting in an approximately 75% reduction in testis size. This is accompanied by larger seminiferous tubules, impaired spermatogenesis, and a hormonal profile indicative of primary hypogonadism. A deficiency in the TH receptor-α fully normalizes testis size and adult testis gene expression in D3KO mice, indicating that the effects of D3 deficiency are mediated through this type of receptor. Similarly, genetic deficiencies in the D2 or in the monocarboxylate transporter 8 partially rescue the abnormalities in testis size and gonadal axis gene expression featured in the D3KO mice. Our study highlights the testis as an important tissue in which determinants of TH action coordinately converge to ensure normal development and identifies D3 as a critical factor in testis development and in testicular protection from thyrotoxicosis. PMID:26727108

  2. Developing Resourceful Humans. Adult Education within the Economic Context.

    ERIC Educational Resources Information Center

    Burton, Lynn Elen, Ed.

    This book, which explores the shifting paradigm from human resource development to developing resourceful humans, establishes the historical position of adult education within the economic context, discusses human capital propositions, and examines the learning dimensions of economic and educational change. The following chapters are included:…

  3. Humanizing Adult Education Research: Five Stories from the 1930's.

    ERIC Educational Resources Information Center

    Hilton, Ronald

    Taken from the author's doctoral dissertation, this award-winning monograph describes a method for humanizing educational research in adult education and provides five stories of adult education efforts in the 1930's as examples of such research. The method described suggests valuing qualitative data as much as quantitative in the field of…

  4. Adult Literacy Education and Human Rights: A View from Afghanistan

    ERIC Educational Resources Information Center

    Andersen, Susan M.; Kooij, Christina S.

    2007-01-01

    In this article, we argue that adult literacy as part of international development is an issue of both human rights and women's rights. We explore this by presenting a case study of the effects of one innovative adult literacy program in Afghanistan that places men and women, as well as various ethnicities, together in the same classroom as…

  5. An in vivo genetic screen in Drosophila identifies the orthologue of human cancer/testis gene SPO11 among a network of targets to inhibit lethal(3)malignant brain tumour growth.

    PubMed

    Rossi, Fabrizio; Molnar, Cristina; Hashiyama, Kazuya; Heinen, Jan P; Pampalona, Judit; Llamazares, Salud; Reina, José; Hashiyama, Tomomi; Rai, Madhulika; Pollarolo, Giulia; Fernández-Hernández, Ismael; Gonzalez, Cayetano

    2017-08-01

    Using transgenic RNAi technology, we have screened over 4000 genes to identify targets to inhibit malignant growth caused by the loss of function of lethal(3)malignant brain tumour in Drosophila in vivo We have identified 131 targets, which belong to a wide range of gene ontologies. Most of these target genes are not significantly overexpressed in mbt tumours hence showing that, rather counterintuitively, tumour-linked overexpression is not a good predictor of functional requirement. Moreover, we have found that most of the genes upregulated in mbt tumours remain overexpressed in tumour-suppressed double-mutant conditions, hence revealing that most of the tumour transcriptome signature is not necessarily correlated with malignant growth. One of the identified target genes is meiotic W68 (mei-W68), the Drosophila orthologue of the human cancer/testis gene Sporulation-specific protein 11 (SPO11), the enzyme that catalyses the formation of meiotic double-strand breaks. We show that Drosophila mei-W68/SPO11 drives oncogenesis by causing DNA damage in a somatic tissue, hence providing the first instance in which a SPO11 orthologue is unequivocally shown to have a pro-tumoural role. Altogether, the results from this screen point to the possibility of investigating the function of human cancer relevant genes in a tractable experimental model organism like Drosophila. © 2017 The Authors.

  6. Cavernous haemangioma of the testis mimicking testicular malignancy in an adolescent.

    PubMed

    Naveed, S; Quari, H; Sharma, H

    2013-11-01

    Haemangioma of the testis is a rare condition. This benign vascular neoplasm may arise either within the testicular parenchyma (intratesticular) as in this case or from adnexal structures of the testis (extratesticular). Intratesticular haemangioma is rarer than extratesticular form. Intratesticular vascular neoplasms are extremely rare tumours and mostly seen in children or young adults. There are 21 reported testicular haemangioma cases in the literature as indexed in PubMed. Since 2007, only 19 cases of cavernous haemangioma have been reported in the literature in PubMed and other indexed sites. We report a case of cavernous haemangioma of the testis to attract attention to testicular haemangioma and also to prevent invasive surgery of the testis.

  7. [Pathological advances in renal, prostatic, bladder and testis neoplasia].

    PubMed

    Rioux-Leclercq, N; Comperat, E; Kammerer-Jacquet, S-F; Camparo, P; Fromont, G

    2016-06-01

    The ISUP (International Society of Urological Pathology) Consensus Conferences between 2012 and 2015 made recommendations regarding the classification, staging, prognostic factors of adult tumors from kidney, prostate, bladder and testis. The main points of these recommendations are highlighted in this article. This article is based on a systematic literature search by using different keywords "cancer, kidney, prostate, bladder, testis, pathology, classification" from Pubmed database. Only publications between 2012 and 2015 were retained. The different Consensus conferences since 2012 in uropathology have provided international guidelines for the classification, grading and staging of tumors in kidney, bladder, prostate and testis. We identified in this article the main points of these new guidelines that are about to be published in the new 2016 WHO classification of urogenital tract tumors in adult. New pathological guidelines in urogenital tumors have to be taken into account for a better diagnosis and therapy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. A comparative study of bifidobacteria in human babies and adults

    PubMed Central

    KHONSARI, Shadi; SUGANTHY, Mayuran; BURCZYNSKA, Beata; DANG, Vu; CHOUDHURY, Manika; PACHENARI, Azra

    2015-01-01

    The composition and diversity of the gut microbiota are known to be different between babies and adults. The aim of this project was to compare the level of bifidobacteria between babies and adults and to investigate the influence of lifestyle factors on the level of this bacterium in the gut. During this study, the levels of bifidobacteria in 10 human babies below 2 years of age were compared with that of 10 human adults above 40 years. The level of bifidobacteria proved to be significantly higher in babies in comparison with adults. This investigation concluded that a combination of several factors, such as age, diet, and BMI, has an important effect on the level of bifidobacteria in adults, while in babies, a combination of diet and age may influence the level of intestinal bifidobacteria. PMID:27200263

  9. Human retrovirus in adult T-cell leukemia/lymphoma.

    PubMed

    Sugamura, K; Hinuma, Y

    1985-03-01

    In this review Kazuo Sugamura and Yorio Hinuma summarize developments in studies on the human retrovirus associated with a unique human T-cell malignancy, adult T-cell leukemia; they also discuss the possible mechanisms of retrovirus-induced leukemogenesis. Copyright © 1985. Published by Elsevier B.V.

  10. Humanities and the Adult Learner in an Information Society.

    ERIC Educational Resources Information Center

    Myers, Dale; Kamholtz, Jonathan

    Humanities courses have often been given little attention in continuing education for adults, possibly because they have been viewed as not "practical" or not "job-oriented" enough in our career-oriented, technologically advanced society. However, the humanities should be an integral part of our culture and of the lives of…

  11. Humanities and the Adult Learner in an Information Society.

    ERIC Educational Resources Information Center

    Myers, Dale; Kamholtz, Jonathan

    Humanities courses have often been given little attention in continuing education for adults, possibly because they have been viewed as not "practical" or not "job-oriented" enough in our career-oriented, technologically advanced society. However, the humanities should be an integral part of our culture and of the lives of…

  12. Aristolochic Acid I Causes Testis Toxicity by Inhibiting Akt and ERK1/2 Phosphorylation.

    PubMed

    Kwak, Dong Hoon; Lee, Seoul

    2016-01-19

    Aristolochic acid (AA) is a natural bioactive substance found in Chinese herbs that induce toxicity during ovarian maturation of animals and humans. Apoptosis is induced by various types of damage and governs the progression of biological cell removal that controls the equilibrium between cell growth and death. However, the AA toxicity mechanism during testis maturation in mouse has not been elucidated and was thus the focus of the present study. This study used TM4 Sertoli cells and an ICR mouse model, both of which were injected with aristolochic acid I (AAI) for 4 weeks. Testis dimensions and weight were surveyed to define AAI cytotoxicity in the mice testis. The MTT assay was used to analyze the cytotoxicity of AAI in TM4 Sertoli cells. An apoptosis expression mediator was analyzed through Western blotting, while the measure of apoptosis-induced cell death of TM4 Sertoli cells and testis tissues was analyzed by the TUNEL assay. We found that AAI strongly inhibits survival in TM4 cells and that AAI significantly activated apoptosis-induced cell death in TM4 Sertoli cells and mice testis tissue. In addition, AAI suppressed the expression of B-cell lymphoma 2 (Bcl-2), a factor related to anti-apoptosis. It markedly improved pro-apoptotic protein expression, including Bcl-2-associated X protein, poly(ADP-ribose) polymerase, and caspase-3 and -9. Furthermore, we observed that AAI significantly reduced the size and weight of mouse testis. Moreover, germ cells and somatic cells in testis were markedly damaged by AAI. In addition, we found that AAI significantly inhibits ERK1/2 and Akt activation in TM4 Sertoli cells and testis tissue. The data obtained in this study indicate that AAI causes severe injury for the period of testis development by impeding apoptosis related to the Akt and ERK1/2 pathway.

  13. Xenografting of sheep testis tissue and isolated cells as a model for preservation of genetic material from endangered ungulates.

    PubMed

    Arregui, Lucía; Rathi, Rahul; Megee, Susan O; Honaramooz, Ali; Gomendio, Montserrat; Roldan, Eduardo R S; Dobrinski, Ina

    2008-07-01

    Recovery of germ cells could be an option for preservation of the genetic pool of endangered animals. In immature males, xenografting of testis tissue provides the opportunity to recover sperm from these animals. In adult animals, xenografting has been less successful, but de novo morphogenesis of functional testis tissue from dissociated testis cells could be an alternative. To assess the potential use of these techniques in endangered bovid species, the domestic sheep was used as a model. Testes from 2-week-old lambs were grafted as tissue fragments or cell suspensions into nude mice. Grafts were recovered at 4, 8, 12 and 16 weeks post grafting. For isolated cells, two additional time points at 35 and 40 weeks after grafting were added. In addition, to analyse the possible effect of social stress among mice within a group on the development of the grafts, testis tissue grafts were recovered 13 weeks post grafting from mice housed individually and in groups. Complete spermatogenesis occurred in sheep testis xenografts at 12 weeks, similar to the situation in situ. Isolated sheep testis cells were able to reorganize and form functional testicular tissue de novo. Housing mice individually or in groups did not have any effect on the development of xenografts. Xenografting of testis tissue might be useful to obtain sperm from immature endangered ungulates that die prematurely. Testis tissue de novo morphogenesis from isolated cells could open interesting options to recover germ cells from mature males with impaired spermatogenesis.

  14. Differentiated human stem cells resemble fetal, not adult, β cells.

    PubMed

    Hrvatin, Sinisa; O'Donnell, Charles W; Deng, Francis; Millman, Jeffrey R; Pagliuca, Felicia Walton; DiIorio, Philip; Rezania, Alireza; Gifford, David K; Melton, Douglas A

    2014-02-25

    Human pluripotent stem cells (hPSCs) have the potential to generate any human cell type, and one widely recognized goal is to make pancreatic β cells. To this end, comparisons between differentiated cell types produced in vitro and their in vivo counterparts are essential to validate hPSC-derived cells. Genome-wide transcriptional analysis of sorted insulin-expressing (INS(+)) cells derived from three independent hPSC lines, human fetal pancreata, and adult human islets points to two major conclusions: (i) Different hPSC lines produce highly similar INS(+) cells and (ii) hPSC-derived INS(+) (hPSC-INS(+)) cells more closely resemble human fetal β cells than adult β cells. This study provides a direct comparison of transcriptional programs between pure hPSC-INS(+) cells and true β cells and provides a catalog of genes whose manipulation may convert hPSC-INS(+) cells into functional β cells.

  15. Two distinct origins for Leydig cell progenitors in the fetal testis

    PubMed Central

    DeFalco, Tony; Takahashi, Satoru; Capel, Blanche

    2011-01-01

    During the differentiation of the mammalian embryonic testis, two compartments are defined: the testis cords and the interstitium. The testis cords give rise to the adult seminiferous tubules, whereas steroidogenic Leydig cells and other less well characterized cell types differentiate in the interstitium (the space between testis cords). Although the process of testis cord formation is essential for male development, it is not entirely understood. It has been viewed as a Sertoli-cell driven process, but growing evidence suggests that interstitial cells play an essential role during testis formation. However, little is known about the origin of the interstitium or the molecular and cellular diversity within this early stromal compartment. To better understand the process of mammalian gonad differentiation, we have undertaken an analysis of developing interstitial/stromal cells in the early mouse testis and ovary. We have discovered molecular heterogeneity in the interstitium and have characterized new markers of distinct cell types in the gonad: MAFB, C-MAF, and VCAM1. Our results show that at least two distinct progenitor lineages give rise to the interstitial/stromal compartment of the gonad: the coelomic epithelium and specialized cells along the gonad-mesonephros border. We demonstrate that both these populations give rise to interstitial precursors that can differentiate into fetal Leydig cells. Our analysis also reveals that perivascular cells migrate into the gonad from the mesonephric border along with endothelial cells and that these vessel-associated cells likely represent an interstitial precursor lineage. This study highlights the cellular diversity of the interstitial cell population and suggests that complex cell-cell interactions among cells in the interstitium are involved in testis morphogenesis. PMID:21255566

  16. Steroid signaling promotes stem cell maintenance in the Drosophila testis.

    PubMed

    Li, Yijie; Ma, Qing; Cherry, Christopher M; Matunis, Erika L

    2014-10-01

    Stem cell regulation by local signals is intensely studied, but less is known about the effects of hormonal signals on stem cells. In Drosophila, the primary steroid twenty-hydroxyecdysone (20E) regulates ovarian germline stem cells (GSCs) but was considered dispensable for testis GSC maintenance. Male GSCs reside in a microenvironment (niche) generated by somatic hub cells and adjacent cyst stem cells (CySCs). Here, we show that depletion of 20E from adult males by overexpressing a dominant negative form of the Ecdysone receptor (EcR) or its heterodimeric partner ultraspiracle (usp) causes GSC and CySC loss that is rescued by 20E feeding, uncovering a requirement for 20E in stem cell maintenance. EcR and USP are expressed, activated and autonomously required in the CySC lineage to promote CySC maintenance, as are downstream genes ftz-f1 and E75. In contrast, GSCs non-autonomously require ecdysone signaling. Global inactivation of EcR increases cell death in the testis that is rescued by expression of EcR-B2 in the CySC lineage, indicating that ecdysone signaling supports stem cell viability primarily through a specific receptor isoform. Finally, EcR genetically interacts with the NURF chromatin-remodeling complex, which we previously showed maintains CySCs. Thus, although 20E levels are lower in males than females, ecdysone signaling acts through distinct cell types and effectors to ensure both ovarian and testis stem cell maintenance.

  17. Polarity Proteins and Cell–Cell Interactions in the Testis

    PubMed Central

    Wong, Elissa W.P.; Cheng, C. Yan

    2009-01-01

    In mammalian testes, extensive junction restructuring takes place in the seminiferous epithelium at the Sertoli–Sertoli and Sertoli–germ cell interface to facilitate the different cellular events of spermatogenesis, such as mitosis, meiosis, spermiogenesis, and spermiation. Recent studies in the field have shown that Rho GTPases and polarity proteins play significant roles in the events of cell–cell interactions. Furthermore, Rho GTPases, such as Cdc42, are working in concert with polarity proteins in regulating cell polarization and cell adhesion at both the blood–testis barrier (BTB) and apical ectoplasmic specialization (apical ES) in the testis of adult rats. In this chapter, we briefly summarize recent findings on the latest status of research and development regarding Cdc42 and polarity proteins and how they affect cell–cell interactions in the testis and other epithelia. More importantly, we provide a new model in which how Cdc42 and components of the polarity protein complexes work in concert with laminin fragments, cytokines, and testosterone to regulate the events of cell–cell interactions in the seminiferous epithelium via a local autocrine-based regulatory loop known as the apical ES—BTB—basement membrane axis. This new functional axis coordinates various cellular events during different stages of the seminiferous epithelium cycle of spermatogenesis. PMID:19815182

  18. The human testis-determining factor SRY localizes in midbrain dopamine neurons and regulates multiple components of catecholamine synthesis and metabolism.

    PubMed

    Czech, Daniel P; Lee, Joohyung; Sim, Helena; Parish, Clare L; Vilain, Eric; Harley, Vincent R

    2012-07-01

    The male gender is determined by the sex-determining region on the Y chromosome (SRY) transcription factor. The unexpected action of SRY in the control of voluntary movement in male rodents suggests a role in the regulation of dopamine transmission and dopamine-related disorders with gender bias, such as Parkinson's disease. We investigated SRY expression in the human brain and function in vitro. SRY immunoreactivity was detected in the human male, but not female substantia nigra pars compacta, within a sub-population of tyrosine hydroxylase (TH) positive neurons. SRY protein also co-localized with TH positive neurons in the ventral tegmental area, and with GAD-positive neurons in the substantia nigra pars reticulata. Retinoic acid-induced differentiation of human precursor NT2 cells into dopaminergic cells increased expression of TH, NURR1, D2 R and SRY. In the human neuroblastoma cell line, M17, SRY knockdown resulted in a reduction in TH, DDC, DBH and MAO-A expression; enzymes which control dopamine synthesis and metabolism. Conversely, SRY over-expression increased TH, DDC, DBH, D2 R and MAO-A levels, accompanied by increased extracellular dopamine levels. A luciferase assay demonstrated that SRY activated a 4.6 kb 5' upstream regulatory region of the human TH promoter/nigral enhancer. Combined, these results suggest that SRY plays a role as a positive regulator of catecholamine synthesis and metabolism in the human male midbrain. This ancillary genetic mechanism might contribute to gender bias in fight-flight behaviours in men or their increased susceptibility to dopamine disorders, such as Parkinson's disease and schizophrenia.

  19. Impact of electronic-cigarette refill liquid on rat testis.

    PubMed

    El Golli, N; Rahali, D; Jrad-Lamine, A; Dallagi, Y; Jallouli, M; Bdiri, Y; Ba, N; Lebret, M; Rosa, J P; El May, M; El Fazaa, S

    2016-07-01

    Electronic cigarettes (e-cigarettes) are becoming the fashionable alternative to decrease tobacco smoking, although their impact on health has not been fully assessed yet. The present study was designed to compare the impact of e-cigarette refill liquid (e-liquid) without nicotine to e-liquid with nicotine on rat testis. For this purpose, e-liquid with nicotine and e-liquid without nicotine (0.5 mg/kg of body weight) were administered to adult male Wistar rats via the intraperitoneally route during four weeks. Results showed that e-liquid with or without nicotine leads to diminished sperm density and viability, such as a decrease in testicular lactate dehydrogenase activity and testosterone level. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) analysis identified a reduction in cytochrome P450 side-chain cleavage (P450 scc) and 17 beta-hydroxysteroid dehydrogenase (17βHSD) mRNA level, two key enzymes of steroidogenesis. Following e-liquid exposure, histopathological examination showed alterations in testis tissue marked by germ cells desquamation, disorganization of the tubular contents of testis and cell deposits in seminiferous tubules. Finally, analysis of oxidative stress status pointed an outbreak of antioxidant enzyme activities such as superoxide dismutase, catalase and gluthatione-S-transferase, as well as an important increase in sulfhydril group content. Taken together, these results indicate that e-liquid per se induces toxicity in Wistar rat testis, similar to e-liquid with nicotine, by disrupting oxidative balance and steroidogenesis.

  20. Analysis of MicroRNA Expression in the Prepubertal Testis

    PubMed Central

    Kim, Jong; Milosavljevic, Aleksandar; Gunaratne, Preethi H.; Matzuk, Martin M.

    2010-01-01

    Only thirteen microRNAs are conserved between D. melanogaster and the mouse; however, conditional loss of miRNA function through mutation of Dicer causes defects in proliferation of premeiotic germ cells in both species. This highlights the potentially important, but uncharacterized, role of miRNAs during early spermatogenesis. The goal of this study was to characterize on postnatal day 7, 10, and 14 the content and editing of murine testicular miRNAs, which predominantly arise from spermatogonia and spermatocytes, in contrast to prior descriptions of miRNAs in the adult mouse testis which largely reflects the content of spermatids. Previous studies have shown miRNAs to be abundant in the mouse testis by postnatal day 14; however, through Next Generation Sequencing of testes from a B6;129 background we found abundant earlier expression of miRNAs and describe shifts in the miRNA signature during this period. We detected robust expression of miRNAs encoded on the X chromosome in postnatal day 14 testes, consistent with prior studies showing their resistance to meiotic sex chromosome inactivation. Unexpectedly, we also found a similar positional enrichment for most miRNAs on chromosome 2 at postnatal day 14 and for those on chromosome 12 at postnatal day 7. We quantified in vivo developmental changes in three types of miRNA variation including 5′ heterogeneity, editing, and 3′ nucleotide addition. We identified eleven putative novel pubertal testis miRNAs whose developmental expression suggests a possible role in early male germ cell development. These studies provide a foundation for interpretation of miRNA changes associated with testicular pathology and identification of novel components of the miRNA editing machinery in the testis. PMID:21206922

  1. Analysis of microRNA expression in the prepubertal testis.

    PubMed

    Buchold, Gregory M; Coarfa, Cristian; Kim, Jong; Milosavljevic, Aleksandar; Gunaratne, Preethi H; Matzuk, Martin M

    2010-12-29

    Only thirteen microRNAs are conserved between D. melanogaster and the mouse; however, conditional loss of miRNA function through mutation of Dicer causes defects in proliferation of premeiotic germ cells in both species. This highlights the potentially important, but uncharacterized, role of miRNAs during early spermatogenesis. The goal of this study was to characterize on postnatal day 7, 10, and 14 the content and editing of murine testicular miRNAs, which predominantly arise from spermatogonia and spermatocytes, in contrast to prior descriptions of miRNAs in the adult mouse testis which largely reflects the content of spermatids. Previous studies have shown miRNAs to be abundant in the mouse testis by postnatal day 14; however, through Next Generation Sequencing of testes from a B6;129 background we found abundant earlier expression of miRNAs and describe shifts in the miRNA signature during this period. We detected robust expression of miRNAs encoded on the X chromosome in postnatal day 14 testes, consistent with prior studies showing their resistance to meiotic sex chromosome inactivation. Unexpectedly, we also found a similar positional enrichment for most miRNAs on chromosome 2 at postnatal day 14 and for those on chromosome 12 at postnatal day 7. We quantified in vivo developmental changes in three types of miRNA variation including 5' heterogeneity, editing, and 3' nucleotide addition. We identified eleven putative novel pubertal testis miRNAs whose developmental expression suggests a possible role in early male germ cell development. These studies provide a foundation for interpretation of miRNA changes associated with testicular pathology and identification of novel components of the miRNA editing machinery in the testis.

  2. Late Pleistocene adult mortality patterns and modern human establishment.

    PubMed

    Trinkaus, Erik

    2011-01-25

    The establishment of modern humans in the Late Pleistocene, subsequent to their emergence in eastern Africa, is likely to have involved substantial population increases, during their initial dispersal across southern Asia and their subsequent expansions throughout Africa and into more northern Eurasia. An assessment of younger (20-40 y) versus older (>40 y) adult mortality distributions for late archaic humans (principally Neandertals) and two samples of early modern humans (Middle Paleolithic and earlier Upper Paleolithic) provides little difference across the samples. All three Late Pleistocene samples have a dearth of older individuals compared with Holocene ethnographic/historical samples. They also lack older adults compared with Holocene paleodemographic profiles that have been critiqued for having too few older individuals for subsistence, social, and demographic viability. Although biased, probably through a combination of preservation, age assessment, and especially Pleistocene mobility requirements, these adult mortality distributions suggest low life expectancy and demographic instability across these Late Pleistocene human groups. They indicate only subtle and paleontologically invisible changes in human paleodemographics with the establishment of modern humans; they provide no support for a life history advantage among early modern humans.

  3. Late Pleistocene adult mortality patterns and modern human establishment

    PubMed Central

    Trinkaus, Erik

    2011-01-01

    The establishment of modern humans in the Late Pleistocene, subsequent to their emergence in eastern Africa, is likely to have involved substantial population increases, during their initial dispersal across southern Asia and their subsequent expansions throughout Africa and into more northern Eurasia. An assessment of younger (20–40 y) versus older (>40 y) adult mortality distributions for late archaic humans (principally Neandertals) and two samples of early modern humans (Middle Paleolithic and earlier Upper Paleolithic) provides little difference across the samples. All three Late Pleistocene samples have a dearth of older individuals compared with Holocene ethnographic/historical samples. They also lack older adults compared with Holocene paleodemographic profiles that have been critiqued for having too few older individuals for subsistence, social, and demographic viability. Although biased, probably through a combination of preservation, age assessment, and especially Pleistocene mobility requirements, these adult mortality distributions suggest low life expectancy and demographic instability across these Late Pleistocene human groups. They indicate only subtle and paleontologically invisible changes in human paleodemographics with the establishment of modern humans; they provide no support for a life history advantage among early modern humans. PMID:21220336

  4. Pluripotent male germline stem cells from goat fetal testis and their survival in mouse testis.

    PubMed

    Hua, Jinlian; Zhu, Haijing; Pan, Shaohui; Liu, Chao; Sun, Junwei; Ma, Xiaoling; Dong, Wuzi; Liu, Weishuai; Li, Wei

    2011-04-01

    Male germline stem cells (mGSCs) are stem cells present in male testis responsible for spermatogenesis during their whole life. Studies have shown that mGSCs can be derived in vitro and resemble embryonic stem cells (ESCs) properties both in the mouse and humans. However, little is know about these cells in domestic animals. Here we report the first successful establishment of goat GSCs derived from 2-5-month fetal testis, and developmental potential assay of these cells both in vitro and in vivo. These cells express pluripotent markers such as Oct4, Sox2, C-myc, and Tert when cultured as human ESCs conditions. Embryoid bodies (EBs) formed by goat mGSCs were induced with 2 × 10(-6) M retinoic acid (RA). Immunofluorescence analysis showed that some cells inside of the EBs were positive for meiosis marker-SCP3, STRA8, and germ cell marker-VASA, and haploid marker-FE-J1, PRM1, indicating their germ cell lineage differentiation. Some cells become elongated sperm-like cells after induction. Approximately 34.88% (30/86) embryos showed cleavage and four embryos were cultured on murine fibroblast feeder and formed small embryonic stem like colonies. However, most stalled at four-cell stage after intracytoplasmic sperm injection (ICSI) of these cells. Transplantation of DAPI labeled mGSCs into the seminiferous tubules of busulfan-treated mice, and showed that mGSCs can colonize, self-renew, and differentiate into germ cells. Thus, we have established a goat GSC cell line and these cells could be differentiated into sperm-like cells in vivo and sperms in vitro, providing a promising platform for generation of transgenic goat for production of specific humanized proteins.

  5. Analysis of fibroblast growth factor 2 (FGF2) gene transcription and protein distribution in the bovine testis.

    PubMed

    Abd-Elmaksoud, Ahmed; Vermehren, Margarete; Nützel, Friedrich; Habermann, Felix Andreas; Sinowatz, Fred

    2005-12-01

    Several fibroblast growth factors (FGFs) are implicated in proliferation and differentiation of both somatic and germ cells during testicular development, as well as in spermatogenesis of adult testis. The expression of FGF2 was studied in the adult bovine testis using quantitative RT-PCR, RNA in situ hybridization, and immunohistochemistry. Quantitative RT-PCR revealed consistent levels of FGF2 mRNA in parenchymal samples of the bovine testis. In situ hybridization localized FGF2 transcripts only in a constant fraction of Leydig and Sertoli cells as well as in modified Sertoli cells of the terminal segments. Immunohistochemistry revealed (a) no FGF2 protein in Sertoli cells (b) moderate cytoplasmic staining in Leydig cells and spermatogonia and (c) strong nuclear and faint cytoplasmic staining in myofibroblasts, in epithelial cells of straight tubules and rete testis and in blood vessels. These observations indicate a pleiotropic effect of FGF2 on the control of spermatogenesis in a paracrine and/or autocrine manner.

  6. Linking adult hippocampal neurogenesis with human physiology and disease.

    PubMed

    Bowers, Megan; Jessberger, Sebastian

    2016-07-01

    We here review the existing evidence linking adult hippocampal neurogenesis and human brain function in physiology and disease. Furthermore, we aim to point out where evidence is missing, highlight current promising avenues of investigation, and suggest future tools and approaches to foster the link between life-long neurogenesis and human brain function. Developmental Dynamics 245:702-709, 2016. © 2016 Wiley Periodicals, Inc.

  7. Maps of the adult human hypothalamus

    PubMed Central

    Lemaire, Jean-Jacques; Nezzar, Hachemi; Sakka, Laurent; Boirie, Yves; Fontaine, Denys; Coste, Aurélien; Coll, Guillaume; Sontheimer, Anna; Sarret, Catherine; Gabrillargues, Jean; De Salles, Antonio

    2013-01-01

    The human hypothalamus is a small deeply located region placed at the crossroad of neurovegetative, neuroendocrine, limbic, and optic systems. Although deep brain stimulation techniques have proven that it could be feasible to modulate these systems, targeting the hypothalamus and in particular specific nuclei and white bundles, is still challenging. Our goal was to make a synthesis of relevant topographical data of the human hypothalamus, under the form of magnetic resonance imaging maps useful for mastering its elaborated structure as well as its neighborhood. As from 1.5 Tesla, Inversion-Recovery sequence allows locating the hypothalamus and most of its components. Spotting hypothalamic compartments is possible according to specific landmarks: the anterior commissure, the mammillary bodies, the preoptic recess, the infundibular recess, the crest between the preoptic and the infundibular recesses, the optical tract, the fornix, and the mammillo-thalamic bundle. The identification of hypothalamus and most of its components could be useful to allow the quantification of local pathological processes and to target specific circuitry to alleviate severe symptoms, using physical or biological agents. PMID:23682342

  8. Expression of Attractin in male reproductive tract of human and mice and its correlation with male reproduction.

    PubMed

    Cheng, Dan; Ming, Yu; Li, Jie; Chi, Yan; Li, Hong-Gang; Zou, Yu-Jie; Xiong, Cheng-Liang

    2014-10-01

    The expression of Attractin mRNA and protein in testis and semen of human and male mice was investigated. Human testis and semen samples were all collected from Reproductive Center of Renmin Hospital, Wuhan University in December, 2012. Testis samples were collected from 7 cases of obstructive azoospermias when they were subjected to diagnosed testis biopsy, and 30 normal human semen samples were obtained from those cases of semen analysis. Adult mice testis tissues were obtained from 10 2-month-old male BALB/c mice, and 60 male mice at different ages were classified into 10 groups (day 1, 5, 10, 15, 21, 28, 35, 42, 56, and 120 respectively, n=6 each). The expression of Attractin mRNA and protein in testis was detected by RT-PCR and Western blotting respectively. Human semen samples were centrifuged into sperm plasma (SP) and sperm extract (SE), and mice sperm samples were collected from the epididymis of 10 adult male BALB/c mice. Western blotting was used to determine the Attractin protein expression level. Attractin mRNA and protein were expressed in the testis of both patients with obstructive azoospermias and adult Bcl/B mice. Quantitative RT-PCR revealed that no Attractin mRNA was detectable in day 1 male BALB/c mice group. The Attractin mRNA and protein levels were low on the day 10, and increased with age until day 56. On the day 120, the expression levels of Attractin were decreased. As for human semen samples, Attractin protein was expressed in both SP and SE, but didn't exist in samples from the epididymis of male BALB/c mice. It was suggested that Attractin acted as a novel active substance and was involved in male reproduction in both human and BALB/c mice, but it exerted a different expression profile in different mammal species.

  9. Human Service Planning as a Collective Adult Learning Experience.

    ERIC Educational Resources Information Center

    Wright, Joan

    Based on a study by the Department of Community Service Education, Cornell University, to evaluate human service planning (HSP) nationwide, this paper discusses the premises that HSP may be defined as community learning and that the community (according to the Robert Boyd and Jerold Apps model for adult education) is both a beneficiary of and…

  10. Expansion of Multipotent Stem Cells from the Adult Human Brain

    PubMed Central

    Murrell, Wayne; Palmero, Emily; Bianco, John; Stangeland, Biljana; Joel, Mrinal; Paulson, Linda; Thiede, Bernd; Grieg, Zanina; Ramsnes, Ingunn; Skjellegrind, Håvard K.; Nygård, Ståle; Brandal, Petter; Sandberg, Cecilie; Vik-Mo, Einar; Palmero, Sheryl; Langmoen, Iver A.

    2013-01-01

    The discovery of stem cells in the adult human brain has revealed new possible scenarios for treatment of the sick or injured brain. Both clinical use of and preclinical research on human adult neural stem cells have, however, been seriously hampered by the fact that it has been impossible to passage these cells more than a very few times and with little expansion of cell numbers. Having explored a number of alternative culturing conditions we here present an efficient method for the establishment and propagation of human brain stem cells from whatever brain tissue samples we have tried. We describe virtually unlimited expansion of an authentic stem cell phenotype. Pluripotency proteins Sox2 and Oct4 are expressed without artificial induction. For the first time multipotency of adult human brain-derived stem cells is demonstrated beyond tissue boundaries. We characterize these cells in detail in vitro including microarray and proteomic approaches. Whilst clarification of these cells’ behavior is ongoing, results so far portend well for the future repair of tissues by transplantation of an adult patient’s own-derived stem cells. PMID:23967194

  11. Adult Education, Basic Human Needs, and Integrated Development Planning

    ERIC Educational Resources Information Center

    Green, Reginald Herbold

    1976-01-01

    This paper argues for an integrated approach to adult education which would require an examination of basic human needs and national development planning each in its own terms. The paper's argument is centered on liberation and participation as ends, not means: Education, development, and planning must be seen and acted on as an integrated whole.…

  12. Expression and interdependencies of pluripotency factors LIN28, OCT3/4, NANOG and SOX2 in human testicular germ cells and tumours of the testis.

    PubMed

    Gillis, A J M; Stoop, H; Biermann, K; van Gurp, R J H L M; Swartzman, E; Cribbes, S; Ferlinz, A; Shannon, M; Oosterhuis, J W; Looijenga, L H J

    2011-08-01

    OCT3/4, NANOG, SOX2 and, most recently, LIN28 have been identified as key regulators of pluripotency in mammalian embryonic and induced stem cells, and are proven to be crucial for generation of the mouse germ-cell lineage. These factors are a hallmark of certain histological types of germ-cell tumours (GCTs). Here, we report novel information on the temporal and spatial expression pattern of LIN28 during normal human male germ-cell development as well as various types of GCTs. To investigate LIN28 expression, immunohistochemical analyses and quantitative proximity ligation assay-based TaqMan protein assays were applied on snap-frozen and formalin-fixed, paraffin-embedded samples as well as representative cell lines. LIN28 was found in primordial germ cells, gonocytes and pre-spermatogonia, in contrast to OCT3/4 and NANOG, which were found only in the first two stages. LIN28 was also found in all precursor lesions (carcinoma in situ and gonadoblastoma) of type II GCTs, as well as the invasive components seminoma and the non-seminomatous elements embryonal carcinoma and yolk sac tumour. Choriocarcinoma showed a heterogeneous pattern, while teratomas and spermatocytic seminomas (type III GCTs) were negative. This expression pattern suggests that LIN28 is associated with malignant behaviour of type II GCTs. Cell line experiments involving siRNA knockdown of LIN28, OCT3/4 and SOX2 showed that LIN28 plays a role in the maintenance of the undifferentiated state of both seminoma and embryonal carcinoma, closely linked to, and likely upstream of OCT3/4 and NANOG. In conclusion, LIN28 regulates the differentiation status of seminoma and embryonal carcinoma and is likely to play a related role in normal human germ-cell development. © 2011 The Authors. International Journal of Andrology © 2011 European Academy of Andrology.

  13. A Single Nucleotide Polymorphism within the Novel Sex-Linked Testis-Specific Retrotransposed PGAM4 Gene Influences Human Male Fertility

    PubMed Central

    Okuda, Hidenobu; Tsujimura, Akira; Irie, Shinji; Yamamoto, Keisuke; Fukuhara, Shinichiro; Matsuoka, Yasuhiro; Takao, Tetsuya; Miyagawa, Yasushi; Nonomura, Norio; Wada, Morimasa; Tanaka, Hiromitsu

    2012-01-01

    Background The development of novel fertilization treatments, including in vitro fertilization and intracytoplasmic injection, has made pregnancy possible regardless of the level of activity of the spermatozoa; however, the etiology of male-factor infertility is poorly understood. Multiple studies, primarily through the use of transgenic animals, have contributed to a list of candidate genes that may affect male infertility in humans. We examined single nucleotide polymorphisms (SNPs) as a cause of male infertility in an analysis of spermatogenesis-specific genes. Methods and Finding We carried out the prevalence of SNPs in the coding region of phosphoglycerate mutase 4 (PGAM4) on the X chromosome by the direct sequencing of PCR-amplified DNA from male patients. Using RT-PCR and western blot analyses, we identified that PGAM4 is a functional retrogene that is expressed predominantly in the testes and is associated with male infertility. PGAM4 is expressed in post-meiotic stages, including spermatids and spermatozoa in the testes, and the principal piece of the flagellum and acrosome in ejaculated spermatozoa. A case-control study revealed that 4.5% of infertile patients carry the G75C polymorphism, which causes an amino acid substitution in the encoded protein. Furthermore, an assay for enzymatic activity demonstrated that this polymorphism decreases the enzyme’s activity both in vitro and in vivo. Conclusion These results suggest that PGAM4, an X-linked retrogene, is a fundamental gene in human male reproduction and may escape meiotic sex chromosome inactivation. These findings provide fresh insight into elucidating the mechanisms of male infertility. PMID:22590500

  14. Torsion of an intra-abdominal testis.

    PubMed

    Lewis; Roller; Parra; Cotlar

    2000-09-01

    To present a case of torsion of a nonneoplastic intra-abdominal testis with an unusual clinical presentation.A 26-year-old active duty Navy Petty Officer presented to the emergency department on 3 occasions over a 5-day period with lower abdominal pain. Physical examination demonstrated acute tenderness in the left lower quadrant with sugestion of a normal spermatic cord and atrophic testis in the left scrotum. Computed tomography scan demonstrated an intra-abdominal lesion near the internal inguinal ring. The patient underwent surgical exploration through an inguinal incision. Torsion of a nonviable intra-abdominal testis was present. The scrotum contained only the vas deferens and cremasteric muscle. An orchiectomy was performed with removal of the vas deferens and other cord structures.The unusual clinical finding of acute torsion of an intra-abdominal testis, associated with an apparent atrophic scrotal testis, presented a confusing clinical picture. Computed tomography scan did not clarify the issue sufficiently to establish a definite preoperative diagnosis. Clinical suspicion prompted early surgical intervention. Review of the current literature produced 60 reported cases of torsion of an intra-abdominal testis. Two thirds of these involved testicular neoplasm, usually seminoma. Although the clinical presentation varied, most patients had recent onset of lower abdominal pain associated with tenderness and, in half the cases, a mass. Patients almost always presented with an absent scrotal testis on the involved side, and not infrequently reported previous surgery thought to be an orchiectomy.Diagnosis of an intra-abdominal testicular torsion is rare, particularly when no neoplasm is present. A high index of suspicion must be maintained whenever there is abdominal pain and undescended testis. The surgical history and imaging studies may not clarify a confusing clinical picture.

  15. Metastasis of Prostate Adenocarcinoma to the Testis

    PubMed Central

    Campara, Zoran; Simic, Dejan; Aleksic, Predrag; Spasic, Aleksandar; Milicevic, Snjezana

    2016-01-01

    Introduction: Prostate carcinoma is the most frequently diagnosed carcinoma in the male population. The most typical places of the metastases are pelvic lymphatic glands, bones and lungs, and very rarely it metastasizes into a testis. The prognostic importance of testicular metastasis of prostate cancer is not yet well-known, due to a very few published cases. According to the known facts, it is certain that a metastasis of the prostate carcinoma into a testis is a sign of an advanced disease. Case report: This work presents a 48-year-old patient, to whom an adenocarcinoma of the prostate has been proven by the pathohistological finding of transrectal biopsy, performed due to the elevated level of prostate-specific antigen (PSA). Nine years after the initial diagnosis, due to a gradual rise of PSA and tumorous enlargement of the left testis, left inguinal orchectomy and right orchectomy were performed. Metastatic dissemination of prostate adenocarcinoma into a testis was determined by a pathohistological analysis of the left testis. Conclusion: The metastasis of the prostate carcinoma into a testis, as a rare localization of the metastatic dissemination, after additionally performed orchectomy along with further oncological therapy, can provide a continuation of a good life quality as well as a control of the disease in a longer time period. PMID:27703299

  16. METABOLOMIC EVALUATION OF RAT LIVER AND TESTIS TO CHARACTERIZE THE TOXICITY OF TRIAZOLE FUNGICIDES

    EPA Science Inventory

    The effects of two triazole fungicides, myclobutanil and triadimefon, on endogenous rat metabolite profiles in blood serum, liver, and testis was assessed using proton nuclear magnetic resonance (1H-NMR) spectroscopy. Adult male Sprague-Dawley rats were dosed daily by gavage for...

  17. METABOLOMIC EVALUATION OF RAT LIVER AND TESTIS TO CHARACTERIZE THE TOXICITY OF TRIAZOLE FUNGICIDES

    EPA Science Inventory

    The effects of two triazole fungicides, myclobutanil and triadimefon, on endogenous rat metabolite profiles in blood serum, liver, and testis was assessed using proton nuclear magnetic resonance (1H-NMR) spectroscopy. Adult male Sprague-Dawley rats were dosed daily by gavage for...

  18. Distinct functional programming of human fetal and adult monocytes.

    PubMed

    Krow-Lucal, Elisabeth R; Kim, Charles C; Burt, Trevor D; McCune, Joseph M

    2014-03-20

    Preterm birth affects 1 out of 9 infants in the United States and is the leading cause of long-term neurologic handicap and infant mortality, accounting for 35% of all infant deaths in 2008. Although cytokines including interferon-γ (IFN-γ), interleukin-10 (IL-10), IL-6, and IL-1 are produced in response to in utero infection and are strongly associated with preterm labor, little is known about how human fetal immune cells respond to these cytokines. We demonstrate that fetal and adult CD14(+)CD16(-) classical monocytes are distinct in terms of basal transcriptional profiles and in phosphorylation of signal transducers and activators of transcription (STATs) in response to cytokines. Fetal monocytes phosphorylate canonical and noncanonical STATs and respond more strongly to IFN-γ, IL-6, and IL-4 than adult monocytes. We demonstrate a higher ratio of SOCS3 to IL-6 receptor in adult monocytes than in fetal monocytes, potentially explaining differences in STAT phosphorylation. Additionally, IFN-γ signaling results in upregulation of antigen presentation and costimulatory machinery in adult, but not fetal, monocytes. These findings represent the first evidence that primary human fetal and adult monocytes are functionally distinct, potentially explaining how these cells respond differentially to cytokines implicated in development, in utero infections, and the pathogenesis of preterm labor.

  19. Identification of human candidate genes for male infertility by digital differential display.

    PubMed

    Olesen, C; Hansen, C; Bendsen, E; Byskov, A G; Schwinger, E; Lopez-Pajares, I; Jensen, P K; Kristoffersson, U; Schubert, R; Van Assche, E; Wahlstroem, J; Lespinasse, J; Tommerup, N

    2001-01-01

    Evidence for the importance of genetic factors in male fertility is accumulating. In the literature and the Mendelian Cytogenetics Network database, 265 cases of infertile males with balanced reciprocal translocations have been described. The candidacy for infertility of 14 testis-expressed transcripts (TETs) were examined by comparing their chromosomal mapping position to the position of balanced reciprocal translocation breakpoints found in the 265 infertile males. The 14 TETs were selected by using digital differential display (electronic subtraction) to search for apparently testis-specific transcripts in the TIGR database. The testis specificity of the 14 TETs was further examined by reverse transcription-polymerase chain reaction (RT-PCR) on adult and fetal tissues showing that four TETs (TET1 to TET4) were testis-expressed only, six TETs (TET5 to TET10) appeared to be differentially expressed and the remaining four TETs (TET11 to TET14) were ubiquitously expressed. Interestingly, the two tesis expressed-only transcripts, TET1 and TET2, mapped to chromosomal regions where seven and six translocation breakpoints have been reported in infertile males respectively. Furthermore, one ubiquitously, but predominantly testis-expressed, transcript, TET11, mapped to 1p32-33, where 13 translocation breakpoints have been found in infertile males. Interestingly, the mouse mutation, skeletal fusions with sterility, sks, maps to the syntenic region in the mouse genome. Another transcript, TET7, was the human homologue of rat Tpx-1, which functions in the specific interaction of spermatogenic cells with Sertoli cells. TPX-1 maps to 6p21 where three cases of chromosomal breakpoints in infertile males have been reported. Finally, TET8 was a novel transcript which in the fetal stage is testis-specific, but in the adult is expressed in multiple tissues, including testis. We named this novel transcript fetal and adult testis-expressed transcript (FATE).

  20. New application of a subcellular fractionation method to kidney and testis for the determination of conjugated linoleic acid in selected cell organelles of healthy and cancerous human tissues.

    PubMed

    Hoffmann, Kristina; Blaudszun, Jörg; Brunken, Claus; Höpker, Wilhelm-Wolfgang; Tauber, Roland; Steinhart, Hans

    2005-03-01

    To clarify the mechanism of the anticarcinogenic effect of conjugated linoleic acid (CLA), its intracellular distribution needs to be determined. Subcellular fractionation using centrifugation techniques is a method that is frequently used for isolation of cell organelles from different tissues. But as the size and density of the organelles differ, the method needs to be optimised for every type of tissue. The novelty of this study is the application of a subcellular fractionation method to human healthy and cancerous renal and testicular tissue. Separation of total tissue homogenate into nuclei, cytosol, and a mixture of mitochondria and plasma membranes was achieved by differential centrifugation. As mitochondria and plasma membranes seemed to be too similar in size and weight to be separated by differential centrifugation, discontinuous density-gradient centrifugation was carried out successfully. The purity of the subcellular fractions was checked by measuring the activity of marker enzymes. All fractions were highly enriched in their corresponding marker enzyme. However, the nuclear fractions of kidney and renal cell carcinoma were slightly contaminated with mitochondria and plasma membrane fractions of all tissues with lysosomes. The fraction designated the cytosolic fraction contained not only cytosol, but also microsomes and lysosomes. The CLA contents of the subcellular fractions were in the range 0.13-0.37% of total fatty acids and were lowest in the plasma membrane fractions of all types of tissue studied. C16:0, C18:0, C18:1 c9, C18:2 n-6, and C20:4 n-6 were found to be the major fatty acids in all the subcellular fractions studied. However, marked variations in fatty acid content between subcellular fractions and between types of tissue were detectable. Because of these differences between tissues, no general statement on characteristic fatty acid profiles of single subcellular fractions is possible.

  1. Coexpression of Nuclear Receptors and Histone Methylation Modifying Genes in the Testis: Implications for Endocrine Disruptor Modes of Action

    PubMed Central

    Anderson, Alison M.; Carter, Kim W.; Anderson, Denise; Wise, Michael J.

    2012-01-01

    Background Endocrine disruptor chemicals elicit adverse health effects by perturbing nuclear receptor signalling systems. It has been speculated that these compounds may also perturb epigenetic mechanisms and thus contribute to the early origin of adult onset disease. We hypothesised that histone methylation may be a component of the epigenome that is susceptible to perturbation. We used coexpression analysis of publicly available data to investigate the combinatorial actions of nuclear receptors and genes involved in histone methylation in normal testis and when faced with endocrine disruptor compounds. Methodology/Principal Findings The expression patterns of a set of genes were profiled across testis tissue in human, rat and mouse, plus control and exposed samples from four toxicity experiments in the rat. Our results indicate that histone methylation events are a more general component of nuclear receptor mediated transcriptional regulation in the testis than previously appreciated. Coexpression patterns support the role of a gatekeeper mechanism involving the histone methylation modifiers Kdm1, Prdm2, and Ehmt1 and indicate that this mechanism is a common determinant of transcriptional integrity for genes critical to diverse physiological endpoints relevant to endocrine disruption. Coexpression patterns following exposure to vinclozolin and dibutyl phthalate suggest that coactivity of the demethylase Kdm1 in particular warrants further investigation in relation to endocrine disruptor mode of action. Conclusions/Significance This study provides proof of concept that a bioinformatics approach that profiles genes related to a specific hypothesis across multiple biological settings can provide powerful insight into coregulatory activity that would be difficult to discern at an individual experiment level or by traditional differential expression analysis methods. PMID:22496781

  2. 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.

  3. Does Acute Normobaric Hypoxia Induce Anapyrexia in Adult Humans?

    PubMed

    Seo, Yongsuk; Gerhart, Hayden D; Vaughan, Jeremiah; Kim, Jung-Hyun; Glickman, Ellen L

    2017-06-01

    Seo, Yongsuk, Hayden D. Gerhart, Jeremiah Vaughan, Jung-Hyun Kim, and Ellen L. Glickman. Does acute normobaric hypoxia induce anapyrexia in adult humans? High Alt Med Biol. 18:185-190, 2017.-Exposure to hypoxia is known to induce a reduction in core body temperature as a protective mechanism, which has been shown in both animals and humans. The purpose of this study was to test if acute exposure to normobaric hypoxia (NH) induces anapyrexia in adult humans in association with decreased peripheral oxygen saturation (SpO2). Ten healthy male subjects were seated in atmospheres of normobaric normoxia 21% (NN21), NH 17% (NH17), and 13% (NH13) O2 for 60 minutes in a counterbalanced manner. Rectal temperature (Tre) was continuously monitored together with the quantification of metabolic heat production (MHP) and body heat storage (S). Baseline physiological measurements showed no differences between the three conditions. SpO2 was significantly decreased in NH17 and NH13 compared with NN21 (p ≤ 0.001). Tre decreased following 60 minutes of resting in all conditions, but, independent of the conditions, showed no association between Tre and levels of hypoxic SpO2. There was also no significant difference in either MHP or S between conditions. The present results showed no evidence of hypoxia-induced anapyrexia in adult humans during 1 hour of resting after exposure to NH either at 13% or 17% O2.

  4. Perivascular mesenchymal progenitors in human fetal and adult liver.

    PubMed

    Gerlach, Jörg C; Over, Patrick; Turner, Morris E; Thompson, Robert L; Foka, Hubert G; Chen, William C W; Péault, Bruno; Gridelli, Bruno; Schmelzer, Eva

    2012-12-10

    The presence of mesenchymal stem cells (MSCs) has been described in various organs. Pericytes possess a multilineage differentiation potential and have been suggested to be one of the developmental sources for MSCs. In human liver, pericytes have not been defined. Here, we describe the identification, purification, and characterization of pericytes in human adult and fetal liver. Flow cytometry sorting revealed that human adult and fetal liver contains 0.56%±0.81% and 0.45%±0.39% of CD146(+)CD45(-)CD56(-)CD34(-) pericytes, respectively. Of these, 41% (adult) and 30% (fetal) were alkaline phosphatase-positive (ALP(+)). In situ, pericytes were localized around periportal blood vessels and were positive for NG2 and vimentin. Purified pericytes could be cultured extensively and had low population doubling times. Immunofluorescence of cultures demonstrated that cells were positive for pericyte and mesenchymal cell markers CD146, NG2, CD90, CD140b, and vimentin, and negative for endothelial, hematopoietic, stellate, muscle, or liver epithelial cell markers von Willebrand factor, CD31, CD34, CD45, CD144, CD326, CK19, albumin, α-fetoprotein, CYP3A7, glial fibrillary acid protein, MYF5, and Pax7 by gene expression; myogenin and alpha-smooth muscle actin expression were variable. Fluorescence-activated cell sorting analysis of cultures confirmed surface expression of CD146, CD73, CD90, CD10, CD13, CD44, CD105, and ALP and absence of human leukocyte antigen-DR. In vitro differentiation assays demonstrated that cells possessed robust osteogenic and myogenic, but low adipogenic and low chondrogenic differentiation potentials. In functional in vitro assays, cells had typical mesenchymal strong migratory and invasive activity. In conclusion, human adult and fetal livers harbor pericytes that are similar to those found in other organs and are distinct from hepatic stellate cells.

  5. [Generation of new nerve cells in the adult human brain].

    PubMed

    Poulsen, Frantz Rom; Meyer, Morten; Rasmussen, Jens Zimmer

    2003-03-31

    Generation of new nerve cells (neurogenesis) is normally considered to be limited to the fetal and early postnatal period. Thus, damaged nerve cells are not expected to be replaced by generation of new cells. The brain is, however, more plastic than previously assumed. This also includes neurogenesis in the adult human brain. In particular two brain regions show continuous division of neural stem and progenitor cells generating neurons and glial cells, namely the subgranular zone of the dentate gyrus and the subventricular zones of the lateral ventricles. From the latter region newly generated neuroblasts (immature nerve cells) migrate toward the olfactory bulb where they differentiate into neurons. In the dentate gyrus the newly generated neurons become functionally integrated in the granule cell layer, where they are believed to be of importance to learning and memory. It is at present not known whether neurogenesis in the adult human brain can be manipulated for specific repair after brain damage.

  6. Somatosensory cortical plasticity in adult humans revealed by magnetoencephalography.

    PubMed Central

    Mogilner, A; Grossman, J A; Ribary, U; Joliot, M; Volkmann, J; Rapaport, D; Beasley, R W; Llinás, R R

    1993-01-01

    Microelectrode recordings in adult mammals have clearly demonstrated that somatosensory cortical maps reorganize following peripheral nerve injuries and functional modifications; however, such reorganization has never been directly demonstrated in humans. Using magnetoencephalography, we have been able to demonstrate the somatotopic organization of the hand area in normal humans with high spatial precision. Somatosensory cortical plasticity was detected in two adults who were studied before and after surgical separation of webbed fingers (syndactyly). The presurgical maps displayed shrunken and nonsomatotopic hand representations. Within weeks following surgery, cortical reorganization occurring over distances of 3-9 mm was evident, correlating with the new functional status of their separated digits. In contrast, no modification of the somatosensory map was observed months following transfer of a neurovascular skin island flap for sensory reconstruction of the thumb in two subjects in whom sensory transfer failed to occur. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8386377

  7. Bacteriology of moderate (chronic) periodontitis in mature adult humans.

    PubMed Central

    Moore, W E; Holdeman, L V; Cato, E P; Smibert, R M; Burmeister, J A; Ranney, R R

    1983-01-01

    A total of 171 taxa was represented among 1,900 bacterial isolates from 60 samples of sites affected with moderate periodontitis in 22 mature adult humans. The composition of the subgingival sulcus flora was statistically significantly different from that of the adjacent supragingival flora and the subgingival flora of 14 people with healthy gingiva, but was not significantly different from that of sulci affected with severe periodontitis in 21 young human adults. The sulcus floras of moderate periodontitis and severe periodontitis shared many of their predominant bacterial species, but there were differences in the relative proportions of some of these species. Similar relationships were found for seven taxa of treponemes that were cultured from the samples. PMID:6642641

  8. Spermatogonial stem cell enrichment using simple grafting of testis and in vitro cultivation

    PubMed Central

    Lim, Jung Jin; Seol, Dong Won; Choi, Kyung Hee; Shin, Dong Hyuk; Kim, Hyung Joon; Song, Seung-Hun; Lee, Dong Ryul

    2014-01-01

    Enrichment of spermatogonial stem cells (SSCs) from the mammalian adult testis faces several limitations owing to their relatively low numbers among many types of advanced germ cells and somatic cells. The aim of the present study was to improve the isolation efficiency of SSCs using a simple tissue grafting method to eliminate the existing advanced germ cells. Sliced testis parenchyma obtained from adult ICR or EGFP-expressing transgenic mice were grafted heterotropically under the dorsal skin of nude mice. The most advanced germ cells disappeared in the grafted tissues after 2–4 weeks. Grafted tissues were dissociated enzymatically and plated in culture dishes. During in vitro culture, significantly more SSCs were obtained from the grafted testes than from non-grafted controls, and the isolated SSCs had proliferative potential and were successfully maintained. Additionally, EGFP-expressing SSCs derived from graft parenchyma were transplanted into bulsufan-treated recipient mice testes. Finally, we obtained EGFP-expressing pups after in vitro fertilization using spermatozoa derived from transplanted SSCs. These results suggest that subcutaneous grafting of testis parenchyma and the subsequent culture methods provide a simple and efficient isolation method to enrich for SSCs in adult testis without specific cell sorting methods and may be useful tools for clinical applications. PMID:25080919

  9. Spermatogonial stem cell enrichment using simple grafting of testis and in vitro cultivation.

    PubMed

    Lim, Jung Jin; Seol, Dong Won; Choi, Kyung Hee; Shin, Dong Hyuk; Kim, Hyung Joon; Song, Seung-Hun; Lee, Dong Ryul

    2014-08-01

    Enrichment of spermatogonial stem cells (SSCs) from the mammalian adult testis faces several limitations owing to their relatively low numbers among many types of advanced germ cells and somatic cells. The aim of the present study was to improve the isolation efficiency of SSCs using a simple tissue grafting method to eliminate the existing advanced germ cells. Sliced testis parenchyma obtained from adult ICR or EGFP-expressing transgenic mice were grafted heterotropically under the dorsal skin of nude mice. The most advanced germ cells disappeared in the grafted tissues after 2-4 weeks. Grafted tissues were dissociated enzymatically and plated in culture dishes. During in vitro culture, significantly more SSCs were obtained from the grafted testes than from non-grafted controls, and the isolated SSCs had proliferative potential and were successfully maintained. Additionally, EGFP-expressing SSCs derived from graft parenchyma were transplanted into bulsufan-treated recipient mice testes. Finally, we obtained EGFP-expressing pups after in vitro fertilization using spermatozoa derived from transplanted SSCs. These results suggest that subcutaneous grafting of testis parenchyma and the subsequent culture methods provide a simple and efficient isolation method to enrich for SSCs in adult testis without specific cell sorting methods and may be useful tools for clinical applications.

  10. Lymphatic Stomata in the Adult Human Pulmonary Ligament

    PubMed Central

    Miura, Masahiro; Iobe, Hiroaki; Kudo, Tomoo; Shimazu, Yoshihito; Aoba, Takaaki; Okudela, Koji; Nagahama, Kiyotaka; Sakamaki, Kentaro; Yoshida, Maki; Nagao, Toshitaka; Nakaya, Takeo; Kurata, Atsushi; Ohtani, Osamu

    2015-01-01

    Abstract Background: Lymphatic stomata are small lymphatic openings in the serosal membrane that communicate with the serosal cavity. Although these stomata have primarily been studied in experimental mammals, little is known concerning the presence and properties of lymphatic stomata in the adult human pleura. Thus, adult human pleurae were examined for the presence or absence of lymphatic stomata. Methods and Results: A total of 26 pulmonary ligaments (13 left and 13 right) were obtained from 15 adult human autopsy cases and examined using electron and light microscopy. The microscopic studies revealed the presence of apertures fringed with D2-40-positive, CD31-positive, and cytokeratin-negative endothelial cells directly communicating with submesothelial lymphatics in all of the pulmonary ligaments. The apertures' sizes and densities varied from case to case according to the serial tissue section. The medians of these aperture sizes ranged from 2.25 to 8.75 μm in the left pulmonary ligaments and from 2.50 to 12.50 μm in the right pulmonary ligaments. The densities of the apertures ranged from 2 to 9 per mm2 in the left pulmonary ligaments and from 2 to 18 per mm2 in the right pulmonary ligaments. However, no significant differences were found regarding the aperture size (p=0.359) and density (p=0.438) between the left and the right pulmonary ligaments. Conclusions: Our study revealed that apertures exhibit structural adequacy as lymphatic stomata on the surface of the pulmonary ligament, thereby providing evidence that lymphatic stomata are present in the adult human pleura. PMID:25526320

  11. Doublecortin expression in the normal and epileptic adult human brain.

    PubMed

    Liu, Y W J; Curtis, M A; Gibbons, H M; Mee, E W; Bergin, P S; Teoh, H H; Connor, B; Dragunow, M; Faull, R L M

    2008-12-01

    Mesial temporal lobe epilepsy (MTLE) is a neurological disorder associated with spontaneous recurrent complex partial seizures and hippocampal sclerosis. Although increased hippocampal neurogenesis has been reported in animal models of MTLE, increased neurogenesis has not been reported in the hippocampus of adult human MTLE cases. Here we showed that cells expressing doublecortin (Dcx), a microtubule-associated protein expressed in migrating neuroblasts, were present in the hippocampus and temporal cortex of the normal and MTLE adult human brain. In particular, increased numbers of Dcx-positive cells were observed in the epileptic compared with the normal temporal cortex. Importantly, 56% of Dcx-expressing cells in the epileptic temporal cortex coexpressed both the proliferative cell marker, proliferating cell nuclear antigen and early neuronal marker, TuJ1, suggesting that they may be newly generated neurons. A subpopulation of Dcx-positive cells in the epileptic temporal cortex also coexpressed the mature neuronal marker, NeuN, suggesting that epilepsy may promote the generation of new neurons in the temporal cortex. This study has identified, for the first time, a novel population of Dcx-positive cells in the adult human temporal cortex that can be upregulated by epilepsy and thus, raises the possibility that these cells may have functional significance in the pathophysiology of epilepsy.

  12. Gene expression during testis development in Duroc boars.

    PubMed

    Lervik, S; Kristoffersen, A B; Conley, L N; Oskam, I C; Hedegaard, J; Ropstad, E; Olsaker, I

    2015-11-01

    Androstenone is a steroid pheromone occurring in the pubertal Leydig cells. Breeding against androstenone can decrease pheromone odour in swine meat but appears to cause unwanted side effects such as delayed onset of puberty. To study causality, global gene expression in developing boar testes at 12, 16, 20 and 27 weeks was investigated using a porcine cDNA microarray. The morphological status and androgenic levels of the same individuals have been described in a previous publication. In the present paper, expression of genes and pathways has been analysed with reference to these findings. Nine clusters of genes with significant differential expression over time and 49 functional charts were found in the analysed testis samples. Prominent pathways in the prepubertal testis were associated with tissue renewal, cell respiration and increased endocytocis. E-cadherines may be associated with the onset of pubertal development. With elevated steroidogenesis (weeks 16 to 27), there was an increase in the expression of genes in the MAPK pathway, STAR and its analogue STARD6. A pubertal shift in genes coding for cellular cholesterol transport was observed. Increased expression of meiotic pathways coincided with the morphological onset of puberty. Puberty-related change in Ca(2+) pathway transcripts, neurosteroids, neuronal changes and signalling in redox pathways suggested a developmental-specific period of neuromorphogenesis. Several growth factors were found to increase differentially over time as the testis matured. There may be interactions between MAPK, STAR and growth factors during specific periods. In conclusion, pathways for neurogenesis, morphological pathways and several transcripts for growth factors, which have known modulating effects on steroidogenesis and gonadotropins in humans and rodents, act at specific ages and developmental stages in the boar testis. The age dependency and complexity shown for development-specific testis transcripts must be considered

  13. Chronic Intake of Green Propolis Negatively Affecting the Rat Testis

    PubMed Central

    Severi-Aguiar, Grasiela Dias de Campos; Pinto, Suellen Josine; Capucho, Cristina; Oliveira, Camila Andrea; Diamante, Maria Aparecida; Barbieri, Renata; Predes, Fabrícia Souza; Dolder, Heidi

    2017-01-01

    Background: Human and animal evidence suggests that environmental toxicants may have an adverse impact on male reproductive health, reducing the population's reproductive output. Owing to the renewed attraction for natural products, some of them constitute effective alternatives to mitigate these effects. Propolis is a candidate for this use because of its intrinsic properties. In many situations, it improved the testicular damage and alleviated the toxic effects induced by environmental contaminant exposure. Objective: The aim of this study was to investigate possible alterations of testicular parameters and certify if its use is really advantageous to the testis, since this could affect rat reproductive function. Materials and Methods: Forty-eight adult male Wistar rats were divided into four groups (Co = control, T1 = 3 mg propolis/kg/day, T2 = 6 mg/kg/day, T3 = 10 mg/kg/day) and were exposed during 56 days. The testes were assessed with morphometrical, stereological, and ultrastructural analyses. Cell proliferation and death were diagnosed, respectively, by immunocytochemistry. Connexin 43 (Cx43) and N-cadherin transcript levels were determined by reverse transcription-polymerase chain reaction. Results: Increased cell proliferation and Leydig cell volume were observed in T2, and in contrast, Cx43 upregulation and cell death were observed in T3. Both T2 and T3 showed ultrastructural abnormalities in testicular parenchyma. Conclusion: We recommend a cautious intake of propolis to avoid deleterious effects. SUMMARY Chronic intake of Brazilian green propolis induced N.-cadherin downregulation and decreased on seminiferous tubule volumeIncrease on connexin 43 expression and cell death and decrease in Leydig cell.(LC) number/testis with the concentration of 10 mg/kg/day were observedIncrease on cell proliferation, cytoplasmic proportion, and volume of LC with the concentration of 6 mg/kg/day was detectedThe presence of empty spaces between spermatids and malformed

  14. Mouse xenograft modeling of human adult acute lymphoblastic leukemia provides mechanistic insights into adult LIC biology

    PubMed Central

    Dey, Aditi; Castleton, Anna Z.; Schwab, Claire; Samuel, Edward; Sivakumaran, Janani; Beaton, Brendan; Zareian, Nahid; Zhang, Christie Yu; Rai, Lena; Enver, Tariq; Moorman, Anthony V.; Fielding, Adele K.

    2014-01-01

    The distinct nature of acute lymphoblastic leukemia (ALL) in adults, evidenced by inferior treatment outcome and different genetic landscape, mandates specific studies of disease-initiating mechanisms. In this study, we used NOD/LtSz-scid IL2Rγ nullc (NSG) mouse xenotransplantation approaches to elucidate leukemia-initiating cell (LIC) biology in primary adult precursor B (pre-B) ALL to optimize disease modeling. In contrast with xenografting studies of pediatric ALL, we found that modification of the NSG host environment using preconditioning total body irradiation (TBI) was indispensable for efficient engraftment of adult non-t(4;11) pre-B ALL, whereas t(4;11) pre-B ALL was successfully reconstituted without this adaptation. Furthermore, TBI-based xenotransplantation of non-t(4;11) pre-B ALL enabled detection of a high frequency of LICs (<1:6900) and permitted frank leukemic engraftment from a remission sample containing drug-resistant minimal residual disease. Investigation of TBI-sensitive stromal-derived factor-1/chemokine receptor type 4 signaling revealed greater functional dependence of non-t(4;11) pre-B ALL on this niche-based interaction, providing a possible basis for the differential engraftment behavior. Thus, our studies establish the optimal conditions for experimental modeling of human adult pre-B ALL and demonstrate the critical protumorogenic role of microenvironment-derived SDF-1 in regulating adult pre-B LIC activity that may present a therapeutic opportunity. PMID:24825861

  15. Acquired undescended testis: putting the pieces together.

    PubMed

    Hack, W W M; Goede, J; van der Voort-Doedens, L M; Meijer, R W

    2012-02-01

    Acquired undescended testis is now a well-recognized disorder. It is seen in 1.5% of pre-pubertal boys and accounts for the 1-2% orchidopexy rate in older boys. Its pathogenesis remains largely unclear, but it may be caused by a fibrous remnant of the processus vaginalis. There is much controversy over its management, and the proper management awaits a randomized-controlled trial. Until now, follow-up data are available only for cases of spontaneous descent or pubertal orchidopexy. It is speculated that acquired undescended testis is in fact congenital and because of a short funiculus at birth, allowing a low-scrotal position early in life. However, as the boy grows, the testis might evolve into an undescended state. When testosterone surges at puberty, spontaneous descent occurs in three of every four cases. © 2011 The Authors. International Journal of Andrology © 2011 European Academy of Andrology.

  16. Calicivirus infection in human immunodeficiency virus seropositive children and adults.

    PubMed

    Rodríguez-Guillén, L; Vizzi, E; Alcalá, A C; Pujol, F H; Liprandi, F; Ludert, J E

    2005-06-01

    The importance of enteric viral infections in HIV-related diarrhea is uncertain. Human caliciviruses have emerged as a leading cause of acute diarrhea worldwide. To evaluate the importance of calicivirus infections in HIV-related diarrhea. Study design 151 fecal samples collected from children and adults infected with HIV, with and without diarrhea, were examined. In addition, 89 fecal samples from non HIV-infected children and adults were also tested. Samples were analyzed by RT-PCR using primer sets specific to Norovirus genogroup I or genogroup II as well as primers designed to react with both Noroviruses and Sapovirus genus. Viruses were detected with equal frequencies in stools from HIV infected and non-infected adults (12%). However, specimens from HIV infected children were more likely than those of HIV-negative children to have caliciviruses (51% versus 24%, P<0.05). Viral infections were not significantly associated with diarrhea neither in children nor in adults, regardless of HIV status. Viruses genetically related to the common Lordsdale virus (Norovirus genogroup II) and London/92 virus (Sapovirus) clusters were detected circulating among children. These results suggest that caliciviruses may be an important opportunistic pathogen in children infected with HIV.

  17. Covert spatial attention is functionally intact in amblyopic human adults

    PubMed Central

    Roberts, Mariel; Cymerman, Rachel; Smith, R. Theodore; Kiorpes, Lynne; Carrasco, Marisa

    2016-01-01

    Certain abnormalities in behavioral performance and neural signaling have been attributed to a deficit of visual attention in amblyopia, a neurodevelopmental disorder characterized by a diverse array of visual deficits following abnormal binocular childhood experience. Critically, most have inferred attention's role in their task without explicitly manipulating and measuring its effects against a baseline condition. Here, we directly investigate whether human amblyopic adults benefit from covert spatial attention—the selective processing of visual information in the absence of eye movements—to the same degree as neurotypical observers. We manipulated both involuntary (Experiment 1) and voluntary (Experiment 2) attention during an orientation discrimination task for which the effects of covert spatial attention have been well established in neurotypical and special populations. In both experiments, attention significantly improved accuracy and decreased reaction times to a similar extent (a) between the eyes of the amblyopic adults and (b) between the amblyopes and their age- and gender-matched controls. Moreover, deployment of voluntary attention away from the target location significantly impaired task performance (Experiment 2). The magnitudes of the involuntary and voluntary attention benefits did not correlate with amblyopic depth or severity. Both groups of observers showed canonical performance fields (better performance along the horizontal than vertical meridian and at the lower than upper vertical meridian) and similar effects of attention across locations. Despite their characteristic low-level vision impairments, covert spatial attention remains functionally intact in human amblyopic adults. PMID:28033433

  18. Covert spatial attention is functionally intact in amblyopic human adults.

    PubMed

    Roberts, Mariel; Cymerman, Rachel; Smith, R Theodore; Kiorpes, Lynne; Carrasco, Marisa

    2016-12-01

    Certain abnormalities in behavioral performance and neural signaling have been attributed to a deficit of visual attention in amblyopia, a neurodevelopmental disorder characterized by a diverse array of visual deficits following abnormal binocular childhood experience. Critically, most have inferred attention's role in their task without explicitly manipulating and measuring its effects against a baseline condition. Here, we directly investigate whether human amblyopic adults benefit from covert spatial attention-the selective processing of visual information in the absence of eye movements-to the same degree as neurotypical observers. We manipulated both involuntary (Experiment 1) and voluntary (Experiment 2) attention during an orientation discrimination task for which the effects of covert spatial attention have been well established in neurotypical and special populations. In both experiments, attention significantly improved accuracy and decreased reaction times to a similar extent (a) between the eyes of the amblyopic adults and (b) between the amblyopes and their age- and gender-matched controls. Moreover, deployment of voluntary attention away from the target location significantly impaired task performance (Experiment 2). The magnitudes of the involuntary and voluntary attention benefits did not correlate with amblyopic depth or severity. Both groups of observers showed canonical performance fields (better performance along the horizontal than vertical meridian and at the lower than upper vertical meridian) and similar effects of attention across locations. Despite their characteristic low-level vision impairments, covert spatial attention remains functionally intact in human amblyopic adults.

  19. The nutrition intervention improved adult human capital and economic productivity.

    PubMed

    Martorell, Reynaldo; Melgar, Paul; Maluccio, John A; Stein, Aryeh D; Rivera, Juan A

    2010-02-01

    This article reviews key findings about the long-term impact of a nutrition intervention carried out by the Institute of Nutrition of Central America and Panama from 1969 to 1977. Results from follow-up studies in 1988-89 and 2002-04 show substantial impact on adult human capital and economic productivity. The 1988-89 study showed that adult body size and work capacity increased for those provided improved nutrition through age 3 y, whereas the 2002-04 follow-up showed that schooling was increased for women and reading comprehension and intelligence increased in both men and women. Participants were 26-42 y of age at the time of the 2002-04 follow-up, facilitating the assessment of economic productivity. Wages of men increased by 46% in those provided with improved nutrition through age 2 y. Findings for cardiovascular disease risk factors were heterogeneous; however, they suggest that improved nutrition in early life is unlikely to increase cardiovascular disease risk later in life and may indeed lower risk. In conclusion, the substantial improvement in adult human capital and economic productivity resulting from the nutrition intervention provides a powerful argument for promoting improvements in nutrition in pregnant women and young children.

  20. Ascent of the testis: fact or fiction.

    PubMed

    Atwell, J D

    1985-08-01

    Ascent of the testis from the normal to an undescended position has been observed in 10 patients. In 9 of them there was a complete hernial sac and it is suggested that the acquired malposition of the testis is due to partial absorption of the processus vaginalis into the parietal peritoneum. Alteration in the length of the inguinal canal with growth may be an additional contributory factor. The mean interval between the original and subsequent observations was 5.2 years, leading to a late orchiopexy at a mean age of 9.4 years.

  1. Human-Animal Interaction and Older Adults: An Overview.

    PubMed

    Gee, Nancy R; Mueller, Megan K; Curl, Angela L

    2017-01-01

    Both pet ownership and animal-assisted therapy are becoming increasingly popular in the United States, and the science of human-animal interaction (HAI) seeks to explore how these relationships with animals can impact health and well-being. In particular, one burgeoning area of research is the role of HAI in healthy aging, given the potential for HAI as an important feature of health and well-being in older adults. The purpose of this review is to summarize and evaluate existing research in this innovative area of scholarship, identifying the potential benefits and risks of both pet ownership and animals in therapeutic settings for older adults. We will also identify recommendations for future research and applications in this developing area of scholarship.

  2. Tumor in undescended intrapelvic testis revealed by supraclavicular lymphadenopathy: a case report and literature review

    PubMed Central

    2013-01-01

    Background Testicular cancer is a rare disease. The incidence of testicular cancer in undescended testicles is of 3 to 48 times greater than in the general population. In the developed countries, the existence of undescended testicles in the adult population is rare, due to systematic practice of elective orchidopexy before the second year of life and orchiectomy in post adolescent males with undescended testicles. Despite these prevention measures, there are still some isolated cases of intra-abdominal testicular tumors in adults. We report a case of testicular cancer in cryptorchid testis revealed by supraclavicular lymphadenopathy. Case presentation We report a case of a 46 year old fertile man with a history of unilateral cryptorchidism who presented with a palpable left supraclavicular mass and absence of the right testicle. On investigations an intrapelvic testis tumor was diagnosed. Laparotomy and complete excision was carried out. The possible association between the undescended testis and cancer transformations is briefly discussed. Conclusion Testicular cancer in undescended testicles should not be ignored. Only early diagnosis and lower of testis in scrotumprevent such clinical forms. PMID:23622500

  3. Comparative Analysis of the Testis and Ovary Transcriptomes in Zebrafish by Combining Experimental and Computational Tools

    PubMed Central

    Li, Yang; Chia, Jer Ming; Bartfai, Richard; Christoffels, Alan; Yue, Gen Hua; Ding, Ke; Ho, Mei Yin; Hill, James A.

    2004-01-01

    Studies on the zebrafish model have contributed to our understanding of several important developmental processes, especially those that can be easily studied in the embryo. However, our knowledge on late events such as gonad differentiation in the zebrafish is still limited. Here we provide an analysis on the gene sets expressed in the adult zebrafish testis and ovary in an attempt to identify genes with potential role in (zebra)fish gonad development and function. We produced 10 533 expressed sequence tags (ESTs) from zebrafish testis or ovary and downloaded an additional 23 642 gonad-derived sequences from the zebrafish EST database. We clustered these sequences together with over 13 000 kidney-derived zebrafish ESTs to study partial transcriptomes for these three organs. We searched for genes with gonad-specific expression by screening macroarrays containing at least 2600 unique cDNA inserts with testis-, ovary- and kidney-derived cDNA probes. Clones hybridizing to only one of the two gonad probes were selected, and subsequently screened with computational tools to identify 72 genes with potentially testis-specific and 97 genes with potentially ovary-specific expression, respectively. PCR-amplification confirmed gonad-specificity for 21 of the 45 clones tested (all without known function). Our study, which involves over 47 000 EST sequences and specialized cDNA arrays, is the first analysis of adult organ transcriptomes of zebrafish at such a scale. The study of genes expressed in adult zebrafish testis and ovary will provide useful information on regulation of gene expression in teleost gonads and might also contribute to our understanding of the development and differentiation of reproductive organs in vertebrates. PMID:18629171

  4. CCM2 expression during prenatal development and adult human neocortex.

    PubMed

    Tanriover, Gamze; Sozen, Berna; Gunel, Murat; Demir, Necdet

    2011-08-01

    Cerebral cavernous malformation (CCM) is one of the most common types of vascular malformations of the central nervous system, affecting nearly one in 200 people. CCM lesions are characterized by grossly dilated vascular channels lined by a single layer of endothelium. Genetic linkage analyses have mapped three CCM loci to CCM1, CCM2 and CCM3. All three causative genes have now been identified allowing new insights into CCM pathophysiology. We focused on the CCM2 protein that might take place in blood vessel formation; we report here the expression patterns of CCM2 in prenatal development and adult human neocortex by means of immunohistochemistry and Western blot analysis. CCM2 was obviously detected in vascular endothelium and neuroglial precursor cells during development and also observed in arterial endothelium, neurons, some of the glial cells in adult neocortex. The expression patterns suggest that it could be one of the arterial markers whether this is a cause or a consequence of an altered vascular identity. CCM2 might play a role during vasculogenesis and angiogenesis during human brain development. Furthermore, with this study, CCM2 have been described for the first time in developing human neocortex.

  5. Molecular basis of lactase levels in adult humans.

    PubMed Central

    Escher, J C; de Koning, N D; van Engen, C G; Arora, S; Büller, H A; Montgomery, R K; Grand, R J

    1992-01-01

    The molecular basis of adult human "lactase deficiency" has long been a subject of controversy. To address this issue, small intestinal biopsies from orienta, black, and white patients were analyzed. Adjacent samples were assayed for lactase and sucrase specific activities and the sucrase/lactase ratio (high ratio signifies lactase deficiency), and the results were compared to lactase steady-state mRNA levels detected in Northern blots probed with a human lactase mDNA. All oriental patients had high ratios and no detectable lactase mRNA. Four black patients had a similar pattern; two with low ratios had detectable mRNA. The group of white patients displayed a range of findings, from high ratio/no mRNA to low ratio/considerable mRNA. Elevated levels of lactase mRNA always correlated with the presence of elevated levels of lactase enzyme activity, suggesting that the difference in levels of adult human intestinal lactase activity among racial groups may be regulated at the level of gene transcription. Images PMID:1737837

  6. Morphology of rat testis preserved in three different fixatives.

    PubMed

    Tu, Lihui; Yu, Lili; Zhang, Huiping

    2011-04-01

    Histopathological examination of testes is important in assessing spermatogenesis and testicular function. Modified Davidson's fluid (mDF) has been proposed as a superior substitute for Bouin's fluid (BF) for fixation of adult animal testes. Besides, 4% paraformaldehyde (PFA) has been commonly used to fix testes with convenience. We compared the morphology of the rat testis fixed in 4% PFA, mDF, or BF using hematoxylin and eosin (HE)-stained sections. Fixation in 4% PFA resulted in obvious tissue shrinkage artifacts, especially between seminiferous epithelium cells. Shrinkage artifacts were also observed in the central area of the testes fixed in BF. Use of mDF did not cause shrinkage artifacts between seminiferous tubules, though a small amount can be observed in seminiferous tubules between germ cells. Clarity of nuclear detail in testes fixed in mDF and BF is better compared to 4% PFA. Our study demonstrated that fixation in mDF provided better morphologic details in the rat testis as compared with 4% PFA and BF.

  7. Isolation and Characterization of Pluripotent Human Spermatogonial Stem Cell-Derived Cells

    PubMed Central

    Kossack, Nina; Meneses, Juanito; Shefi, Shai; Nguyen, Ha Nam; Chavez, Shawn; Nicholas, Cory; Gromoll, Joerg; Turek, Paul J; Reijo-Pera, Renee A

    2009-01-01

    Several reports have documented the derivation of pluripotent cells (multipotent germline stem cells) from spermatogonial stem cells obtained from the adult mouse testis. These spermatogonia-derived stem cells express embryonic stem cell markers and differentiate to the three primary germ layers, as well as the germline. Data indicate that derivation may involve reprogramming of endogenous spermatogonia in culture. Here, we report the derivation of human multipotent germline stem cells (hMGSCs) from a testis biopsy. The cells express distinct markers of pluripotency, form embryoid bodies that contain derivatives of all three germ layers, maintain a normal XY karyotype, are hypomethylated at the H19 locus, and express high levels of telomerase. Teratoma assays indicate the presence of human cells 8 weeks post-transplantation but limited teratoma formation. Thus, these data suggest the potential to derive pluripotent cells from human testis biopsies but indicate a need for novel strategies to optimize hMGSC culture conditions and reprogramming. PMID:18927477

  8. Transgenic characterization of two testis-specific promoters in the silkworm, Bombyx mori.

    PubMed

    Xu, J; Bi, H; Chen, R; Aslam, A F M; Li, Z; Ling, L; Zeng, B; Huang, Y; Tan, A

    2015-04-01

    Sex-specific regulatory elements are key components for developing insect genetic sexing systems. The current insect genetic sexing system mainly uses a female-specific modification system whereas little success was reported on male-specific genetic modification. In the silkworm Bombyx mori, a lepidopteran model insect with economic importance, a transgene-based, female-specific lethality system has been established based on sex-specific alternative splicing factors and a female-specific promoter BmVgp (vitellogenin promoter) has been identified. However, no male-specific regulatory elements have yet been identified. Here we report the transgenic identification of two promoters that drive reporter gene expression in a testis-specific manner in B. mori. Putative promoter sequences from the B. mori Radial spoke head 1 gene (BmR1) and beta-tubulin 4 gene (Bmβ4) were introduced using piggybac-based germline transformation. In transgenic silkworms, expression of the reporter gene enhanced green fluorescent protein (EGFP) directed by either BmR1 promoter (BmR1p) or Bmβ4p showed precisely testis-specific manners from the larval to adult stage. Furthermore, EGFP expression of these two transgenic lines showed different localization in the testis, indicating that BmR1p or Bmβ4p might be used as distinct regulatory elements in directing testis-specific gene expression. Identification of these testis-specific promoters not only contributes to a better understanding of testis-specific gene function in insects, but also has potential applications in sterile insect techniques for pest management.

  9. Free radicals in adolescent varicocele testis.

    PubMed

    Romeo, Carmelo; Santoro, Giuseppe

    2014-01-01

    We examine the relationship between the structure and function of the testis and the oxidative and nitrosative stress, determined by an excessive production of free radicals and/or decreased availability of antioxidant defenses, which occur in the testis of adolescents affected by varicocele. Moreover, the effects of surgical treatment on oxidative stress were provided. We conducted a PubMed and Medline search between 1980 and 2014 using "adolescent," "varicocele," "free radicals," "oxidative and nitrosative stress," "testis," and "seminiferous tubules" as keywords. Cross-references were checked in each of the studies, and relevant articles were retrieved. We conclude that increased concentration of free radicals, generated by conditions of hypoxia, hyperthermia, and hormonal dysfunction observed in adolescent affected by varicocele, can harm germ cells directly or indirectly by influencing nonspermatogenic cells and basal lamina. With regard to few available data in current literature, further clinical trials on the pre- and postoperative ROS and RNS levels together with morphological studies of the cellular component of the testis are fundamental for complete comprehension of the role played by free radicals in the pathogenesis of adolescent varicocele and could justify its pharmacological treatment with antioxidants.

  10. Free Radicals in Adolescent Varicocele Testis

    PubMed Central

    Romeo, Carmelo; Santoro, Giuseppe

    2014-01-01

    We examine the relationship between the structure and function of the testis and the oxidative and nitrosative stress, determined by an excessive production of free radicals and/or decreased availability of antioxidant defenses, which occur in the testis of adolescents affected by varicocele. Moreover, the effects of surgical treatment on oxidative stress were provided. We conducted a PubMed and Medline search between 1980 and 2014 using “adolescent,” “varicocele,” “free radicals,” “oxidative and nitrosative stress,” “testis,” and “seminiferous tubules” as keywords. Cross-references were checked in each of the studies, and relevant articles were retrieved. We conclude that increased concentration of free radicals, generated by conditions of hypoxia, hyperthermia, and hormonal dysfunction observed in adolescent affected by varicocele, can harm germ cells directly or indirectly by influencing nonspermatogenic cells and basal lamina. With regard to few available data in current literature, further clinical trials on the pre- and postoperative ROS and RNS levels together with morphological studies of the cellular component of the testis are fundamental for complete comprehension of the role played by free radicals in the pathogenesis of adolescent varicocele and could justify its pharmacological treatment with antioxidants. PMID:25580183

  11. Eye contact elicits bodily self-awareness in human adults.

    PubMed

    Baltazar, Matias; Hazem, Nesrine; Vilarem, Emma; Beaucousin, Virginie; Picq, Jean-Luc; Conty, Laurence

    2014-10-01

    Eye contact is a typical human behaviour known to impact concurrent or subsequent cognitive processing. In particular, it has been suggested that eye contact induces self-awareness, though this has never been formally proven. Here, we show that the perception of a face with a direct gaze (that establishes eye contact), as compared to either a face with averted gaze or a mere fixation cross, led adult participants to rate more accurately the intensity of their physiological reactions induced by emotional pictures. Our data support the view that bodily self-awareness becomes more acute when one is subjected to another's gaze. Importantly, this effect was not related to a particular arousal state induced by eye contact perception. Rejecting the arousal hypothesis, we suggest that eye contact elicits a self-awareness process by enhancing self-focused attention in humans. We further discuss the implications of this proposal. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Ontogeny of morningness-eveningness across the adult human lifespan

    NASA Astrophysics Data System (ADS)

    Randler, Christoph

    2016-02-01

    Sleep timing of humans can be classified alongside a continuum from early to late sleepers, with some people (larks) having an early activity, early bed, and rise times and others (owls) with a more nocturnally orientated activity. Only a few studies reported that morningness-eveningness changes significantly during the adult lifespan based on community samples. Here, I applied a different methodological approach to seek for evidence for the age-related changes in morningness-eveningness preferences by using a meta-data from all available studies. The new aspect of this cross-sectional approach is that only a few studies themselves address the age-related changes of the adult lifespan development, but that many studies are available that provide exactly the data needed. The studies came from 27 countries and included 36,939 participants. Age was highly significantly correlated with scores on the Composite Scale of Morningness ( r = 0.70). This relationship seems linear, because a linear regression explained nearly the same amount of variance compared to other models such as logarithmic, quadratic, or cubic models. The standard deviation of age correlated with the standard deviation of CSM scores ( r = 0.55), suggesting when there is much variance in age in a study; in turn, there is much variance in morningness. This meta-analytical approach shows that morningness-eveningness changes across the adult lifespan and that older age is related to higher morningness.

  13. Microvascular pressure distribution in the hamster testis.

    PubMed

    Sweeney, T E; Rozum, J S; Desjardins, C; Gore, R W

    1991-05-01

    Convective transport is a critical element in the regulation of steroidogenesis and spermatogenesis in the testis. Steroid hormones are distributed to their target cells within seminiferous tubules via interstitial fluid. The movement of interstitial fluid and lymph, which transports protein hormones and many of the substrates required for spermatogenesis and steroidogenesis, is driven by capillary filtration. Despite the importance of convective transport in testicular function, however, the mechanisms regulating transvascular exchange in the testis are unknown. As a first step in understanding this process, we measured directly the microvascular hydrostatic pressure distribution in the hamster testis (pentobarbital sodium, 70 mg/kg ip). Using a servo-null transducer, intravascular pressure was measured in all vessel types accessible beneath the surface of the testis of 19 animals. Systemic arterial pressure averaged 89 +/- 2 (SE) mmHg. The most significant observations were that mean capillary pressure was extremely low (10.1 +/- 0.8 mmHg) and remarkably constant (range 8.2-13.3 mmHg), despite a 45 mmHg range in systemic mean arterial pressure among the animals observed. The maintenance of a low hydrostatic pressure in testicular capillaries may serve to sustain fluid filtration at a rate that prevents washout of essential solutes while preserving convective transport. Unfortunately, the anatomical and functional characteristics that determine this unique microvascular environment may also expose the testis to significant pathological risks. For example, the large pre- to postcapillary resistance ratio observed suggests that testicular capillaries must be highly susceptible to increases in venous pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Torsion of a Large Appendix Testis Misdiagnosed as Pyocele

    PubMed Central

    Meher, Susanta; Rath, Satyajit; Sharma, Rakesh; Sasmal, Prakash Kumar; Mishra, Tushar Subhadarshan

    2015-01-01

    Torsion of the appendix testis is not an uncommon cause of acute hemiscrotum. It is frequently misdiagnosed as acute epididymitis, orchitis, or torsion of testis. Though conservative management is the treatment of choice for this condition, prompt surgical intervention is warranted when testicular torsion is suspected. We report a case of torsion of a large appendix testis misdiagnosed as pyocele. Emergency exploration of it revealed a large appendix testis with torsion and early features of gangrene. After excision of the appendix testis, the wound was closed with an open drain. The patient had an uneventful and smooth postoperative recovery. PMID:25861514

  15. Molecular cloning of a novel nuclear factor, TDRP1, in spermatogenic cells of testis and its relationship with spermatogenesis

    SciTech Connect

    Wang, Xuanchun; Jiang, Haowen; Zhou, Wenbai; Zhang, Zhaoyun; Yang, Zhihong; Lu, Yong; Lu, Bin; Wang, Xiang; Ding, Qiang; Hu, Renming

    2010-03-26

    We reported the identification of a novel gene termed TDRP (encoding testis development-related protein) that might be involved in spermatogenesis. The human TDRP gene had two distinct transcripts, TDRP1 and TDRP2, which encoded proteins of 183 aa and 198 aa respectively. Tdrp mRNA was predominantly expressed in testis tissue. We generated rabbit polyclonal antibodies specific against human TDRP1. Immunohistochemistry analysis showed TDRP1 was expressed in spermatogenic cells, especially with high expression in spermatocytes. We provided evidence that TDRP1 distributed in both cytoplasm and nuclei of spermatogenic cells. Expression patterns of Tdrp1 mRNA and its protein were investigated in the rat testis tissues of different developmental stages. Both Tdrp1 mRNA and its protein were barely detected in the testis of neonatal rats, increased remarkably at 3 weeks postpartum, and peaked at 2 months postpartum. We also investigated TDRP1 expressions in testis tissues of azoospermic men with defective spermatogenesis. Western blot analysis showed that TDRP1 expressions were significantly lower in the testis tissues of azoospermic men compared with normal controls. These current data demonstrated that as a nuclear factor, TDRP1 might play an important role in spermatogenesis.

  16. Human Handling Promotes Compliant Behavior in Adult Laboratory Rabbits

    PubMed Central

    Swennes, Alton G; Alworth, Leanne C; Harvey, Stephen B; Jones, Carolyn A; King, Christopher S; Crowell-Davis, Sharon L

    2011-01-01

    Routine laboratory procedures can be stressful for laboratory animals. We wanted to determine whether human handling of adult rabbits could induce a degree of habituation, reducing stress and facilitating research-related manipulation. To this end, adult New Zealand white rabbits were handled either frequently or minimally. After being handled over 3 wk, these rabbits were evaluated by novel personnel and compared with minimally handled controls. Evaluators subjectively scored the rabbits for their relative compliance or resistance to being scruffed and removed from their cages, being transported to a treatment room, and their behavior at all stages of the exercise. Upon evaluation, handled rabbits scored significantly more compliant than nontreated controls. During evaluation, behaviors that the rabbits displayed when they were approached in their cages and while being handled outside their cages were recorded and compared between study groups. Handled rabbits displayed behavior consistent with a reduction in human-directed fear. This study illustrates the potential for handling to improve compliance in laboratory procedures and reduce fear-related behavior in laboratory rabbits. Such handling could be used to improve rabbit welfare through the reduction of stress and exposure to novel stimuli. PMID:21333162

  17. Human handling promotes compliant behavior in adult laboratory rabbits.

    PubMed

    Swennes, Alton G; Alworth, Leanne C; Harvey, Stephen B; Jones, Carolyn A; King, Christopher S; Crowell-Davis, Sharon L

    2011-01-01

    Routine laboratory procedures can be stressful for laboratory animals. We wanted to determine whether human handling of adult rabbits could induce a degree of habituation, reducing stress and facilitating research-related manipulation. To this end, adult New Zealand white rabbits were handled either frequently or minimally. After being handled over 3 wk, these rabbits were evaluated by novel personnel and compared with minimally handled controls. Evaluators subjectively scored the rabbits for their relative compliance or resistance to being scruffed and removed from their cages, being transported to a treatment room, and their behavior at all stages of the exercise. Upon evaluation, handled rabbits scored significantly more compliant than nontreated controls. During evaluation, behaviors that the rabbits displayed when they were approached in their cages and while being handled outside their cages were recorded and compared between study groups. Handled rabbits displayed behavior consistent with a reduction in human-directed fear. This study illustrates the potential for handling to improve compliance in laboratory procedures and reduce fear-related behavior in laboratory rabbits. Such handling could be used to improve rabbit welfare through the reduction of stress and exposure to novel stimuli.

  18. Laminin chains in developing and adult human myotendinous junctions.

    PubMed

    Pedrosa-Domellöf, F; Tiger, C F; Virtanen, I; Thornell, L E; Gullberg, D

    2000-02-01

    In addition to being the specialized site for transmission of force from the muscle to the tendon, the myotendinous junction (MTJ) also plays an important role in muscle splitting during morphogenesis. An early event in the formation of the MTJ is a regional deposition of basement membranes. We used immunocytochemistry to investigate the distribution of laminin chains during the development of MTJs in human limb muscle at 8-22 weeks of gestation (wg) and in adult MTJs. We used polyclonal antibodies and a new monoclonal antibody (MAb) against the human laminin alpha1 G4/G5 domains. At 8-10 wg, laminin alpha1 and laminin alpha5 chains were specifically localized to the MTJ. Laminin alpha1 chain remained restricted to the MTJ at 22 wg as the laminin beta2 chain had appeared, whereas the laminin alpha5 chain became deposited along the entire length of the myotubes from 12 wg. In the adult MTJ, only vestigial amounts of laminin alpha1 and laminin alpha5 chains could be detected. On the basis of co-distribution data, we speculate that laminin alpha1 chain in the forming MTJ undergoes an isoform switch from laminin 1 to laminin 3. Our data indicate a potentially important role for laminin alpha1 chain in skeletal muscle formation. (J Histochem Cytochem 48:201-209, 2000)

  19. Comprehensive comparison of neonate and adult human platelet transcriptomes

    PubMed Central

    Caparrós-Pérez, Eva; López-Andreo, Mª José; Llanos, Mª Carmen; Rivera, José; Palma-Barqueros, Verónica; Blanco, Jose E.; Vicente, Vicente; Martínez, Constantino; Ferrer-Marín, Francisca

    2017-01-01

    Understanding the underlying mechanisms of the well-substantiated platelet hyporeactivity in neonates is of interest given their implications for the clinical management of newborns, a population at higher bleeding risk than adults (especially sick and preterm infants), as well as for gaining insight into the regulatory mechanisms of platelet biology. Transcriptome analysis is useful in identifying mRNA signatures affecting platelet function. However, human fetal/neonatal platelet transcriptome analysis has never before been reported. We have used mRNA expression array for the first time to compare platelet transcriptome changes during development. Microarray analysis was performed in pure platelet RNA obtained from adult and cord blood, using the same platform in two independent laboratories. A high correlation was obtained between array results for both adult and neonate platelet samples. There was also good agreement between results in our adult samples and outcomes previously reported in three different studies. Gene enrichment analysis showed that immunity- and platelet function-related genes are highly expressed at both developmental stages. Remarkably, 201 genes were found to be differentially expressed throughout development. In particular, neonatal platelets contain higher levels of mRNA that are associated with protein synthesis and processing, while carrying significantly lower levels of genes involved in calcium transport/metabolism and cell signaling (including GNAZ). Overall, our results point to variations in platelet transcriptome as possibly underlining the hypo-functional phenotype of neonatal platelets and provide further support for the role of platelets in cellular immune response. Better characterization of the platelet transcriptome throughout development can contribute to elucidate how transcriptome changes impact different pathological conditions. PMID:28813466

  20. Angiotensin converting enzyme in the testis and epididymis of mammals.

    PubMed

    Jaiswal, A; Joshi, P; Kumar, M V; Panda, J N; Singh, L N

    1984-01-01

    Angiotensin converting enzyme (ACE) activity has been reported in testis and epididymis of seven different animal species. Among all the species, the mouse testis and epididymis showed the highest converting enzyme activity followed by rat testis and epididymis. The lowest activity was detected in buffalo testis and rabbit epididymis. Most of the testicular enzyme was found concentrated in the 107,00 X g sediment while the epididymal enzyme was equally distributed between sediment and supernatant. ACE levels of different regions of the rat testis and epididymis was analyzed. The gradient of ACE was found increasing from caput to cauda. A major fraction of testicular and epididymal ACE activity was found in their respective fluid. ACE appeared only in mature rats, rabbits and mice testis and epididymis. Sexually stimulated rabbits showed significant ACE increase in the testis. In vitro characterization studies were conducted.

  1. Distribution of Tight Junction Proteins in Adult Human Salivary Glands

    PubMed Central

    Maria, Ola M.; Kim, Jung-Wan Martin; Gerstenhaber, Jonathan A.; Baum, Bruce J.; Tran, Simon D.

    2008-01-01

    Tight junctions (TJs) are an essential structure of fluid-secreting cells, such as those in salivary glands. Three major families of integral membrane proteins have been identified as components of the TJ: claudins, occludin, and junctional adhesion molecules (JAMs), plus the cytosolic protein zonula occludens (ZO). We have been working to develop an orally implantable artificial salivary gland that would be suitable for treating patients lacking salivary parenchymal tissue. To date, little is known about the distribution of TJ proteins in adult human salivary cells and thus what key molecular components might be desirable for the cellular component of an artificial salivary gland device. Therefore, the aim of this study was to determine the distribution of TJ proteins in human salivary glands. Salivary gland samples were obtained from 10 patients. Frozen and formalin-fixed paraffin-embedded sections were stained using IHC methods. Claudin-1 was expressed in ductal, endothelial, and ∼25% of serous cells. Claudins-2, -3, and -4 and JAM-A were expressed in both ductal and acinar cells, whereas claudin-5 was expressed only in endothelial cells. Occludin and ZO-1 were expressed in acinar, ductal, and endothelial cells. These results provide new information on TJ proteins in two major human salivary glands and should serve as a reference for future studies to assess the presence of appropriate TJ proteins in a tissue-engineered human salivary gland. (J Histochem Cytochem 56:1093–1098, 2008) PMID:18765838

  2. Localization of S-100 proteins in the testis and epididymis of poultry and rabbits

    PubMed Central

    Abd-Elmaksoud, Ahmed; Marei, Hany E. S.

    2014-01-01

    The present investigation was conducted to demonstrate S-100 protein in the testis and epididymis of adult chickens, Sudani ducks, pigeons, and rabbits. This study may represent the first indication for the presence of S-100 in the male reproductive organs of these species and might therefore serve as a milestone for further reports. In the testis of chickens, pigeons and rabbits, intense S-100 was seen in Sertoli cells. S-100 was also seen in the endothelial lining of blood vessels in rabbit testis. On the contrary, no S-100 reaction was detected in the Sertoli cells of Sudani ducks. In epididymis, the localization of S-100 had varied according to species studied; it was seen in the basal cells (BC) of epididymal duct in duck, non-ciliated cells of the distal efferent ductules in pigeons and ciliated cells of the efferent ductules and BC of rabbit epididymis. Conversely, S-100 specific staining was not detected in the epithelial lining of the rooster and pigeon epididymal duct as well as the principal cells of the rabbit epididymis. In conclusion, the distribution of the S-100 proteins in the testis and epididymis might point out to its roles in the male reproduction. PMID:25276477

  3. Neuropeptide Y in the adult and fetal human pineal gland.

    PubMed

    Møller, Morten; Phansuwan-Pujito, Pansiri; Badiu, Corin

    2014-01-01

    Neuropeptide Y was isolated from the porcine brain in 1982 and shown to be colocalized with noradrenaline in sympathetic nerve terminals. The peptide has been demonstrated to be present in sympathetic nerve fibers innervating the pineal gland in many mammalian species. In this investigation, we show by use of immunohistochemistry that neuropeptide Y is present in nerve fibers of the adult human pineal gland. The fibers are classical neuropeptidergic fibers endowed with large boutons en passage and primarily located in a perifollicular position with some fibers entering the pineal parenchyma inside the follicle. The distance from the immunoreactive terminals to the pinealocytes indicates a modulatory function of neuropeptide Y for pineal physiology. Some of the immunoreactive fibers might originate from neurons located in the brain and be a part of the central innervation of the pineal gland. In a series of human fetuses, neuropeptide Y-containing nerve fibers was present and could be detected as early as in the pineal of four- to five-month-old fetuses. This early innervation of the human pineal is different from most rodents, where the innervation starts postnatally.

  4. Congenital Erythropoietic Porphyria with Undescended Testis

    PubMed Central

    Arora, Sandeep; Harith, Arun Kumar; Sodhi, Neha

    2016-01-01

    Hereditary porphyrias are a group of metabolic disorders of heme biosynthesis pathway that are characterized by acute neurovisceral symptoms, skin lesions, or both. Congenital erythropoietic porphyria (CEP) is an extremely rare disease with a mutation in the gene that codes for uroporphyrinogen III synthase leading to accumulation of porphyrin in different tissues and marked cutaneous photosensitivity. We report a case of CEP with infancy onset blistering, photosensitivity, red colored urine, and teeth along with scarring. Examination revealed an undescended testis of the left side. Mutation analysis revealed mutation in the uroporphyrinogen III synthase gene (UROS) resulting in c. 56 A > G (Tyr19Cys). The presence of undescended testis with a rare mutation in a case of CEP which itself is an extremely rare condition make the case interesting. PMID:27512208

  5. Congenital Erythropoietic Porphyria with Undescended Testis.

    PubMed

    Arora, Sandeep; Harith, Arun Kumar; Sodhi, Neha

    2016-01-01

    Hereditary porphyrias are a group of metabolic disorders of heme biosynthesis pathway that are characterized by acute neurovisceral symptoms, skin lesions, or both. Congenital erythropoietic porphyria (CEP) is an extremely rare disease with a mutation in the gene that codes for uroporphyrinogen III synthase leading to accumulation of porphyrin in different tissues and marked cutaneous photosensitivity. We report a case of CEP with infancy onset blistering, photosensitivity, red colored urine, and teeth along with scarring. Examination revealed an undescended testis of the left side. Mutation analysis revealed mutation in the uroporphyrinogen III synthase gene (UROS) resulting in c. 56 A > G (Tyr19Cys). The presence of undescended testis with a rare mutation in a case of CEP which itself is an extremely rare condition make the case interesting.

  6. Identification of sperm mRNA biomarkers associated with testis injury during preclinical testing of pharmaceutical compounds.

    PubMed

    Dere, Edward; Spade, Daniel J; Hall, Susan J; Altemus, Aimee; Smith, James D; Phillips, Jonathan A; Moffit, Jeffrey S; Blanchard, Kerry T; Boekelheide, Kim

    2017-04-01

    The human testis is sensitive to toxicant-induced injury but current methods for detecting adverse effects are limited, insensitive and unreliable. Animal studies use sensitive histopathological endpoints to assess toxicity, but require testicular tissue that is not available during human clinical trials. More sensitive and reliable molecular biomarkers of testicular injury are needed to better monitor testicular toxicity in both clinical and preclinical. Adult male Wistar Han rats were exposed for 4weeks to compounds previously associated with testicular injury, including cisplatin (0, 0.2, 0.3, or 0.4mg/kg/day), BI665915 (0, 20, 70, 100mg/kg/d), BI665636 (0, 20, 100mg/kg/d) or BI163538 (0, 70, 150, 300mg/kg/d) to evaluate reproductive toxicity and assess changes in sperm mRNA levels. None of the compounds resulted in any significant changes in body, testis or epididymis weights, nor were there decreases in testicular homogenization resistant spermatid head counts. Histopathological evaluation found that only BI665915 treatment caused any testicular effects, including minor germ cell loss and disorganization of the seminiferous tubule epithelium, and an increase in the number of retained spermatid heads. A custom PCR-array panel was used to assess induced changes in sperm mRNA. BI665915 treatment resulted in a significant increase in clusterin (Clu) levels and decreases in GTPase, IMAP family member 4 (Gimap4), prostaglandin D2 synthase (Ptgds) and transmembrane protein with EGF like and two follistatin like domains 1 (Tmeff1) levels. Correlation analysis between transcript levels and quantitative histopathological endpoints found a modest association between Clu with retained spermatid heads. These results demonstrate that sperm mRNA levels are sensitive molecular indicators of testicular injury that can potentially be translated into a clinical setting.

  7. Phantom testis syndrome: prevalence, phenomenology and putative mechanisms.

    PubMed

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

    2010-02-01

    Chronic phantom pain has been found in up to 78% of limb amputees and is a major complication of limb amputation. Less is known about phantom phenomena after the amputation of other, i.e. visceral, parts of the body. In a retrospective design, we identified 539 patients in whom one testis was removed between 1995 and 2005. The operative technique was a unilateral standard radical inguinal orchiectomy. The underlying pathology in all cases was a testicular germ cell tumour. All patients received a detailed questionnaire asking about the occurrence of phantom testis pain (pain felt in the removed testis), phantom testis sensations (non-painful sensations as if the removed testis was still intact) and hallucinations (illusionary perceptions on the removed testis). Furthermore, we asked about the occurrence and clinical presentation of pain before and after surgery and about pre-operative testicular pain. Out of 238 respondents, 125 patients (53%) reported any kind of phantom experience. The prevalence of phantom testis pain was 25% (60/238), non-painful phantom sensations 16% (37/238) and male gonad hallucinations 12% (28/238). Patients with phantom symptoms reported pre-operative pain in the removed testis more often than patients without phantom symptoms. This study presents first data on the clinical characteristics and possible mechanisms of the phantom testis syndrome after surgical removal of one testis.

  8. Benign Testis Mass After Viral Infection.

    PubMed

    Hurtt, Robbie; Pound, Charles; Bean, Christopher

    2017-05-01

    We present two cases of viral associated orchitis and subsequent testis masses concerning for malignancy both on physical exam and scrotal ultrasound. In both cases, the patients underwent radical orchiectomy after a discussion of management options. Both pathologic analyses were negative for malignancy, and our literature search revealed no other similar case reports. We review our two cases specifically, as well as briefly review orchitis and discuss possible management strategies of similar cases.

  9. Bilateral synchronous plasmacytoma of the testis

    PubMed Central

    Joseph, Rona; Soman, Lali V.

    2016-01-01

    Extramedullary plasmacytoma (EMP) is usually seen in the head and neck regions and in the upper respiratory, gastrointestinal, and central nervous systems. Testis is a rare site for EMP, and bilateral synchronous testicular plasmacytoma occurring as an isolated event at initial presentation has been reported only once previously. We present herein the second such report in a 70-year-old man who underwent bilateral orchidectomy. PMID:27034568

  10. Sex Determination of Adult Human Maxillary Sinuses on Panoramic Radiographs

    PubMed Central

    Leao de Queiroz, Cristhiane; Terada, Andrea Sayuri Silveira Dias; Dezem, Thais Uenoyama; Gomes de Araújo, Lais; Galo, Rodrigo; Oliveira-Santos, Christiano

    2016-01-01

    Absract The purpose of this study was to evaluate dimensions of adult human maxillary sinuses on panoramic radiographs and their possible application on the sex determination for forensic purposes. The sample comprised 64 database panoramic radiographs from individuals aged 20 years or older (32 male and 32 female subjects), with complete permanent dentition (or absence of third molars). One examiner measured the width and height of the right and left maxillary sinuses using the software Image J 1.47v (National Institutes of Health, Bethesda, USA). Measurements were repeated to calculate intra-observer agreement. Chi-Square test, Kappa, ANOVA and T-Student were used for results analysis for p≤ 0.05. Intra-observer agreement with correlation Kappa ranged between 0.38 and 0.96. For female subjects, the mean height and width of the left maxillary sinus were 28.7856mm and 44.6178mm, respectively. And right maxillary sinus was 27.7163mm for height and 45.1850mm for width. Male subjects were found to have the mean height and width of the left maxillary sinus 30.9981mm and 48.7753mm, respectively. And right maxillary sinus was 30.7403mm for height and 48.5753mm for width. There was a statistically significant difference in the height and width of maxillary sinuses between males and females. It can be concluded that maxillary sinuses height and width on panoramic radiographs can be used to determine the gender of adult human subjects. PMID:27847394

  11. The adult human pubic symphysis: a systematic review

    PubMed Central

    Becker, Ines; Woodley, Stephanie J; Stringer, Mark D

    2010-01-01

    The pubic symphysis is a unique joint consisting of a fibrocartilaginous disc sandwiched between the articular surfaces of the pubic bones. It resists tensile, shearing and compressive forces and is capable of a small amount of movement under physiological conditions in most adults (up to 2 mm shift and 1° rotation). During pregnancy, circulating hormones such as relaxin induce resorption of the symphyseal margins and structural changes in the fibrocartilaginous disc, increasing symphyseal width and mobility. This systematic review of the English, German and French literature focuses on the normal anatomy of the adult human pubic symphysis. Although scientific studies of the joint have yielded useful descriptive data, comparison of results is hampered by imprecise methodology and/or poorly controlled studies. Several aspects of the anatomy of the pubic symphysis remain unknown or unclear: the precise attachments of surrounding ligaments and muscles; the arrangement of connective tissue fibres within the interpubic disc and the origin, structure and function of its associated interpubic cleft; the biomechanical consequences of sexual dimorphism; potential ethnic variations in morphology; and its precise innervation and blood supply. These deficiencies hinder our understanding of the normal form and function of the joint, which is particularly relevant when attempting to understand the mechanisms underlying pregnancy-related pubic symphyseal pain, a neglected and relatively common cause of pubic pain. A better understanding of the normal anatomy of the human pubic symphysis should improve our understanding of such problems and contribute to better treatments for patients suffering from symphyseal pain and dysfunction. PMID:20840351

  12. Sex Determination of Adult Human Maxillary Sinuses on Panoramic Radiographs.

    PubMed

    Leao de Queiroz, Cristhiane; Terada, Andrea Sayuri Silveira Dias; Dezem, Thais Uenoyama; Gomes de Araújo, Lais; Galo, Rodrigo; Oliveira-Santos, Christiano; Alves da Silva, Ricardo Henrique

    2016-09-01

    The purpose of this study was to evaluate dimensions of adult human maxillary sinuses on panoramic radiographs and their possible application on the sex determination for forensic purposes. The sample comprised 64 database panoramic radiographs from individuals aged 20 years or older (32 male and 32 female subjects), with complete permanent dentition (or absence of third molars). One examiner measured the width and height of the right and left maxillary sinuses using the software Image J 1.47v (National Institutes of Health, Bethesda, USA). Measurements were repeated to calculate intra-observer agreement. Chi-Square test, Kappa, ANOVA and T-Student were used for results analysis for p≤ 0.05. Intra-observer agreement with correlation Kappa ranged between 0.38 and 0.96. For female subjects, the mean height and width of the left maxillary sinus were 28.7856mm and 44.6178mm, respectively. And right maxillary sinus was 27.7163mm for height and 45.1850mm for width. Male subjects were found to have the mean height and width of the left maxillary sinus 30.9981mm and 48.7753mm, respectively. And right maxillary sinus was 30.7403mm for height and 48.5753mm for width. There was a statistically significant difference in the height and width of maxillary sinuses between males and females. It can be concluded that maxillary sinuses height and width on panoramic radiographs can be used to determine the gender of adult human subjects.

  13. Thyroid Hormone Function in the Rat Testis

    PubMed Central

    Gao, Ying; Lee, Will M.; Cheng, C. Yan

    2014-01-01

    Thyroid hormones are emerging regulators of testicular function since Sertoli, germ, and Leydig cells are found to express thyroid hormone receptors (TRs). These testicular cells also express deiodinases, which are capable of converting the pro-hormone T4 to the active thyroid hormone T3, or inactivating T3 or T4 to a non-biologically active form. Furthermore, thyroid hormone transporters are also found in the testis. Thus, the testis is equipped with the transporters and the enzymes necessary to maintain the optimal level of thyroid hormone in the seminiferous epithelium, as well as the specific TRs to execute thyroid hormone action in response to different stages of the epithelial cycle of spermatogenesis. Studies using genetic models and/or goitrogens (e.g., propylthiouracil) have illustrated a tight physiological relationship between thyroid hormone and testicular function, in particular, Sertoli cell differentiation status, mitotic activity, gap junction function, and blood–testis barrier assembly. These findings are briefly summarized and discussed herein. PMID:25414694

  14. The Treatment of the Incompletely Descended Testis

    PubMed Central

    Wilson, D. S. Poole

    1939-01-01

    (1) Under three years of age the diagnosis of the incompletely descended testis is uncertain. (2) The policy of awaiting spontaneous descent may be pursued until 10 years of age but, unless the testis lies in the superior scrotal position, this policy should not be persisted in thereafter. (3) Hormonal therapy may be employed before operative treatment as a means of determining testes which will descend spontaneously. It should only be used in the prepuberty period. (4) Operative treatment may be safely carried out at any age after 3 years and should be completed before puberty. The optimum period is between 8 and 11 years. The Bevan operation may be successful when the testis is very mobile but the most consistent results are obtained by the septal transposition or Keetley-Torek operations. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 8Fig. 9Fig. 10Fig. 13Fig. 14Fig. 15Fig. 16Fig. 18Fig. 19Fig. 20Fig. 21Fig. 22 PMID:19991991

  15. Ossified Ligamentum Longitudinale Anterius in Adult Human Dry Vertebrae

    PubMed Central

    Venumadhav, Nelluri; KS, Siddaraju

    2014-01-01

    Background: The ligamentum longitudinale anterius is a broad and strong band of fibrous tissue that runs along the anterior surfaces of the bodies of the vertebrae. Aim: The study was undertaken to evaluate the incidence of ossified ligamentum longitudinale anterius in adult dry human vertebra. Materials and Methods: This study was carried out on 95 sets of dry human vertebral columns irrespective of age and sex at Mayo Institute of Medical Sciences- Barabanki,-UP, Melaka Manipal Medical College-Manipal University and Department of Anatomy, KMCT Medical College, Manassery- Calicut, India. All the sets of vertebral columns were macroscopically inspected for the ossified ligamentum longitudinale anterius. Results: It was observed that out of 95 sets of vertebral columns, 27 (28.42%) vertebral columns showed ossification. Out of 27 vertebral columns, 17 (17.89%) vertebral columns showed segmental type of ossification, 2 (2.11%) vertebral columns showed continuous type of ossification and 8 (8.42%) vertebral columns showed mixed type of ossification at different vertebral level. Conclusion: Such type of ossification will affect the biomechanics of the spine and may result in stiff neck, low back pain, dysphagia, odynophagia, compression of the brachial plexus, aphonia, immobility or mucosal thickening of larynx. Hence, knowledge of such abnormalities should be kept in mind to minimise serious complications in any surgical intervention or investigative procedures in the region. PMID:25302180

  16. A biokinetic model for systemic technetium in adult humans

    DOE PAGES

    Leggett, Richard Wayne; Giussani, Augusto

    2015-04-10

    The International Commission on Radiological Protection (ICRP) currently is updating its biokinetic and dosimetric models for internally deposited radionuclides. Technetium (Tc), the lightest element that exists only in radioactive form, has two important isotopes from the standpoint of potential risk to humans: the long-lived isotope 99Tm(T1/2=2.1x105 y) is present in high concentration in nuclear waste, and the short-lived isotope 99mTc (T1/2=6.02 h) is the most commonly used radionuclide in diagnostic nuclear medicine. This paper reviews data on the biological behavior of technetium and proposes a biokinetic model for systemic technetium in the adult human body for use in radiation protection.more » Compared with the ICRP s current occupational model for systemic technetium, the proposed model provides a more realistic description of the paths of movement of technetium in the body; provides greater consistency with experimental and medical data; and, for most radiosensitive organs, yields substantially different estimates of cumulative activity (total radioactive decays within the organ) following uptake of 99Tm or 99mTc to blood.« less

  17. Comprehensive cellular-resolution atlas of the adult human brain.

    PubMed

    Ding, Song-Lin; Royall, Joshua J; Sunkin, Susan M; Ng, Lydia; Facer, Benjamin A C; Lesnar, Phil; Guillozet-Bongaarts, Angie; McMurray, Bergen; Szafer, Aaron; Dolbeare, Tim A; Stevens, Allison; Tirrell, Lee; Benner, Thomas; Caldejon, Shiella; Dalley, Rachel A; Dee, Nick; Lau, Christopher; Nyhus, Julie; Reding, Melissa; Riley, Zackery L; Sandman, David; Shen, Elaine; van der Kouwe, Andre; Varjabedian, Ani; Write, Michelle; Zollei, Lilla; Dang, Chinh; Knowles, James A; Koch, Christof; Phillips, John W; Sestan, Nenad; Wohnoutka, Paul; Zielke, H Ronald; Hohmann, John G; Jones, Allan R; Bernard, Amy; Hawrylycz, Michael J; Hof, Patrick R; Fischl, Bruce; Lein, Ed S

    2016-11-01

    Detailed anatomical understanding of the human brain is essential for unraveling its functional architecture, yet current reference atlases have major limitations such as lack of whole-brain coverage, relatively low image resolution, and sparse structural annotation. We present the first digital human brain atlas to incorporate neuroimaging, high-resolution histology, and chemoarchitecture across a complete adult female brain, consisting of magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and 1,356 large-format cellular resolution (1 µm/pixel) Nissl and immunohistochemistry anatomical plates. The atlas is comprehensively annotated for 862 structures, including 117 white matter tracts and several novel cyto- and chemoarchitecturally defined structures, and these annotations were transferred onto the matching MRI dataset. Neocortical delineations were done for sulci, gyri, and modified Brodmann areas to link macroscopic anatomical and microscopic cytoarchitectural parcellations. Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains. This interactive online digital atlas is integrated with existing Allen Institute for Brain Science gene expression atlases and is publicly accessible as a resource for the neuroscience community. J. Comp. Neurol. 524:3127-3481, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. Copyright © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

  18. A biokinetic model for systemic technetium in adult humans

    SciTech Connect

    Leggett, Richard Wayne; Giussani, Augusto

    2015-04-10

    The International Commission on Radiological Protection (ICRP) currently is updating its biokinetic and dosimetric models for internally deposited radionuclides. Technetium (Tc), the lightest element that exists only in radioactive form, has two important isotopes from the standpoint of potential risk to humans: the long-lived isotope 99Tm(T1/2=2.1x105 y) is present in high concentration in nuclear waste, and the short-lived isotope 99mTc (T1/2=6.02 h) is the most commonly used radionuclide in diagnostic nuclear medicine. This paper reviews data on the biological behavior of technetium and proposes a biokinetic model for systemic technetium in the adult human body for use in radiation protection. Compared with the ICRP s current occupational model for systemic technetium, the proposed model provides a more realistic description of the paths of movement of technetium in the body; provides greater consistency with experimental and medical data; and, for most radiosensitive organs, yields substantially different estimates of cumulative activity (total radioactive decays within the organ) following uptake of 99Tm or 99mTc to blood.

  19. An anatomically comprehensive atlas of the adult human brain transcriptome

    PubMed Central

    Guillozet-Bongaarts, Angela L.; Shen, Elaine H.; Ng, Lydia; Miller, Jeremy A.; van de Lagemaat, Louie N.; Smith, Kimberly A.; Ebbert, Amanda; Riley, Zackery L.; Abajian, Chris; Beckmann, Christian F.; Bernard, Amy; Bertagnolli, Darren; Boe, Andrew F.; Cartagena, Preston M.; Chakravarty, M. Mallar; Chapin, Mike; Chong, Jimmy; Dalley, Rachel A.; David Daly, Barry; Dang, Chinh; Datta, Suvro; Dee, Nick; Dolbeare, Tim A.; Faber, Vance; Feng, David; Fowler, David R.; Goldy, Jeff; Gregor, Benjamin W.; Haradon, Zeb; Haynor, David R.; Hohmann, John G.; Horvath, Steve; Howard, Robert E.; Jeromin, Andreas; Jochim, Jayson M.; Kinnunen, Marty; Lau, Christopher; Lazarz, Evan T.; Lee, Changkyu; Lemon, Tracy A.; Li, Ling; Li, Yang; Morris, John A.; Overly, Caroline C.; Parker, Patrick D.; Parry, Sheana E.; Reding, Melissa; Royall, Joshua J.; Schulkin, Jay; Sequeira, Pedro Adolfo; Slaughterbeck, Clifford R.; Smith, Simon C.; Sodt, Andy J.; Sunkin, Susan M.; Swanson, Beryl E.; Vawter, Marquis P.; Williams, Derric; Wohnoutka, Paul; Zielke, H. Ronald; Geschwind, Daniel H.; Hof, Patrick R.; Smith, Stephen M.; Koch, Christof; Grant, Seth G. N.; Jones, Allan R.

    2014-01-01

    Neuroanatomically precise, genome-wide maps of transcript distributions are critical resources to complement genomic sequence data and to correlate functional and genetic brain architecture. Here we describe the generation and analysis of a transcriptional atlas of the adult human brain, comprising extensive histological analysis and comprehensive microarray profiling of ~900 neuroanatomically precise subdivisions in two individuals. Transcriptional regulation varies enormously by anatomical location, with different regions and their constituent cell types displaying robust molecular signatures that are highly conserved between individuals. Analysis of differential gene expression and gene co-expression relationships demonstrates that brain-wide variation strongly reflects the distributions of major cell classes such as neurons, oligodendrocytes, astrocytes and microglia. Local neighbourhood relationships between fine anatomical subdivisions are associated with discrete neuronal subtypes and genes involved with synaptic transmission. The neocortex displays a relatively homogeneous transcriptional pattern, but with distinct features associated selectively with primary sensorimotor cortices and with enriched frontal lobe expression. Notably, the spatial topography of the neocortex is strongly reflected in its molecular topography— the closer two cortical regions, the more similar their transcriptomes. This freely accessible online data resource forms a high-resolution transcriptional baseline for neurogenetic studies of normal and abnormal human brain function. PMID:22996553

  20. Comprehensive cellular‐resolution atlas of the adult human brain

    PubMed Central

    Royall, Joshua J.; Sunkin, Susan M.; Ng, Lydia; Facer, Benjamin A.C.; Lesnar, Phil; Guillozet‐Bongaarts, Angie; McMurray, Bergen; Szafer, Aaron; Dolbeare, Tim A.; Stevens, Allison; Tirrell, Lee; Benner, Thomas; Caldejon, Shiella; Dalley, Rachel A.; Dee, Nick; Lau, Christopher; Nyhus, Julie; Reding, Melissa; Riley, Zackery L.; Sandman, David; Shen, Elaine; van der Kouwe, Andre; Varjabedian, Ani; Write, Michelle; Zollei, Lilla; Dang, Chinh; Knowles, James A.; Koch, Christof; Phillips, John W.; Sestan, Nenad; Wohnoutka, Paul; Zielke, H. Ronald; Hohmann, John G.; Jones, Allan R.; Bernard, Amy; Hawrylycz, Michael J.; Hof, Patrick R.; Fischl, Bruce

    2016-01-01

    ABSTRACT Detailed anatomical understanding of the human brain is essential for unraveling its functional architecture, yet current reference atlases have major limitations such as lack of whole‐brain coverage, relatively low image resolution, and sparse structural annotation. We present the first digital human brain atlas to incorporate neuroimaging, high‐resolution histology, and chemoarchitecture across a complete adult female brain, consisting of magnetic resonance imaging (MRI), diffusion‐weighted imaging (DWI), and 1,356 large‐format cellular resolution (1 µm/pixel) Nissl and immunohistochemistry anatomical plates. The atlas is comprehensively annotated for 862 structures, including 117 white matter tracts and several novel cyto‐ and chemoarchitecturally defined structures, and these annotations were transferred onto the matching MRI dataset. Neocortical delineations were done for sulci, gyri, and modified Brodmann areas to link macroscopic anatomical and microscopic cytoarchitectural parcellations. Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains. This interactive online digital atlas is integrated with existing Allen Institute for Brain Science gene expression atlases and is publicly accessible as a resource for the neuroscience community. J. Comp. Neurol. 524:3127–3481, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:27418273

  1. Ossified ligamentum longitudinale anterius in adult human dry vertebrae.

    PubMed

    Kosuri, Kalyan Chakravarthi; Venumadhav, Nelluri; Ks, Siddaraju

    2014-08-01

    The ligamentum longitudinale anterius is a broad and strong band of fibrous tissue that runs along the anterior surfaces of the bodies of the vertebrae. The study was undertaken to evaluate the incidence of ossified ligamentum longitudinale anterius in adult dry human vertebra. This study was carried out on 95 sets of dry human vertebral columns irrespective of age and sex at Mayo Institute of Medical Sciences- Barabanki,-UP, Melaka Manipal Medical College-Manipal University and Department of Anatomy, KMCT Medical College, Manassery- Calicut, India. All the sets of vertebral columns were macroscopically inspected for the ossified ligamentum longitudinale anterius. It was observed that out of 95 sets of vertebral columns, 27 (28.42%) vertebral columns showed ossification. Out of 27 vertebral columns, 17 (17.89%) vertebral columns showed segmental type of ossification, 2 (2.11%) vertebral columns showed continuous type of ossification and 8 (8.42%) vertebral columns showed mixed type of ossification at different vertebral level. Such type of ossification will affect the biomechanics of the spine and may result in stiff neck, low back pain, dysphagia, odynophagia, compression of the brachial plexus, aphonia, immobility or mucosal thickening of larynx. Hence, knowledge of such abnormalities should be kept in mind to minimise serious complications in any surgical intervention or investigative procedures in the region.

  2. The Effect of Body Mass on Outdoor Adult Human Decomposition.

    PubMed

    Roberts, Lindsey G; Spencer, Jessica R; Dabbs, Gretchen R

    2017-02-23

    Forensic taphonomy explores factors impacting human decomposition. This study investigated the effect of body mass on the rate and pattern of adult human decomposition. Nine males and three females aged 49-95 years ranging in mass from 73 to 159 kg who were donated to the Complex for Forensic Anthropology Research between December 2012 and September 2015 were included in this study. Kelvin accumulated degree days (KADD) were used to assess the thermal energy required for subjects to reach several total body score (TBS) thresholds: early decomposition (TBS ≥6.0), TBS ≥12.5, advanced decomposition (TBS ≥19.0), TBS ≥23.0, and skeletonization (TBS ≥27.0). Results indicate no significant correlation between body mass and KADD at any TBS threshold. Body mass accounted for up to 24.0% of variation in decomposition rate depending on stage, and minor differences in decomposition pattern were observed. Body mass likely has a minimal impact on postmortem interval estimation.

  3. Adult human liver mesenchymal progenitor cells express phenylalanine hydroxylase.

    PubMed

    Baruteau, Julien; Nyabi, Omar; Najimi, Mustapha; Fauvart, Maarten; Sokal, Etienne

    2014-09-01

    Phenylketonuria (PKU) is one of the most prevalent inherited metabolic diseases and is accountable for a severe encephalopathy by progressive intoxication of the brain by phenylalanine. This results from an ineffective L-phenylalanine hydroxylase enzyme (PAH) due to a mutated phenylalanine hydroxylase (PAH) gene. Neonatal screening programs allow an early dietetic treatment with restrictive phenylalanine intake. This diet prevents most of the neuropsychological disabilities but remains challenging for lifelong compliance. Adult-derived human liver progenitor cells (ADHLPC) are a pool of precursors that can differentiate into hepatocytes. We aim to study PAH expression and PAH activity in a differenciated ADHLPC. ADHLPC were isolated from human hepatocyte primary culture of two different donors and differenciated under specific culture conditions. We demonstrated the high expression of PAH and a large increase of PAH activity in differenciated LPC. The age of the donor, the cellular viability after liver digestion and cryopreservation affects PAH activity. ADHLPC might therefore be considered as a suitable source for cell therapy in PKU.

  4. The proteasome inhibitor bortezomib induces testicular toxicity by upregulation of oxidative stress, AMP-activated protein kinase (AMPK) activation and deregulation of germ cell development in adult murine testis

    SciTech Connect

    Li, Wei; Fu, Jianfang; Zhang, Shun; Zhao, Jie; Xie, Nianlin; Cai, Guoqing

    2015-06-01

    Understanding how chemotherapeutic agents mediate testicular toxicity is crucial in light of compelling evidence that male infertility, one of the severe late side effects of intensive cancer treatment, occurs more often than they are expected to. Previous study demonstrated that bortezomib (BTZ), a 26S proteasome inhibitor used to treat refractory multiple myeloma (MM), exerts deleterious impacts on spermatogenesis in pubertal mice via unknown mechanisms. Here, we showed that intermittent treatment with BTZ resulted in fertility impairment in adult mice, evidenced by testicular atrophy, desquamation of immature germ cells and reduced caudal sperm storage. These deleterious effects may originate from the elevated apoptosis in distinct germ cells during the acute phase and the subsequent disruption of Sertoli–germ cell anchoring junctions (AJs) during the late recovery. Mechanistically, balance between AMP-activated protein kinase (AMPK) activation and Akt/ERK pathway appeared to be indispensable for AJ integrity during the late testicular recovery. Of particular interest, the upregulated testicular apoptosis and the following disturbance of Sertoli–germ cell interaction may both stem from the excessive oxidative stress elicited by BTZ exposure. We also provided the in vitro evidence that AMPK-dependent mechanisms counteract follicle-stimulating hormone (FSH) proliferative effects in BTZ-exposed Sertoli cells. Collectively, BTZ appeared to efficiently prevent germ cells from normal development via multiple mechanisms in adult mice. Employment of antioxidants and/or AMPK inhibitor may represent an attractive strategy of fertility preservation in male MM patients exposed to conventional BTZ therapy and warrants further investigation. - Highlights: • Intermittent treatment with BTZ caused fertility impairment in adult mice. • BTZ treatment elicited apoptosis during early phase of testicular recovery. • Up-regulation of oxidative stress by BTZ treatment

  5. Systematic Analysis of the Phosphoproteome and Kinase-substrate Networks in the Mouse Testis*

    PubMed Central

    Qi, Lin; Liu, Zexian; Wang, Jing; Cui, Yiqiang; Guo, Yueshuai; Zhou, Tao; Zhou, Zuomin; Guo, Xuejiang; Xue, Yu; Sha, Jiahao

    2014-01-01

    Spermatogenesis is a complex process closely associated with the phosphorylation-orchestrated cell cycle. Elucidating the phosphorylation-based regulations should advance our understanding of the underlying molecular mechanisms. Here we present an integrative study of phosphorylation events in the testis. Large-scale phosphoproteome profiling in the adult mouse testis identified 17,829 phosphorylation sites in 3955 phosphoproteins. Although only approximately half of the phosphorylation sites enriched by IMAC were also captured by TiO2, both the phosphoprotein data sets identified by the two methods significantly enriched the functional annotation of spermatogenesis. Thus, the phosphoproteome profiled in this study is a highly useful snapshot of the phosphorylation events in spermatogenesis. To further understand phosphoregulation in the testis, the site-specific kinase-substrate relations were computationally predicted for reconstructing kinase-substrate phosphorylation networks. A core sub-kinase-substrate phosphorylation networks among the spermatogenesis-related proteins was retrieved and analyzed to explore the phosphoregulation during spermatogenesis. Moreover, network-based analyses demonstrated that a number of protein kinases such as MAPKs, CDK2, and CDC2 with statistically more site-specific kinase-substrate relations might have significantly higher activities and play an essential role in spermatogenesis, and the predictions were consistent with previous studies on the regulatory roles of these kinases. In particular, the analyses proposed that the activities of POLO-like kinases (PLKs) might be dramatically higher, while the prediction was experimentally validated by detecting and comparing the phosphorylation levels of pT210, an indicator of PLK1 activation, in testis and other tissues. Further experiments showed that the inhibition of POLO-like kinases decreases cell proliferation by inducing G2/M cell cycle arrest. Taken together, this systematic

  6. Testis stereology, seminiferous epithelium cycle length, and daily sperm production in the ocelot (Leopardus pardalis).

    PubMed

    Silva, R C; Costa, G M J; Andrade, L M; França, L R

    2010-01-15

    Similar to most wild felids, the ocelot (Leopardus pardalis) is an endangered species. However, knowledge regarding reproductive biology of the ocelot is very limited. Germ cell transplantation is an effective technique for investigating spermatogenesis and stem cell biology in mammals, and the morphologic characterization of germ cells and knowledge of cycle length are potential tools for tracking the development of transplanted germ cells. Our goal was to investigate basic aspects related to testis structure, particularly spermatogenesis, in the ocelot. Four adult males were used. After unilateral orchiectomy, testis samples were routinely prepared for histologic, stereologic, and autoradiographic analyses. Testis weight and the gonadosomatic index were 11+/-0.6g and 0.16+/-0.01%, respectively, whereas the volume density of seminiferous tubules and Leydig cells was 83.2+/-1.6% and 9.8+/-1.5%. Based on the acrosomic system, eight stages of spermatogenesis were characterized, and germ cell morphology was very similar to that of domestic cats. Each spermatogenic cycle lasted 12.5+/-0.4 d, and the entire spermatogenic process lasted 56.3+/-1.9 d. Individual Leydig cell volume was 2522mum(3), whereas the number of Leydig and Sertoli cells per gram of testis was 38+/-5x10(6) and 46+/-3x10(6). Approximately 4.5 spermatids were found per Sertoli cell, whereas daily sperm production per gram of testis was 18.3+/-1x10(6), slightly higher than values reported for other felids. The knowledge obtained in this study could be very useful to the preservation of the ocelot using domestic cat testes to generate and propagate the ocelot genome.

  7. Cryopreservation of porcine spermatogonial stem cells by slow-freezing testis tissue in trehalose.

    PubMed

    Lee, Y-A; Kim, Y-H; Ha, S-J; Kim, K-J; Kim, B-J; Kim, B-G; Choi, S-H; Kim, I-C; Schmidt, J A; Ryu, B-Y

    2014-03-01

    Spermatogonial stem cells provide the foundation for continued adult spermatogenesis and their manipulation can facilitate assisted reproductive technologies or the development of transgenic animals. Because the pig is an important agricultural and biomedical research animal, the development of practical application techniques to manipulate the pig Spermatogonial stem cell is needed. The ability to preserve porcine Spermatogonial stem cell or testis tissue long term is one of these fundamental techniques. The objective of this study was to optimize methods to cryopreserve porcine Spermatogonial stem cell when freezing testis cells or testis tissue. To identify the most efficient cryopreservation technique, porcine testis cells (cell freezing) or testis tissue (tissue freezing) were frozen in medium containing dimethyl sulfoxide (DMSO) and fetal bovine serum (FBS) or DMSO, FBS, and various concentrations of trehalose (50, 100, or 200 mM). After thawing, undifferentiated germ cells were enriched and treatments were evaluated for cryopreservation efficiency. The tissue freezing method resulted in significantly greater germ cell recovery (P = 0.041) and proliferation capacity (P < 0.001) compared to the cell freezing treatment. Regardless of freezing method (cell vs. tissue), addition of 200 mM trehalose to freezing medium increased germ cell recovery and proliferation capacity compared to cells frozen using the same freezing method without trehalose. Interestingly, addition of trehalose to the tissue freezing medium significantly increased germ cell recovery (P = 0.012) and proliferation capacity (P = 0.004) compared to the cell freezing treatment supplemented with trehalose. To confirm that cryopreservation in trehalose improves the survival of Spermatogonial stem cell, testis cells enriched for undifferentiated germ cells were xenotransplanted into recipient mouse testes. Germ cells recovered from tissue frozen with 200 mM trehalose generated significantly more (P

  8. Professional Fulfillment and Satisfaction of US and Canadian Adult Education and Human Resource Development Faculty

    ERIC Educational Resources Information Center

    Peterson, Shari L.; Wiesenberg, Faye

    2004-01-01

    This comparative study explored the professional fulfillment and job satisfaction of US and Canadian college and university faculty in the fields of Adult Education and Human Resource Development. In Autumn 2001, we disseminated electronically "The Adult Education and Human Resource Development Faculty Survey" to a selected sample of Canadian and…

  9. Testis asymmetry and sperm length in Rhacophorus omeimontis.

    PubMed

    Mi, Zhi Ping; Liao, Wen Bo; Jin, Long; Lou, Shang Ling; Cheng, Jian; Wu, Hua

    2012-06-01

    Theory predicts that the degree of testes asymmetry should be positively correlated with male body condition in species with directional testis asymmetry. We tested this prediction in Rhacophorus omeimontis, a species in which females mate with more than one male. Our results showed that the treefrogs did not exhibit the absence of directional asymmetry in testis size, but rather the occurrence of fluctuating asymmetry. Moreover, we also tested differences in body size, body mass, testis mass, testis asymmetry, and sperm size among initially paired, jointly paired, and unpaired males. We found that body size and mass, testis mass, testis asymmetry and sperm length did not differ among the three male types. Testis mass showed a positive relationship with soma mass, but the correlations between the extent of fluctuating testis asymmetry and sperm length, and between testis mass and sperm length were not significant. Our data suggest that testes size and sperm length do not play an important role in determining male mating success in the presence of sperm competition.

  10. Clinics in diagnostic imaging (114). Rupture of the right testis.

    PubMed

    Muttarak, M; Thinyu, S; Lojanapiwat, B

    2007-03-01

    A 22-year-old man, who was kicked in the scrotum during Thai kickboxing, presented with a painful swelling of the right hemiscrotum. Scrotal ultrasonography (US) showed an enlarged right testis with heterogeneous echogenicity and irregular contours. Colour Doppler US showed vascularity in the upper pole of the right testis and avascularity in the lower pole. Emergency exploration of the right hemiscrotum revealed laceration of the lower pole of the right testis. Debridement and repair of the right testis were performed. The clinical manifestations, role of US and US findings of scrotal trauma are discussed.

  11. Effects of plants and plant products on the testis

    PubMed Central

    D'Cruz, Shereen Cynthia; Vaithinathan, Selvaraju; Jubendradass, Rajamanickam; Mathur, Premendu Prakash

    2010-01-01

    For centuries, plants and plant-based products have been used as a valuable and safe natural source of medicines for treating various ailments. The therapeutic potential of most of these plants could be ascribed to their anticancer, antidiabetic, hepatoprotective, cardioprotective, antispasmodic, analgesic and various other pharmacological properties. However, several commonly used plants have been reported to adversely affect male reproductive functions in wildlife and humans. The effects observed with most of the plant and plant-based products have been attributed to the antispermatogenic and/or antisteroidogenic properties of one or more active ingredients. This review discusses the detrimental effects of some of the commonly used plants on various target cells in the testis. A deeper insight into the molecular mechanisms of action of these natural compounds could pave the way for developing therapeutic strategies against their toxicity. PMID:20562897

  12. Aspiration biopsy of testis: another method for histologic examination

    SciTech Connect

    Nseyo, U.O.; Englander, L.S.; Huben, R.P.; Pontes, J.E.

    1984-08-01

    The most important method for evaluating the pathogenesis of male infertility is open testicular biopsy. Herein the authors describe a method of aspiration biopsy of testis for histologic examination. Sexually mature dogs and rats treated with chemotherapeutic agents and ionizing radiation were followed with periodic testicular aspiration biopsy during and after treatment. The histologic findings from the aspiration biopsy compare with the results of routine histologic examination in assessing spermatogenetic activity and delineating pathologic changes. The puncture in the experimental animals was performed under general anesthesia. In human patients testicular biopsy could be done under local anesthesia in an outpatient clinic. The procedure would be less painful, minimally invasive, and more cost-effective.

  13. Effects of plants and plant products on the testis.

    PubMed

    D'Cruz, Shereen Cynthia; Vaithinathan, Selvaraju; Jubendradass, Rajamanickam; Mathur, Premendu Prakash

    2010-07-01

    For centuries, plants and plant-based products have been used as a valuable and safe natural source of medicines for treating various ailments. The therapeutic potential of most of these plants could be ascribed to their anticancer, antidiabetic, hepatoprotective, cardioprotective, antispasmodic, analgesic and various other pharmacological properties. However, several commonly used plants have been reported to adversely affect male reproductive functions in wildlife and humans. The effects observed with most of the plant and plant-based products have been attributed to the antispermatogenic and/or antisteroidogenic properties of one or more active ingredients. This review discusses the detrimental effects of some of the commonly used plants on various target cells in the testis. A deeper insight into the molecular mechanisms of action of these natural compounds could pave the way for developing therapeutic strategies against their toxicity.

  14. Immunocytochemical localization of androgen receptor in the comb, uropygial gland, testis, and epididymis in the domestic chicken.

    PubMed

    Shanbhag, B A; Sharp, P J

    1996-01-01

    Nuclear, but not cytoplasmic androgen receptors (AR), were localized immunocytochemically in the comb, uropygial (preen) gland, testis, and epididymis of juvenile and adult cockerels. Androgen receptor immunoreactivity (AR-ir) was seen in the comb, in the stratum germinativum of the epidermis and in fibromucoid cells in the dermis in juvenile and adult cockerels. AR-ir was observed in the glandular epithelial (sebum-producing) cells lining the peripheral and middle sections of the tubules in the uropygial gland. AR-ir was not detected in innermost part of the tubules which conduct the sebum to the surface of the skin. AR-ir labeling was not observed in the uropygial gland of juveniles. In the testis, AR-ir was seen in the Leydig cells, in adults but not juveniles. The epithelial cells lining the tubules in the epididymis contained AR-ir in both juveniles and adults.

  15. A murine fer testis-specific transcript (ferT) encodes a truncated Fer protein.

    PubMed Central

    Fischman, K; Edman, J C; Shackleford, G M; Turner, J A; Rutter, W J; Nir, U

    1990-01-01

    A cDNA for a potential tyrosine kinase-encoding mRNA was isolated from a mouse testis cDNA library. In a survey of eight mouse tissues, a transcript of 2.4 kilobases restricted to testis tissue was found. The mRNA encodes a 453-amino-acid protein of 51,383 daltons, the smallest tyrosine kinase protein ever described. RNA synthesized from the cDNA template directs the synthesis of a 51,000-Mr protein in a cell-free translation system. The carboxy-terminal 409 amino acids are 98 and 90% identical to the carboxy halves of the rat and human Fer proteins, respectively. This suggests that the cDNA represents an alternatively spliced testis-specific fer mRNA and is therefore termed by us ferT. On the basis of the appearance time of the fer mRNA in the testis of maturing neonatal mice, we speculate on the role played by this protein in the development of this organ. Images PMID:2294399

  16. Acute effect of prolactin on ornithine decarboxylase activity in the rat testis.

    PubMed

    de Las Heras, M A; Calandra, R S

    1992-01-01

    A study was conducted to evaluate the effect of the acute treatment with prolactin (PRL) on ornithine decarboxylase (ODC) activity in the rat testis. Injection of a single SC dose of ovine PRL to puberal rats resulted in the activation of ODC from whole testis. This effect was maximal at 4 h after injection, and statistically significant at the dose of 500 micrograms. The effect of PRL was confined to the interstitial space; no change was observed in seminiferous tubules. PRL was unable to further increase testicular ODC activity when injected together with a stimulatory dose of human chorionic gonadotropin (hCG). The effect of PRL was mimicked by injection of a single dose of the dopamine antagonist sulpiride, which provoked a ninefold increase in serum PRL levels. In contrast, PRL did not stimulate testicular ODC activity in hypophysectomized rats, either under basal conditions or during treatment with PRL-hCG, indicating the requirement of a functional hypophysis for the expression of PRL action. These results suggest that the stimulation of testicular ODC activity by PRL is a marker of the trophic response of the testis to this hormone, different from the stimulation of steroidogenesis. This activity could be useful for the study of PRL action on the testis as well as of the interaction between PRL and LH at the testicular level.

  17. A comparative study of mast cells and eosinophil leukocytes in the mammalian testis.

    PubMed

    Anton, F; Morales, C; Aguilar, R; Bellido, C; Aguilar, E; Gaytán, F

    1998-05-01

    The existence of a physiological integration between the immune and endocrine systems has long been recognized. In spite of the abundant literature data on the presence of cells of the immune system in the testis, mast cells and eosinophil leukocytes have received little attention. We have studied the presence, distribution and numbers of mast cells and eosinophils in the testes of 12 mammalian species. Mast cells were frequently found in equine (stallion, ass and mule) and human testis, whereas eosinophils were nearly absent. On the contrary, eosinophils were abundant in the hare testis, while mast cells were lacking. Both cells types were present in high numbers in swine (wild and domestic boar) testis. Otherwise, mast cells and eosinophils were absent from the testicular parenchyma of several species (rat, dog, cat, bull and deer), although they were present, in most cases, around blood vessels in the tunica albuginea. The presence of high numbers of mast cells and/or eosinophil leukocytes in the testicular parenchyma of some species suggest a role for these cells in local regulatory pathways.

  18. Postnatal sexual development of testis and epididymis in the rabbit: growth and maturity patterns of macroscopic and microscopic markers.

    PubMed

    García-Tomás, M; Sánchez, J; Piles, M

    2009-01-15

    We examined the macroscopic variables related to the size of testis and epididymis, and the microscopic variables related to the tissue composition of testis to determine the onset of the male reproductive activity. The present work was carried out using two genetic lines of rabbits showing different reproductive aptitudes to assess the effects of genetic line and birth season on age-related changes of the testes and epididymis. The Caldes and Prat genetic lines showed similar developmental profiles for most of the variables studied. The main changes in the development pattern were observed at younger ages. The Caldes genetic line presented a greater live weight and a smaller testicular volume that the Prat genetic line at any age. No differences in the studied microscopic variables were found between the two genetic lines, except in the variable percentage of seminiferous tubules with presence of lumen. A significant effect of the birth season was found in live weight, testis volume, epididymis volume, percentage of seminiferous tubules with presence of elongated spermatids and diameter of seminiferous tubules. The absolute values and the values relatives to its own value at the adult stage of the variables live weight, testis volume, epididymis volume and in variables related to the functional maturity were lower in animals born in the summer season. Volume growth for both testis and epididymis was delayed in animals born in the summer season.

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

    PubMed

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

    2016-10-01

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

  20. Testis hormone-sensitive lipase expression in spermatids is governed by a short promoter in transgenic mice.

    PubMed

    Blaise, R; Guillaudeux, T; Tavernier, G; Daegelen, D; Evrard, B; Mairal, A; Holm, C; Jégou, B; Langin, D

    2001-02-16

    A testicular form of hormone-sensitive lipase (HSL(tes)), a triacylglycerol lipase, and cholesterol esterase, is expressed in male germ cells. Northern blot analysis showed HSL(tes) mRNA expression in early spermatids. Immunolocalization of the protein in human and rodent seminiferous tubules indicated that the highest level of expression occurred in elongated spermatids. We have previously shown that 0.5 kilobase pairs of the human HSL(tes) promoter directs testis-specific expression of a chloramphenicol acetyltransferase reporter gene in transgenic mice and determined regions binding nuclear proteins expressed in testis but not in liver (Blaise, R., Grober, J., Rouet, P., Tavernier, G., Daegelen, D., and Langin, D. (1999) J. Biol. Chem. 274, 9327-9334). Mutation of a SRY/Sox-binding site in one of the regions did not impair in vivo testis-specific expression of the reporter gene. Further transgenic analyses established that 95 base pairs upstream of the transcription start site were sufficient for correct testis expression. In gel retardation assays using early spermatid nuclear extracts, a germ cell-specific DNA-protein interaction was mapped between -46 and -29 base pairs. The DNA binding nuclear protein showed properties of zinc finger transcription factors. Mutation of the region abolished reporter gene activity in transgenic mice, showing that it is necessary for testis expression of HSL(tes).

  1. Features of hand-foot crawling behavior in human adults.

    PubMed

    Maclellan, M J; Ivanenko, Y P; Cappellini, G; Sylos Labini, F; Lacquaniti, F

    2012-01-01

    Interlimb coordination of crawling kinematics in humans shares features with other primates and nonprimate quadrupeds, and it has been suggested that this is due to a similar organization of the locomotor pattern generators (CPGs). To extend the previous findings and to further explore the neural control of bipedal vs. quadrupedal locomotion, we used a crawling paradigm in which healthy adults crawled on their hands and feet at different speeds and at different surface inclinations (13°, 27°, and 35°). Ground reaction forces, limb kinematics, and electromyographic (EMG) activity from 26 upper and lower limb muscles on the right side of the body were collected. The EMG activity was mapped onto the spinal cord in approximate rostrocaudal locations of the motoneuron pools to characterize the general features of cervical and lumbosacral spinal cord activation. The spatiotemporal pattern of spinal cord activity significantly differed between quadrupedal and bipedal gaits. In addition, participants exhibited a large range of kinematic coordination styles (diagonal vs. lateral patterns), which is in contrast to the stereotypical kinematics of upright bipedal walking, suggesting flexible coupling of cervical and lumbosacral pattern generators. Results showed strikingly dissimilar directional horizontal forces for the arms and legs, considerably retracted average leg orientation, and substantially smaller sacral vs. lumbar motoneuron activity compared with quadrupedal gait in animals. A gradual transition to a more vertical body orientation (increasing the inclination of the treadmill) led to the appearance of more prominent sacral activity (related to activation of ankle plantar flexors), typical of bipedal walking. The findings highlight the reorganization and adaptation of CPG networks involved in the control of quadrupedal human locomotion and a high specialization of the musculoskeletal apparatus to specific gaits.

  2. 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.

  3. Metric analysis of basal sphenoid angle in adult human skulls

    PubMed Central

    Netto, Dante Simionato; Nascimento, Sergio Ricardo Rios; Ruiz, Cristiane Regina

    2014-01-01

    Objective To analyze the variations in the angle basal sphenoid skulls of adult humans and their relationship to sex, age, ethnicity and cranial index. Methods The angles were measured in 160 skulls belonging to the Museum of the Universidade Federal de São Paulo Department of Morphology. We use two flexible rules and a goniometer, having as reference points for the first rule the posterior end of the ethmoidal crest and dorsum of the sella turcica, and for the second rule the anterior margin of the foramen magnum and clivus, measuring the angle at the intersection of two. Results The average angle was 115.41°, with no statistical correlation between the value of the angle and sex or age. A statistical correlation was noted between the value of the angle and ethnicity, and between the angle and the horizontal cranial index. Conclusions The distribution of the angle basal sphenoid was the same in sex, and there was correlation between the angle and ethnicity, being the proportion of non-white individuals with an angle >125° significantly higher than that of whites with an angle >125°. There was correlation between the angle and the cranial index, because skulls with higher cranial index tend to have higher basiesfenoidal angle too. PMID:25295452

  4. Spirituality of Adult Education and Training. Professional Practices in Adult Education and Human Resource Development Series.

    ERIC Educational Resources Information Center

    English, Leona M.; Fenwick, Tara J.; Parsons, Jim

    This book explores how spirituality intersects with the lives of adult educators and trainers. The following are among the topics discussed: (1) spirituality's role within the context of adult education and training and defining spirituality (the original spiritual purpose of adult education, as illustrated in the history of the Chautauqua,…

  5. Long-term testicular volume after orchiopexy at diagnosis of acquired undescended testis.

    PubMed

    van der Plas, Evelyn M; Zijp, Gerda W; Froeling, Frank M J A; van der Voort-Doedens, Laszla M; Meij-de Vries, Annebeth; Goede, Joery; Hack, Wilfried W M

    2013-07-01

    We studied long-term outcomes of orchiopexy at diagnosis of acquired undescended testes using ultrasound to determine testicular volume. Patients who had undergone orchiopexy for acquired undescended testis at diagnosis were recruited to assess testicular volume. Testis volume was measured by ultrasound and compared with recently developed normative values for testicular size. For young adults (older than 18 years) volumes were grouped and compared to normative values reported in the literature. In all unilateral cases testicular volume was compared with its counterpart. A total of 155 patients 5.1 to 26.6 years old (181 acquired undescended testes) were included in the study. Mean ± SD followup was 6.6 ± 3.8 years (range 1.4 to 15.5). For all patients 18 years old or younger (125 patients, 143 testes) operated testis volume was 0.1 to 12.7 ml (mean ± SD 2.5 ± 2.9), which was significantly smaller than the normative values (50th percentile) for the same age (p <0.001). Mean ± SD testis volume in young adults (38 testes) was 8.1 ± 3.7 ml, compared to a mean volume of 13.4 ml reported in the literature (p <0.001). In unilateral cases the mean volume of the testes fixed by orchiopexy differed significantly from their counterparts (3.4 ± 3.3 ml vs 4.6 ± 4.6 ml, p <0.001). The long-term volumes at diagnosis of acquired undescended testes after orchiopexy were significantly less than the normative values at all ages. In unilateral cases the volumes were also significantly less compared to the contralateral testes. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  6. Epigallocatechin-3-gallate increases maximal oxygen uptake in adult humans.

    PubMed

    Richards, Jennifer C; Lonac, Mark C; Johnson, Tyler K; Schweder, Melani M; Bell, Christopher

    2010-04-01

    Epigallocatechin-3-gallate (EGCG), a component of green tea, increases endurance performance in animals and promotes fat oxidation during cycle ergometer exercise in adult humans. We have investigated the hypothesis that short-term consumption of EGCG delays the onset of the ventilatory threshold (VT) and increases maximal oxygen uptake (VO2max). In this randomized, repeated-measures, double-blind study, 19 healthy adults (11 males and 8 females, age = 26 ± 2 yr (mean ± SE)) received seven placebo or seven EGCG (135-mg) pills. Forty-eight hours before data collection, participants began consuming three pills per day; the last pill was taken 2 h before exercise testing. VT and VO2max were determined from breath-by-breath indirect calorimetry data collected during continuous incremental stationary cycle ergometer exercise (20-35 W·min(-1)), from rest until volitional fatigue. Each condition/exercise test was separated by a minimum of 14 d. Compared with placebo, short-term EGCG consumption increased VO2max (3.123 ± 0.187 vs 3.259 ± 0.196 L·min(-1), P = 0.04). Maximal work rate (301 ± 15 vs 301 ± 16 W, P = 0.98), maximal RER (1.21 ± 0.01 vs 1.22 ± 0.02, P = 0.27), and maximal HR were unaffected (180 ± 3 vs 180 ± 3 beats·min(-1), P = 0.87). In a subset of subjects (n = 11), maximal cardiac output (determined via open-circuit acetylene breathing) was also unaffected by EGCG (29.6 ± 2.2 vs 30.2 ± 1.4 L·min(-1), P = 0.70). Contrary to our hypothesis, EGCG decreased VO2 at VT (1.57 ± 0.11 vs 1.48 ± 0.10 L·min(-1)), but this change was not significant (P = 0.06). Short-term consumption of EGCG increased VO2max without affecting maximal cardiac output, suggesting that EGCG may increase arterial-venous oxygen difference.

  7. A putative fourth Na+,K(+)-ATPase alpha-subunit gene is expressed in testis.

    PubMed Central

    Shamraj, O I; Lingrel, J B

    1994-01-01

    The Na+,K(+)-ATPase alpha subunit has three known isoforms, alpha 1, alpha 2 and alpha 3, each encoded by a separate gene. This study was undertaken to determine the functional status of a fourth human alpha-like gene, ATP1AL2. Partial genomic sequence analysis revealed regions exhibiting sequence similarity with exons 3-6 of the Na+,K(+)-ATPase alpha isoform genes. ATP1AL2 cDNAs spanning the coding sequence of a novel P-type ATPase alpha subunit were isolated from a rat testis library. The predicted polypeptide is 1028 amino acids long and exhibits 76-78% identity with the rat Na+,K(+)-ATPase alpha 1, alpha 2 and alpha 3 isoforms, indicating that ATP1AL2 may encode a fourth Na+,K(+)-ATPase alpha isoform. A 3.9-kb mRNA is expressed abundantly in human and rat testis. Images Fig. 2 Fig. 5 PMID:7809153

  8. Tubular Ectasia of the Rete Testis: A Diagnostic Dilemma

    PubMed Central

    Nair, Rajesh; Abbaraju, J; Rajbabu, K; Anjum, F; Sriprasad, S

    2008-01-01

    Tubular ectasia of the rete testis is a pathologically benign process with complex and varied aetiology. It must be differentiated from neoplastic disease of the testis clinically with patient age, mode of presentation, tumour marker status and the characteristic ultrasound and Doppler study findings. Awareness and diagnosis of this clinical entity can prevent unnecessary surgical intervention in these patients. PMID:18831860

  9. Peritubular myoid cells in the testis: their structure and function.

    PubMed

    Maekawa, M; Kamimura, K; Nagano, T

    1996-03-01

    Peritubular myoid cells, surrounding the seminiferous tubules in the testis, have been found in all mammalian species, but their organization in the peritubular interstitial tissue varies by species. In laboratory rodents, including rats, hamsters and mice, only one layer of myoid cells is seen in the testis. The cells in these animals are joined by junctional complexes as are epithelial cells. On the other hand, several cellular layers exist in the lamina propria of the seminiferous tubule in the human and some other animals. Myoid cells contain abundant actin filaments which are distributed in the cells in a species-specific manner. In the rat, the filaments within one myoid cell run both longitudinally and circularly to the long axis of the seminiferous tubule, exhibiting a lattice-work pattern. The arrangement of the actin filaments in the cells changes during postnatal development, and the disruption of spermatogenesis, such as cryptorchidism, seems to affect further the arrangement of the filaments. Other cytoskeletal proteins, including myosin, desmin/vimentin and alpha-actinin, are also found in the cells. Myoid cells have been shown to be contractile, involved in the transport of spermatozoa and testicular fluid in the tubule. Several substances (prostaglandins, oxytocin, TGF beta, NO/cGMP) have been suggested to affect the contraction of the cell, though the mechanisms of the contraction are still unknown. Recent in vitro studies have demonstrated that the cells secrete a number of substances including extracellular matrix components (fibronectin, type I and IV collagens, proteoglycans) and growth factors (PModS, TGF beta, IGF-I, activin-A). Some of these substances are known to affect the Sertoli cell function. Furthermore, it has been reported that myoid cells contain androgen receptors and are involved in retinol processing. Considering all this, it is evident that peritubular myoid cells not only provide structural integrity to the tubule but also

  10. Cancer of the undescended or maldescended testis.

    PubMed

    Batata, M A; Whitmore, W F; Hilaris, B S; Tokita, N; Grabstald, H

    1976-02-01

    An analysis of 45 cryptorchids (by history or examination) with a testicular cancer treated at Memorial Hospital, between 1934 and 1973, is presented. Twenty-five patients had the cryptorchid state repaired at ages four to 27 years, either spontaneously or by orchiopexy or hormonal therapy. Ipsilateral (24) or contralateral (one) intrascrotal testis tumors developed four to 47 years later. Twenty cryptorchid patients presented with ipsilateral inguinal (eleven), abdominal (seven), or contralateral intrascrotal (two) tumors. There were 18 pure seminomas, 17 embryonal carcinomas, nine teratocarcinomas, and one reticulum cell sarcoma. Five year survival rates as estimated by the product-limit method were 60% for the unrepaired cases and 41% for the repaired cases. The survival seems to follow histologic type and anatomical stage, whether the testis is within the scrotum or not. Five year survival similarly estimated was 78% in the seminomas and 29% in the other tumors. Twelve of thirteen survivors (including nine with seminoma) received postoperative irradiation to the regional lymphatics and eleven were without recurrent tumor for periods ranging from six to 28 years.

  11. Transcriptional profiling of adult neural stem-like cells from the human brain.

    PubMed

    Sandberg, Cecilie Jonsgar; Vik-Mo, Einar O; Behnan, Jinan; Helseth, Eirik; Langmoen, Iver A

    2014-01-01

    There is a great potential for the development of new cell replacement strategies based on adult human neural stem-like cells. However, little is known about the hierarchy of cells and the unique molecular properties of stem- and progenitor cells of the nervous system. Stem cells from the adult human brain can be propagated and expanded in vitro as free floating neurospheres that are capable of self-renewal and differentiation into all three cell types of the central nervous system. Here we report the first global gene expression study of adult human neural stem-like cells originating from five human subventricular zone biopsies (mean age 42, range 33-60). Compared to adult human brain tissue, we identified 1,189 genes that were significantly up- and down-regulated in adult human neural stem-like cells (1% false discovery rate). We found that adult human neural stem-like cells express stem cell markers and have reduced levels of markers that are typical of the mature cells in the nervous system. We report that the genes being highly expressed in adult human neural stem-like cells are associated with developmental processes and the extracellular region of the cell. The calcium signaling pathway and neuroactive ligand-receptor interactions are enriched among the most differentially regulated genes between adult human neural stem-like cells and adult human brain tissue. We confirmed the expression of 10 of the most up-regulated genes in adult human neural stem-like cells in an additional sample set that included adult human neural stem-like cells (n = 6), foetal human neural stem cells (n = 1) and human brain tissues (n = 12). The NGFR, SLITRK6 and KCNS3 receptors were further investigated by immunofluorescence and shown to be heterogeneously expressed in spheres. These receptors could potentially serve as new markers for the identification and characterisation of neural stem- and progenitor cells or as targets for manipulation of cellular fate.

  12. Hyperoxia Induces Inflammation and Cytotoxicity in Human Adult Cardiac Myocytes.

    PubMed

    Hafner, Christina; Wu, Jing; Tiboldi, Akos; Hess, Moritz; Mitulovic, Goran; Kaun, Christoph; Krychtiuk, Konstantin Alexander; Wojta, Johann; Ullrich, Roman; Tretter, Eva Verena; Markstaller, Klaus; Klein, Klaus Ulrich

    2017-04-01

    Supplemental oxygen (O2) is used as adjunct therapy in anesthesia, emergency, and intensive care medicine. We hypothesized that excessive O2 levels (hyperoxia) can directly injure human adult cardiac myocytes (HACMs). HACMs obtained from the explanted hearts of transplantation patients were exposed to constant hyperoxia (95% O2), intermittent hyperoxia (alternating 10 min exposures to 5% and 95% O2), constant normoxia (21% O2), or constant mild hypoxia (5% O2) using a bioreactor. Changes in cell morphology, viability as assessed by lactate dehydrogenase (LDH) release and trypan blue (TB) staining, and secretion of vascular endothelial growth factor (VEGF), macrophage migration inhibitory factor (MIF), and various pro-inflammatory cytokines (interleukin, IL; chemokine C-X-C motif ligand, CXC; granulocyte-colony stimulating factor, G-CSF; intercellular adhesion molecule, ICAM; chemokine C-C motif ligand, CCL) were compared among treatment groups at baseline (0 h) and after 8, 24, and 72 h of treatment. Changes in HACM protein expression were determined by quantitative proteomic analysis after 48 h of exposure. Compared with constant normoxia and mild hypoxia, constant hyperoxia resulted in a higher TB-positive cell count, greater release of LDH, and elevated secretion of VEGF, MIF, IL-1β, IL-6, IL-8, CXCL-1, CXCL-10, G-CSF, ICAM-1, CCL-3, and CCL-5. Cellular inflammation and cytotoxicity gradually increased and was highest after 72 h of constant and intermittent hyperoxia. Quantitative proteomic analysis revealed that hypoxic and hyperoxic O2 exposure differently altered the expression levels of proteins involved in cell-cycle regulation, energy metabolism, and cell signaling. In conclusion, constant and intermittent hyperoxia induced inflammation and cytotoxicity in HACMs. Cell injury occurred earliest and was greatest after constant hyperoxia, but even relatively brief repeating hyperoxic episodes induced a substantial inflammatory response.

  13. Adult Education and the Human Environment: Transactions of a Celebration.

    ERIC Educational Resources Information Center

    Jones-Quartey, K. A. B., Ed.; And Others

    The document comprises a collection of speeches and seminar reports arising from the 25th anniversary celebration of the Institute of Adult Education at the University of Ghana. The theme of the celebration, introduced in the first chapter, was Adult Education and Man's Environment--the Next Quarter-Century. The second chapter comprises the…

  14. Regulation of the blood-testis barrier by a local axis in the testis: role of laminin α2 in the basement membrane.

    PubMed

    Gao, Ying; Mruk, Dolores; Chen, Haiqi; Lui, Wing-Yee; Lee, Will M; Cheng, C Yan

    2017-02-01

    Laminin α2 is one of the constituent components of the basement membrane (BM) in adult rat testes. Earlier studies that used a mouse genetic model have shown that a deletion of laminin α2 impedes male fertility by disrupting ectoplasmic specialization (ES; a testis-specific, actin-rich anchoring junction) function along the length of Sertoli cell in the testis. This includes ES at the Sertoli cell-elongating/elongated spermatid interface, which is known as apical ES and possibly the Sertoli-Sertoli cell interface, known as basal ES, at the blood-testis barrier (BTB). Studies have also illustrated that there is a local regulatory axis that functionally links cellular events of spermiation that occur near the luminal edge of tubule lumen at the apical ES and the basal ES/BTB remodeling near the BM at opposite ends of the seminiferous epithelium during the epithelial cycle, known as the apical ES-BTB-BM axis. However, the precise role of BM in this axis remains unknown. Here, we show that laminin α2 in the BM serves as the crucial regulator in this axis as laminin α2, likely its 80-kDa fragment from the C terminus, was found to be transported across the seminiferous epithelium at stages VIII-IX of the epithelial cycle, from the BM to the luminal edge of the tubule, possibly being used to modulate apical ES restructuring at these stages. Of more importance, a knockdown of laminin α2 in Sertoli cells was shown to induce the Sertoli cell tight junction permeability barrier disruption via changes in localization of adhesion proteins at the tight junction and basal ES at the Sertoli cell BTB. These changes were found to be mediated by a disruption of F-actin organization that was induced by changes in the spatiotemporal expression of actin binding/regulatory proteins. Furthermore, laminin α2 knockdown also perturbed microtubule (MT) organization by considerable down-regulation of MT polymerization via changes in the spatiotemporal expression of EB1 (end

  15. [Should the contralateral testis be systematically biopsied after orchidectomy for unilateral germ cell tumour of the testis?].

    PubMed

    Iborra, François; Mottet, Nicolas

    2005-04-01

    Intratubular neoplasia (ITN) of the testis is a precursor of germ cell tumour, apart from spermatocytic seminoma. It is often detected in testicular tissue adjacent to germ cell tumours, but is less common in the contralateral testis. Early diagnosis of ITN by testicular biopsy would allow earlier, conservative management. However, this approach remains highly controversial except in very specific indications.

  16. A caecal pseoudotumour with an incidental adenomatoid testicular tumour in a man with right undescended testis: a case report.

    PubMed

    Muturi, Alex; Kotecha, Vihar; Ojee, Cynthia; Mang'oka, Desmond; Muthuri, John

    2016-09-01

    Inflammatory pseudotumour refers to a non-malignant tumour-like mass resulting from an inflammatory reaction that is composed of granulation tissue with leukocyte infiltration that commonly occurs in the paediatric or young adult population. These tumours occur more commonly in the lungs and the orbit but rarely does it affect the gastrointestinal tract. It poses a clinical diagnostic challenge since it is a benign condition than can mimic the malignant counterpart. Our case is a rare presentation of the caecal pseudotumour in the presence of a right undescended abdominal testis evaluated as a caecal tumour with a differential diagnosis of a testicular malignancy. We report a 53-year-old male who presented with clinical signs suggestive of right colon tumour and undescended right testis. Intra-operatively, a caecal mass was found with no clearly discernable appendix and extensive adhesion of the right colon to the retroperitoneum, to the liver and gall bladder. A testis was found adherent to the posterior aspect of the caecum and terminal ileum. A right hemicolectomy was performed. Histopathology findings revealed an inflammatory mass with abundant fibroblast proliferation and chronic inflammatory cells infiltrate, involving bowel wall and periceacal adipose tissue; no malignant cells were identified. The testis had within it an adenomatoid tumour nodule. He had uneventful recovery and was discharged home 7 days post-operatively. At the moment, he is symptoms free. The occurrence of right colonic inflammatory pseudotumour and co-existent adenomatoid testicular tumour arising from a cryptorchid testis is very unusual. This would make one incline towards a malignant testicular lesion in the presence of cryptorchidism. Testicular adenomatoid tumour is a rare benign neoplasm, mostly affecting fully descended testis and usually does not warrant orchidectomy for purposes of preserving testicular function. On the other hand, surgical resection remains the only safe and

  17. The role of vitamin D in male fertility: A focus on the testis.

    PubMed

    de Angelis, Cristina; Galdiero, Mariano; Pivonello, Claudia; Garifalos, Francesco; Menafra, Davide; Cariati, Federica; Salzano, Ciro; Galdiero, Giacomo; Piscopo, Mariangela; Vece, Alfonso; Colao, Annamaria; Pivonello, Rosario

    2017-09-01

    In the last decade, vitamin D has emerged as a pleiotropic molecule with a multitude of autocrine, paracrine and endocrine functions, mediated by classical genomic as well as non-classical non-genomic actions, on multiple target organs and systems. The expression of vitamin D receptor and vitamin D metabolizing enzymes in male reproductive system, particularly in the testis, suggests the occurrence of vitamin D synthesis and regulation as well as function in the testis. The role of vitamin D in the modulation of testis functions, including hormone production and spermatogenesis, has been investigated in animals and humans. Experimental studies support a beneficial effect of vitamin D on male fertility, by modulating hormone production through genomic and non-genomic actions, and, particularly, by improving semen quality essentially through non-genomic actions. However, clinical studies in humans are controversial. Indeed, vitamin D seems to contribute to the modulation of the bioavailable rather than total testosterone. Moreover, although an increased prevalence or risk for testosterone deficiency was reported in men with vitamin D deficiency in observational studies, the majority of interventional studies demonstrated the lack of effect of vitamin D supplementation on circulating levels of testosterone. The most consistent effect of vitamin D was reported on semen quality. Indeed, vitamin D was shown to be positively associated to sperm motility, and to exert direct actions on spermatozoa, including non-genomic driven modulation of intracellular calcium homeostasis and activation of molecular pathways involved in sperm motility, capacitation and acrosome reaction. The current review provides a summary of current knowledge on the role of vitamin D in male fertility, by reporting clinical and experimental studies in humans and animals addressing the relationship between vitamin D and testis function.

  18. Brain stem auditory evoked responses in human infants and adults

    NASA Technical Reports Server (NTRS)

    Hecox, K.; Galambos, R.

    1974-01-01

    Brain stem evoked potentials were recorded by conventional scalp electrodes in infants (3 weeks to 3 years of age) and adults. The latency of one of the major response components (wave V) is shown to be a function both of click intensity and the age of the subject; this latency at a given signal strength shortens postnatally to reach the adult value (about 6 msec) by 12 to 18 months of age. The demonstrated reliability and limited variability of these brain stem electrophysiological responses provide the basis for an optimistic estimate of their usefulness as an objective method for assessing hearing in infants and adults.

  19. Brain stem auditory evoked responses in human infants and adults

    NASA Technical Reports Server (NTRS)

    Hecox, K.; Galambos, R.

    1974-01-01

    Brain stem evoked potentials were recorded by conventional scalp electrodes in infants (3 weeks to 3 years of age) and adults. The latency of one of the major response components (wave V) is shown to be a function both of click intensity and the age of the subject; this latency at a given signal strength shortens postnatally to reach the adult value (about 6 msec) by 12 to 18 months of age. The demonstrated reliability and limited variability of these brain stem electrophysiological responses provide the basis for an optimistic estimate of their usefulness as an objective method for assessing hearing in infants and adults.

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

    EPA Science Inventory

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

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

    EPA Science Inventory

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

  2. Comprehensive functional characterization of cancer-testis antigens defines obligate participation in multiple hallmarks of cancer.

    PubMed

    Maxfield, Kimberly E; Taus, Patrick J; Corcoran, Kathleen; Wooten, Joshua; Macion, Jennifer; Zhou, Yunyun; Borromeo, Mark; Kollipara, Rahul K; Yan, Jingsheng; Xie, Yang; Xie, Xian-Jin; Whitehurst, Angelique W

    2015-11-16

    Tumours frequently activate genes whose expression is otherwise biased to the testis, collectively known as cancer-testis antigens (CTAs). The extent to which CTA expression represents epiphenomena or confers tumorigenic traits is unknown. In this study, to address this, we implemented a multidimensional functional genomics approach that incorporates 7 different phenotypic assays in 11 distinct disease settings. We identify 26 CTAs that are essential for tumor cell viability and/or are pathological drivers of HIF, WNT or TGFβ signalling. In particular, we discover that Foetal and Adult Testis Expressed 1 (FATE1) is a key survival factor in multiple oncogenic backgrounds. FATE1 prevents the accumulation of the stress-sensing BH3-only protein, BCL-2-Interacting Killer (BIK), thereby permitting viability in the presence of toxic stimuli. Furthermore, ZNF165 promotes TGFβ signalling by directly suppressing the expression of negative feedback regulatory pathways. This action is essential for the survival of triple negative breast cancer cells in vitro and in vivo. Thus, CTAs make significant direct contributions to tumour biology.

  3. Regulation of cell junction dynamics by cytokines in the testis – a molecular and biochemical perspective*

    PubMed Central

    Lui, Wing-Yee; Cheng, C. Yan

    2009-01-01

    Studies in the past decade in the field have demonstrated the significance of cytokines in regulating epithelial and endothelial cell junctions including tight and anchoring junctions in multiple organs including the testis. There are mounting evidences in recent years that cytokines play a crucial role in the restructuring of junctions at the Sertoli-Sertoli and Sertoli-germ cell interface in the seminiferous epithelium during spermatogenesis. These earlier studies, however, were focused on the effects of cytokines in maintaining the steady-state protein levels of integral membrane proteins at the sites of the blood-testis barrier (BTB), and anchoring junctions at the Sertoli-Sertoli and Sertoli-germ cell interface, such as basal and apical ectoplasmic specialization, respectively. The molecular pathway(s) and/or mechanism(s) underlying these effects remain virtually unexplored until very recently. Herein, we summarize and provide some discussions on studies that focused on the role of cytokines in regulating junction restructuring events in epithelia from a molecular and biochemical perspective. Specifically we use the adult rat or mouse testis as a model to highlight the significance of transcriptional and translational regulation. Specific areas of research that require further attentions are also highlighted. PMID:17521954

  4. Spermatogonial stem cells in the testis of an endangered bovid: Indian black buck (Antilope cervicapra L.).

    PubMed

    Goel, Sandeep; Reddy, Niranjan; Mahla, Ranjeet Singh; Suman, Sanjay Kumar; Pawar, Rahul Mohanchandra

    2011-07-01

    Numerous wild bovids are facing threat of extinction owing to the loss of habitat and various other reasons. Spermatogonial stem cells (SSCs) represent the only germline stem cells in adult body that are capable of self-renewal and that can undergo differentiation to produce haploid germ cells. SSCs can, therefore, serve as a useful resource for preservation of germplasm of threatened and endangered mammals. The Indian black buck (Antilope cervicapra L.) is a small Indian antelope that is listed as endangered by the Indian Wildlife Protection Act, 1972. Immunohistochemical analysis of testes tissues of black buck revealed the presence of spermatogonia that were specifically stained by lectin-Dolichos biflorus agglutinin (DBA). The expression of pluripotent cell-specific markers, NANOG and stage-specific embryonic antigen-1 (SSEA-1), was detected in spermatogonia. Interestingly, the expression of POU5F1 (OCT3/4) was absent from spermatogonia, however, it was detected in differentiating cells such as spermatocytes and round spermatids but not in elongated spermatids. The expression of NANOG protein was also present in spermatocytes but absent in round and elongated spermatids. Using the testis transplantation assay, stem cell potential of black buck spermatogonia was confirmed as indicated by the presence of colonized DBA-stained cells in the basal membrane of seminiferous tubules of xenotransplanted mice testis. The findings from this study suggest the presence of SSCs in the testis of an endangered bovid for the first time and open new possibility to explore the use of SSCs in conservation.

  5. Comprehensive functional characterization of cancer–testis antigens defines obligate participation in multiple hallmarks of cancer

    PubMed Central

    Maxfield, Kimberly E.; Taus, Patrick J.; Corcoran, Kathleen; Wooten, Joshua; Macion, Jennifer; Zhou, Yunyun; Borromeo, Mark; Kollipara, Rahul K.; Yan, Jingsheng; Xie, Yang; Xie, Xian-Jin; Whitehurst, Angelique W.

    2015-01-01

    Tumours frequently activate genes whose expression is otherwise biased to the testis, collectively known as cancer–testis antigens (CTAs). The extent to which CTA expression represents epiphenomena or confers tumorigenic traits is unknown. In this study, to address this, we implemented a multidimensional functional genomics approach that incorporates 7 different phenotypic assays in 11 distinct disease settings. We identify 26 CTAs that are essential for tumor cell viability and/or are pathological drivers of HIF, WNT or TGFβ signalling. In particular, we discover that Foetal and Adult Testis Expressed 1 (FATE1) is a key survival factor in multiple oncogenic backgrounds. FATE1 prevents the accumulation of the stress-sensing BH3-only protein, BCL-2-Interacting Killer (BIK), thereby permitting viability in the presence of toxic stimuli. Furthermore, ZNF165 promotes TGFβ signalling by directly suppressing the expression of negative feedback regulatory pathways. This action is essential for the survival of triple negative breast cancer cells in vitro and in vivo. Thus, CTAs make significant direct contributions to tumour biology. PMID:26567849

  6. Erdosteine protects rat testis tissue from hypoxic injury by reducing apoptotic cell death.

    PubMed

    Guven, A; Ickin, M; Uzun, O; Bakar, C; Balbay, E Gulec; Balbay, O

    2014-02-01

    The purpose of this study was to examine the effects of hypobaric hypoxia on testis morphology and the effects of erdosteine on testis tissue. Caspase-3 and hypoxia-inducible factor 1α expressions were detected by immunohistochemistry. Adult male Wistar rats were placed in a hypobaric hypoxic chamber. Rats in the erdosteine group were exposed to the same conditions and treated orally with erdosteine (20 mg kg(-1) daily) at the same time from the first day of hypoxic exposure for 2 weeks. The normoxia group was evaluated as the control. The hypoxia group showed decreased height of spermatogenic epithelium in some seminiferous tubules, vacuolisation in spermatogenic epithelial cells, deterioration and gaps in the basal membrane and an increase in blood vessels in the interstitial area. The erdosteine group showed amelioration of both epithelial cell vacuolisation and basal membrane deterioration. Numbers of hypoxia-inducible factor 1α-immunostained Sertoli and Leydig cells were significantly higher in the hypoxia group than in the erdosteine group. The number of seminiferous tubules with caspase-3-immunostained germ cells was highest in the hypoxia group and decreased in the erdosteine and normoxia groups respectively. Based on these observations, erdosteine protects testis tissue from hypoxic injury by reducing apoptotic cell death.

  7. Adult Continuing Education and Human Resource Development: Present Competitors, Potential Partners

    ERIC Educational Resources Information Center

    Smith, Douglas H.

    2006-01-01

    Adult Continuing Education (ACE) and Human Resource Development (HRD) have grown tremendously in the last quarter century. ACE experienced tremendous growth in the 60s and 70s, with over 17 million attending colleges and universities, and local school and community adult education programs by the end of the 1970s. More ACE programs were started…

  8. Behavioral and magnetoencephalographic correlates of plasticity in the adult human brain

    PubMed Central

    Ramachandran, V. S.

    1993-01-01

    Recent behavioral and physiological evidence suggests that even brief sensory deprivation can lead to the rapid emergence of new and functionally effective neural connections in the adult human brain. Images Fig. 2 PMID:8248123

  9. The Mammalian Blood-Testis Barrier: Its Biology and Regulation

    PubMed Central

    Cheng, C. Yan

    2015-01-01

    Spermatogenesis is the cellular process by which spermatogonia develop into mature spermatids within seminiferous tubules, the functional unit of the mammalian testis, under the structural and nutritional support of Sertoli cells and the precise regulation of endocrine factors. As germ cells develop, they traverse the seminiferous epithelium, a process that involves restructuring of Sertoli-germ cell junctions, as well as Sertoli-Sertoli cell junctions at the blood-testis barrier. The blood-testis barrier, one of the tightest tissue barriers in the mammalian body, divides the seminiferous epithelium into 2 compartments, basal and adluminal. The blood-testis barrier is different from most other tissue barriers in that it is not only comprised of tight junctions. Instead, tight junctions coexist and cofunction with ectoplasmic specializations, desmosomes, and gap junctions to create a unique microenvironment for the completion of meiosis and the subsequent development of spermatids into spermatozoa via spermiogenesis. Studies from the past decade or so have identified the key structural, scaffolding, and signaling proteins of the blood-testis barrier. More recent studies have defined the regulatory mechanisms that underlie blood-testis barrier function. We review here the biology and regulation of the mammalian blood-testis barrier and highlight research areas that should be expanded in future studies. PMID:26357922

  10. Characterization and expression of trypsinogen and trypsin in medaka testis.

    PubMed

    Rajapakse, Sanath; Ogiwara, Katsueki; Takahashi, Takayki

    2014-12-01

    Previously, we reported that the medaka testis abundantly expresses the mRNA for trypsinogen, which is a well-known pancreatic proenzyme that is secreted into and activated in the intestine. Currently, we report our characterization of the medaka trypsin using a recombinant enzyme and show that this protein is a serine protease that shares properties with trypsins from other species. Two polypeptides (28- and 26-kDa) were detected in the testis extracts by Western blot analysis using antibodies that are specific for medaka trypsinogen. The 28-kDa polypeptide was shown to be trypsinogen (inactive precursor), and the 26-kDa polypeptide was shown to be trypsin (active protease). We did not detect enteropeptidase, which is the specific activator of trypsinogen, in the testis extract. Immunohistochemical analyses using the same trypsinogen-specific antibody produced a strong signal in the spermatogonia and spermatozoa of the mature medaka testis. Substantial staining was found with spermatocytes, whereas extremely weak signals were observed with spermatids. In vitro incubation of testis fragments with the trypsinogen antibody strongly inhibited the release of sperm from the testis into the medium. Trypsin activity was detected in sperm extracts using gelatin zymographic analysis. Immunocytochemistry showed that trypsinogen and trypsin were localized to the cell membranes surrounding the sperm head. Collectively, these results suggest that trypsin plays an important role in the testis function of the medaka.

  11. Gene expression profiling in liver and testis of rats to characterize the toxicity of triazole fungicides

    SciTech Connect

    Tully, Douglas B.; Bao Wenjun; Goetz, Amber K.; Blystone, Chad R.; Ren, Hongzu; Schmid, Judith E.; Strader, Lillian F.; Wood, Carmen R.; Best, Deborah S.; Narotsky, Michael G.; Wolf, Douglas C.; Rockett, John C.; Dix, David J. . E-mail: dix.david@epa.gov

    2006-09-15

    Four triazole fungicides were studied using toxicogenomic techniques to identify potential mechanisms of action. Adult male Sprague-Dawley rats were dosed for 14 days by gavage with fluconazole, myclobutanil, propiconazole, or triadimefon. Following exposure, serum was collected for hormone measurements, and liver and testes were collected for histology, enzyme biochemistry, or gene expression profiling. Body and testis weights were unaffected, but liver weights were significantly increased by all four triazoles, and hepatocytes exhibited centrilobular hypertrophy. Myclobutanil exposure increased serum testosterone and decreased sperm motility, but no treatment-related testis histopathology was observed. We hypothesized that gene expression profiles would identify potential mechanisms of toxicity and used DNA microarrays and quantitative real-time PCR (qPCR) to generate profiles. Triazole fungicides are designed to inhibit fungal cytochrome P450 (CYP) 51 enzyme but can also modulate the expression and function of mammalian CYP genes and enzymes. Triazoles affected the expression of numerous CYP genes in rat liver and testis, including multiple Cyp2c and Cyp3a isoforms as well as other xenobiotic metabolizing enzyme (XME) and transporter genes. For some genes, such as Ces2 and Udpgtr2, all four triazoles had similar effects on expression, suggesting possible common mechanisms of action. Many of these CYP, XME and transporter genes are regulated by xeno-sensing nuclear receptors, and hierarchical clustering of CAR/PXR-regulated genes demonstrated the similarities of toxicogenomic responses in liver between all four triazoles and in testis between myclobutanil and triadimefon. Triazoles also affected expression of multiple genes involved in steroid hormone metabolism in the two tissues. Thus, gene expression profiles helped identify possible toxicological mechanisms of the triazole fungicides.

  12. Morphology of the fetal rat testis preserved in different fixatives.

    PubMed

    Howroyd, Paul; Hoyle-Thacker, Renee; Lyght, Otis; Williams, Delorise; Kleymenova, Elena

    2005-01-01

    Histopathological examination of the testes of exposed fetuses and neonates is important in assessing the developmental effects of environmental toxins, including sex hormone modulators. Modified Davidson's fluid (mDF) has been suggested as a superior substitute for Bouin's fluid for fixation of adult animal testes. We compared the morphology of fetal rat testes stained with hematoxylin and eosin (H&E) or immunochemically after fixation in 10% neutral buffered formalin (NBF), Bouin's fluid, or mDF. Fixation in mDF resulted in more sharply defined nuclear detail and better preservation of cellular cytoplasm on H&E-stained sections of rat testes on gestation day 19. Use of Bouin's fluid did not allow satisfactory detection of apoptotic cells by fluorescent terminal deoxynucleotide transferase-mediated deoxy-UTP nick labeling. Staining with the immunoperoxidase system and the conventional chromogen diaminobenzidine tetrahydrochloride to visualize 5-bromo-2-deoxyuridine-positive cells demonstrated that the number of positive nuclei and intensity of staining were similar with all 3 fixatives. Immunostaining for cytoskeletal protein vimentin was more intense and provided better details of the Sertoli cell cytoplasm with formalin fixation than with mDF. Our study demonstrates that fixation in mDF provided better morphologic detail in the fetal rat testis compared with 10% NBF and Bouin's fluid and illustrates the importance of establishing the correct fixation conditions for each immunostaining protocol.

  13. Switching on sex: transcriptional regulation of the testis-determining gene Sry.

    PubMed

    Larney, Christian; Bailey, Timothy L; Koopman, Peter

    2014-06-01

    Mammalian sex determination hinges on the development of ovaries or testes, with testis fate being triggered by the expression of the transcription factor sex-determining region Y (Sry). Reduced or delayed Sry expression impairs testis development, highlighting the importance of its accurate spatiotemporal regulation and implying a potential role for SRY dysregulation in human intersex disorders. Several epigenetic modifiers, transcription factors and kinases are implicated in regulating Sry transcription, but it remains unclear whether or how this farrago of factors acts co-ordinately. Here we review our current understanding of Sry regulation and provide a model that assembles all known regulators into three modules, each converging on a single transcription factor that binds to the Sry promoter. We also discuss potential future avenues for discovering the cis-elements and trans-factors required for Sry regulation.

  14. Gilgamesh is required for the maintenance of germline stem cells in Drosophila testis.

    PubMed

    Chen, Dongsheng; Zhu, Xiangxiang; Zhou, Lijuan; Wang, Jian; Tao, Xiaoqian; Wang, Shuang; Sun, Fuling; Kan, Xianzhao; Han, Zhengqi; Gu, Yuelin

    2017-07-18

    Emerging evidence supports that stem cells are regulated by both intrinsic and extrinsic mechanisms. However, factors that determine the fate of stem cells remain incompletely understood. The Drosophila testis provides an exclusive powerful model in searching for potential important regulatory factors and their underlying mechanisms for controlling the fate of germline stem cells (GSCs). In this study, we have found that Drosophila gilgamesh (gish), which encodes a homologue of human CK1-γ (casein kinase 1-gamma), is required intrinsically for GSC maintenance. Our genetic analyses indicate gish is not required for Dpp/Gbb signaling silencing of bam and is dispensable for Dpp/Gbb signaling-dependent Dad expression. Finally, we show that overexpression of gish fail to dramatically increase the number of GSCs. These findings demonstrate that gish controls the fate of GSCs in Drosophila testis by a novel Dpp/Gbb signaling-independent pathway.

  15. Targeting testis-specific proteins to inhibit spermatogenesis: lesson from endocrine disrupting chemicals

    PubMed Central

    Wan, HT; Mruk, Dolores D; Wong, Chris KC; Cheng, C Yan

    2014-01-01

    Introduction Exposure to endocrine disrupting chemicals (EDCs) has recently been linked to declining fertility in men in both developed and developing countries. Since many EDCs possess intrinsic estrogenic or androgenic activities, thus, the gonad is one of the major targets of EDCs. Areas covered For the past 2 decades, studies found in the literature regarding the disruptive effects of these EDCs on reproductive function in human males and also rodents were mostly focused on oxidative stress-induced germ cell apoptosis, disruption of steroidogenesis, abnormal sperm production and disruption of spermatogenesis in particular cell adhesion function and the blood–testis-barrier (BTB) function. Herein, we highlight recent findings in the field illustrating testis-specific proteins are also targets of EDCs. Expert opinion This information should be helpful in developing better therapeutic approach to manage ECD-induced reproductive toxicity. This information is also helpful to identify potential targets for male contraceptive development. PMID:23600530

  16. [Reseach Advances on Cancer-Testis Antigens in Multiple Myeloma -Review].

    PubMed

    Yang, Zhi-Rui; Yu, Li; Zhu, Hai-Yan

    2017-02-01

    Cancer-testis antigens (CTA) are a class of tumor-associated antigens, which are mainly located in X chromosome. CTA restrictively expressed in normal testis, ovary, placenta and so on. Their expression in other normal tissues is much lower, even can not be detected. However, their expressions are aberrantly high in human cancers. Based on CTA encoding immunogenic proteins, they can be regulated by epigentics, CTA provides very attractive targets for cancer immunotherapy. Multiple myeloma (MM) is incurable and has a low cureative rate and a high relapse rate. CTA have been detected in many MM cell lines and primary MM cells, they may be relaled to clinical prognosis. This reviews briefly summarized the research advances of CTA in the immune therapy of multiple myeloma, so as to provide a valuable therapeutic idea for myeloma.

  17. Expression of 17beta-hydroxysteroid dehydrogenease in testis of the ascidian Ciona intestinalis [corrected].

    PubMed

    Kho, Kang Hee; Inaba, Kazuo

    2004-10-31

    Ascidians have been employed as model organisms in investigating spermatogenesis. 17beta-hydroxysteroid dehydrogenase (HSD) is a steroidogenic enzyme essential for invertebrate spermatogenesis. A homologue of HSD was found in the EST database of Ciona intestinalis and cloned. Sequence analysis showed significant homology to zebra fish, sea urchin and human 17beta-HSD. The gene has an open reading frame (ORF) of 918 nucleotides coding for a polypeptide of 306 amino acids and a calculated mass of 35-kDa. Immunoblotting with an antibody raised against HSD recognized a 35-kDa protein purified from the C. intestinalis testis. The HSD protein was localized in steroidogenic cells in the Ciona testis. These results suggest that C. intestinalis 17beta-HSD is equivalent to the enzyme of vertebrate Leydig cells and that 17beta-HSD could be a phylogenetic marker for organisms producing steroids.

  18. Metastasis of sigmoid colon cancer in cryptorchid testis: report of a case.

    PubMed

    Rampa, Mario; Battaglia, Luigi; Caprotti, Andrea; Gazzano, Giacomo; Prestianni, Pierpaolo; Muscarà, Cecilia; Vannelli, Alberto

    2012-01-01

    Isolated testicular metastasis from colorectal cancer is considered an unusual event. In this case report we describe for the first time a metastasis from an adenocarcinoma of the sigmoid colon to a cryptorchid testis. The patient developed a painless testicular nodule three years after the diagnosis of primary sigmoid colon cancer. Recent reports have suggested that the incidence of genitourinary abnormalities in human males has increased over the past 50 years; in particular, cryptorchid testes increase the clinical risk factors for primary or metastatic testicular cancer. In conclusion, there should be awareness of the risk of metastasis of colorectal cancer to the testis in the workup of patients with testicular symptoms. Furthermore, patients with colorectal cancer and cryptorchidism should be managed with a single surgical intervention: when the primary colorectal tumor is removed, the cryptorchid testicle should also be removed to reduce the risk of late metastases.

  19. A rare variant of inguinal hernia: Cryptorchid testis at the age of 50 years. Etiopathogenicity, prognosis and management

    PubMed Central

    Kassir, Radwan; Dubois, Joelle; Berremila, Sid-Ali; Baccot, Sylviane; Boueil-Bourlier, Alexia; Tiffet, Olivier

    2014-01-01

    INTRODUCTION Cryptorchidism is characterized by the extra-scrotal position of the testis. The surgical community has little to no knowledge of cryptorchid testis in adults apart from of pediatric surgeons. Therefore, we sought to describe this unusual cause of inguinal hernia. PRESENTATION OF CASE A 50-year-old man was referred with a inguinal hernia. Diagnosis of cryptorchidism was made during surgery, as the patient underwent an operation for repair of his left inguinal hernia. The testicle was non-viable and a left testicle was resected. Histopathology report confirmed a atrophic testis without testicular germ cell tumor (TGCT). DISCUSSION This is an extremely rare case of cryptorchidism revealed in an adult. The patient remained asymptomatic for 50 years. Most studies have concluded that there is a direct correlation between how long the testis was subjected to a cryptorchid position and TGCT incidence. The recommended age of surgical correction is before the age of 2 years. In our case, we did not find correlation between the time of surgery and risk of TGCT. Histopathology report confirmed the presence of leydig cells, seminiferous tubule and Sertoli cells without TGCT. Very little is known about link between cryptorchidism and TGCT. The correct diagnosis of inguinal hernia is usually made during an inguinal hernia repair. CONCLUSION The surgeon must always be alert to the possibility of cryptorchid testis during a surgical exploration of an inguinal hernia. In suspected cases, laparoscopy ultrasonographic, CT scan and laparoscopy evaluation may be helpful in diagnosing of this atypical inguinal hernia before surgery. PMID:24892247

  20. Newborn human skin fibroblasts senesce in vitro without acquiring adult growth factor requirements

    SciTech Connect

    Wharton, W.

    1984-01-01

    Cultures of human fibroblasts were prepared from chest skin obtained either from newborns (less than 3 months old) or adults (more than 35 years old) and maintained in vitro until they senesced. Adult cells grew logarithmically in medium supplemented with whole blood serum but not with platelet-poor plasma. Early passage cells obtained from newborns grew equally well in either plasma- or serum-supplemented medium. The difference in growth factor requirements between adult and newborn cells persisted through the lifespan of the cells; i.e., newborn cells did not develop adult hormonal requirements when maintained in culture. Thus, in vitro cellular aging can be distinguished from some types of differentiation.

  1. Expression of Cancer-Testis Genes in Brain Tumors

    PubMed Central

    Lee, Myoung-Hee; Kim, Ealmaan; Kim, In-Soo; Yim, Man-Bin; Kim, Sang-Pyo

    2008-01-01

    Objective Cancer-testis (CT) genes are considered promising candidates for immunotherapeutic approaches. The aim of this study was to investigate which CT genes should be targeted in immunotherapy for brain tumors. Methods We investigated the expression of 6 CT genes (MAGE-E1, SOX-6, SCP-1, SSX-2, SSX-4, and HOM-TES-85) using reverse-transcription polymerase chain reaction in 26 meningiomas and 32 other various brain tumor specimens, obtained from the patients during tumor surgery from 2000 to 2005. Results The most frequently expressed CT genes of meningiomas were MAGE-E1, which were found in 22/26 (85%) meningioma samples, followed by SOX-6 (9/26 or 35%). Glioblastomas were most frequently expressed SOX-6 (6/7 or 86%), MAGE-E1 (5/7 or 71%), followed by SSX-2 (2/7 or 29%) and SCP-1 (1/7 or 14%). However, 4 astrocytomas, 3 anaplastic astrocytomas, and 3 oligodendroglial tumors only expressed MAGE-E1 and SOX-6. Schwannomas also expressed SOX-6 (5/6 or 83%), MAGE-E1 (4/6 or 67%), and SCP-1 (2/6 or 33%). Conclusion The data presented here suggest that MAGE-E1 and SOX-6 genes are expressed in a high percentage of human central nervous system tumors, which implies the CT genes could be the potential targets of immunotherapy for human central nervous system tumors. PMID:19096642

  2. Investigation of genes important in neurodevelopment disorders in adult human brain.

    PubMed

    Maussion, Gilles; Diallo, Alpha B; Gigek, Carolina O; Chen, Elizabeth S; Crapper, Liam; Théroux, Jean-Francois; Chen, Gary G; Vasuta, Cristina; Ernst, Carl

    2015-10-01

    Several neurodevelopmental disorders (NDDs) are caused by mutations in genes expressed in fetal brain, but little is known about these same genes in adult human brain. Here, we test the hypothesis that genes associated with NDDs continue to have a role in adult human brain to explore the idea that NDD symptoms may be partially a result of their adult function rather than just their neurodevelopmental function. To demonstrate adult brain function, we performed expression analyses and ChIPseq in human neural stem cell(NSC) lines at different developmental stages and adult human brain, targeting two genes associated with NDDs, SATB2 and EHMT1, and the WNT signaling gene TCF7L2, which has not been associated with NDDs. Analysis of DNA interaction sites in neural stem cells reveals high (40-50 %) overlap between proliferating and differentiating cells for each gene in temporal space. Studies in adult brain demonstrate that consensus sites are similar to NSCs but occur at different genomic locations. We also performed expression analyses using BrainSpan data for NDD-associated genes SATB2, EHMT1, FMR1, MECP2, MBD5, CTNND2, RAI1, CHD8, GRIN2A, GRIN2B, TCF4, SCN2A, and DYRK1A and find high expression of these genes in adult brain, at least comparable to developing human brain, confirming that genes associated with NDDs likely have a role in adult tissue. Adult function of genes associated with NDDs might be important in clinical disease presentation and may be suitable targets for therapeutic intervention.

  3. Human Capital Development: Reforms for Adult and Community Education

    ERIC Educational Resources Information Center

    Choy, Sarojni; Haukka, Sandra

    2007-01-01

    The adult and community education (ACE) sector is consistently responsive to changing community needs and government priorities. It is this particular function that has drawn ACE into the lifelong learning debate as one model for sustaining communities. The responsiveness of ACE means that the sector and its programs continue to make valuable…

  4. Adult Literacy Programs in Uganda. Africa Region Human Development Series.

    ERIC Educational Resources Information Center

    Okech, Anthony; Carr-Hill, Roy A.; Katahoire, Anne R.; Kakooza, Teresa; Ndidde, Alice N.; Oxenham, John

    This report evaluates the outcomes and cost effectiveness of adult literacy programs in Ugandan villages and compares government programs with those provided by nongovernmental organizations (NGOs). Part 1 describes evaluation objectives, government and NGO literacy programs and the rural socioeconomic context, and evaluation design. About 100…

  5. The Human Function Compunction: Teleological Explanation in Adults

    ERIC Educational Resources Information Center

    Kelemen, Deborah; Rosset, Evelyn

    2009-01-01

    Research has found that children possess a broad bias in favor of teleological--or purpose-based--explanations of natural phenomena. The current two experiments explored whether adults implicitly possess a similar bias. In Study 1, undergraduates judged a series of statements as "good" (i.e., correct) or "bad" (i.e., incorrect) explanations for…

  6. "Adult Education Is about Human Being in All Its Aspects"

    ERIC Educational Resources Information Center

    Stanistreet, Paul

    2011-01-01

    Derek Legge, who celebrated his 95th birthday at the end of last month, is one of the most dedicated and influential of the largely unsung heroes of the adult education movement in Britain. As modesty is one of the many qualities with which his friends and colleagues credit him, he is certain to shrink from the description, but there is little…

  7. Organic and inorganic transporters of the testis: A review

    PubMed Central

    Klein, David M; Cherrington, Nathan J

    2014-01-01

    Transporters have a huge impact on the toxicology and pharmacological effects of xenobiotics in addition to being implicated in several diseases. While these important proteins have been well studied in organs such as the kidney or liver, characterization of transporters in the testis is still in the early stages. Knowledge of transporter function may greatly advance the field's understanding of the physiological and toxicological processes that occur in the testis. Several foundational studies involving both organic and inorganic transporters have been critical in furthering our understanding of how the testis interacts with endogenous and xenobiotic compounds. This review provides an overview of how transporters function, their clinical significance, and highlights what is known for many of the important transporters in the testis. PMID:26413398

  8. Unique Presentation of Intra-Abdominal Testis: Small Bowel Obstruction

    PubMed Central

    Bassiouny, Ibrahim E.; Abbas, Tariq O.; Alansari, Amani N.; Ali, Mansour A.

    2011-01-01

    We describe here a two-year-old male who required urgent laparotomy to relieve a strangulated small bowel caused by internal herniation around an intra-abdominal testis. This clinical presentation has not been reported previously. PMID:22084802

  9. Ameboid cells in spermatogenic cysts of caecilian testis.

    PubMed

    Smita, Mathew; Jancy, M George; Akbarsha, M A; Oommen, Oommen V

    2005-03-01

    Sertoli cells constitute a permanent feature of the testis lobules in caecilians irrespective of the functional state of the testis. The developing germ cells are intimately associated with the Sertoli cells, which are adherent to the basal lamina, until spermiation. There are irregularly shaped cells in the cores of the testis lobules that interact with germ cells at the face opposite to their attachment with Sertoli cells. These irregularly shaped (ameboid) cells first appear in the lumen of the cysts containing primary spermatocytes and are continually present until spermiation. We did not observe any cytoplasmic continuity between a Sertoli cell and an ameboid cell. Both light microscopic and TEM observations reveal a phagocytic role for the ameboid cells: they scavenge the residual bodies shed by spermatozoa. Organization of the ameboid cells is grossly different from that of the spermatogenic and Sertoli cells. They appear to develop from the epithelium at the juncture of the collecting ductule with the testis lobule.

  10. An Inventory of Skills and Attitudes Necessary for a Career in Human Services/Adult Care.

    ERIC Educational Resources Information Center

    Broadbent, William

    This document is an inventory of skills identified as necessary by professionals in the human services field specializing in adult care. It is intended as a mechanism whereby educators can compare that which they teach against what the human services industry feels is relevant. Introductory material discusses the process of the occupational…

  11. An Inventory of Skills and Attitudes Necessary for a Career in Human Services/Adult Care.

    ERIC Educational Resources Information Center

    Broadbent, William

    This document is an inventory of skills identified as necessary by professionals in the human services field specializing in adult care. It is intended as a mechanism whereby educators can compare that which they teach against what the human services industry feels is relevant. Introductory material discusses the process of the occupational…

  12. Torsion of the Appendix Testis in a Neonate

    PubMed Central

    Krishnan, Arvind; Rich, Mark A.; Swana, Hubert S.

    2016-01-01

    Torsion of the appendix testis is a rare cause of scrotal swelling in the neonatal period. We present a case of torsion of the appendix testis in a one-day-old male. We discuss the physical examination and radiologic studies used to make the diagnosis. Nonoperative therapy was recommended and the patient has done well. Recognition of this condition in the neonatal period can prevent surgical intervention and its associated risks. PMID:27379193

  13. Cloning and characterization of SOX5, a new member of the human SOX gene family

    SciTech Connect

    Wunderle, V.M.; Critcher, R.; Goodfellow, P.N.; Ashworth, A.

    1996-09-01

    The mammalian Y-linked testis determining gene, SRY, encodes a protein with a DNA binding motif known as the HMG box. A large family of genes sharing a high similarity with the SRY HMG box and named Sox (Sry-related HMG box) in mouse and SOX in human has been identified from various organisms. We have cloned SOX5, a new member of the human SOX gene family. SOX5 cDNAs isolated from a human adult testis cDNA library show a high similarity with the mouse Sox5 transcript over a large region identical in all the human cDNAs. However, comparison of the 5{prime} unique sequences of the cDNAs suggests that the SOX5 gene is subject to alternative splicing. Genomic analysis identified a SOX5 pseudogene located on 8q21.1, whereas the SOX5 gene itself, which contains a minimum of five introns, maps to 12p12.1. In contrast to the mouse gene, the human SOX5 gene is expressed in a variety of human tissues, and different size transcripts are observed in adult testis and fetal brain. 19 refs., 5 figs.

  14. Screening targeted testis-specific genes for molecular assessment of aberrant sperm quality

    PubMed Central

    Liu, Xue Xia; Shen, Xiao Fang; Liu, Fu-Jun

    2016-01-01

    Teratospermia is a heterogeneous and complex disorder, which is closely associated with male fertility. Genes and gene products associated with teratospermia may serve as targeted biomarkers that help understand the underlying mechanisms of male infertility; however, systematic information on the subject remains to be elucidated. The present study performed a comparative bioinformatics analysis to identify biomarkers associated with sperm quality, particular focusing on testis-specific biomarkers. A stepwise screening approach identified 1,085 testis/epididymis-specific genes and 3,406 teratospermia-associated genes, resulting in 348 testis-specific genes associated with aberrant sperm quality. These genes were functionally associated with the reproduction process. Gene products corresponding to heat shock protein family A (Hsp70) member 4 like (HSPA4L) and phosphoglycerate kinase 2 were characterized at the cellular level in human testes and ejaculated spermatozoa. HSPA4L expression in sperm was revealed to be associated with sperm quality. The present study provided a novel insight into the understanding of sperm quality, and a potential method for the diagnosis and assessment of sperm quality in the event of male infertility. PMID:27356588

  15. Sodium fluoride and sulfur dioxide affected male reproduction by disturbing blood-testis barrier in mice.

    PubMed

    Zhang, Jianhai; Li, Zhihui; Qie, Mingli; Zheng, Ruibo; Shetty, Jagathpala; Wang, Jundong

    2016-08-01

    Fluoride and sulfur dioxide (SO2), two well-known environmental toxicants, have been implicated to have adverse effects on male reproductive health in humans and animals. The objective of this study to investigate if the BTB is one of the pathways that lead to reproductive toxicity of sodium fluoride and sulfur dioxide alone or in combination, in view of the key role of blood testis barrier (BTB) in testis. The results showed that a marked decrease in sperm quality, and altered morphology and ultrastructure of BTB in testis of mice exposure to fluoride (100 mg NaF/L in drinking water) or/and sulfur dioxide (28 mg SO2/m(3), 3 h/day). Meanwhile, the mRNA expression levels of some vital BTB-associated proteins, including occluding, claudin-11, ZO-1, Ncadherin, α-catenin, and connexin-43 were all strikingly reduced after NaF exposure, although only the reduction of DSG-2 was statistically significant in all treatment groups. Moreover, the proteins expressions also decreased significantly in claudin-11, N-cadherin, α-catenin, connexin-43 and desmoglein-2 in mice treated with fluoride and/or SO2. These changes in BTB structure and constitutive proteins may therefore be connected with the low sperm quality in these mice. The role of fluoride should deserves more attention in this process. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Cloning and Characterization of Novel Testis-Specific Diacylglycerol Kinase η Splice Variants 3 and 4

    PubMed Central

    Murakami, Eri; Shionoya, Takao; Komenoi, Suguru; Suzuki, Yuji; Sakane, Fumio

    2016-01-01

    Diacylglycerol kinase (DGK) phosphorylates DG to generate phosphatidic acid. Recently, we found that a new alternative splicing product of the DGKη gene, DGKη3, which lacks exon 26 encoding 31 amino acid residues, was expressed only in the secondary spermatocytes and round spermatids of the testis. In this study, we cloned the full length DGKη3 gene and confirmed the endogenous expression of its protein product. During the cloning procedure, we found a new testis-specific alternative splicing product of the DGKη gene, DGKη4, which lacks half of the catalytic domain. We examined the DGK activity and subcellular localization of DGKη3 and η4. DGKη3 had almost the same activity as DGKη1, whereas the activity of DGKη4 was not detectable. In resting NEC8 cells (human testicular germ cell tumor cell line), DGKη1, η3 and η4 were broadly distributed in the cytoplasm. When osmotically shocked, DGKη1 and η4 were distributed in punctate vesicles in the cytoplasm. In contrast, DGKη3 was partly translocated to the plasma membrane and co-localized with the actin cytoskeleton. These results suggest that DGKη3 and η4 have properties different from those of DGKη1 and that they play roles in the testis in a different manner. PMID:27643686

  17. Cancer/testis antigen NY-SAR-35 enhances cell proliferation, migration, and invasion.

    PubMed

    Song, Myung-Ha; Kim, Ye-Rin; Lee, Jun-Won; Lee, Chang-Hun; Lee, Sang-Yull

    2016-02-01

    The cancer/testis antigen NY-SAR-35 is aberrantly expressed in various cancer tissues and cancer cell lines but not in normal tissues except for the testis. A previous study demonstrated that the expression of NY-SAR-35 is activated by hypomethylation in cancer cells. However, the functions of this antigen remain unexplored. In the present study, we investigated the role of NY-SAR‑35 in human embryonic kidney (HEK) 293 cells using exogenous expression system of the gene. NY-SAR‑35 was predominantly expressed at the cytoplasm and was mainly observed in spermatogonia and spermatocytes. Expression of NY-SAR-35 in stable HEK293 transfectant clones was 2-fold higher than the control cells promoting cell growth and proliferation. NY-SAR-35 overexpression also enhanced cell migration and invasion ~2-fold and 4-fold more than the control, respectively. In contrast, small interfering RNA-mediated knockdown of NY-SAR-35 suppressed cell proliferation, migration, and invasion in HEK293 stable transfectants. We concluded that NY-SAR-35 as a cancer/testis antigen enhanced cell proliferation and invasion.

  18. Conservation and expression of PIWI-interacting RNA pathway genes in male and female adult gonad of amniotes.

    PubMed

    Lim, Shu Ly; Tsend-Ayush, Enkhjargal; Kortschak, R Daniel; Jacob, Reuben; Ricciardelli, Carmela; Oehler, Martin K; Grützner, Frank

    2013-12-01

    The PIWI-interacting RNA (piRNA) pathway is essential for germline development and transposable element repression. Key elements of this pathway are members of the piRNA-binding PIWI/Argonaute protein family and associated factors (e.g., VASA, MAELSTROM, and TUDOR domain proteins). PIWI-interacting RNAs have been identified in mouse testis and oocytes, but information about the expression of the different piRNA pathway genes, in particular in the mammalian ovary, remains incomplete. We investigated the evolution and expression of piRNA pathway genes in gonads of amniote species (chicken, platypus, and mouse). Database searches confirm a high level of conservation and revealed lineage-specific gain and loss of Piwi genes in vertebrates. Expression analysis in mammals shows that orthologs of Piwi-like (Piwil) genes, Mael (Maelstrom), Mvh (mouse vasa homolog), and Tdrd1 (Tudor domain-containing protein 1) are expressed in platypus adult testis. In contrast to mouse, Piwil4 is expressed in platypus and human adult testis. We found evidence for Mael and Piwil2 expression in mouse Sertoli cells. Importantly, we show mRNA expression of Piwil2, Piwil4, and Mael in oocytes and supporting cells of human, mouse, and platypus ovary. We found no Piwil1 expression in mouse and chicken ovary. The conservation of gene expression in somatic parts of the gonad and germ cells of species that diverged over 800 million yr ago indicates an important role in adult male and female gonad.

  19. Molecular Evolution of the Testis TAFs of Drosophila

    PubMed Central

    Davis, Jerel C.; Lenkov, Kapa; Bolival, Benjamin; Fuller, Margaret T.; Petrov, Dmitri A.

    2009-01-01

    The basal transcription machinery is responsible for initiating transcription at core promoters. During metazoan evolution, its components have expanded in number and diversified to increase the complexity of transcriptional regulation in tissues and developmental stages. To explore the evolutionary events and forces underlying this diversification, we analyzed the evolution of the Drosophila testis TAFs (TBP-associated factors), paralogs of TAFs from the basal transcription factor TFIID that are essential for normal transcription during spermatogenesis of a large set of specific genes involved in terminal differentiation of male gametes. There are five testis-specific TAFs in Drosophila, each expressed only in primary spermatocytes and each a paralog of a different generally expressed TFIID subunit. An examination of the presence of paralogs across taxa as well as molecular clock dating indicates that all five testis TAFs likely arose within a span of ∼38 My 63–250 Ma by independent duplication events from their generally expressed paralogs. Furthermore, the evolution of the testis TAFs has been rapid, with apparent further accelerations in multiple Drosophila lineages. Analysis of between-species divergence and intraspecies polymorphism indicates that the major forces of evolution on these genes have been reduced purifying selection, pervasive positive selection, and coevolution. Other genes that exhibit similar patterns of evolution in the Drosophila lineages are also characterized by enriched expression in the testis, suggesting that the pervasive positive selection acting on the tTAFs is likely to be related to their expression in the testis. PMID:19244474

  20. Mice depleted of the coxsackievirus and adenovirus receptor display normal spermatogenesis and an intact blood-testis barrier.

    PubMed

    Sultana, Taranum; Hou, Mi; Stukenborg, Jan-Bernd; Töhönen, Virpi; Inzunza, Jose; Chagin, Andrei S; Sollerbrant, Kerstin

    2014-06-01

    The coxsackievirus and adenovirus receptor (CXADR (CAR)) is a cell adhesion molecule expressed mainly in epithelial cells. Numerous evidence indicate that CXADR has an important role in testis development and function of the blood-testis barrier (BTB) in vitro. The role of CXADR in testis physiology in vivo has, however, not been addressed. We therefore constructed a conditional CXADR knockout (cKO) mouse model in which CXADR can be depleted at any chosen timepoint by the administration of tamoxifen. We report for the first time that testicular depletion of CXADR in adult and pubertal mice does not alter BTB permeability or germ cell migration across the BTB during spermatogenesis. Adult cKO mice display normal junctional ultra-structure and localization of the junctional proteins claudin-3, occludin, junction-associated molecule-A (JAM-A), and ZO1. The BTB was intact with no leakage of biotin and lanthanum tracers into the tubular lumen. Adult CXADR cKO mice were fertile with normal sperm parameters and litter size. Breeding experiments and genotyping of the pups demonstrated that CXADR-negative sperm could fertilize WT eggs. In addition, knocking down CXADR from postnatal day 9 (P9) does not affect testicular development and BTB formation. These cKO mice were analyzed at P49 and P90 and display an intact barrier and uncompromised fertility. We conclude that CXADR possesses no direct role in testicular physiology in vivo. © 2014 Society for Reproduction and Fertility.

  1. Alternative Sources of Adult Stem Cells: Human Amniotic Membrane

    NASA Astrophysics Data System (ADS)

    Wolbank, Susanne; van Griensven, Martijn; Grillari-Voglauer, Regina; Peterbauer-Scherb, Anja

    Human amniotic membrane is a highly promising cell source for tissue engineering. The cells thereof, human amniotic epithelial cells (hAEC) and human amniotic mesenchymal stromal cells (hAMSC), may be immunoprivileged, they represent an early developmental status, and their application is ethically uncontroversial. Cell banking strategies may use freshly isolated cells or involve in vitro expansion to increase cell numbers. Therefore, we have thoroughly characterized the effect of in vitro cultivation on both phenotype and differentiation potential of hAEC. Moreover, we present different strategies to improve expansion including replacement of animal-derived supplements by human platelet products or the introduction of the catalytic subunit of human telomerase to extend the in vitro lifespan of amniotic cells. Characterization of the resulting cultures includes phenotype, growth characteristics, and differentiation potential, as well as immunogenic and immunomodulatory properties.

  2. Hormonal status of male reproductive system: androgens and estrogens in the testis and epididymis. In vivo and in vitro approaches.

    PubMed

    Bilińska, Barbara; Wiszniewska, Barbara; Kosiniak-Kamysz, Kazimierz; Kotula-Balak, Małgorzata; Gancarczyk, Monika; Hejmej, Anna; Sadowska, Jolanta; Marchlewicz, Mariola; Kolasa, Agnieszka; Wenda-Rózewicka, Lidia

    2006-01-01

    The purpose of this article was to summarize our results on the role of androgens and estrogens in human, rodent and equine testes and epididymides, in both, physiological and patological conditions, obtained in the space of the Solicited Project (084/PO6/2002) financially supported by the State Committee for Scientific Research during the last three years. Testosterone produced by Leydig cells of the testes is clearly the major androgen in the circulation of men and adult males of most mammalian species. However, androgen metabolites make up a significant fraction of total circulating steroids. Moreover, androgen metabolism may proceed to amplify the action of testosterone through its conversion to dihydrotestosterone (DHT) or its aromatization to estradiol. The distribution of androgen and estrogen receptors (ARs and ERs) within male reproductive tissues is important because of their crucial role in mediating androgen and/or estrogen action. Attempts were undertaken to discuss not only the role of aromatase and ERs in mediating the action of estrogens in the male, but also the importance of DHT in hormonal regulation of the epididymis. In the latter, alterations caused by finasteride treatment and lead-induced oxidative stress are described. Male reproductive function of the testis and epididymis reflected by the alterations in enzymatic activity, distribution of steroid hormone receptors, differences in steroid hormone levels and altered gene expression of antioxidant enzymes are also discussed.

  3. Postnatal and adult neurogenesis in the development of human disease.

    PubMed

    Danzer, Steve C

    2008-10-01

    The mammalian brain contains a population of neurons that are continuously generated from late embryogenesis through adulthood-after the generation of almost all other neuronal types. This brain region-the hippocampal dentate gyrus-is in a sense, therefore, persistently immature. Postnatal and adult neurogenesis is likely an essential feature of the dentate, which is critical for learning and memory. Protracted neurogenesis after birth would allow the new cells to develop in conjunction with external events-but it may come with a price: while neurogenesis in utero occurs in a protected environment, children and adults are exposed to any number of hazards, such as toxins and infectious agents. Mature neurons might be resistant to such exposures, but new neurons may be vulnerable. Consistent with this prediction, in adult rodents seizures disrupt the integration of newly generated granule cells, whereas mature granule cells are comparatively unaffected. Significantly, abnormally interconnected cells may contribute to epileptogenesis and/or associated cognitive and memory deficits. Finally, studies increasingly indicate that new granule cells are extremely sensitive to a host of endogenous and exogenous factors, raising the possibility that disrupted granule cell integration may be a common feature of many neurological diseases.

  4. Morphometric aspects of rat testis development.

    PubMed Central

    Gaytan, F; Lucena, M C; Munoz, E; Paniagua, R

    1986-01-01

    A morphometric study of rat testis development and ageing (from 5 to 360 days of age) has been carried out. The testicular volume increases from 10.28 +/- 0.35 mm3 (5 days of age) to 1819.43 +/- 52.67 mm3 (360 days of age), showing the most rapid increase between 20 and 70 days of age (22.6 times). The mean tubular diameter increases from 62.25 +/- 1.50 micron (5 days of age) to 280.81 +/- 9.77 microns (360 days of age) and the tubular length from 2.74 +/- 0.18 m (5 days of age) to 25.45 +/- 1.76 m (360 days of age). Up to 15 days of age, the increase in testicular volume was mainly due to the increase in tubular length, whereas from this age onwards the tubular growth was similar in both length and diameter. Tubular development had nearly finished at 70 days of age. PMID:3429301

  5. The emerging role of connexin 43 in testis pathogenesis.

    PubMed

    Chevallier, D; Carette, D; Gilleron, J; Segretain, D; Pointis, G

    2013-09-01

    Direct intercellular communication is mediated by gap junctions and their constitutive proteins, the connexins, which are organized in a hexameric arrangement forming a channel between adjacent cells. Connexins are essential for cell homeostasis and are also involved in many physiological processes such as cell growth, differentiation and death. Spermatogenesis is a sophisticated model of germ cell proliferation, differentiation, survival and apoptosis, in which one connexin isoform, connexin 43, plays an essential role as evidenced by the targeted genetic deletion of Cx43 gene. A controlled balance of germ cell growth is a prerequisite to maintain either normal level of spermatozoa necessary for fertility and/or to limit an uncontrolled and anarchic germ cell proliferation, a major risk for germ cell tumor cell development. In the present review, we highlight the emerging role of connexins in testis pathogenesis, specifically in two intimately interconnected human testicular diseases: azoospermia with impaired spermatogenesis and testicular germ cell tumors, whose incidence increased during the last decades. This review proposes the gap junction protein connexin 43 as a new potential cancer diagnostic and prognostic marker, as well as a promising therapeutic target for testicular diseases.

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

    PubMed

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

    2006-04-01

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

  7. [Dietary phytoestrogen and its potential benefits in adult human health].

    PubMed

    Garrido, Argelia; de la Maza, María Pía; Valladares, Luis

    2003-11-01

    Human diet contains a series of bioactive vegetal compounds that can improve human health. Among these, there has been a special interest for phytoestrogens. This article reviews the evidence about the potential benefits of phytoestrogens for human health. Forty eight manuscripts were selected for their study design and relevance to human health. The cell growth inhibitory effects of phytoestrogens and their implication in breast cancer are reviewed. Also the effects of these compounds on serum lipid levels and the effectiveness of a phytoestrogen derivate, ipriflavone, on the prevention of osteoporosis are analyzed. Although these compounds have a great potential for improving health, there is still not enough evidence to recommend the routine use of phytoestrogens.

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

    PubMed Central

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

    1996-01-01

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

  9. Drug transporter, P-glycoprotein (MDR1), is an integrated component of the mammalian blood-testis barrier§

    PubMed Central

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

    2009-01-01

    Throughout spermatogenesis, leptotene spermatocytes traverse the blood-testis barrier (BTB) to enter the adluminal compartment of the seminiferous epithelium for continued development. At the same time, the integrity of the BTB, which is constituted by co-existing tight junctions (TJ), basal ectoplasmic specializations (basal ES) and desmosome-like junctions, must be maintained since a breach in barrier function can result in spermatogenic arrest and infertility. There is evidence to suggest that drug transporters may function at the BTB, but little is known about how they contribute to spermatogenesis. In this study, we investigate the role of P-glycoprotein (P-gp), a drug efflux pump, in BTB dynamics. A survey by RT-PCR revealed several transport proteins to be expressed by the testis, including Mdr1 (gene symbol for P-gp), Mrp1, Abcc5 and Slc15a1. It was also demonstrated that P-gp localizes to the BTB in all stages of the epithelial cycle in the adult rat testis, as well as to the Sertoli cell elongated spermatid interface in stages VII–VIII. We continued our study by examining the levels of several transporters in the testis following oral administration of Adjudin, a compound known to affect Sertoli-germ cell adhesion. In this experiment, the steady-state levels of P-gp, MRP1, ABCG1 and SLC15A1 were all found to increase by several-fold within hours of Adjudin treatment during junction restructuring. More importantly, an increase in P-gp association with TJ proteins (e.g., occludin, claudin-11 and JAM-A) was noted when testis lysates from Adjudin-treated rats were used for co-immunoprecipitation experiments, suggesting that P-gp may enhance BTB function during Sertoli-germ cell junction restructuring. PMID:19720156

  10. Nasopharyngeal carriage of Streptococcus pneumoniae in adults infected with human immunodeficiency virus in Jakarta, Indonesia.

    PubMed

    Harimurti, Kuntjoro; Saldi, Siti R F; Dewiasty, Esthika; Khoeri, Miftahuddin M; Yunihastuti, Evi; Putri, Tiara; Tafroji, Wisnu; Safari, Dodi

    2016-01-01

    This study investigated the distribution of serotype and antimicrobial susceptibility of Streptococcus pneumoniae carried by adults infected with human immunodeficiency virus (HIV) in Jakarta, Indonesia. Specimens of nasopharyngeal swab were collected from 200 HIV infected adults aged 21 to 63 years. Identification of S. pneumoniae was done by optochin susceptibility test and PCR for the presence of psaA and lytA genes. Serotyping was performed with sequential multiplex PCR and antibiotic susceptibility with the disk diffusion method. S. pneumoniae strains were carried by 10% adults with serotype 6A/B 20% was common serotype among cultured strains in 20 adults. Most of isolates were susceptible to chloramphenicol (80%) followed by clindamycin (75%), erythromycin (75%), penicillin (55%), and tetracycline (50%). This study found resistance to sulphamethoxazole/trimethoprim was most common with only 15% of strains being susceptible. High non-susceptibility to sulphamethoxazole/trimethoprim was observed in S. pneumoniae strains carried by HIV infected adults in Jakarta, Indonesia.

  11. Molecular Mechanism of Adult Neurogenesis and its Association with Human Brain Diseases

    PubMed Central

    Liu, He; Song, Ni

    2016-01-01

    Recent advances in neuroscience challenge the old dogma that neurogenesis occurs only during embryonic development. Mounting evidence suggests that functional neurogenesis occurs throughout adulthood. This review article discusses molecular factors that affect adult neurogenesis, including morphogens, growth factors, neurotransmitters, transcription factors, and epigenetic factors. Furthermore, we summarize and compare current evidence of associations between adult neurogenesis and human brain diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and brain tumors. PMID:27375363

  12. TRANSCRIPTIONAL REGULATION OF CELL ADHESION AT THE BLOOD-TESTIS BARRIER AND SPERMATOGENESIS IN THE TESTIS

    PubMed Central

    Lui, Wing-Yee; Cheng, C. Yan

    2014-01-01

    Spermatogenesis involves precise co-ordination of multiple cellular events that take place in the seminiferous epithelium composed of Sertoli cells and developing germ cells during the seminiferous epithelial cycle. Given the cyclic and co-ordinated nature of spermatogenesis, temporal and spatial expression of certain genes pertinent to a specific cellular event are essential. As such, transcriptional regulation is one of the major regulatory machineries in controlling the cell type- and stage-specific gene expression, some of which are under the influence of gonadotropins (e.g., FSH and LH) and sex steroids (e.g., testosterone and estradiol-17β). Recent findings regarding transcriptional control of spermatogenesis, most notably target genes at the Sertoli-Sertoli and Sertoli-spermatid interface at the site of the blood-testis barrier (BTB) and apical ectoplasmic specialization (apical ES), respectively, involving in cell adhesion are reviewed and discussed herein. This is a much neglected area of research and a concerted effort by investigators is needed to understand transcriptional regulation of cell adhesion function in the testis particularly at the BTB during spermatogenesis. PMID:23397630

  13. Hepatobiliary disposition of 17-OHPC and taurocholate in fetal human hepatocytes: a comparison with adult human hepatocytes.

    PubMed

    Sharma, Shringi; Ellis, Ewa C S; Gramignoli, Roberto; Dorko, Kenneth; Tahan, Veysel; Hansel, Marc; Mattison, Donald R; Caritis, Steve N; Hines, Ronald N; Venkataramanan, Raman; Strom, Stephen C

    2013-02-01

    Little information is available in the literature regarding the expression and activity of transporters in fetal human liver or cultured cells. A synthetic progesterone structural analog, 17α-hydroxyprogesterone caproate (17-OHPC), is used in the prevention of spontaneous abortion in women with a history of recurrent miscarriage (habitual abortion). 17-OHPC has been reported to traverse the placental barrier and gain access to fetal circulation. In this study, the role of transporters in the disposition of 17-OHPC in fetal and adult human hepatocytes was examined. Progesterone metabolites have been reported to induce trans-inhibition of bile acid transporter, ABCB11. Thus, we investigated the effect of 17-OHPC or its metabolites on [(3)H]taurocholic acid transport in sandwich-cultured human fetal and adult hepatocytes. 17-OHPC was taken up rapidly into the cells and transported out partially by an active efflux process that was significantly inhibited by cold temperature, cyclosporine, verapamil, and rifampin. The active efflux mechanism was observed in both adult and fetal hepatocyte cultures. 17-OHPC produced a concentration-dependent inhibition of taurocholate efflux into canaliculi in sandwich-cultured adult and fetal human hepatocytes. However, given the high concentrations required to cause inhibition of these transport processes, no adverse effects would be anticipated from therapeutic levels of 17-OHPC. We also evaluated the expression of various hepatic transporters (ABCB1, ABCB4, SLCO1B1, SLCO1B3, SLCO2B1, ABCB11, SLC10A1, ABCC2, ABCC3, ABCC4, and ABCG2) in fetal and adult hepatocytes. With the exception of ABCB4, all transporters examined were expressed, albeit at lower mRNA levels in fetal hepatocytes compared with adults.

  14. Hepatobiliary Disposition of 17-OHPC and Taurocholate in Fetal Human Hepatocytes: A Comparison with Adult Human Hepatocytes

    PubMed Central

    Sharma, Shringi; Ellis, Ewa C. S.; Gramignoli, Roberto; Dorko, Kenneth; Tahan, Veysel; Hansel, Marc; Mattison, Donald R.; Caritis, Steve N.; Hines, Ronald N.; Venkataramanan, Raman

    2013-01-01

    Little information is available in the literature regarding the expression and activity of transporters in fetal human liver or cultured cells. A synthetic progesterone structural analog, 17α-hydroxyprogesterone caproate (17-OHPC), is used in the prevention of spontaneous abortion in women with a history of recurrent miscarriage (habitual abortion). 17-OHPC has been reported to traverse the placental barrier and gain access to fetal circulation. In this study, the role of transporters in the disposition of 17-OHPC in fetal and adult human hepatocytes was examined. Progesterone metabolites have been reported to induce trans-inhibition of bile acid transporter, ABCB11. Thus, we investigated the effect of 17-OHPC or its metabolites on [3H]taurocholic acid transport in sandwich-cultured human fetal and adult hepatocytes. 17-OHPC was taken up rapidly into the cells and transported out partially by an active efflux process that was significantly inhibited by cold temperature, cyclosporine, verapamil, and rifampin. The active efflux mechanism was observed in both adult and fetal hepatocyte cultures. 17-OHPC produced a concentration-dependent inhibition of taurocholate efflux into canaliculi in sandwich-cultured adult and fetal human hepatocytes. However, given the high concentrations required to cause inhibition of these transport processes, no adverse effects would be anticipated from therapeutic levels of 17-OHPC. We also evaluated the expression of various hepatic transporters (ABCB1, ABCB4, SLCO1B1, SLCO1B3, SLCO2B1, ABCB11, SLC10A1, ABCC2, ABCC3, ABCC4, and ABCG2) in fetal and adult hepatocytes. With the exception of ABCB4, all transporters examined were expressed, albeit at lower mRNA levels in fetal hepatocytes compared with adults. PMID:23129211

  15. Androgen responsive adult human prostatic epithelial cell lines immortalized by human papillomavirus 18.

    PubMed

    Bello, D; Webber, M M; Kleinman, H K; Wartinger, D D; Rhim, J S

    1997-06-01

    Prostate cancer and benign tumors of the prostate are the two most common neoplastic diseases in men in the United States, however, research on their causes and treatment has been slow because of the difficulty in obtaining fresh samples of human tissue and a lack of well characterized cell lines which exhibit growth and differentiation characteristics of normal prostatic epithelium. Non-neoplastic adult human prostatic epithelial cells from a white male donor were immortalized with human papillomavirus 18 which resulted in the establishment of the RWPE-1 cell line. Cells from the RWPE-1 cell line were further transformed by v-Ki-ras to establish the RWPE-2 cell line. The objectives of this study were to: (1) establish the prostatic epithelial origin and androgen responsiveness of RWPE-1 and RWPE-2 cell lines; (2) examine their response to growth factors; and (3) establish the malignant characteristics of the RWPE-2 cell line. Immunoperoxidase staining showed that both RWPE-1 and RWPE-2 cells express cytokeratins 8 and 18, which are characteristic of luminal prostatic epithelial cells, but they also coexpress basal cell cytokeratins. These cell lines show growth stimulation and prostate specific antigen (PSA) and androgen receptor (AR) expression in response to the synthetic androgen mibolerone, which establishes their prostatic epithelial origin. Both cell lines also show a dose-dependent growth stimulation by EGF and bFGF and growth inhibition when exposed to TGF-beta, however, the transformed RWPE-2 cells are less responsive. RWPE-1 cells neither grow in agar nor form tumors when injected into nude mice with or without Matrigel. However, RWPE-2 cells form colonies in agar and tumors in nude mice. In the in vitro invasion assay, RWPE-1 cells are not invasive whereas RWPE-2 cells are invasive. Nuclear expression of p53 and Rb proteins was heterogeneous but detectable by immunostaining in both cell lines. The RWPE-1 cells, which show many normal cell

  16. Hesperetin induces melanin production in adult human epidermal melanocytes.

    PubMed

    Usach, Iris; Taléns-Visconti, Raquel; Magraner-Pardo, Lorena; Peris, José-Esteban

    2015-06-01

    One of the major sources of flavonoids for humans are citrus fruits, hesperidin being the predominant flavonoid. Hesperetin (HSP), the aglycon of hesperidin, has been reported to provide health benefits such as antioxidant, anti-inflammatory and anticarcinogenic effects. However, the effect of HSP on skin pigmentation is not clear. Some authors have found that HSP induces melanogenesis in murine B16-F10 melanoma cells, which, if extrapolated to in vivo conditions, might protect skin against photodamage. Since the effect of HSP on normal melanocytes could be different to that observed on melanoma cells, the described effect of HSP on murine melanoma cells has been compared to the effect obtained using normal human melanocytes. HSP concentrations of 25 and 50 µM induced melanin synthesis and tyrosinase activity in human melanocytes in a concentration-dependent manner. Compared to control melanocytes, 25 µM HSP increased melanin production and tyrosinase activity 1.4-fold (p < 0.01) and 1.1-fold (p < 0.01), respectively, and the corresponding increases in the case of 50 µM HSP were 1.9-fold (p < 0.001) and 1.3-fold (p < 0.001). Therefore, HSP could be considered a valuable photoprotective substance if its capacity to increase melanin production in human melanocyte cultures could be reproduced on human skin.

  17. A century of trends in adult human height.

    PubMed

    2016-07-26

    Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5-22.7) and 16.5 cm (13.3-19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8-144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.

  18. A century of trends in adult human height

    PubMed Central

    2016-01-01

    Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3–19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8–144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries. DOI: http://dx.doi.org/10.7554/eLife.13410.001 PMID:27458798

  19. Undescended testis: how extensive should the work up be?

    PubMed

    Shera, Altaf Hussain; Baba, Aejaz Ahsan; Gupta, Shyam Kumar; Gupta, Geetanjali; Sherwani, Afak Yusuf

    2010-01-01

    The aim of this study was to highlight various anomalies associated with undescended testis and to determine how much work up is necessary for this condition. The study was conducted in the department of Pediatric Surgery SKIMS Srinagar, Kashmir. All patients between 0-14 years of age who attended out patient department (OPD) from January 2002 to December 2003 with maldescent of testes were included in the study. Detailed relevant history and physical examination findings were recorded in all the cases. Baseline investigations were performed along with ultrasonography of the abdomen. In relevant cases other investigations like intravenous urography, micturating cystourethrography, CT scan and laparoscopy were performed as and when indicated. A total of 250 cases of undescended testis were registered during this period. Maximum number of cases were in the age group of 5-10 years. In 130 (52%) cases the right testis was undescended while 75 (30%) had left sided undescended testis and 45 (18%) had bilateral undescended testis. Maldescended testis comprised 11% of the admissions. The majority of cases were having gestational age of 37 weeks or more. The associated anomalies picked up on investigations included duplication of upper urinary tract (3.2%), hydronephrosis and polycystic kidney (0.8% each), horseshoe kidney, ectopic kidney, crossed renal ectopia (0.4% each) Posterior urethral valves, Prune belly syndrome (0.4%) and spina bifida (0.4%). On detailed clinical examination of genitalia several abnormalities were picked which included hydrocele, hypospadias, hernia, chordee, micropenis and ambiguous genitalia. We recommend ultrasonography to be done in all cases of undescended testis in addition to a thorough history and physical examination. Intravenous pyelography, micturating cystourethrogram, CT scan and other investigations should be performed selectively based on history, physical examination or ultrasound findings.

  20. A novel, testis-specific mRNA transcript encoding an NH2-terminal truncated nitric-oxide synthase.

    PubMed

    Wang, Y; Goligorsky, M S; Lin, M; Wilcox, J N; Marsden, P A

    1997-04-25

    mRNA diversity represents a major theme of neuronal nitric-oxide synthase (nNOS) gene expression in somatic cells/tissues. Given that gonads often express unique and biologically informative variants of complex genes, we determined whether unique variants of nNOS are expressed in the testis. Analysis of cDNA clones isolated from human testis identified a novel, testis-specific nNOS (TnNOS) mRNA transcript. A predicted 3294-base pair open reading frame encodes an NH2-terminal truncated protein of 1098 amino acids. Measurement of calcium-activated L-[14C]citrulline formation and nitric oxide release in CHO-K1 cells stably transfected with the TnNOS cDNA indicates that this protein is a calcium-dependent nitric-oxide synthase with catalytic activity comparable to that of full-length nNOS. TnNOS transcripts exhibit novel 5' mRNA sequences encoded by two unique exons spliced to exon 4 of the full-length nNOS. Characterization of the genomic structure indicates that exonic regions used by the novel TnNOS are expressed from intron 3 of the NOS1 gene. Although lacking canonical TATA and CAAT boxes, the 5'-flanking region of the TnNOS exon 1 contains multiple putative cis-regulatory elements including those implicated in testis-specific gene expression. The downstream promoter of the human nNOS gene, which directs testis-specific expression of a novel NH2-terminal truncated nitric-oxide synthase, represents the first reported example in the NOS gene family of transcriptional diversity producing a variant NOS protein.

  1. Molecular Cloning, mRNA Expression, and Localization of the G-protein Subunit Galphaq in Sheep Testis and Epididymis

    PubMed Central

    Li, Zhen; Lu, Jieli; Sun, Xiaowei; Pang, Quanhai; Zhao, Yiwen

    2016-01-01

    The reproductive function of G-protein subunit Galphaq (GNAQ), a member of the G protein alpha subunit family, has been extensively studied in humans and rats. However, no data is available on its status in ruminants. The objectives of this study were to evaluate the expression pattern of the GNAQ in the testis and epididymis of sheep by polymerase chain reaction (PCR). The mRNA expression levels were detected by real-time fluorescent quantitative PCR, and cellular localization of GNAQ in the testis and epididymis was examined by immunohistochemistry. Additionally, GNAQ protein was qualitatively evaluated via western blot, with the results indicating that similarities between GNAQ mRNA levels from sheep was highly conserved with those observed in Bos taurus and Sus scrofa. Our results also indicated that GNAQ exists in the caput and cauda epididymis of sheep, while GNAQ in the testis and epididymis was localized to Leydig cells, spermatogonial stem cells, spermatocytes, Sertoli cells, spermatid, principal cells, and epididymis interstitial cells. The concentrations of GNAQ mRNA and protein in the caput and cauda epididymis were significantly greater than those observed in the corpus epididymis (p<0.01) and testis (p<0.05). Our results indicated that GNAQ exists at high concentrations in the caput and cauda epididymis of sheep, suggesting that GNAQ may play an important role in gonad development and sperm maturation. PMID:27004818

  2. Immune physiology and oogenesis in fetal and adult humans, ovarian infertility, and totipotency of adult ovarian stem cells.

    PubMed

    Bukovsky, Antonin; Caudle, Michael R; Virant-Klun, Irma; Gupta, Satish K; Dominguez, Roberto; Svetlikova, Marta; Xu, Fei

    2009-03-01

    It is still widely believed that while oocytes in invertebrates and lower vertebrates are periodically renewed throughout life, oocytes in humans and higher vertebrates are formed only during the fetal/perinatal period. However, this dogma is questioned, and clashes with Darwinian evolutionary theory. Studies of oogenesis and follicular renewal from ovarian stem cells (OSCs) in adult human ovaries, and of the role of third-party bone marrow-derived cells (monocyte-derived tissue macrophages and T lymphocytes) could help provide a better understanding of the causes of ovarian infertility, its prevention, and potential treatment. We have reported differentiation of distinct cell types from OSC and the production of new eggs in cultures derived from premenopausal and postmenopausal human ovaries. OSCs are also capable of producing neural/neuronal cells in vitro after sequential stimulation with sex steroid combinations. Hence, OSC represent a unique type of totipotent adult stem cells, which could be utilized for autologous treatment of premature ovarian failure and also for autologous stem cell therapy of neurodegenerative diseases without use of allogeneic embryonic stem cells or somatic cell nuclear transfer. The in vivo application of sex steroid combinations may augment the proliferation of existing neural stem cells and their differentiation into mature neuronal cells (systemic regenerative therapy). Such treatment may also stimulate the transdifferentiation of autologous neural stem cell precursors into neural stem cells useful for topical or systemic regenerative treatment.

  3. Adult humans' understanding of support relations: an up-linkage replication.

    PubMed

    Silva, Francisco J; Ten Hope, Merritt I; Tucker, Ali L

    2014-12-01

    In an up-linkage replication, three experiments examined adult humans' folk physics, i.e., their naturally occurring and spontaneous understanding of the physical world, using a violation of expectation (VOE) task and stimuli similar to those used to study chimpanzees', monkeys', and rooks' folk physics. Unlike what has been reported with nonhuman primates, adult humans did not look longer at physically impossible than possible events, though they did rate the physically impossible events as more interesting and novel than the possible events. These results underscore that behavior during a VOE experiment has many possible causes, only one of which may be a subject's folk physics.

  4. Comparison of proliferating cells between human adult and fetal eccrine sweat glands.

    PubMed

    Li, Hai-Hong; Fu, Xiao-Bing; Zhang, Lei; Zhou, Gang

    2008-04-01

    Studies of sweat glands had demonstrated that there were degenerating cells and proliferating cells in the eccrine sweat glands. To compare the differences in the proliferating cells between human adult and fetal eccrine sweat glands, immunostaining of proliferating-associated proliferating cell nuclear antigen (PCNA) and Ki67 nuclear antigen (Ki67) was performed, and the location and the percentage of the positive staining cells were analyzed. The results showed that a few cells of the secretory and ductal portion in both the adult and fetal eccrine sweat glands stained positive with Ki67 and PCNA. The labeling index of PCNA in adult eccrine sweat glands was 34.71 +/- 8.37%, while that in the fetal was 62.72 +/- 6.54%. The labeling index of PCNA in fetal eccrine sweat glands was higher than that in adult. Myoepithelial cells were negative staining with anti-PCNA antibody in adult eccrine sweat glands, while in the fetal a few myoepithelial cells were positive staining. Labeling index of Ki67 in adult eccrine sweat glands was similar to that in the fetal, ranging from 0.5 to 4.3%. Myoepithelial cells of the adult and fetal eccrine sweat glands both were negative staining with anti-Ki67 antibody. We concluded that the myoepithelial cells had proliferating ability only in fetal eccrine sweat glands, and that the proliferating ability of fetal eccrine sweat glands was stronger than that of the adult.

  5. The landscape of genomic imprinting across diverse adult human tissues.

    PubMed

    Baran, Yael; Subramaniam, Meena; Biton, Anne; Tukiainen, Taru; Tsang, Emily K; Rivas, Manuel A; Pirinen, Matti; Gutierrez-Arcelus, Maria; Smith, Kevin S; Kukurba, Kim R; Zhang, Rui; Eng, Celeste; Torgerson, Dara G; Urbanek, Cydney; Li, Jin Billy; Rodriguez-Santana, Jose R; Burchard, Esteban G; Seibold, Max A; MacArthur, Daniel G; Montgomery, Stephen B; Zaitlen, Noah A; Lappalainen, Tuuli

    2015-07-01

    Genomic imprinting is an important regulatory mechanism that silences one of the parental copies of a gene. To systematically characterize this phenomenon, we analyze tissue specificity of imprinting from allelic expression data in 1582 primary tissue samples from 178 individuals from the Genotype-Tissue Expression (GTEx) project. We characterize imprinting in 42 genes, including both novel and previously identified genes. Tissue specificity of imprinting is widespread, and gender-specific effects are revealed in a small number of genes in muscle with stronger imprinting in males. IGF2 shows maternal expression in the brain instead of the canonical paternal expression elsewhere. Imprinting appears to have only a subtle impact on tissue-specific expression levels, with genes lacking a systematic expression difference between tissues with imprinted and biallelic expression. In summary, our systematic characterization of imprinting in adult tissues highlights variation in imprinting between genes, individuals, and tissues. © 2015 Baran et al.; Published by Cold Spring Harbor Laboratory Press.

  6. The landscape of genomic imprinting across diverse adult human tissues

    PubMed Central

    Baran, Yael; Subramaniam, Meena; Biton, Anne; Tukiainen, Taru; Tsang, Emily K.; Rivas, Manuel A.; Pirinen, Matti; Gutierrez-Arcelus, Maria; Smith, Kevin S.; Kukurba, Kim R.; Zhang, Rui; Eng, Celeste; Torgerson, Dara G.; Urbanek, Cydney; Li, Jin Billy; Rodriguez-Santana, Jose R.; Burchard, Esteban G.; Seibold, Max A.; MacArthur, Daniel G.; Montgomery, Stephen B.; Zaitlen, Noah A.; Lappalainen, Tuuli

    2015-01-01

    Genomic imprinting is an important regulatory mechanism that silences one of the parental copies of a gene. To systematically characterize this phenomenon, we analyze tissue specificity of imprinting from allelic expression data in 1582 primary tissue samples from 178 individuals from the Genotype-Tissue Expression (GTEx) project. We characterize imprinting in 42 genes, including both novel and previously identified genes. Tissue specificity of imprinting is widespread, and gender-specific effects are revealed in a small number of genes in muscle with stronger imprinting in males. IGF2 shows maternal expression in the brain instead of the canonical paternal expression elsewhere. Imprinting appears to have only a subtle impact on tissue-specific expression levels, with genes lacking a systematic expression difference between tissues with imprinted and biallelic expression. In summary, our systematic characterization of imprinting in adult tissues highlights variation in imprinting between genes, individuals, and tissues. PMID:25953952

  7. A recurrent p.Arg92Trp variant in steroidogenic factor-1 (NR5A1) can act as a molecular switch in human sex development

    PubMed Central

    Bashamboo, Anu; Donohoue, Patricia A.; Vilain, Eric; Rojo, Sandra; Calvel, Pierre; Seneviratne, Sumudu N.; Buonocore, Federica; Barseghyan, Hayk; Bingham, Nathan; Rosenfeld, Jill A.; Mulukutla, Surya Narayan; Jain, Mahim; Burrage, Lindsay; Dhar, Shweta; Balasubramanyam, Ashok; Lee, Brendan; Dumargne, Marie-Charlotte; Eozenou, Caroline; Suntharalingham, Jenifer P.; de Silva, KSH; Lin, Lin; Bignon-Topalovic, Joelle; Poulat, Francis; Lagos, Carlos F.; McElreavey, Ken; Achermann, John C.

    2016-01-01

    Cell lineages of the early human gonad commit to one of the two mutually antagonistic organogenetic fates, the testis or the ovary. Some individuals with a 46,XX karyotype develop testes or ovotestes (testicular or ovotesticular disorder of sex development; TDSD/OTDSD), due to the presence of the testis-determining gene, SRY. Other rare complex syndromic forms of TDSD/OTDSD are associated with mutations in pro-ovarian genes that repress testis development (e.g. WNT4); however, the genetic cause of the more common non-syndromic forms is unknown. Steroidogenic factor-1 (known as NR5A1) is a key regulator of reproductive development and function. Loss-of-function changes in NR5A1 in 46,XY individuals are associated with a spectrum of phenotypes in humans ranging from a lack of testis formation to male infertility. Mutations in NR5A1 in 46,XX women are associated with primary ovarian insufficiency, which includes a lack of ovary formation, primary and secondary amenorrhoea as well as early menopause. Here, we show that a specific recurrent heterozygous missense mutation (p.Arg92Trp) in the accessory DNA-binding region of NR5A1 is associated with variable degree of testis development in 46,XX children and adults from four unrelated families. Remarkably, in one family a sibling raised as a girl and carrying this NR5A1 mutation was found to have a 46,XY karyotype with partial testicular dysgenesis. These unique findings highlight how a specific variant in a developmental transcription factor can switch organ fate from the ovary to testis in mammals and represents the first missense mutation causing isolated, non-syndromic 46,XX testicular/ovotesticular DSD in humans. PMID:27378692

  8. Identification of a dendritic cell population in normal testis and in chronically inflamed testis of rats with autoimmune orchitis.

    PubMed

    Rival, Claudia; Lustig, Livia; Iosub, Radu; Guazzone, Vanesa A; Schneider, Eva; Meinhardt, Andreas; Fijak, Monika

    2006-05-01

    Experimental autoimmune orchitis (EAO) in the rat is the primary chronic animal model for the investigation of one of the main causes of male infertility, viz., testicular inflammation. Dendritic cells (DC) are potent antigen-presenting cells that play a fundamental role in autoimmune disease. We investigated the number of DC in normal testis and examined whether DC infiltrated the testis during the development of EAO. EAO was induced by active immunization with testis homogenate and adjuvants in two strains of rat (Wistar and Sprague Dawley). The presence of DC in testis was determined, 50 and 80 days after the first immunization, by immunohistochemical staining with specific antibodies (OX-62 and CD11c), and then the total number of DC was measured by stereological analysis. Labeled cells were found only in the interstitial compartment and within granulomas of EAO animals. The number of DC in EAO testes increased compared with control rats in both strains, whereas the number of OX-62+ and CD11c+ cells in adjuvant controls remained unchanged compared with untreated rats. Interspecies variations in the quantity of DC were found, with the total number of DC per testis in untreated and adjuvant control Sprague-Dawley rats being about three times higher than that seen in Wistar rats. Moreover, the increase in DC numbers at 80 days was less prominent in EAO testes of Sprague-Dawley rats than in the Wistar strain in which EAO was more severe and showed a higher number of granulomae. Thus, we have identified the DC population in normal and chronically inflamed testis. The increase in DC observed in EAO suggests that, under inflammatory conditions, the modified action(s) of these cells is a factor in the induction of the autoimmune response in testis.

  9. Oncogenic cancer/testis antigens: prime candidates for immunotherapy.

    PubMed

    Gjerstorff, Morten F; Andersen, Mads H; Ditzel, Henrik J

    2015-06-30

    Recent developments have set the stage for immunotherapy as a supplement to conventional cancer treatment. Consequently, a significant effort is required to further improve efficacy and specificity, particularly the identification of optimal therapeutic targets for clinical testing. Cancer/testis antigens are immunogenic, highly cancer-specific, and frequently expressed in various types of cancer, which make them promising candidate targets for cancer immunotherapy, including cancer vaccination and adoptive T-cell transfer with chimeric T-cell receptors. Our current understanding of tumor immunology and immune escape suggests that targeting oncogenic antigens may be beneficial, meaning that identification of cancer/testis antigens with oncogenic properties is of high priority. Recent work from our lab and others provide evidence that many cancer/testis antigens, in fact, have oncogenic functions, including support of growth, survival and metastasis. This novel insight into the function of cancer/testis antigens has the potential to deliver more effective cancer vaccines. Moreover, immune targeting of oncogenic cancer/testis antigens in combination with conventional cytotoxic therapies or novel immunotherapies such as checkpoint blockade or adoptive transfer, represents a highly synergistic approach with the potential to improve patient survival.

  10. Direct Generation of Human Neuronal Cells from Adult Astrocytes by Small Molecules.

    PubMed

    Gao, Longfei; Guan, Wuqiang; Wang, Min; Wang, Huihan; Yu, Jiali; Liu, Qing; Qiu, Binlong; Yu, Yongchun; Ping, Yifang; Bian, Xiuwu; Shen, Li; Pei, Gang

    2017-03-14

    Astrocytes, due to the proximity to neuronal lineage and capability to proliferate, are ideal starting cells to regenerate neurons. Human fetal astrocytes have been successfully converted into neuronal cells by small molecules, which offered a broader range of further applications than transcription factor-mediated neuronal reprogramming. Here we report that human adult astrocytes could also be converted into neuronal cells by a different set of small molecules. These induced cells exhibited typical neuronal morphologies, expressed neuronal markers, and displayed neuronal electrophysiological properties. Genome-wide RNA-sequencing analysis showed that the global gene expression profile of induced neuronal cells resembled that of human embryonic stem cell-differentiated neurons. When transplanted into post-natal mouse brains, these induced neuronal cells could survive and become electrophysiologically mature. Altogether, our study provides a strategy to directly generate transgene-free neuronal cells from human adult astrocytes by small molecules. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Impact of growth hormone hypersecretion on the adult human kidney.

    PubMed

    Grunenwald, Solange; Tack, Ivan; Chauveau, Dominique; Bennet, Antoine; Caron, Philippe

    2011-12-01

    Acromegaly is most often secondary to a GH-secreting pituitary adenoma with increased Insulin-like Growth Factor type 1 (IGF-1) level. The consequences of GH/IGF-1 hypersecretion reflect the diversity of action of these hormones. The genes of the GH receptor (GHR), IGF-1, IGF-1 receptor (IGF-1R) and IGF-binding proteins (IGF-BP) are physiologically expressed in the adult kidney, suggesting a potential role of the somatotropic axis on renal structure and functions. The expression of these proteins is highly organized and differs according to the anatomical and functional segments of the nephron suggesting different roles of GH and IGF-1 in these segments. In animals, chronic exposure to high doses of GH induces glomerulosclerosis and increases albuminuria. Studies in patients with GH hypersecretion have identified numerous targets of GH/IGF-1 axis on the kidney: 1) an impact on renal filtration with increased glomerular filtration rate (GFR), 2) a structural impact with an increase in kidney weight and glomerular hypertrophy, and 3) a tubular impact leading to hyperphosphatemia, hypercalciuria and antinatriuretic effects. Despite the increased glomerular filtration rate observed in patients with GH hypersecretion, GH is an inefficient treatment for chronic renal failure. GH and IGF-1 seem to be involved in the physiopathology of diabetic nephropathy; this finding offers the possibility of targeting the GH/IGF-1 axis for the prevention and the treatment of diabetic nephropathy. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  12. Testosterone affects language areas of the adult human brain.

    PubMed

    Hahn, Andreas; Kranz, Georg S; Sladky, Ronald; Kaufmann, Ulrike; Ganger, Sebastian; Hummer, Allan; Seiger, Rene; Spies, Marie; Vanicek, Thomas; Winkler, Dietmar; Kasper, Siegfried; Windischberger, Christian; Swaab, Dick F; Lanzenberger, Rupert

    2016-05-01

    Although the sex steroid hormone testosterone is integrally involved in the development of language processing, ethical considerations mostly limit investigations to single hormone administrations. To circumvent this issue we assessed the influence of continuous high-dose hormone application in adult female-to-male transsexuals. Subjects underwent magnetic resonance imaging before and after 4 weeks of testosterone treatment, with each scan including structural, diffusion weighted and functional imaging. Voxel-based morphometry analysis showed decreased gray matter volume with increasing levels of bioavailable testosterone exclusively in Broca's and Wernicke's areas. Particularly, this may link known sex differences in language performance to the influence of testosterone on relevant brain regions. Using probabilistic tractography, we further observed that longitudinal changes in testosterone negatively predicted changes in mean diffusivity of the corresponding structural connection passing through the extreme capsule. Considering a related increase in myelin staining in rodents, this potentially reflects a strengthening of the fiber tract particularly involved in language comprehension. Finally, functional images at resting-state were evaluated, showing increased functional connectivity between the two brain regions with increasing testosterone levels. These findings suggest testosterone-dependent neuroplastic adaptations in adulthood within language-specific brain regions and connections. Importantly, deteriorations in gray matter volume seem to be compensated by enhancement of corresponding structural and functional connectivity. Hum Brain Mapp 37:1738-1748, 2016. © 2016 Wiley Periodicals, Inc.

  13. Testosterone affects language areas of the adult human brain

    PubMed Central

    Hahn, Andreas; Kranz, Georg S.; Sladky, Ronald; Kaufmann, Ulrike; Ganger, Sebastian; Hummer, Allan; Seiger, Rene; Spies, Marie; Vanicek, Thomas; Winkler, Dietmar; Kasper, Siegfried; Windischberger, Christian; Swaab, Dick F.

    2016-01-01

    Abstract Although the sex steroid hormone testosterone is integrally involved in the development of language processing, ethical considerations mostly limit investigations to single hormone administrations. To circumvent this issue we assessed the influence of continuous high‐dose hormone application in adult female‐to‐male transsexuals. Subjects underwent magnetic resonance imaging before and after 4 weeks of testosterone treatment, with each scan including structural, diffusion weighted and functional imaging. Voxel‐based morphometry analysis showed decreased gray matter volume with increasing levels of bioavailable testosterone exclusively in Broca's and Wernicke's areas. Particularly, this may link known sex differences in language performance to the influence of testosterone on relevant brain regions. Using probabilistic tractography, we further observed that longitudinal changes in testosterone negatively predicted changes in mean diffusivity of the corresponding structural connection passing through the extreme capsule. Considering a related increase in myelin staining in rodents, this potentially reflects a strengthening of the fiber tract particularly involved in language comprehension. Finally, functional images at resting‐state were evaluated, showing increased functional connectivity between the two brain regions with increasing testosterone levels. These findings suggest testosterone‐dependent neuroplastic adaptations in adulthood within language‐specific brain regions and connections. Importantly, deteriorations in gray matter volume seem to be compensated by enhancement of corresponding structural and functional connectivity. Hum Brain Mapp 37:1738–1748, 2016. © 2016 Wiley Periodicals, Inc. PMID:26876303

  14. Bacteriology of severe periodontitis in young adult humans.

    PubMed Central

    Moore, W E; Holdeman, L V; Smibert, R M; Hash, D E; Burmeister, J A; Ranney, R R

    1982-01-01

    A total of 78 bacteriological samples were taken from the supragingival tooth surface after superficial cleaning with toothpicks or from the periodontal sulci of 42 affected sites in 21 adolescents or young adults with severe generalized periodontitis. Of 190 bacterial species, subspecies, or serotypes detected among 2,723 isolates, 11 species exceeded 1% of the subgingival flora and were most closely associated with the diseased sulci. Eleven others were also sufficiently frequent to be suspect agents of tissue destruction. Many of these species are known pathogens of other body sites. In addition, 10 species of Treponema were isolated. One of these and the "large treponeme" were also more closely associated with severe periodontitis than they were with healthy sites or gingivitis. There were highly significant differences between the composition of the flora of the affected sulci and the flora of (i) the adjacent supragingival tooth surface, (ii) the gingival crevice of periodontally healthy people, and (iii) sites with a gingival index score of 0 or 2 in experimental gingivitis studies. The floras of different individuals were also significantly different. There was no statistically detectable effect of sampling per se upon the composition of the flora of subsequent samples from the same sites. The composition of the supragingival flora of the patients with severe generalized periodontitis that had serum antibody to Actinobacillus actinomycetemcomitans was significantly different from the supragingival flora of patients without this serum antibody. However, there was no statistically significant difference in the composition of their subgingival floras. PMID:7152665

  15. Perinatal inflammation and adult psychopathology: From preclinical models to humans.

    PubMed

    Depino, Amaicha Mara

    2017-09-07

    Perinatal environment plays a crucial role in brain development and determines its function through life. Epidemiological studies and clinical reports link perinatal exposure to infection and/or immune activation to various psychiatric disorders. In addition, accumulating evidence from animal models shows that perinatal inflammation can affect various behaviors relevant to psychiatric disorders such as schizophrenia, autism, anxiety and depression. Remarkably, the effects on behavior and brain function do not always depend on the type of inflammatory stimulus or the perinatal age targeted, so diverse inflammatory events can have similar consequences on the brain. Moreover, other perinatal environmental factors that affect behavior (e.g. diet and stress) also elicit inflammatory responses. Understanding the interplay between perinatal environment and inflammation on brain development is required to identify the mechanisms through which perinatal inflammation affect brain function in the adult animal. Evidence for the role of the peripheral immune system and glia on perinatal programming of behavior is discussed in this review, along with recent evidence for the role of epigenetic mechanisms affecting gene expression in the brain. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Fascicles of the adult human Achilles tendon - an anatomical study.

    PubMed

    Szaro, Paweł; Witkowski, Grzegorz; Smigielski, Robert; Krajewski, Paweł; Ciszek, Bogdan

    2009-12-01

    The Achilles or calcaneal tendon is the structural base for the biomechanical work of the ankle joint. The purpose of this study is to describe the internal structure of the human Achilles tendon. The anatomy of the Achilles tendon has been described in lower mammals in which it has three parts which can be dissected from its beginning to the insertion onto the calcaneus. The partial ruptures of each part suggest that the human Achilles tendon may also be composed of parts. The Achilles tendon is one of the most commonly torn tendons in the human body. Each segment of the Achilles tendon described by us can be ruptured separately, which can cause a partial dysfunction in flexion of the ankle joint as observed in clinical practice. We dissected 20 Achilles tendons previously fixed in 10% formaldehyde and 20 fresh-frozen Achilles tendons, paying particular attention to the relationship between the lateral and medial heads of the gastrocnemius and the soleus muscles. The layer-by-layer method and a microscope were used in our study. We found that the medial group of fibers from the medial head of the gastrocnemius muscle constitutes the posterior layer of the tendon. The lateral border of the tendon is composed of the fibers from the lateral part of the medial head of the gastrocnemius muscle. The fibers from the lateral head of the gastrocnemius muscle constitute the anterior layer of the Achilles tendon. The fibers from the soleus muscle are located in the anteromedial part of the Achilles tendon. Our findings are supported by clinical descriptions and observations of the partial rupture of the Achilles tendon. 2009 Elsevier GmbH.

  17. Contact and perspective taking improve humanness standards and perceptions of humanness of older adults and people with dementia: a cross-sectional survey study.

    PubMed

    Miron, Anca M; McFadden, Susan H; Hermus, Nathan J; Buelow, Jennifer; Nazario, Amanda S; Seelman, Katarena

    2017-10-01

    No empirical work has systematically explored perceptions of humanness of people with dementia and of older adults and the variables that could improve these perceptions. We thus investigated the role of contact and perspective taking in improving perceptions of humanness of these social groups. To do so, we developed a new concept, humanness standards, defined as the amount of evidence of ability impairment needed to conclude that elderly people and those with dementia have lost personhood. We used a cross-sectional survey design (n = 619) to assess participants' humanness standards and perceptions of uniquely human characteristics and human nature characteristics of two social groups (people with dementia and older adults). Half the participants (n = 311) completed a survey about people with dementia and half (n = 308) assessed older adults. People with dementia were perceived as possessing humanness characteristics to a lesser extent than were older adults. For both groups, contact predicted enhanced perceptions of humanness characteristics. Participants' degree of contact with individuals with dementia also predicted humanness standards, but only under low perspective-taking conditions. As predicted, for older adults, participants set the highest humanness impairment thresholds in the high contact/high perspective-taking condition. We conclude that while social programs that bring persons with dementia and other individuals in contact could change humanness standards and perceptions of humanness characteristics of people with dementia, in the case of elderly adults, the contact must be supplemented by variables that facilitate taking the perspective of the person.

  18. Purification and partial characterization of myosin II from rat testis.

    PubMed

    Dias, Decivaldo dos Santos; Coelho, Milton Vieira

    2007-10-01

    The intent, in this work, was to isolate rat testis myosin II. Testis 40,000 x g x 40' supernatant was frozen at -20 degrees C for 48 h and, after it was thawed and centrifuged. The precipitate, after washed twice, was enriched in three polypeptides bands: p205, p43 and one that migrated together with the front of the gel. These polypeptides were solubilized in pH 10.8 at 27 degrees C and separated in Sephacryl S-400 column. Three low weight polypeptides co-eluted together with p205. The p205 was marked with anti-myosin II, possess actin-stimulated Mg-ATPase activity and co-sedimented with F-actin in the absence, but not in the presence, of ATP. In the present study, we have been developing a method for purification of myosin II from rat testis.

  19. Does the adult human ciliary body epithelium contain "true" retinal stem cells?

    PubMed

    Frøen, Rebecca; Johnsen, Erik O; Nicolaissen, Bjørn; Facskó, Andrea; Petrovski, Goran; Moe, Morten C

    2013-01-01

    Recent reports of retinal stem cells being present in several locations of the adult eye have sparked great hopes that they may be used to treat the millions of people worldwide who suffer from blindness as a result of retinal disease or injury. A population of proliferative cells derived from the ciliary body epithelium (CE) has been considered one of the prime stem cell candidates, and as such they have received much attention in recent years. However, the true nature of these cells in the adult human eye has still not been fully elucidated, and the stem cell claim has become increasingly controversial in light of new and conflicting reports. In this paper, we will try to answer the question of whether the available evidence is strong enough for the research community to conclude that the adult human CE indeed harbors stem cells.

  20. Genetic and functional characterization of clonally derived adult human brown adipocytes

    PubMed Central

    Shinoda, Kosaku; Luijten, Ineke H N; Hasegawa, Yutaka; Hong, Haemin; Sonne, Si B; Kim, Miae; Xue, Ruidan; Chondronikola, Maria; Cypess, Aaron M; Tseng, Yu-Hua; Nedergaard, Jan; Sidossis, Labros S; Kajimura, Shingo

    2015-01-01

    Brown adipose tissue (BAT) acts in mammals as a natural defense system against hypothermia, and its activation to a state of increased energy expenditure is believed to protect against the development of obesity. Even though the existence of BAT in adult humans has been widely appreciated1–8, its cellular origin and molecular identity remain elusive largely because of high cellular heterogeneity within various adipose tissue depots. To understand the nature of adult human brown adipocytes at single cell resolution, we isolated clonally derived adipocytes from stromal vascular fractions of adult human BAT from two individuals and globally analyzed their molecular signatures. We used RNA sequencing followed by unbiased genome-wide expression analyses and found that a population of uncoupling protein 1 (UCP1)-positive human adipocytes possessed molecular signatures resembling those of a recruitable form of thermogenic adipocytes (that is, beige adipocytes). In addition, we identified molecular markers that were highly enriched in UCP1-positive human adipocytes, a set that included potassium channel K3 (KCNK3) and mitochondrial tumor suppressor 1 (MTUS1). Further, we functionally characterized these two markers using a loss-of-function approach and found that KCNK3 and MTUS1 were required for beige adipocyte differentiation and thermogenic function. The results of this study present new opportunities for human BAT research, such as facilitating cell-based disease modeling and unbiased screens for thermogenic regulators. PMID:25774848

  1. Canonical Genetic Signatures of the Adult Human Brain

    PubMed Central

    Hawrylycz, Michael; Miller, Jeremy A.; Menon, Vilas; Feng, David; Dolbeare, Tim; Guillozet-Bongaarts, Angela L.; Jegga, Anil G.; Aronow, Bruce J.; Lee, Chang-Kyu; Bernard, Amy; Glasser, Matthew F.; Dierker, Donna L.; Menche, Jörge; Szafer, Aaron; Collman, Forrest; Grange, Pascal; Berman, Kenneth A.; Mihalas, Stefan; Yao, Zizhen; Stewart, Lance; Barabási, Albert-László; Schulkin, Jay; Phillips, John; Ng, Lydia; Dang, Chinh; Haynor, David R.; Jones, Allan; Van Essen, David C.; Koch, Christof; Lein, Ed

    2015-01-01

    The structure and function of the human brain are highly stereotyped, implying a conserved molecular program responsible for its development, cellular structure, and function. We applied a correlation-based metric of “differential stability” (DS) to assess reproducibility of gene expression patterning across 132 structures in six individual brains, revealing meso-scale genetic organization. The highest DS genes are highly biologically relevant, with enrichment for brain-related biological annotations, disease associations, drug targets, and literature citations. Using high DS genes we identified 32 anatomically diverse and reproducible gene expression signatures, which represent distinct cell types, intracellular components, and/or associations with neurodevelopmental and neurodegenerative disorders. Genes in neuron-associated compared to non-neuronal networks showed higher preservation between human and mouse; however, many diversely-patterned genes displayed dramatic shifts in regulation between species. Finally, highly consistent transcriptional architecture in neocortex is correlated with resting state functional connectivity, suggesting a link between conserved gene expression and functionally relevant circuitry. PMID:26571460

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

    PubMed Central

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

    2003-01-01

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

  3. NIRS Measurement of Venous Oxygen Saturation in the Adult Human Head

    NASA Astrophysics Data System (ADS)

    Brown, Derek W.; Haensse, Daniel; Bauschatz, Andrea; Wolf, Martin

    Provided that both the breathing frequency remains constant and that the temporal resolution of the instrument is sufficiently high, NIRS spiroximetry enables measurement of cerebral SvO2 in healthy human adults. Furthermore, simultaneous measurements of StO2, SaO2, and SvO2 enable calculation of both OEF and the compartmental distribution of cerebral blood volume.

  4. Equality and Human Capital: Conflicting Concepts within State-Funded Adult Education in Ireland

    ERIC Educational Resources Information Center

    Hurley, Kevin

    2015-01-01

    This article offers a critique of the concept of equality as it informs the White Paper on Adult Education: Learning for Life (2000). It also outlines the extent to which human capital theory can be seen to have effectively colonised lifelong learning from the outset of its adoption by the European Union with highly constraining implications for…

  5. Bridging the Gap between Human Resource Development and Adult Education: Part Two, the Critical Turn

    ERIC Educational Resources Information Center

    Hatcher, Tim; Bowles, Tuere

    2006-01-01

    Human resource development (HRD) as a scholarly endeavor and as a practice is often criticized in the adult education (AE) literature and by AE scholars as manipulative and oppressive and, through training and other interventions, controlling workers for strictly economic ends (Baptiste, 2001; Cunningham, 2004; Schied, 2001; Welton, 1995). The…

  6. An Assessemnt of Graduate Adult Education and Human Resource Development Programs: A U.S. Perspective

    ERIC Educational Resources Information Center

    Akdere, Mesut; Conceicao, Simone C. O.

    2009-01-01

    Due to recent changes in the workplace, the workforce and higher education have driven academic programs of adult education (AE) and human resource development (HRD) in the U.S. to become more integrated as part of the mission of institutions of higher education. In this exploratory study, existing graduate programs in AE and HRD in the U.S. were…

  7. Equality and Human Capital: Conflicting Concepts within State-Funded Adult Education in Ireland

    ERIC Educational Resources Information Center

    Hurley, Kevin

    2015-01-01

    This article offers a critique of the concept of equality as it informs the White Paper on Adult Education: Learning for Life (2000). It also outlines the extent to which human capital theory can be seen to have effectively colonised lifelong learning from the outset of its adoption by the European Union with highly constraining implications for…

  8. Treatment of Human-Caused Trauma: Attrition in the Adult Outcomes Research

    ERIC Educational Resources Information Center

    Matthieu, Monica; Ivanoff, Andre

    2006-01-01

    Attrition or dropout is the failure of a participant to complete, comply, or the prematurely discontinuation or discharge from treatment, resulting in lost data and affecting outcomes. This review of 10 years of adult posttraumatic stress disorder (PTSD) treatment outcome literature specific to Criterion A events of human origin examines how…

  9. Perspectives on Adult Education, Human Resource Development, and the Emergence of Workforce Development

    ERIC Educational Resources Information Center

    Jacobs, Ronald L.

    2006-01-01

    This article presents a perspective on the relationship between adult education and human resource development of the past two decades and the subsequent emergence of workforce development. The lesson taken from the article should be more than simply a recounting of events related to these fields of study. Instead, the more general lesson may be…

  10. Concept Maps: Practice Applications in Adult Education and Human Resource Development

    ERIC Educational Resources Information Center

    Daley, Barbara J.

    2010-01-01

    Concept maps can be used as both a cognitive and constructivist learning strategy in teaching and learning in adult education and human resource development. The maps can be used to understand course readings, analyze case studies, develop reflective thinking and enhance research skills. The creation of concept maps can also be supported by the…

  11. Bridging the Gap between Human Resource Development and Adult Education: Part One, Assumptions, Definitions, and Critiques

    ERIC Educational Resources Information Center

    Hatcher, Tim; Bowles, Tuere

    2006-01-01

    Human resource development (HRD) as a scholarly endeavor and as a practice is often criticized in the adult education (AE) literature and by AE scholars as manipulative and oppressive and, through training and other interventions, controlling workers for strictly economic ends (Baptiste, 2001; Cunningham, 2004; Schied, 2001; Welton, 1995).…

  12. Perspectives on Adult Education, Human Resource Development, and the Emergence of Workforce Development

    ERIC Educational Resources Information Center

    Jacobs, Ronald L.

    2014-01-01

    This article presents a perspective on the relationship between adult education and human resource development of the past two decades and the subsequent emergence of workforce development. The lesson taken from the article should be more than simply a recounting of events related to these fields of study. Instead, the more general lesson may be…

  13. Bridging the Gap between Human Resource Development and Adult Education: Part Two, the Critical Turn

    ERIC Educational Resources Information Center

    Hatcher, Tim; Bowles, Tuere

    2014-01-01

    Human resource development (HRD) as a scholarly endeavor and as a practice is often criticized in the adult education (AE) literature and by AE scholars as manipulative and oppressive and, through training and other interventions, controlling workers for strictly economic ends (Baptiste, 2001; Cunningham, 2004; Schied, 2001; Welton, 1995). The…

  14. Bridging the Gap between Human Resource Development and Adult Education: Part One, Assumptions, Definitions, and Critiques

    ERIC Educational Resources Information Center

    Hatcher, Tim; Bowles, Tuere

    2013-01-01

    Human resource development (HRD) as a scholarly endeavor and as a practice is often criticized in the adult education (AE) literature and by AE scholars as manipulative and oppressive and, through training and other interventions, controlling workers for strictly economic ends (Baptiste, 2001; Cunningham, 2004; Schied, 2001; Welton, 1995).…

  15. Emotions and Human Concern: Adult Education and the Philosophical Thought of Martha Nussbaum

    ERIC Educational Resources Information Center

    Plumb, Donovan

    2014-01-01

    This article argues that philosopher Martha Nussbaum's reflections on the role of the emotions in human flourishing can contribute in important ways to our understanding of the emotions in adult education contexts. The article summarises Nussbaum's exploration of the contributions of classical philosophers like Socrates, Aristotle, and…

  16. Complete Genome Sequence of Human Adenovirus 7 Associated with Fatal Adult Pneumonia.

    PubMed

    Yatsyshina, Svetlana B; Ageeva, Margarita R; Deviatkin, Andrey A; Pimkina, Ekaterina V; Markelov, Mikhail L; Dedkov, Vladimir G; Safonova, Marina V; Shumilina, Elena Y; Lukashev, Alexander N; Shipulin, German A

    2016-10-27

    Human adenovirus 7 (hAdv7) 19BOVLB/Volgograd/Rus/2014 was isolated from the autopsy material from an adult with fatal pneumonia in Volgograd, Russia, in March 2014. Whole-genome sequencing of the virus isolate was performed.

  17. Emotions and Human Concern: Adult Education and the Philosophical Thought of Martha Nussbaum

    ERIC Educational Resources Information Center

    Plumb, Donovan

    2014-01-01

    This article argues that philosopher Martha Nussbaum's reflections on the role of the emotions in human flourishing can contribute in important ways to our understanding of the emotions in adult education contexts. The article summarises Nussbaum's exploration of the contributions of classical philosophers like Socrates, Aristotle, and…

  18. Isolation of alveolar epithelial type II progenitor cells from adult human lungs

    PubMed Central

    Fujino, Naoya; Kubo, Hiroshi; Suzuki, Takaya; Ota, Chiharu; Hegab, Ahmed E; He, Mei; Suzuki, Satoshi; Suzuki, Takashi; Yamada, Mitsuhiro; Kondo, Takashi; Kato, Hidemasa; Yamaya, Mutsuo

    2011-01-01

    Resident stem/progenitor cells in the lung are important for tissue homeostasis and repair. However, a progenitor population for alveolar type II (ATII) cells in adult human lungs has not been identified. The aim of this study is to isolate progenitor cells from adult human lungs with the ability to differentiate into ATII cells. We isolated colony-forming cells that had the capability for self-renewal and the potential to generate ATII cells in vitro. These undifferentiated progenitor cells expressed surface markers of mesenchymal stem cells (MSCs) and surfactant proteins associated with ATII cells, such as CD90 and pro-surfactant protein-C (pro-SP-C), respectively. Microarray analyses indicated that transcripts associated with lung development were enriched in the pro-SP-C+/CD90+ cells compared with bone marrow-MSCs. Furthermore, pathological evaluation indicated that pro-SP-C and CD90 double-positive cells were present within alveolar walls in normal lungs, and significantly increased in ATII cell hyperplasias contributing to alveolar epithelial repair in damaged lungs. Our findings demonstrated that adult human lungs contain a progenitor population for ATII cells. This study is a first step toward better understanding of stem cell biology in adult human lung alveoli. PMID:21079581

  19. Bridging the Gap between Human Resource Development and Adult Education: Part One, Assumptions, Definitions, and Critiques

    ERIC Educational Resources Information Center

    Hatcher, Tim; Bowles, Tuere

    2013-01-01

    Human resource development (HRD) as a scholarly endeavor and as a practice is often criticized in the adult education (AE) literature and by AE scholars as manipulative and oppressive and, through training and other interventions, controlling workers for strictly economic ends (Baptiste, 2001; Cunningham, 2004; Schied, 2001; Welton, 1995).…

  20. Perspectives on Adult Education, Human Resource Development, and the Emergence of Workforce Development

    ERIC Educational Resources Information Center

    Jacobs, Ronald L.

    2014-01-01

    This article presents a perspective on the relationship between adult education and human resource development of the past two decades and the subsequent emergence of workforce development. The lesson taken from the article should be more than simply a recounting of events related to these fields of study. Instead, the more general lesson may be…

  1. Adult attachment style is associated with cerebral μ-opioid receptor availability in humans.

    PubMed

    Nummenmaa, Lauri; Manninen, Sandra; Tuominen, Lauri; Hirvonen, Jussi; Kalliokoski, Kari K; Nuutila, Pirjo; Jääskeläinen, Iiro P; Hari, Riitta; Dunbar, Robin I M; Sams, Mikko

    2015-09-01

    Human attachment behavior mediates establishment and maintenance of social relationships. Adult attachment characteristically varies on anxiety and avoidance dimensions, reflecting the tendencies to worry about the partner breaking the social bond (anxiety) and feeling uncomfortable about depending on others (avoidance). In primates and other mammals, the endogenous μ-opioid system is linked to long-term social bonding, but evidence of its role in human adult attachment remains more limited. We used in vivo positron emission tomography to reveal how variability in μ-opioid receptor (MOR) availability is associated with adult attachment in humans. We scanned 49 healthy subjects using a MOR-specific ligand [(11) C]carfentanil and measured their attachment avoidance and anxiety with the Experiences in Close Relationships-Revised scale. The avoidance dimension of attachment correlated negatively with MOR availability in the thalamus and anterior cingulate cortex, as well as the frontal cortex, amygdala, and insula. No associations were observed between MOR availability and the anxiety dimension of attachment. Our results suggest that the endogenous opioid system may underlie interindividual differences in avoidant attachment style in human adults, and that differences in MOR availability are associated with the individuals' social relationships and psychosocial well-being. © 2015 Wiley Periodicals, Inc.

  2. Bridging the Gap between Human Resource Development and Adult Education: Part Two, the Critical Turn

    ERIC Educational Resources Information Center

    Hatcher, Tim; Bowles, Tuere

    2014-01-01

    Human resource development (HRD) as a scholarly endeavor and as a practice is often criticized in the adult education (AE) literature and by AE scholars as manipulative and oppressive and, through training and other interventions, controlling workers for strictly economic ends (Baptiste, 2001; Cunningham, 2004; Schied, 2001; Welton, 1995). The…

  3. Initial development of an electronic testis rigidity tester.

    PubMed

    Mirilas, Petros; Tsakiridis, Odysseus

    2011-03-22

    We aimed to develop our previously presented mechanical device, the Testis Rigidity Tester (TRT), into an electronic system (Electronic Testis Rigidity Tester, ETRT) by applying tactile imaging, which has been used successfully with other solid organs. A measuring device, located at the front end of the ETRT incorporates a tactile sensor comprising an array of microsensors. By application of a predetermined deformation of 2 mm, increased pressure alters linearly the resistance of each microsensor, producing changes of voltage. These signals were amplified, filtered, and digitized, and then processed by an electronic collector system, which presented them as a color-filled contour plot of the area of the testis coming into contact with the sensor. Testis models of different rigidity served for initial evaluation of ETRT; their evacuated central spaces contained different, increasing glue masses. An independent method of rigidity measurement, using an electric weight scale and a micrometer, showed that the more the glue injected, the greater the force needed for a 2-mm deformation. In a preliminary test, a single sensor connected to a multimeter showed similar force measurement for the same deformation in these phantoms. For each of the testis models compressed in the same manner, the ETRT system offered a map of pressures, represented by a color scale within the contour plot of the contact area with the sensor. ETRT found certain differences in rigidity between models that had escaped detection by a blind observer. ETRT is easy to use and provides a color-coded "insight" of the testis internal structure. After experimental testing, it could be valuable in intraoperative evaluation of testes, so that the surgeon can decide about orchectomy or orcheopexy.

  4. Rat testis as a radiobiological in vivo model for radionuclides.

    PubMed

    Grafström, G; Jönsson, B-A; El Hassan, A M; Tennvall, J; Strand, S-E

    2006-01-01

    The radiobiological effect of intracellularly localised radionuclides emitting low energy electrons (Auger electrons) has received much attention. Most in vivo studies reported have been performed in the mouse testis. We have investigated the rat testis as an in vivo radiobiological model, with sperm-head survival, testis weight loss and also alteration in the blood plasma hormone levels of FSH and LH as radiobiological endpoints. Validation of the rat testis model was evaluated by using mean absorbed doses of up to 10 Gy from intratesticularly (i.t.) injected (111)In oxine or local X-ray irradiation. Biokinetics of the i.t. injected radionuclide was analysed by scintillation camera imaging and used in the absorbed dose estimation. By the analysis of the autoradiographs, the activity distribution was revealed. Cell fractionation showed (111)In to be mainly associated with the cell nuclei. External irradiations were monitored by thermoluminescence dosimeters. The sperm-head survival was the most sensitive radiobiological parameter correlated to the mean absorbed dose, with a D(37) of 2.3 Gy for (111)In oxine and 1.3 Gy for X rays. The levels of plasma pituitary gonadal hormones FSH and LH were elevated for absorbed doses >7.7 Gy. This investigation shows that the radiobiological model based on the rat testis has several advantages compared with the previously commonly used mouse testis model. The model is appropriate for further investigations of basic phenomena such as radiation geometry, intracellular kinetics and heterogeneity, crucial for an understanding of the biological effect of low-energy electrons.

  5. Triorchidism: Presenting as Undescended Testis in a Case of Indirect Inguinal Hernia.

    PubMed

    Bhandarwar, Ajay H; Gandhi, Saurabh S; Patel, Chintan B; Wagh, Amol N; Gawli, Virendra; Jain, Nimesh A

    2016-04-26

    Triorchidism is the commonest variety of polyorchidism, an entity with more than two testis is an extremely rare congenital anomaly of the testis. Although excision of the abnormal testis is a safer alternative proposed, recent literature suggests more conservative approach in normal testes with watchful regular follow up to screen for malignancy. This case presented as a left inguinal swelling diagnosed as indirect left inguinal hernia. The left side testis was of smaller size (about half) with normal sperm count, morphology and motility. Intraoperatively indirect inguinal hernia was noted with supernumerary testis at deep ring in addition to normal left testis in left scrotal sac. The ectopic testis were small (2.5×2.5×1 cm) lacking epididymis and with short vas deferens. An evident normal semen analysis and varied anatomy, the decision for orchidectomy of ectopic testis was taken. The histopathological finding was consistent with arrest in germ cell development.

  6. Triorchidism: Presenting as Undescended Testis in a Case of Indirect Inguinal Hernia

    PubMed Central

    Gandhi, Saurabh S.; Patel, Chintan B.; Wagh, Amol N.; Gawli, Virendra; Jain, Nimesh A.

    2016-01-01

    Triorchidism is the commonest variety of polyorchidism, an entity with more than two testis is an extremely rare congenital anomaly of the testis. Although excision of the abnormal testis is a safer alternative proposed, recent literature suggests more conservative approach in normal testes with watchful regular follow up to screen for malignancy. This case presented as a left inguinal swelling diagnosed as indirect left inguinal hernia. The left side testis was of smaller size (about half) with normal sperm count, morphology and motility. Intraoperatively indirect inguinal hernia was noted with supernumerary testis at deep ring in addition to normal left testis in left scrotal sac. The ectopic testis were small (2.5×2.5×1 cm) lacking epididymis and with short vas deferens. An evident normal semen analysis and varied anatomy, the decision for orchidectomy of ectopic testis was taken. The histopathological finding was consistent with arrest in germ cell development. PMID:27478577

  7. Rehabilitation in adults with human immunodeficiency virus-related diseases.

    PubMed

    O'Dell, M W; Dillon, M E

    1992-06-01

    The acquired immunodeficiency syndrome is a fatal disorder of cell-mediated immunity caused by the human immunodeficiency virus (HIV). As many as one million Americans infected with HIV can expect improved survival with more advanced treatment approaches. Complications of HIV infection occur in the brain, spinal cord, muscle, nerve, joints and other organ systems, which lead to extensive impairments. As survival increases, rehabilitation professionals can anticipate a greater number of referrals for the assessment and management of physical disability in persons with HIV infection. This article reviews HIV-related disease, impairment, disability and handicap pertinent to rehabilitation medicine. An agenda for future research is also proposed. Current knowledge and models or rehabilitation care can be applied to HIV-related physical disability in an effort to improve overall quality of life.

  8. Characterization of human foetal intestinal alkaline phosphatase. Comparison with the isoenzymes from the adult intestine and human tumour cell lines.

    PubMed Central

    Behrens, C M; Enns, C A; Sussman, H H

    1983-01-01

    The molecular structure of human foetal intestinal alkaline phosphatase was defined by high-resolution two-dimensional polyacrylamide-gel electrophoresis and amino acid inhibition studies. Comparison was made with the adult form of intestinal alkaline phosphatase, as well as with alkaline phosphatases isolated from cultured foetal amnion cells (FL) and a human tumour cell line (KB). Two non-identical subunits were isolated from the foetal intestinal isoenzyme, one having same molecular weight and isoelectric point as placental alkaline phosphatase, and the other corresponding to a glycosylated subunit of the adult intestinal enzyme. The FL-cell and KB-cell alkaline phosphatases were also found to contain two subunits similar to those of the foetal intestinal isoenzyme. Characterization of neuraminidase digests of the non-placental subunit showed it to be indistinguishable from the subunits of the adult intestinal isoenzyme. This implies that no new phosphatase structural gene is involved in the transition from the expression of foetal to adult intestinal alkaline phosphatase, but that the molecular changes involve suppression of the placental subunit and loss of neuraminic acid from the non-placental subunit. Enzyme-inhibition studies demonstrated an intermediate response to the inhibitors tested for the foetal intestinal, FL-cell and KB-cell isoenzymes when compared with the placental, adult intestinal and liver forms. This result is consistent with the mixed-subunit structure observed for the former set of isoenzymes. In summary, this study has defined the molecular subunit structure of the foetal intestinal form of alkaline phosphatase and has demonstrated its expression in a human tumour cell line. Images Fig. 1. PMID:6882358

  9. Pseudoneoplastic lesions of the testis and paratesticular structures

    PubMed Central

    Mikuz, G.; Boccon-Gibod, L.; Trias, I.; Arce, Y.; Montironi, R.; Egevad, L.; Scarpelli, M.; Lopez-Beltran, A.

    2007-01-01

    Pseudotumors or tumor-like proliferations (non-neoplastic masses) and benign mimickers (non-neoplastic cellular proliferations) are rare in the testis and paratesticular structures. Clinically, these lesions (cysts, ectopic tissues, and vascular, inflammatory, or hyperplastic lesions) are of great interest for the reason that, because of the topography, they may be relevant as differential diagnoses. The purpose of this paper is to present an overview of the pseudoneoplasic entities arising in the testis and paratesticular structures; emphasis is placed on how the practicing pathologist may distinguish benign mimickers and pseudotumors from true neoplasia. These lesions can be classified as macroscopic or microscopic mimickers of neoplasia. PMID:17805564

  10. Sex cord-gonadal stromal tumor of the rete testis.

    PubMed

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

    2009-01-01

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

  11. Expression of neurotrimin in the normal and injured adult human spinal cord.

    PubMed

    Grijalva, I; Li, X; Marcillo, A; Salzer, J L; Levi, A D

    2006-05-01

    Neurotrimin (Ntm) is a member of the family of neural cell adhesion molecules. Its expression pattern suggests that Ntm promotes axonal fasciculation, guides nerve fibers to specific targets and stabilizes synapses as it accumulates coincident with synaptogenesis. Strong labeling of Ntm was observed in motor and sensory areas of the postnatal rat cortex. It is not known whether Ntm is present in adult human spinal cord (SC). In the present study, a monoclonal antibody specific for Ntm (1B1), is applied to the first study of the expression of Ntm in normal and injured adult human SC. (1) To investigate the expression pattern of Ntm in adult normal human SC, and (2) to observe the changes of Ntm expression after SC injury and compare the differences between normal and injured adult human SC. Human SC tissue was obtained from necropsies of patients with (n=5) and without (n=4) SC injury. The 1B1 Ntm monoclonal antibody was used for immunohistochemical staining on paraffin embedded sections with an ABC kit. (1) In total, 12 slides were analyzed for each group from both cervical and thoracic levels. Motor neurons and Clarke's neurons and glial-like cells were mild to moderately positive in all uninjured SC specimens. (2) In injured SC, no staining was observed in the injury epicenter between two and three levels proximally and distally, but was detected five levels away. (3) In patients older than 67 years of age, Ntm-positive inclusions were present in the white matter of the SC with or without injury. (4) Some meningeal cells were strongly Ntm-positive, especially in the uninjured human SC. Ntm is expressed by motor and Clarke's neurons and glial cells in uninjured human SC. The downregulation of Ntm in the injured SC suggests that its expression is regulated by afferent input. Spinal Cord (2006) 44, 275-279. doi:10.1038/sj.sc.3101840; published online 20 September 2005.

  12. DUX4 Binding to Retroelements Creates Promoters That Are Active in FSHD Muscle and Testis

    PubMed Central

    Young, Janet M.; Whiddon, Jennifer L.; Yao, Zizhen; Kasinathan, Bhavatharini; Snider, Lauren; Geng, Linda N.; Balog, Judit; Tawil, Rabi; van der Maarel, Silvère M.; Tapscott, Stephen J.

    2013-01-01

    The human double-homeodomain retrogene DUX4 is expressed in the testis and epigenetically repressed in somatic tissues. Facioscapulohumeral muscular dystrophy (FSHD) is caused by mutations that decrease the epigenetic repression of DUX4 in somatic tissues and result in mis-expression of this transcription factor in skeletal muscle. DUX4 binds sites in the human genome that contain a double-homeobox sequence motif, including sites in unique regions of the genome as well as many sites in repetitive elements. Using ChIP-seq and RNA-seq on myoblasts transduced with DUX4 we show that DUX4 binds and activates transcription of mammalian apparent LTR-retrotransposons (MaLRs), endogenous retrovirus (ERVL and ERVK) elements, and pericentromeric satellite HSATII sequences. Some DUX4-activated MaLR and ERV elements create novel promoters for genes, long non-coding RNAs, and antisense transcripts. Many of these novel transcripts are expressed in FSHD muscle cells but not control cells, and thus might contribute to FSHD pathology. For example, HEY1, a repressor of myogenesis, is activated by DUX4 through a MaLR promoter. DUX4-bound motifs, including those in repetitive elements, show evolutionary conservation and some repeat-initiated transcripts are expressed in healthy testis, the normal expression site of DUX4, but more rarely in other somatic tissues. Testis expression patterns are known to have evolved rapidly in mammals, but the mechanisms behind this rapid change have not yet been identified: our results suggest that mobilization of MaLR and ERV elements during mammalian evolution altered germline gene expression patterns through transcriptional activation by DUX4. Our findings demonstrate a role for DUX4 and repetitive elements in mammalian germline evolution and in FSHD muscular dystrophy. PMID:24278031

  13. 40 CFR 26.1704 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted before April 7, 2006. 26.1704 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted before...

  14. 40 CFR 26.1704 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted before April 7, 2006. 26.1704 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted before...

  15. 40 CFR 26.1705 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted after April 7, 2006. 26.1705 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted after...

  16. 40 CFR 26.1705 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults initiated after April 7, 2006. 26.1705 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults initiated after...

  17. 40 CFR 26.1705 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted after April 7, 2006. 26.1705 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted after...

  18. 40 CFR 26.1704 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted before April 7, 2006. 26.1704 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted before...

  19. 40 CFR 26.1705 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted after April 7, 2006. 26.1705 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted after...

  20. 40 CFR 26.1705 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults initiated after April 7, 2006. 26.1705 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults initiated after...

  1. Self-Control and Impulsiveness in Nondieting Adult Human Females: Effects of Visual Food Cues and Food Deprivation

    ERIC Educational Resources Information Center

    Forzano, Lori-Ann B.; Chelonis, John J.; Casey, Caitlin; Forward, Marion; Stachowiak, Jacqueline A.; Wood, Jennifer

    2010-01-01

    Self-control can be defined as the choice of a larger, more delayed reinforcer over a smaller, less delayed reinforcer, and impulsiveness as the opposite. Previous research suggests that exposure to visual food cues affects adult humans' self-control. Previous research also suggests that food deprivation decreases adult humans' self-control. The…

  2. Self-Control and Impulsiveness in Nondieting Adult Human Females: Effects of Visual Food Cues and Food Deprivation

    ERIC Educational Resources Information Center

    Forzano, Lori-Ann B.; Chelonis, John J.; Casey, Caitlin; Forward, Marion; Stachowiak, Jacqueline A.; Wood, Jennifer

    2010-01-01

    Self-control can be defined as the choice of a larger, more delayed reinforcer over a smaller, less delayed reinforcer, and impulsiveness as the opposite. Previous research suggests that exposure to visual food cues affects adult humans' self-control. Previous research also suggests that food deprivation decreases adult humans' self-control. The…

  3. Purinergic responses of calcium-dependent signaling pathways in cultured adult human astrocytes.

    PubMed

    Hashioka, Sadayuki; Wang, Yun Fan; Little, Jonathan P; Choi, Hyun B; Klegeris, Andis; McGeer, Patrick L; McLarnon, James G

    2014-01-22

    The properties of Ca2+ signaling mediated by purinergic receptors are intrinsically linked with functional activity of astrocytes. At present little is known concerning Ca2+-dependent purinergic responses in adult human astrocytes. This work has examined effects of purinergic stimulation to alter levels of intracellular Ca2+ in adult human astrocytes. Ca2+-sensitive spectrofluorometry was carried out to determine mobilization of intracellular Ca2+ following adenosine triphosphate (ATP) or 3'-O-(4-benzoyl)benzoyl-ATP (Bz-ATP) stimulation of adult human astrocytes. In some experiments pharmacological modulation of Ca2+ pathways was applied to help elucidate mechanisms of Ca2+ signaling. RT-PCR was also performed to confirm human astrocyte expression of specific purinoceptors which were indicated from imaging studies. The endogenous P2 receptor agonist ATP (at 100 μM or 1 mM) applied in physiological saline solution (PSS) evoked a rapid increase of [Ca2+]i to a peak amplitude with the decay phase of response exhibiting two components. The two phases of decay consisted of an initial rapid component which was followed by a secondary slower component. In the presence of Ca2+-free solution, the secondary phase of decay was absent indicating this prolonged component was due to influx of Ca2+. This prolonged phase of decay was also attenuated with the store-operated channel (SOC) inhibitor gadolinium (at 2 μM) added to standard PSS, suggesting this component was mediated by SOC activation. These results are consistent with ATP activation of P2Y receptor (P2YR) in adult human astrocytes leading to respective rapid [Ca2+]i mobilization from intracellular stores followed by Ca2+ entry through SOC. An agonist for P2X7 receptor (P2X7R), BzATP induced a very different response compared with ATP whereby BzATP (at 300 μM) elicited a slowly rising increase in [Ca2+]i to a plateau level which was sustained in duration. The BzATP-induced increase in [Ca2+]i was not enhanced with

  4. Purinergic responses of calcium-dependent signaling pathways in cultured adult human astrocytes

    PubMed Central

    2014-01-01

    Background The properties of Ca2+ signaling mediated by purinergic receptors are intrinsically linked with functional activity of astrocytes. At present little is known concerning Ca2+-dependent purinergic responses in adult human astrocytes. This work has examined effects of purinergic stimulation to alter levels of intracellular Ca2+ in adult human astrocytes. Ca2+-sensitive spectrofluorometry was carried out to determine mobilization of intracellular Ca2+ following adenosine triphosphate (ATP) or 3′-O-(4-benzoyl)benzoyl-ATP (Bz-ATP) stimulation of adult human astrocytes. In some experiments pharmacological modulation of Ca2+ pathways was applied to help elucidate mechanisms of Ca2+ signaling. RT-PCR was also performed to confirm human astrocyte expression of specific purinoceptors which were indicated from imaging studies. Results The endogenous P2 receptor agonist ATP (at 100 μM or 1 mM) applied in physiological saline solution (PSS) evoked a rapid increase of [Ca2+]i to a peak amplitude with the decay phase of response exhibiting two components. The two phases of decay consisted of an initial rapid component which was followed by a secondary slower component. In the presence of Ca2+-free solution, the secondary phase of decay was absent indicating this prolonged component was due to influx of Ca2+. This prolonged phase of decay was also attenuated with the store-operated channel (SOC) inhibitor gadolinium (at 2 μM) added to standard PSS, suggesting this component was mediated by SOC activation. These results are consistent with ATP activation of P2Y receptor (P2YR) in adult human astrocytes leading to respective rapid [Ca2+]i mobilization from intracellular stores followed by Ca2+ entry through SOC. An agonist for P2X7 receptor (P2X7R), BzATP induced a very different response compared with ATP whereby BzATP (at 300 μM) elicited a slowly rising increase in [Ca2+]i to a plateau level which was sustained in duration. The BzATP-induced increase in [Ca2+]i

  5. A humanized version of Foxp2 does not affect ultrasonic vocalization in adult mice.

    PubMed

    Hammerschmidt, K; Schreiweis, C; Minge, C; Pääbo, S; Fischer, J; Enard, W

    2015-11-01

    The transcription factor FOXP2 has been linked to severe speech and language impairments in humans. An analysis of the evolution of the FOXP2 gene has identified two amino acid substitutions that became fixed after the split of the human and chimpanzee lineages. Studying the functional consequences of these two substitutions in the endogenous Foxp2 gene of mice showed alterations in dopamine levels, striatal synaptic plasticity, neuronal morphology and cortico-striatal-dependent learning. In addition, ultrasonic vocalizations (USVs) of pups had a significantly lower average pitch than control littermates. To which degree adult USVs would be affected in mice carrying the 'humanized' Foxp2 variant remained unclear. In this study, we analyzed USVs of 68 adult male mice uttered during repeated courtship encounters with different females. Mice carrying the Foxp2(hum/hum) allele did not differ significantly in the number of call elements, their element structure or in their element composition from control littermates. We conclude that neither the structure nor the usage of USVs in adult mice is affected by the two amino acid substitutions that occurred in FOXP2 during human evolution. The reported effect for pup vocalization thus appears to be transient. These results are in line with accumulating evidence that mouse USVs are hardly influenced by vocal learning. Hence, the function and evolution of genes that are necessary, but not sufficient for vocal learning in humans, must be either studied at a different phenotypic level in mice or in other organisms.

  6. The mechanical properties of human ribs in young adult.

    PubMed

    Pezowicz, Celina; Głowacki, Maciej

    2012-01-01

    A good understanding of thoracic biomechanics is important for complete examination and control of chest behaviour under conditions of physiological and pathological work, and under the impact of external forces leading to traumatic loading of the chest. The purpose of the study was to analyse the mechanical properties of human ribs obtained from individuals under the age of 25 with scoliosis deformation and to correlate them with geometric properties of ribs. Thirty three fragments of ribs (9th to 12th) were tested in three-point bending. Rib fragments were collected intraoperatively from female patients treated for scoliosis in the thoracic, thoracolumbar, and lumbar spine. The results were used to determine the maximum failure force, stiffness, and Young's modulus. A significant relationship was found between the age and elastic modulus of the ribs. The analysis was carried out for two age groups, i.e., between the ages of 10 and 15 and between the ages of 16 and 22, and statistically significant differences were obtained for Young's modulus (p = 0.0001) amounting to, respectively, 2.79 ± 1.34 GPa for the first group and 7.44 ± 2.85 GPa for the second group. The results show a significant impact of age on the mechanical properties of ribs.

  7. Neural-competent cells of adult human dermis belong to the Schwann lineage.

    PubMed

    Etxaniz, Usue; Pérez-San Vicente, Adrián; Gago-López, Nuria; García-Dominguez, Mario; Iribar, Haizea; Aduriz, Ariane; Pérez-López, Virginia; Burgoa, Izaskun; Irizar, Haritz; Muñoz-Culla, Maider; Vallejo-Illarramendi, Ainara; Leis, Olatz; Matheu, Ander; Martín, Angel G; Otaegui, David; López-Mato, María Paz; Gutiérrez-Rivera, Araika; MacLellan, Robb; Izeta, Ander

    2014-11-11

    Resident neural precursor cells (NPCs) have been reported for a number of adult tissues. Understanding their physiological function or, alternatively, their activation after tissue damage or in vitro manipulation remains an unsolved issue. Here, we investigated the source of human dermal NPCs in adult tissue. By following an unbiased, comprehensive approach employing cell-surface marker screening, cell separation, transcriptomic characterization, and in vivo fate analyses, we found that p75NTR(+) precursors of human foreskin can be ascribed to the Schwann (CD56(+)) and perivascular (CD56(-)) cell lineages. Moreover, neural differentiation potential was restricted to the p75NTR(+)CD56(+) Schwann cells and mediated by SOX2 expression levels. Double-positive NPCs were similarly obtained from human cardiospheres, indicating that this phenomenon might be widespread.

  8. Neural-Competent Cells of Adult Human Dermis Belong to the Schwann Lineage

    PubMed Central

    Etxaniz, Usue; Pérez-San Vicente, Adrián; Gago-López, Nuria; García-Dominguez, Mario; Iribar, Haizea; Aduriz, Ariane; Pérez-López, Virginia; Burgoa, Izaskun; Irizar, Haritz; Muñoz-Culla, Maider; Vallejo-Illarramendi, Ainara; Leis, Olatz; Matheu, Ander; Martín, Angel G.; Otaegui, David; López-Mato, María Paz; Gutiérrez-Rivera, Araika; MacLellan, Robb; Izeta, Ander

    2014-01-01

    Summary Resident neural precursor cells (NPCs) have been reported for a number of adult tissues. Understanding their physiological function or, alternatively, their activation after tissue damage or in vitro manipulation remains an unsolved issue. Here, we investigated the source of human dermal NPCs in adult tissue. By following an unbiased, comprehensive approach employing cell-surface marker screening, cell separation, transcriptomic characterization, and in vivo fate analyses, we found that p75NTR+ precursors of human foreskin can be ascribed to the Schwann (CD56+) and perivascular (CD56−) cell lineages. Moreover, neural differentiation potential was restricted to the p75NTR+CD56+ Schwann cells and mediated by SOX2 expression levels. Double-positive NPCs were similarly obtained from human cardiospheres, indicating that this phenomenon might be widespread. PMID:25418723

  9. Human Spermatozoa as a Model for Detecting Missing Proteins in the Context of the Chromosome-Centric Human Proteome Project.

    PubMed

    Jumeau, Fanny; Com, Emmanuelle; Lane, Lydie; Duek, Paula; Lagarrigue, Mélanie; Lavigne, Régis; Guillot, Laëtitia; Rondel, Karine; Gateau, Alain; Melaine, Nathalie; Guével, Blandine; Sergeant, Nicolas; Mitchell, Valérie; Pineau, Charles

    2015-09-04

    The Chromosome-Centric Human Proteome Project (C-HPP) aims at cataloguing the proteins as gene products encoded by the human genome in a chromosome-centric manner. The existence of products of about 82% of the genes has been confirmed at the protein level. However, the number of so-called "missing proteins" remains significant. It was recently suggested that the expression of proteins that have been systematically missed might be restricted to particular organs or cell types, for example, the testis. Testicular function, and spermatogenesis in particular, is conditioned by the successive activation or repression of thousands of genes and proteins including numerous germ cell- and testis-specific products. Both the testis and postmeiotic germ cells are thus promising sites at which to search for missing proteins, and ejaculated spermatozoa are a potential source of proteins whose expression is restricted to the germ cell lineage. A trans-chromosome-based data analysis was performed to catalog missing proteins in total protein extracts from isolated human spermatozoa. We have identified and manually validated peptide matches to 89 missing proteins in human spermatozoa. In addition, we carefully validated three proteins that were scored as uncertain in the latest neXtProt release (09.19.2014). A focus was then given to the 12 missing proteins encoded on chromosomes 2 and 14, some of which may putatively play roles in ciliation and flagellum mechanistics. The expression pattern of C2orf57 and TEX37 was confirmed in the adult testis by immunohistochemistry. On the basis of transcript expression during human spermatogenesis, we further consider the potential for discovering additional missing proteins in the testicular postmeiotic germ cell lineage and in ejaculated spermatozoa. This project was conducted as part of the C-HPP initiatives on chromosomes 14 (France) and 2 (Switzerland). The mass spectrometry proteomics data have been deposited with the Proteome

  10. Towards Scarless Wound Healing: A Comparison of Protein Expression between Human, Adult and Foetal Fibroblasts

    PubMed Central

    Ho, Sonia; Marçal, Helder; Foster, Leslie John Ray

    2014-01-01

    Proteins from human adult and foetal fibroblast cell lines were compared, focusing on those involved in wound healing. Proteins were separated through two-dimensional gel electrophoresis (2DE). Differences in protein spot intensity between the lineages were quantified through 3D gel scanning densitometry. Selected protein spots were excised, subjected to tryptic digests, prior to separation using HPLC with a linear ion trap mass spectrometer, and identified. Protein maps representing the proteomes from adult and foetal fibroblasts showed similar distributions but revealed differences in expression levels. Heat shock cognate 71 kDA protein, Tubulin alpha-1A chain, actin cytoplasmic-1, and neuron cytoplasmic protein were all expressed in significantly higher concentrations by foetal fibroblasts, nearly double those observed for their adult counterparts. Fructose bisphosphate aldolase A, Cofilin-1, Peroxiredoxin-1, Lactotransferrin Galectin-1, Profilin-1, and Calreticulin were expressed at comparatively higher concentrations by the adult fibroblasts. Significant differences in the expression levels of some proteins in human adult and foetal fibroblasts correlated with known differences in wound healing behaviour. This data may assist in the development of technologies to promote scarless wound healing and better functional tissue repair and regeneration. PMID:24605334

  11. Towards scarless wound healing: a comparison of protein expression between human, adult and foetal fibroblasts.

    PubMed

    Ho, Sonia; Marçal, Helder; Foster, Leslie John Ray

    2014-01-01

    Proteins from human adult and foetal fibroblast cell lines were compared, focusing on those involved in wound healing. Proteins were separated through two-dimensional gel electrophoresis (2DE). Differences in protein spot intensity between the lineages were quantified through 3D gel scanning densitometry. Selected protein spots were excised, subjected to tryptic digests, prior to separation using HPLC with a linear ion trap mass spectrometer, and identified. Protein maps representing the proteomes from adult and foetal fibroblasts showed similar distributions but revealed differences in expression levels. Heat shock cognate 71 kDA protein, Tubulin alpha-1A chain, actin cytoplasmic-1, and neuron cytoplasmic protein were all expressed in significantly higher concentrations by foetal fibroblasts, nearly double those observed for their adult counterparts. Fructose bisphosphate aldolase A, Cofilin-1, Peroxiredoxin-1, Lactotransferrin Galectin-1, Profilin-1, and Calreticulin were expressed at comparatively higher concentrations by the adult fibroblasts. Significant differences in the expression levels of some proteins in human adult and foetal fibroblasts correlated with known differences in wound healing behaviour. This data may assist in the development of technologies to promote scarless wound healing and better functional tissue repair and regeneration.

  12. Larval food quantity affects the capacity of adult mosquitoes to transmit human malaria

    PubMed Central

    Shapiro, Lillian L. M.; Murdock, Courtney C.; Jacobs, Gregory R.; Thomas, Rachel J.; Thomas, Matthew B.

    2016-01-01

    Adult traits of holometabolous insects are shaped by conditions experienced during larval development, which might impact interactions between adult insect hosts and parasites. However, the ecology of larval insects that vector disease remains poorly understood. Here, we used Anopheles stephensi mosquitoes and the human malaria parasite Plasmodium falciparum, to investigate whether larval conditions affect the capacity of adult mosquitoes to transmit malaria. We reared larvae in two groups; one group received a standard laboratory rearing diet, whereas the other received a reduced diet. Emerging adult females were then provided an infectious blood meal. We assessed mosquito longevity, parasite development rate and prevalence of infectious mosquitoes over time. Reduced larval food led to increased adult mortality and caused a delay in parasite development and a slowing in the rate at which parasites invaded the mosquito salivary glands, extending the time it took for mosquitoes to become infectious. Together, these effects increased transmission potential of mosquitoes in the high food regime by 260–330%. Such effects have not, to our knowledge, been shown previously for human malaria and highlight the importance of improving knowledge of larval ecology to better understand vector-borne disease transmission dynamics. PMID:27412284

  13. Biological differences between neonatal and adult human hematopoietic stem/progenitor cells.

    PubMed

    Mayani, Hector

    2010-03-01

    From the first studies performed by Broxmeyer and his group, in the late 1980s, evidence was presented indicating that hematopoietic progenitor cells from human umbilical cord blood (UCB) possessed certain in vitro biological features that differed from those observed in their adult counterparts. Throughout the past 20 years, these observations have been confirmed and expanded by several groups, using both in vitro and in vivo models. Today, it is widely recognized that stem and progenitor cells present in UCB are biologically different from those present in adult marrow or peripheral blood. As compared to cells from adult subjects, UCB-derived hematopoietic cells possess higher proliferation and expansion potentials, and their capacity to self-renew is also superior to that of adult cells. Although the mechanisms responsible for such biological differences are still not fully understood, telomere dynamics, cell cycle progression, certain transcription factor pathways, differential gene expression, and the autocrine production of particular cytokines are some of the mechanisms that have been implicated. Understanding, at the cellular and molecular levels, the biological differences between neonatal and adult hematopoietic cells has a 2-fold relevance. On the one hand, it will help to understand and characterize basic principles and mechanisms involved in human developmental biology; on the other hand, it will help to gain a deeper knowledge on the biology of hematopoietic cell transplants and to improve and optimize such a clinical procedure.

  14. Neuroscience of human social interactions and adult attachment style.

    PubMed

    Vrtička, Pascal; Vuilleumier, Patrik

    2012-01-01

    attachment insecurity and particularly anxiety. Emotion regulation strategies such as reappraisal or suppression of social emotions are also differentially modulated by attachment style. This research does not only help better understand the neural underpinnings of human social behavior, but also provides important insights on psychopathological conditions where attachment dysregulation is likely to play an important (causal) role.

  15. Neuroscience of human social interactions and adult attachment style

    PubMed Central

    Vrtička, Pascal; Vuilleumier, Patrik

    2012-01-01

    attachment insecurity and particularly anxiety. Emotion regulation strategies such as reappraisal or suppression of social emotions are also differentially modulated by attachment style. This research does not only help better understand the neural underpinnings of human social behavior, but also provides important insights on psychopathological conditions where attachment dysregulation is likely to play an important (causal) role. PMID:22822396

  16. A transit-amplifying population underpins the efficient regenerative capacity of the testis.

    PubMed

    Carrieri, Claudia; Comazzetto, Stefano; Grover, Amit; Morgan, Marcos; Buness, Andreas; Nerlov, Claus; O'Carroll, Dónal

    2017-06-05

    The spermatogonial stem cell (SSC) that supports spermatogenesis throughout adult life resides within the GFRα1-expressing A type undifferentiated spermatogonia. The decision to commit to spermatogenic differentiation coincides with the loss of GFRα1 and reciprocal gain of Ngn3 (Neurog3) expression. Through the analysis of the piRNA factor Miwi2 (Piwil4), we identify a novel population of Ngn3-expressing spermatogonia that are essential for efficient testicular regeneration after injury. Depletion of Miwi2-expressing cells results in a transient impact on testicular homeostasis, with this population behaving strictly as transit amplifying cells under homeostatic conditions. However, upon injury, Miwi2-expressing cells are essential for the efficient regenerative capacity of the testis, and also display facultative stem activity in transplantation assays. In summary, the mouse testis has adopted a regenerative strategy to expand stem cell activity by incorporating a transit-amplifying population to the effective stem cell pool, thus ensuring rapid and efficient tissue repair. © 2017 Carrieri et al.

  17. AMAP-1, a novel testis-specific AMY-1-binding protein, is differentially expressed during the course of spermatogenesis.

    PubMed

    Yukitake, Hiroshi; Furusawa, Makoto; Taira, Takahiro; Iguchi-Ariga, Sanae M M; Ariga, Hiroyoshi

    2002-08-19

    AMY-1 has been identified by us as a c-Myc-binding protein and was found to stimulate c-Myc transcription activity. AMY-1 was also found to be associated with AKAP84/149 in the mitochondria in somatic cells and sperm, suggesting that it plays a role in spermatogenesis. To access the molecular function of AMY-1, a two-hybrid screening of cDNAs encoding AMY-1-binding proteins was carried out with AMY-1 as a bait using a human testis cDNA library, and a clone encoding a novel protein, AMAP-1, was obtained. The amap-1 gene was mapped at human chromosome 17q21. AMY-1 was found to bind to and be colocalized with AMAP-1 in human 293T and HeLa cells. AMAP-1 was found to be specifically expressed in the testis and expressed post-meiotically in the testis, as was AMY-1. These results suggest that both AMAP-1 and AMY-1 play roles in spermatogenesis.

  18. The response of the anterior striatum during adult human vocal learning.

    PubMed

    Simmonds, Anna J; Leech, Robert; Iverson, Paul; Wise, Richard J S

    2014-08-15

    Research on mammals predicts that the anterior striatum is a central component of human motor learning. However, because vocalizations in most mammals are innate, much of the neurobiology of human vocal learning has been inferred from studies on songbirds. Essential for song learning is a pathway, the homolog of mammalian cortical-basal ganglia "loops," which includes the avian striatum. The present functional magnetic resonance imaging (fMRI) study investigated adult human vocal learning, a skill that persists throughout life, albeit imperfectly given that late-acquired languages are spoken with an accent. Monolingual adult participants were scanned while repeating novel non-native words. After training on the pronunciation of half the words for 1 wk, participants underwent a second scan. During scanning there was no external feedback on performance. Activity declined sharply in left and right anterior striatum, both within and between scanning sessions, and this change was independent of training and performance. This indicates that adult speakers rapidly adapt to the novel articulatory movements, possibly by using motor sequences from their native speech to approximate those required for the novel speech sounds. Improved accuracy correlated only with activity in motor-sensory perisylvian cortex. We propose that future studies on vocal learning, using different behavioral and pharmacological manipulations, will provide insights into adult striatal plasticity and its potential for modification in both educational and clinical contexts.

  19. The response of the anterior striatum during adult human vocal learning

    PubMed Central

    Leech, Robert; Iverson, Paul; Wise, Richard J. S.

    2014-01-01

    Research on mammals predicts that the anterior striatum is a central component of human motor learning. However, because vocalizations in most mammals are innate, much of the neurobiology of human vocal learning has been inferred from studies on songbirds. Essential for song learning is a pathway, the homolog of mammalian cortical-basal ganglia “loops,” which includes the avian striatum. The present functional magnetic resonance imaging (fMRI) study investigated adult human vocal learning, a skill that persists throughout life, albeit imperfectly given that late-acquired languages are spoken with an accent. Monolingual adult participants were scanned while repeating novel non-native words. After training on the pronunciation of half the words for 1 wk, participants underwent a second scan. During scanning there was no external feedback on performance. Activity declined sharply in left and right anterior striatum, both within and between scanning sessions, and this change was independent of training and performance. This indicates that adult speakers rapidly adapt to the novel articulatory movements, possibly by using motor sequences from their native speech to approximate those required for the novel speech sounds. Improved accuracy correlated only with activity in motor-sensory perisylvian cortex. We propose that future studies on vocal learning, using different behavioral and pharmacological manipulations, will provide insights into adult striatal plasticity and its potential for modification in both educational and clinical contexts. PMID:24805076

  20. Predictions of ozone absorption in human lungs from newborn to adult

    SciTech Connect

    Overton, J.H.; Graham, R.C. )

    1989-01-01

    Although children are an important human population, dosimetry models for gases have been used to predict absorption mainly in laboratory animals and adult humans. To correct this omission, we have used several sources of data on age-dependent lower respiratory tract (LRT) volumes, age-dependent airway dimensions, a model of the adult tracheobronchial region, and a model of the adult acinus to construct theoretical LRT lung models for humans from birth to adulthood. An ozone (O3) dosimetry model was then used to estimate the regional and local uptake of O3 in the (theoretical) LRT of children and adults. For sedentary or quiet breathing, the LRT distribution of absorbed O3, the percent uptake (84 to 88%) and the centriacinar O3 tissue dose are not very sensitive to age. For maximal work during exercise, predicted LRT uptakes range from 87 to 93%, and the regional percent uptakes are more dependent on age than during quiet breathing. In general, the total quantity of O3 absorbed per minute increases with age. Regardless of age and state of breathing, the largest tissue dose of O3 is predicted to occur in the centriacinar region, where many animal studies show the maximal morphological damage from O3.

  1. HMGA2 Moderately Increases Fetal Hemoglobin Expression in Human Adult Erythroblasts

    PubMed Central

    de Vasconcellos, Jaira F.; Lee, Y. Terry; Byrnes, Colleen; Tumburu, Laxminath; Rabel, Antoinette; Miller, Jeffery L.

    2016-01-01

    Induction of fetal hemoglobin (HbF) has therapeutic importance for patients with beta-hemoglobin disorders. Previous studies showed that let-7 microRNAs (miRNAs) are highly regulated in erythroid cells during the fetal-to-adult developmental transition, and that targeting let-7 mediated the up-regulation of HbF to greater than 30% of the total globin levels in human adult cultured erythroblasts. HMGA2 is a member of the high-mobility group A family of proteins and a validated target of the let-7 family of miRNAs. Here we investigate whether expression of HMGA2 directly regulates fetal hemoglobin in adult erythroblasts. Let-7 resistant HMGA2 expression was studied after lentiviral transduction of CD34(+) cells. The transgene was regulated by the erythroid-specific gene promoter region of the human SPTA1 gene (HMGA2-OE). HMGA2-OE caused significant increases in gamma-globin mRNA expression and HbF to around 16% of the total hemoglobin levels compared to matched control transductions. Interestingly, no significant changes in KLF1, SOX6, GATA1, ZBTB7A and BCL11A mRNA levels were observed. Overall, our data suggest that expression of HMGA2, a downstream target of let-7 miRNAs, causes moderately increased gamma-globin gene and protein expression in adult human erythroblasts. PMID:27861570

  2. Human Centred Design Considerations for Connected Health Devices for the Older Adult

    PubMed Central

    Harte, Richard P.; Glynn, Liam G.; Broderick, Barry J.; Rodriguez-Molinero, Alejandro; Baker, Paul M. A.; McGuiness, Bernadette; O’Sullivan, Leonard; Diaz, Marta; Quinlan, Leo R.; ÓLaighin, Gearóid

    2014-01-01

    Connected health devices are generally designed for unsupervised use, by non-healthcare professionals, facilitating independent control of the individuals own healthcare. Older adults are major users of such devices and are a population significantly increasing in size. This group presents challenges due to the wide spectrum of capabilities and attitudes towards technology. The fit between capabilities of the user and demands of the device can be optimised in a process called Human Centred Design. Here we review examples of some connected health devices chosen by random selection, assess older adult known capabilities and attitudes and finally make analytical recommendations for design approaches and design specifications. PMID:25563225

  3. Rai14 (retinoic acid induced protein 14) is involved in regulating f-actin dynamics at the ectoplasmic specialization in the rat testis*.

    PubMed

    Qian, Xiaojing; Mruk, Dolores D; Cheng, C Yan

    2013-01-01

    Rai14 (retinoic acid induced protein 14) is an actin binding protein first identified in the liver, highly expressed in the placenta, the testis, and the eye. In the course of studying actin binding proteins that regulate the organization of actin filament bundles in the ectoplasmic specialization (ES), a testis-specific actin-rich adherens junction (AJ) type, Rai14 was shown to be one of the regulatory proteins at the ES. In the rat testis, Rai14 was found to be expressed by Sertoli and germ cells, structurally associated with actin and an actin cross-linking protein palladin. Its expression was the highest at the ES in the seminiferous epithelium of adult rat testes, most notably at the apical ES at the Sertoli-spermatid interface, and expressed stage-specifically during the epithelial cycle in stage VII-VIII tubules. However, Rai14 was also found at the basal ES near the basement membrane, associated with the blood-testis barrier (BTB) in stage VIII-IX tubules. A knockdown of Rai14 in Sertoli cells cultured in vitro by RNAi was found to perturb the Sertoli cell tight junction-permeability function in vitro, mediated by a disruption of F-actin, which in turn led to protein mis-localization at the Sertoli cell BTB. When Rai14 in the testis in vivo was knockdown by RNAi, defects in spermatid polarity and adhesion, as well as spermatid transport were noted mediated via changes in F-actin organization and mis-localization of proteins at the apical ES. In short, Rai14 is involved in the re-organization of actin filaments in Sertoli cells during the epithelial cycle, participating in conferring spermatid polarity and cell adhesion in the testis.

  4. Ultrastructural evidence of exosome secretion by progenitor cells in adult mouse myocardium and adult human cardiospheres.

    PubMed

    Barile, Lucio; Gherghiceanu, Mihaela; Popescu, Laurentiu M; Moccetti, Tiziano; Vassalli, Giuseppe

    2012-01-01

    The demonstration of beneficial effects of cell therapy despite the persistence of only few transplanted cells in vivo suggests secreted factors may be the active component of this treatment. This so-called paracrine hypothesis is supported by observations that culture media conditioned by progenitor cells contain growth factors that mediate proangiogenic and cytoprotective effects. Cardiac progenitor cells in semi-suspension culture form spherical clusters (cardiospheres) that deliver paracrine signals to neighboring cells. A key component of paracrine secretion is exosomes, membrane vesicles that are stored intracellularly in endosomal compartments and are secreted when these structures fuse with the cell plasma membrane. Exosomes have been identified as the active component of proangiogenic effects of bone marrow CD34⁺ stem cells in mice and the regenerative effects of embryonic mesenchymal stem cells in infarcted hearts in pigs and mice. Here, we provide electron microscopic evidence of exosome secretion by progenitor cells in mouse myocardium and human cardiospheres. Exosomes are emerging as an attractive vector of paracrine signals delivered by progenitor cells. They can be stored as an "off-the-shelf" product. As such, exosomes have the potential for circumventing many of the limitations of viable cells for therapeutic applications in regenerative medicine.

  5. Binding of furosemide to albumin isolated from human fetal and adult serum.

    PubMed

    Viani, A; Cappiello, M; Silvestri, D; Pacifici, G M

    1991-01-01

    Albumin was isolated from pooled fetal serum from 58 placentas obtained at normal delivery at term and from pooled adult plasma from 8 individuals. Albumin isolation was carried out by means of PEG precipitation followed by ion-exchange chromatography on DEAE-Sephadex A 50 and then on SP-Sephadex C 50. The electrophoresis on SDS-polyacrylamide gels showed only one spot that comigrated with commercial human albumin. Binding to albumin was measured by equilibrium dialysis of an aliquot of albumin solution (0.7 ml) against the same volume of 0.13 M sodium orthophosphate buffer (pH 7.4). At a total concentration of 2 micrograms/ml (therapeutic range), the unbound fraction of furosemide was 2.71% (fetal albumin) and 2.51% (adult albumin). Two classes of binding sites for furosemide were observed in fetal and adult albumin. The number of binding sites (moles of furosemide per mole of albumin) was 1.22 (fetal albumin) and 1.58 (adult albumin) for the high-affinity site and 2.97 (fetal albumin) and 3.25 (adult albumin) for the low-affinity site. The association constants (M-1) were 3.1 X 10(4) (fetal albumin) and 2.6 X 10(4) (adult albumin) for the high-affinity set of sites and 0.83 X 10(4) (fetal albumin) and 1.0 X 10(4) (adult albumin) low-affinity site. The displacement of furosemide from albumin was studied with therapeutic concentrations of several drugs. Valproic acid, salicylic acid, azapropazone and tolbutamide had the highest displacing effects which were significantly higher with fetal than with adult albumin.

  6. Mesotheliomas of the tunica vaginalis testis and hernial sacs.

    PubMed

    Grove, A; Jensen, M L; Donna, A

    1989-01-01

    Three histologically and immunohistochemically well-documented cases of mesothelioma of the tunica vaginalis testis and hernial sac are presented. Analysis and follow-up data on our three patients and a review of 30 previously reported cases have revealed a varied and often unpredictable clinical course. A classification into high- and lowgrade malignant tumours is suggested, based on clinical and pathological findings.

  7. Intratesticular grafts: the testis as an exceptional immunologically privileged site.

    PubMed

    Whitmore, W F; Gittes, R F

    1978-01-01

    The testis is an immunologically privileged site despite a normal lymphatic drainage, whereas the anterior chamber of the eye is a privileged site because it lacks normal lymphatics. Parathyroid grafts were transplanted between several strains of inbred rats (Buffalo leads to Lewis and Lewis X Brown Norway F1 leads to Lewis). Allografts were placed in the testis, thigh muscle, prostate, lymph nodes, anterior chamber of the eye and adrenal gland. The survival of intratesticular allografts also was tested in animals whose pituitary gonadotropins were suppressed by testosterone and estradiol implants. The effects of steroid implants were documented by measuring testosterone and progesterone concentrations in the serum and whole testis homogenates of these animals. Allograft survival was judged by fasting plasma calcium concentrations. The data show that 1) the adrenal is included among naturally occurring immunologically privileged sites, 2) the prolonged survival of intratesticular allografts may be related to the local production of steroid hormones, although allograft survival is not critically dependent on pituitary gonadotropins and 3) temperature differences and a high zinc concentration within the testis are not important to allograft survival.

  8. Comparative Analysis of Testis Protein Evolution in Rodents

    PubMed Central

    Turner, Leslie M.; Chuong, Edward B.; Hoekstra, Hopi E.

    2008-01-01

    Genes expressed in testes are critical to male reproductive success, affecting spermatogenesis, sperm competition, and sperm–egg interaction. Comparing the evolution of testis proteins at different taxonomic levels can reveal which genes and functional classes are targets of natural and sexual selection and whether the same genes are targets among taxa. Here we examine the evolution of testis-expressed proteins at different levels of divergence among three rodents, mouse (Mus musculus), rat (Rattus norvegicus), and deer mouse (Peromyscus maniculatus), to identify rapidly evolving genes. Comparison of expressed sequence tags (ESTs) from testes suggests that proteins with testis-specific expression evolve more rapidly on average than proteins with maximal expression in other tissues. Genes with the highest rates of evolution have a variety of functional roles including signal transduction, DNA binding, and egg–sperm interaction. Most of these rapidly evolving genes have not been identified previously as targets of selection in comparisons among more divergent mammals. To determine if these genes are evolving rapidly among closely related species, we sequenced 11 of these genes in six Peromyscus species and found evidence for positive selection in five of them. Together, these results demonstrate rapid evolution of functionally diverse testis-expressed proteins in rodents, including the identification of amino acids under lineage-specific selection in Peromyscus. Evidence for positive selection among closely related species suggests that changes in these proteins may have consequences for reproductive isolation. PMID:18689890

  9. Increase in average testis size of Canadian beef bulls.

    PubMed

    García Guerra, Alvaro; Hendrick, Steve; Barth, Albert D

    2013-05-01

    Selection for adequate testis size in beef bulls is an important part of bull breeding soundness evaluation. Scrotal circumference (SC) is highly correlated with paired testis weight and is a practical method for estimating testis weight in the live animal. Most bulls presented for sale in Canada have SC included in the presale information. Scrotal circumference varies by age and breed, and may change over time due to selection for larger testis size. Therefore, it is important to periodically review the mean SC of various cattle breeds to provide valid bull selection criteria. Scrotal circumference data were obtained from bulls sold in western Canada from 2008 to 2011 and in Quebec from 2006 to 2010. Average scrotal circumferences for the most common beef breeds in Canada have increased significantly in the last 25 years. Differences between breeds have remained unchanged and Simmental bulls still have the largest SC at 1 year of age. Data provided here could aid in the establishment of new suggested minimum SC measurements for beef bulls.

  10. Increase in average testis size of Canadian beef bulls

    PubMed Central

    Guerra, Álvaro García; Hendrick, Steve; Barth, Albert D.

    2013-01-01

    Selection for adequate testis size in beef bulls is an important part of bull breeding soundness evaluation. Scrotal circumference (SC) is highly correlated with paired testis weight and is a practical method for estimating testis weight in the live animal. Most bulls presented for sale in Canada have SC included in the presale information. Scrotal circumference varies by age and breed, and may change over time due to selection for larger testis size. Therefore, it is important to periodically review the mean SC of various cattle breeds to provide valid bull selection criteria. Scrotal circumference data were obtained from bulls sold in western Canada from 2008 to 2011 and in Quebec from 2006 to 2010. Average scrotal circumferences for the most common beef breeds in Canada have increased significantly in the last 25 years. Differences between breeds have remained unchanged and Simmental bulls still have the largest SC at 1 year of age. Data provided here could aid in the establishment of new suggested minimum SC measurements for beef bulls. PMID:24155433

  11. Toxic effects of cadmium on testis of birds and mammals: a review.

    PubMed

    Marettová, E; Maretta, M; Legáth, J

    2015-04-01

    In humans and other mammals, cadmium (Cd) causes various damages to different organs and tissues of the body. This review presents a comprehensive overview on the effect of Cd on the structure of seminiferous tubules, Leydig cells and blood vessels in the testis. The main observation of the effect of Cd is destruction of the seminiferous tubules with severe necrotic areas. Damage is to all stages of developing germ cells by inducing their structural changes and the apoptotic cell death. Sertoli supporting cells are considered the most vulnerable cells. Their damage results in cytoplasmic rearrangement and disruption of inter-Sertoli tight junctions resulting in increased permeability of the blood-testis barrier, structural changes in the Leydig cells and decreased testosterone secretion. After long time of Cd exposure an increase of the amount of interstitial connective tissue occurs. In blood vessels Cd exposure causes various morphological and physiological changes in vascular endothelial cells and smooth muscle cells. In humans and other mammals, the range of effect depends on the dose, route, ways, and duration of exposure. After necrosis of the sensitive cells Cd produced lesions in surrounding tissue and activate free cells. Atrophy of the seminiferous tubules is followed by Leydig cell regeneration and interstitial revascularization. In birds, spermatogenic cells underwent irreversible degeneration or atrophy of seminiferous tubules in the absence of significant vascular lesions.

  12. Ectopic Expression of Testis Germ Cell Proteins in Cancer and Its Potential Role in Genomic Instability

    PubMed Central

    Nielsen, Aaraby Yoheswaran; Gjerstorff, Morten Frier

    2016-01-01

    Genomic instability is a hallmark of human cancer and an enabling factor for the genetic alterations that drive cancer development. The processes involved in genomic instability resemble those of meiosis, where genetic material is interchanged between homologous chromosomes. In most types of human cancer, epigenetic changes, including hypomethylation of gene promoters, lead to the ectopic expression of a large number of proteins normally restricted to the germ cells of the testis. Due to the similarities between meiosis and genomic instability, it has been proposed that activation of meiotic programs may drive genomic instability in cancer cells. Some germ cell proteins with ectopic expression in cancer cells indeed seem to promote genomic instability, while others reduce polyploidy and maintain mitotic fidelity. Furthermore, oncogenic germ cell proteins may indirectly contribute to genomic instability through induction of replication stress, similar to classic oncogenes. Thus, current evidence suggests that testis germ cell proteins are implicated in cancer development by regulating genomic instability during tumorigenesis, and these proteins therefore represent promising targets for novel therapeutic strategies. PMID:27275820

  13. Sertoli cells are the target of environmental toxicants in the testis - a mechanistic and therapeutic insight.

    PubMed

    Gao, Ying; Mruk, Dolores D; Cheng, C Yan

    2015-01-01

    Sertoli cells support germ cell development in the testis via an elaborate network of cell junctions that confers structural, communicating, and signaling support. However, Sertoli cell junctions and cytoskeletons are the target of environmental toxicants. Because germ cells rely on Sertoli cells for the provision of structural/functional/nutritional support, exposure of males to toxicants leads to germ cell exfoliation due to Sertoli cell injuries. Interestingly, the molecular mechanism(s) by which toxicants induce cytoskeletal disruption that leads to germ cell exfoliation is unclear, until recent years, which are discussed herein. This information can possibly be used to therapeutically manage toxicant-induced infertility/subfertility in human males. In this review, we provide a brief update on the use of Sertoli cell system developed for rodents and humans in vitro, which can be deployed in any research laboratory with minimal upfront setup costs. These systems can be used to collect reliable data applicable to studies in vivo. We also discuss the latest findings on the mechanisms by which toxicants induce Sertoli cell injury, in particular cytoskeletal disruption. We also identify candidate molecules that are likely targets of toxicants. We provide two hypothetical models delineating the mechanism by which toxicants induce germ cell exfoliation and blood-testis barrier disruption. We also discuss molecules that are the targets of toxicants as therapeutic candidates.

  14. CB1 cannabinoid receptor enrichment in the ependymal region of the adult human spinal cord.

    PubMed

    Paniagua-Torija, Beatriz; Arevalo-Martin, Angel; Ferrer, Isidro; Molina-Holgado, Eduardo; Garcia-Ovejero, Daniel

    2015-12-04

    Cannabinoids are involved in the regulation of neural stem cell biology and their receptors are expressed in the neurogenic niches of adult rodents. In the spinal cord of rats and mice, neural stem cells can be found in the ependymal region, surrounding the central canal, but there is evidence that this region is largely different in adult humans: lacks a patent canal and presents perivascular pseudorosettes, typically found in low grade ependymomas. Using Laser Capture Microdissection, Taqman gene expression assays and immunohistochemistry, we have studied the expression of endocannabinoid system components (receptors and enzymes) at the human spinal cord ependymal region. We observe that ependymal region is enriched in CB1 cannabinoid receptor, due to high CB1 expression in GFAP+ astrocytic domains. However, in human spinal cord levels that retain central canal patency we found ependymal cells with high CB1 expression, equivalent to the CB1(HIGH) cell subpopulation described in rodents. Our results support the existence of ependymal CB1(HIGH) cells across species, and may encourage further studies on this subpopulation, although only in cases when central canal is patent. In the adult human ependyma, which usually shows central canal absence, CB1 may play a different role by modulating astrocyte functions.

  15. In vivo perfusion of human skin substitutes with microvessels formed by adult circulating endothelial progenitor cells.

    PubMed

    Kung, Elaine F; Wang, Feiya; Schechner, Jeffrey S

    2008-02-01

    At present, tissue-engineered human skin substitutes (HSSs) mainly function as temporary bioactive dressings due to inadequate perfusion. Failure to form functional vascular networks within the initial posttransplantation period compromises cell survival of the graft and its long-term viability in the wound bed. Our goal was to demonstrate that adult circulating endothelial progenitor cells (EPCs) seeded onto HSS can form functional microvessels capable of graft neovascularization and perfusion. Adult peripheral blood mononuclear cells (PBMCs) underwent CD34 selection and endothelial cell (EC) culture conditions. After in vitro expansion, flow cytometry verified EC phenotype before their incorporation into HSS. After 2 weeks in vivo, immunohistochemical analysis, immunofluorescent microscopy, and microfil polymer perfusion were performed. CD34+ PBMCs differentiated into EPC demonstrating characteristic EC morphology and expression of CD31, Tie-2, and E-selectin after TNFalpha-induction. Numerous human CD31 and Ulex europaeus agglutinin-1 (UEA-1) microvessels within the engineered grafts (HSS/EPCs) inosculated with recipient murine circulation. Limitation of murine CD31 immunoreactivity to HSS margins showed angiogenesis was attributable to human EPC at 2 weeks posttransplantation. Delivery of intravenous rhodamine-conjugated UEA-1 and microfil polymer to HSS/EPCs demonstrated enhanced perfusion by functional microvessels compared to HSS control without EPCs. We successfully engineered functional microvessels in HSS by incorporating adult circulating EPCs. This autologous EC source can form vascular conduits enabling perfusion and survival of human bioengineered tissues.

  16. CB1 cannabinoid receptor enrichment in the ependymal region of the adult human spinal cord

    PubMed Central

    Paniagua-Torija, Beatriz; Arevalo-Martin, Angel; Ferrer, Isidro; Molina-Holgado, Eduardo; Garcia-Ovejero, Daniel

    2015-01-01

    Cannabinoids are involved in the regulation of neural stem cell biology and their receptors are expressed in the neurogenic niches of adult rodents. In the spinal cord of rats and mice, neural stem cells can be found in the ependymal region, surrounding the central canal, but there is evidence that this region is largely different in adult humans: lacks a patent canal and presents perivascular pseudorosettes, typically found in low grade ependymomas. Using Laser Capture Microdissection, Taqman gene expression assays and immunohistochemistry, we have studied the expression of endocannabinoid system components (receptors and enzymes) at the human spinal cord ependymal region. We observe that ependymal region is enriched in CB1 cannabinoid receptor, due to high CB1 expression in GFAP+ astrocytic domains. However, in human spinal cord levels that retain central canal patency we found ependymal cells with high CB1 expression, equivalent to the CB1HIGH cell subpopulation described in rodents. Our results support the existence of ependymal CB1HIGH cells across species, and may encourage further studies on this subpopulation, although only in cases when central canal is patent. In the adult human ependyma, which usually shows central canal absence, CB1 may play a different role by modulating astrocyte functions. PMID:26634814

  17. The testis of the mice C57/BL6 offspring in adulthood have alterations due to maternal caffeine consumption.

    PubMed

    Cavalcante, Fernanda Silveira; Aiceles, Verônica; Moraes, Diana de Freitas Serapião; Alves-Pereira, Jorge Luiz; Faria, Tatiane Silva; Ramos, Cristiane da Fonte

    2014-01-01

    To investigate the effects of the maternal caffeine consumption during pregnancy to adult male testis mice offspring. Twenty pregnant mice were divided into control group (c) and caffeine group (cf). dams received daily saline or 20 mg/kg of caffeine subcutaneously. Male offspring were monitored daily until 13th week. The testis were used to evaluate both the proliferation (pcna) and apoptosis (bax); leptin receptor (ob-r); aromatase; follicle stimulating hormone (fshr), luteinizing hormone (lhr) and androgen receptors (ar); steroidogenic acute regulatory protein (star); vascular endothelial growth factor (vegf) and estrogen receptors (erα and erβ) by western blotting. Serum concentrations of testosterone, estradiol and leptin were measured. There was a significant reduction in food intake and the body mass gain (p<0.05) in the cf ; pcna (p=0.01), fshr (p=0.02), star (p=0.0007), vegf (p=0.009), ar (p=0.03) in the cf. while an increase were note in bax (p=0.01), ob-r (p=0.02), lhr (p=0.04) and in the aromatase (p=0.03) in the cf. only erα and erβ were not changed by maternal caffeine. The serum testosterone levels in the cf offspring were 90% lower than in the c offspring (p=0.04). Maternal caffeine consumption has a role and alters the testis of the offspring in adulthood.

  18. Novel expression of resistin in rat testis: functional role and regulation by nutritional status and hormonal factors.

    PubMed

    Nogueiras, Ruben; Barreiro, M Luz; Caminos, Jorge E; Gaytán, Francisco; Suominen, Janne S; Navarro, Victor M; Casanueva, Felipe F; Aguilar, Enrique; Toppari, Jorma; Diéguez, Carlos; Tena-Sempere, Manuel

    2004-07-01

    Resistin, a recently cloned adipose-secreted factor, is primarily involved in the modulation of insulin sensitivity and adipocyte differentiation. However, additional metabolic or endocrine functions of this molecule remain largely unexplored. In this study, a series of experiments were undertaken to explore the potential expression, regulation and functional role of this novel adipocytokine in rat testis. Resistin gene expression was demonstrated in rat testis throughout postnatal development, with maximum mRNA levels in adult specimens. At this age, resistin peptide was immunodetected in interstitial Leydig cells and Sertoli cells within seminiferous tubules. Testicular expression of resistin was under hormonal regulation of pituitary gonadotropins and showed stage-specificity, with peak expression values at stages II-VI of the seminiferous epithelial cycle. In addition, testicular resistin mRNA was down-regulated by the selective agonist of PPARgamma, rosiglitazone, in vivo and in vitro. Similarly, fasting and central administration of the adipocyte-derived factor, leptin, evoked a significant reduction in testicular resistin mRNA levels, whereas they remained unaltered in a model of diet-induced obesity. From a functional standpoint, resistin, in a dose-dependent manner, significantly increased both basal and choriogonadotropin-stimulated testosterone secretion in vitro. Overall, our present results provide the first evidence for the expression, regulation and functional role of resistin in rat testis. These data underscore a reproductive facet of this recently cloned molecule, which may operate as a novel endocrine integrator linking energy homeostasis and reproduction.

  19. Effects of Common Fig (Ficus carica) Leaf Extracts on Sperm Parameters and Testis of Mice Intoxicated with Formaldehyde

    PubMed Central

    Naghdi, Majid; Maghbool, Maryam; Seifalah-Zade, Morteza; Mahaldashtian, Maryam; Makoolati, Zohreh; Kouhpayeh, Seyed Amin; Ghasemi, Afsaneh; Fereydouni, Narges

    2016-01-01

    Formaldehyde (FA) is the leading cause of cellular injury and oxidative damage in testis that is one of the main infertility causes. There has been an increasing evidence of herbal remedies use in male infertility treatment. This assay examines the role of Ficus carica (Fc) leaf extracts in sperm parameters and testis of mice intoxicated with FA. Twenty-five adult male mice were randomly divided into control; sham; FA-treated (10 mg/kg twice per day); Fc-treated (200 mg/kg); and FA + Fc-treated groups. Cauda epididymal spermatozoa were analyzed for viability, count, and motility. Testes were weighed and gonadosomatic index (GSI) was calculated. Also, histoarchitecture of seminiferous tubules was assessed in the Haematoxylin and Eosin stained paraffin sections. The findings showed that FA significantly decreased GSI and increased percentage of immotile sperm compared with control group. Disorganized and vacuolated seminiferous epithelium, spermatogenic arrest, and lumen filled with immature germ cells were also observed in the testes. However, Fc leaf extracts improved sperm count, nonprogressive motility of spermatozoa, and GSI in FA-treated testes. Moreover, seminiferous tubule with spermatogenic arrest was rarely seen, indicating that Fc has the positive effects on testis and epididymal sperm parameters exposed with FA. PMID:26904140

  20. Does bone marrow-derived mesenchymal stem cell transfusion prevent antisperm antibody production after traumatic testis rupture?

    PubMed

    Aghamir, Seyyed Mohammad Kazem; Salavati, Alborz; Yousefie, Reza; Tootian, Zahra; Ghazaleh, Noushin; Jamali, Mostafa; Azimi, Pourya

    2014-07-01

    To determine whether transfusion of mesenchymal stem cells (MSCs) could prevent humoral immune response and autoimmunization against sperms after traumatic testis rupture. Immunomodulatory properties of MSCs have been evaluated by a prospective cohort on 50 adult BALB/c mice. In each interventional arms of study, controlled testis rupture and surgical repair were exerted. In addition to tissue repair, single dose of 5×10(5) MSCs labeled by green fluorescent protein was delivered intravenously to 20 cases (cell therapy group). After euthanizing, seroconversion of antisperm antibody (ASA) was compared between 2 interventional groups as response of humoral immune system. Lung and testis tissues were examined for green fluorescent protein-positive cells to assess whether presence of stem cells is correlated with seroconversion rates. Six cases had been lost during the study. Fourteen of 16 mice in cell therapy control group formed ASA (87.5%) but 6 of 18 mice (33.3%) in cell therapy group were immunized and formed ASA (P=.002). Transplanted cells were traced in lungs of 55% (n=10) of cell therapy group and none were found in trauma site. Small volume of mice blood was our main limitation to trace seroconversion or quantitative measurement of ASA in each case. In this in vivo model of autoimmune infertility, bone marrow-derived MSC transfusion showed immunosuppressive effects on antibody production. Considering immunomodulatory properties of MSCs even in allogeneic settings, novel clinical application should be investigated further. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2012-08-01

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

  2. Effects of flutamide in the rat testis on the expression of occludin, an integral member of the tight junctions.

    PubMed

    Gye, Myung Chan; Ohsako, Seiichiroh

    2003-07-20

    In an effort to uncover the gonadal impairment by the antiandrogen flutamide (FM) in males, the effect of subacute administration of FM on the expression of tight junction (TJ) genes that build the blood-testis barrier (BTB) was investigated in adult rat testis. At 13 weeks old of age male rats were given vehicle (corn oil) or FM (25 mg/kg per day, in corn oil) orally for 6 days. At 8 days (D8) after the first dose, testicular expression of the occludin, claudin-1, and -11 was analyzed by semiquantitative RT-PCR. The testicular weight of the FM-treated rats on D8 was a little but significantly higher than in the control group. On D8 the expression of occludin in the FM-treated animals was significantly decreased but claudin-1 and -11 were not altered significantly. Because FM administration inhibits germ cell differentiation, it is likely that the down-regulated occludin expression in FM-rat testes may be attributed to the alteration in the paracrine interaction between Sertoli cells and germ cells in testis. It also emphasized that FM might have differentially affected the transcription of TJ genes in Sertoli cells building the BTB. These findings provide a rationale for a number of observations on the gonadal impairment by FM in males and suggest that FM is potentially harmful to spermatogenesis by alteration of the BTB.

  3. Identification of a Novel Testis-specific Gene in Mice and Its Potential Roles in Spermatogenesis

    PubMed Central

    Tang, Aifa; Yu, Zhendong; Gui, Yaoting; Zhu, Hui; Long, Yun; Cai, Zhiming

    2007-01-01

    Aim Identification of a novel gene in mouse testis and its relation to spermatogenesis. Methods Genes expressed during different developmental stages of the mouse testis were screened by DNA microarray. The results of chip analysis were authenticated by reverse transcription-polymerase chain reaction (RT-PCR) technique, as well as the tissue distribution of the selected genes. The characteristics of the selected genes were analyzed by bioinformatics tools. Results A novel gene, TSC77, was identified and located at the mouse chromosome 2G1. The full cDNA length of TSC77 was 2280 bp, with a 2046 bp open reading frame encoding a 681 amino acids protein with a predicted molecular weight of 77.17 kDa. The results of subcellular localization of GFP-TSC77 fusion protein indicated TSC77 protein was located in the nucleus of Cos-7 cells. The analysis of multiple amino acid sequence alignment showed that TSC77 protein was highly homologous with the human CAI40813 (C2orf26 gene, 76%), and rat XP_230651 (77%). Three putative domains including nicotine amide dinucleotide phosphate (NAD(P))-nitrite reductase (NirB) domain, uncharacterized NAD flavin adenine dinucleotide (FAD)-dependent dehydrogenases (HcaD) domain, and nicotinamide adenine dinucleotide (NADH) dehydrogenase (Ndh) domain were predicted at the protein site 168-309, 187-245, 181-216, respectively. Gene expression anlysis showed that the mouse TSC77 is preferentially expressed in the mouse testis and its expression increased gradually from the day 9 to day 21. Conclusion Based on its expression during mouse development, TSC77 may play an important role during mouse spermatogenesis. PMID:17309138

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

    PubMed

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

    2017-02-24

    Large amounts of fat deposition often lead to loss of reproductive efficiency in humans and animals. We used broiler chickens as a model species to conduct a two-directional selection for and against abdominal fat over 19 generations, which resulted in a lean and a fat line. Direct selection for abdominal fat content also indirectly resulted in significant differences (P < 0.05) in testis weight (TeW) and in TeW as a percentage of total body weight (TeP) between the lean and fat lines. A total of 475 individuals from the generation 11 (G11) were genotyped. Genome-wide association studies revealed two regions on chicken chromosomes 3 and 10 that were associated with TeW and TeP. Forty G16 individuals (20 from each line), were further profiled by focusing on these two chromosomal regions, to identify candidate genes with functions that may be potentially related to testis growth and development. Of the nine candidate genes identified with database mining, a significant association was confirmed for one gene, TCF21, based on mRNA expression analysis. Gene expression analysis of the TCF21 gene was conducted again across 30 G19 individuals (15 individuals from each line) and the results confirmed the findings on the G16 animals. This study revealed that the TCF21 gene is related to testis growth and development in male broilers. This finding will be useful to guide future studies to understand the genetic mechanisms that underlie reproductive efficiency.

  5. Posthatching development of Alligator mississippiensis ovary and testis.

    PubMed

    Moore, Brandon C; Hamlin, Heather J; Botteri, Nicole L; Lawler, Ashley N; Mathavan, Ketan K; Guillette, Louis J

    2010-05-01

    We investigated ovary and testis development of Alligator mississippiensis during the first 5 months posthatch. To better describe follicle assembly and seminiferous cord development, we used histochemical techniques to detect carbohydrate-rich extracellular matrix components in 1-week, 1-month, 3-month, and 5-month-old gonads. We found profound morphological changes in both ovary and testis. During this time, oogenesis progressed up to diplotene arrest and meiotic germ cells increasingly interacted with follicular cells. Concomitant with follicles becoming invested with full complements of granulosa cells, a periodic acid Schiff's (PAS)-positive basement membrane formed. As follicles enlarged and thecal layers were observed, basement membranes and thecal compartments gained periodic acid-methionine silver (PAMS)-reactive fibers. The ovarian medulla increased first PAS- and then PAMS reactivity as it fragmented into wide lacunae lined with low cuboidal to squamous epithelia. During this same period, testicular germ cells found along the tubule margins were observed progressing from spermatogonia to round spermatids located within the center of tubules. Accompanying this meiotic development, interstitial Leydig cell clusters become more visible and testicular capsules thickened. During the observed testis development, the thickening tunica albuginea and widening interstitial tissues showed increasing PAS- and PAMS reactivity. We observed putative intersex structures in both ovary and testis. On the coelomic aspect of testes were cell clusters with germ cell morphology and at the posterior end of ovaries, we observed "medullary rests" resembling immature testis cords. We hypothesize laboratory conditions accelerated gonad maturation due to optimum conditions, including nutrients and temperature. Laboratory alligators grew more rapidly and with increased body conditions compared with previous measured, field-caught animals. Additionally, we predict the morphological

  6. Post-hatching development of Alligator mississippiensis ovary and testis

    PubMed Central

    Moore, Brandon C.; Hamlin, Heather J.; Botteri, Nicole L.; Lawler, Ashley N.; Mathavan, Ketan K.; Guillette, Louis J.

    2009-01-01

    We investigated ovary and testis development of Alligator mississippiensis during the first five months post-hatch. To better describe follicle assembly and seminiferous cord development, we employed histochemical techniques to detect carbohydrate-rich extracellular matrix components in one-week, one-month, three-month, and five-month-old gonads. We found profound morphological changes in both ovary and testis. During this time, oogenesis progressed up to diplotene arrest and meiotic germ cells increasingly interacted with follicular cells. Concomitant with follicles becoming invested with full complements of granulosa cells, a periodic acid Schiff’s (PAS)-positive basement membrane formed. As follicles enlarged and thecal layers were observed, basement membranes and thecal compartments gained periodic acid-methionine silver (PAMS)-reactive fibers. The ovarian medulla increased first PAS- and then PAMS-reactivity as it fragmented into wide lacunae lined with low cuboidal to squamous epithelia. During this same period, testicular germ cells found along the tubule margins were observed progressing from spermatogonia to round spermatids located within the center of tubules. Accompanying this meiotic development, interstitial Leydig cell clusters become more visible and testicular capsules thickened. During the observed testis development, the thickening tunica albuginea and widening interstitial tissues showed increasing PAS- and PAMS-reactivity. We observed putative inter-sex structures in both ovary and testis. On the coelomic aspect of testes were cell clusters with germ cell morphology and at the posterior end of ovaries, we observed “medullary rests” resembling immature testis cords. We hypothesize laboratory conditions accelerated gonad maturation due to optimum conditions, including nutrients and temperature. Laboratory alligators grew more rapidly and with increased body conditions compared to previous measured, field-caught animals. Additionally, we

  7. Human and monkey striatal interneurons are derived from the medial ganglionic eminence but not from the adult subventricular zone.

    PubMed

    Wang, Congmin; You, Yan; Qi, Dashi; Zhou, Xing; Wang, Lei; Wei, Song; Zhang, Zhuangzhi; Huang, Weixi; Liu, Zhidong; Liu, Fang; Ma, Lan; Yang, Zhengang

    2014-08-13

    In adult rodent and monkey brains, newly born neurons in the subventricular zone (SVZ) in the wall of the lateral ventricle migrate into the olfactory bulb (OB) via the rostral migratory stream (RMS). A recent study reported that interneurons are constantly generating in the adult human striatum from the SVZ. In contrast, by taking advantage of the continuous expression of Sp8 from the neuroblast stage through differentiation into mature interneurons, we found that the adult human SVZ does not generate new interneurons for the striatum. In the adult human SVZ and RMS, very few neuroblasts were observed, and most of them expressed the transcription factor Sp8. Neuroblasts in the adult rhesus monkey SVZ-RMS-OB pathway also expressed Sp8. In addition, we observed that Sp8 was expressed by most adult human and monkey OB interneurons. However, very few Sp8+ cells were in the adult human striatum. This suggests that neuroblasts in the adult human SVZ and RMS are likely destined for the OB, but not for the striatum. BrdU-labeling results also revealed few if any newly born neurons in the adult rhesus monkey striatum. Finally, on the basis of transcription factor expression, we provide strong evidence that the vast majority of interneurons in the human and monkey striatum are generated from the medial ganglionic eminence during embryonic developmental stages, as they are in rodents. We conclude that, although a small number of neuroblasts exist in the adult human SVZ, they do not migrate into the striatum and become mature striatal interneurons.

  8. Identification and characterization of neuroblasts in the subventricular zone and rostral migratory stream of the adult human brain

    PubMed Central

    Wang, Congmin; Liu, Fang; Liu, Ying-Ying; Zhao, Cai-Hong; You, Yan; Wang, Lei; Zhang, Jingxiao; Wei, Bin; Ma, Tong; Zhang, Qiangqiang; Zhang, Yue; Chen, Rui; Song, Hongjun; Yang, Zhengang

    2011-01-01

    It is of great interest to identify new neurons in the adult human brain, but the persistence of neurogenesis in the subventricular zone (SVZ) and the existence of the rostral migratory stream (RMS)-like pathway in the adult human forebrain remain highly controversial. In the present study, we have described the general configuration of the RMS in adult monkey, fetal human and adult human brains. We provide evidence that neuroblasts exist continuously in the anterior ventral SVZ and RMS of the adult human brain. The neuroblasts appear singly or in pairs without forming chains; they exhibit migratory morphologies and co-express the immature neuronal markers doublecortin, polysialylated neural cell adhesion molecule and βIII-tubulin. Few of these neuroblasts appear to be actively proliferating in the anterior ventral SVZ but none in the RMS, indicating that neuroblasts distributed along the RMS are most likely derived from the ventral SVZ. Interestingly, no neuroblasts are found in the adult human olfactory bulb. Taken together, our data suggest that the SVZ maintains the ability to produce neuroblasts in the adult human brain. PMID:21577236

  9. Origin of germ cells and formation of new primary follicles in adult human ovaries

    PubMed Central

    Bukovsky, Antonin; Caudle, Michael R; Svetlikova, Marta; Upadhyaya, Nirmala B

    2004-01-01

    Recent reports indicate that functional mouse oocytes and sperm can be derived in vitro from somatic cell lines. We hypothesize that in adult human ovaries, mesenchymal cells in the tunica albuginea (TA) are bipotent progenitors with a commitment for both primitive granulosa and germ cells. We investigated ovaries of twelve adult women (mean age 32.8 ± 4.1 SD, range 27–38 years) by single, double, and triple color immunohistochemistry. We show that cytokeratin (CK)+ mesenchymal cells in ovarian TA differentiate into surface epithelium (SE) cells by a mesenchymal-epithelial transition. Segments of SE directly associated with ovarian cortex are overgrown by TA, forming solid epithelial cords, which fragment into small (20 micron) epithelial nests descending into the lower ovarian cortex, before assembling with zona pellucida (ZP)+ oocytes. Germ cells can originate from SE cells which cover the TA. Small (10 micron) germ-like cells showing PS1 meiotically expressed oocyte carbohydrate protein are derived from SE cells via asymmetric division. They show nuclear MAPK immunoexpression, subsequently divide symmetrically, and enter adjacent cortical vessels. During vascular transport, the putative germ cells increase to oocyte size, and are picked-up by epithelial nests associated with the vessels. During follicle formation, extensions of granulosa cells enter the oocyte cytoplasm, forming a single paranuclear CK+ Balbiani body supplying all the mitochondria of the oocyte. In the ovarian medulla, occasional vessels show an accumulation of ZP+ oocytes (25–30 microns) or their remnants, suggesting that some oocytes degenerate. In contrast to males, adult human female gonads do not preserve germline type stem cells. This study expands our previous observations on the formation of germ cells in adult human ovaries. Differentiation of primitive granulosa and germ cells from the bipotent mesenchymal cell precursors of TA in adult human ovaries represents a most

  10. PET imaging of neurogenic activity in the adult brain: Toward in vivo imaging of human neurogenesis.

    PubMed

    Tamura, Yasuhisa; Kataoka, Yosky

    2017-01-01

    Neural stem cells are present in 2 neurogenic regions, the subventricular zone (SVZ) and the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG), and continue to generate new neurons throughout life. Adult hippocampal neurogenesis is linked to a variety of psychiatric disorders such as depression and anxiety, and to the therapeutic effects of antidepressants, as well as learning and memory. In vivo imaging for hippocampal neurogenic activity may be used to diagnose psychiatric disorders and evaluate the therapeutic efficacy of antidepressants. However, these imaging techniques remain to be established until now. Recently, we established a quantitative positron emission tomography (PET) imaging technique for neurogenic activity in the adult brain with 3'-deoxy-3'-[(18)F]fluoro-L-thymidine ([(18)F]FLT) and probenecid, a drug transporter inhibitor in blood-brain barrier. Moreover, we showed that this PET imaging technique can monitor alterations in neurogenic activity in the hippocampus of adult rats with depression and following treatment with an antidepressant. This PET imaging method may assist in diagnosing depression and in monitoring the therapeutic efficacy of antidepressants. In this commentary, we discuss the possibility of in vivo PET imaging for neurogenic activity in adult non-human primates and humans.

  11. Recapitulating adult human immune traits in laboratory mice by normalizing environment

    PubMed Central

    Beura, Lalit K.; Hamilton, Sara E.; Bi, Kevin; Schenkel, Jason M.; Odumade, Oludare A.; Casey, Kerry A.; Thompson, Emily A.; Fraser, Kathryn A.; Rosato, Pamela C.; Filali-Mouhim, Ali; Sekaly, Rafick P.; Jenkins, Marc K.; Vezys, Vaiva; Haining, W. Nicholas; Jameson, Stephen C.; Masopust, David

    2016-01-01

    Our current understanding of immunology was largely defined in laboratory mice because of experimental advantages including inbred homogeneity, tools for genetic manipulation, the ability to perform kinetic tissue analyses starting with the onset of disease, and tractable models. Comparably reductionist experiments are neither technically nor ethically possible in humans. Despite revealing many fundamental principals of immunology, there is growing concern that mice fail to capture relevant aspects of the human immune system, which may account for failures to translate disease treatments from bench to bedside1–8. Laboratory mice live in abnormally hygienic “specific pathogen free” (SPF) barrier facilities. Here we show that the standard practice of laboratory mouse husbandry has profound effects on the immune system and that environmental changes result in better recapitulation of features of adult humans. Laboratory mice lack effector-differentiated and mucosally distributed memory T cells, which more closely resembles neonatal than adult humans. These cell populations were present in free-living barn populations of feral mice, pet store mice with diverse microbial experience, and were induced in laboratory mice after co-housing with pet store mice, suggesting a role for environment. Consequences of altering mouse housing profoundly impacted the cellular composition of the innate and adaptive immune system and resulted in global changes in blood cell gene expression patterns that more closely aligned with immune signatures of adult humans rather than neonates, altered the mouse’s resistance to infection, and impacted T cell differentiation to a de novo viral infection. These data highlight the impact of environment on the basal immune state and response to infection and suggest that restoring physiological microbial exposure in laboratory mice could provide a relevant tool for modeling immunological events in free-living organisms, including humans. PMID

  12. Isolation, Characterization, and Differentiation of Progenitor Cells from Human Adult Adrenal Medulla

    PubMed Central

    Santana, Magda M.; Chung, Kuei-Fang; Vukicevic, Vladimir; Rosmaninho-Salgado, Joana; Kanczkowski, Waldemar; Cortez, Vera; Hackmann, Karl; Bastos, Carlos A.; Mota, Alfredo; Schrock, Evelin; Bornstein, Stefan R.; Cavadas, Cláudia

    2012-01-01

    Chromaffin cells, sympathetic neurons of the dorsal ganglia, and the intermediate small intensely fluorescent cells derive from a common neural crest progenitor cell. Contrary to the closely related sympathetic nervous system, within the adult adrenal medulla a subpopulation of undifferentiated progenitor cells persists, and recently, we established a method to isolate and differentiate these progenitor cells from adult bovine adrenals. However, no studies have elucidated the existence of adrenal progenitor cells within the human adrenal medulla. Here we describe the isolation, characterization, and differentiation of chromaffin progenitor cells obtained from adult human adrenals. Human chromaffin progenitor cells were cultured in low-attachment conditions for 10–12 days as free-floating spheres in the presence of fibroblast growth factor-2 (FGF-2) and epidermal growth factor. These primary human chromosphere cultures were characterized by the expression of several progenitor markers, including nestin, CD133, Notch1, nerve growth factor receptor, Snai2, Sox9, Sox10, Phox2b, and Ascl1 on the molecular level and of Sox9 on the immunohistochemical level. In opposition, phenylethanolamine N-methyltransferase (PNMT), a marker for differentiated chromaffin cells, significantly decreased after 12 days in culture. Moreover, when plated on poly-l-lysine/laminin-coated slides in the presence of FGF-2, human chromaffin progenitor cells were able to differentiate into two distinct neuron-like cell types, tyrosine hydroxylase (TH)+/β-3-tubulin+ cells and TH−/β-3-tubulin+ cells, and into chromaffin cells (TH+/PNMT+). This study demonstrates the presence of progenitor cells in the human adrenal medulla and reveals their potential use in regenerative medicine, especially in the treatment of neuroendocrine and neurodegenerative diseases. PMID:23197690

  13. Normalizing the environment recapitulates adult human immune traits in laboratory mice.

    PubMed

    Beura, Lalit K; Hamilton, Sara E; Bi, Kevin; Schenkel, Jason M; Odumade, Oludare A; Casey, Kerry A; Thompson, Emily A; Fraser, Kathryn A; Rosato, Pamela C; Filali-Mouhim, Ali; Sekaly, Rafick P; Jenkins, Marc K; Vezys, Vaiva; Haining, W Nicholas; Jameson, Stephen C; Masopust, David

    2016-04-28

    Our current understanding of immunology was largely defined in laboratory mice, partly because they are inbred and genetically homogeneous, can be genetically manipulated, allow kinetic tissue analyses to be carried out from the onset of disease, and permit the use of tractable disease models. Comparably reductionist experiments are neither technically nor ethically possible in humans. However, there is growing concern that laboratory mice do not reflect relevant aspects of the human immune system, which may account for failures to translate disease treatments from bench to bedside. Laboratory mice live in abnormally hygienic specific pathogen free (SPF) barrier facilities. Here we show that standard laboratory mouse husbandry has profound effects on the immune system and that environmental changes produce mice with immune systems closer to those of adult humans. Laboratory mice--like newborn, but not adult, humans--lack effector-differentiated and mucosally distributed memory T cells. These cell populations were present in free-living barn populations of feral mice and pet store mice with diverse microbial experience, and were induced in laboratory mice after co-housing with pet store mice, suggesting that the environment is involved in the induction of these cells. Altering the living conditions of mice profoundly affected the cellular composition of the innate and adaptive immune systems, resulted in global changes in blood cell gene expression to patterns that more closely reflected the immune signatures of adult humans rather than neonates, altered resistance to infection, and influenced T-cell differentiation in response to a de novo viral infection. These data highlight the effects of environment on the basal immune state and response to infection and suggest that restoring physiological microbial exposure in laboratory mice could provide a relevant tool for modelling immunological events in free-living organisms, including humans.

  14. Isolation, characterization, and differentiation of progenitor cells from human adult adrenal medulla.

    PubMed

    Santana, Magda M; Chung, Kuei-Fang; Vukicevic, Vladimir; Rosmaninho-Salgado, Joana; Kanczkowski, Waldemar; Cortez, Vera; Hackmann, Klaus; Bastos, Carlos A; Mota, Alfredo; Schrock, Evelin; Bornstein, Stefan R; Cavadas, Cláudia; Ehrhart-Bornstein, Monika

    2012-11-01

    Chromaffin cells, sympathetic neurons of the dorsal ganglia, and the intermediate small intensely fluorescent cells derive from a common neural crest progenitor cell. Contrary to the closely related sympathetic nervous system, within the adult adrenal medulla a subpopulation of undifferentiated progenitor cells persists, and recently, we established a method to isolate and differentiate these progenitor cells from adult bovine adrenals. However, no studies have elucidated the existence of adrenal progenitor cells within the human adrenal medulla. Here we describe the isolation, characterization, and differentiation of chromaffin progenitor cells obtained from adult human adrenals. Human chromaffin progenitor cells were cultured in low-attachment conditions for 10-12 days as free-floating spheres in the presence of fibroblast growth factor-2 (FGF-2) and epidermal growth factor. These primary human chromosphere cultures were characterized by the expression of several progenitor markers, including nestin, CD133, Notch1, nerve growth factor receptor, Snai2, Sox9, Sox10, Phox2b, and Ascl1 on the molecular level and of Sox9 on the immunohistochemical level. In opposition, phenylethanolamine N-methyltransferase (PNMT), a marker for differentiated chromaffin cells, significantly decreased after 12 days in culture. Moreover, when plated on poly-l-lysine/laminin-coated slides in the presence of FGF-2, human chromaffin progenitor cells were able to differentiate into two distinct neuron-like cell types, tyrosine hydroxylase (TH)(+)/β-3-tubulin(+) cells and TH(-)/β-3-tubulin(+) cells, and into chromaffin cells (TH(+)/PNMT(+)). This study demonstrates the presence of progenitor cells in the human adrenal medulla and reveals their potential use in regenerative medicine, especially in the treatment of neuroendocrine and neurodegenerative diseases.

  15. A Comparison of Pure Tone Auditory Thresholds in Human Infants and Adults.

    PubMed

    Sinnott, Joan M; Pisoni, David B; Aslin, Richard N

    1983-01-01

    Pure tone auditory thresholds for frequencies from .250 to 8.0 kHz were obtained from 277-to-11-month-old human infants and nine adults using a go-no-go operant head-turning technique combined with an adaptive staircase (tracking) discrimination procedure. New methods were devised for maintaining infants under stimulus control during threshold testing through the use of randomly interleaved "probe" and "catch" trials. Reliable threshold data were obtained from every infant studied, and identical threshold criteria were applied to infants and adults alike. Although infant thresholds were 17-27 dB higher than those of adults, infant inter-subject variability was no greater than that of adults. Adult audiograms were nearly flat between frequencies of .500 and 8.0 kHz with sensitivity ranging between 7 and 14 dB SPL. Infant audiograms were flat between frequencies of .500 and 4.0 kHz, with sensitivity ranging between 30 and 36 dB SPL. The most sensitive frequency for infants was 8.0 kHz (25 dB SPL).

  16. Molecular subtypification of human papillomavirus in male adult individuals with recurrent respiratory papillomatosis.

    PubMed

    García-Romero, Carmen S; Akaki-Caballero, Matsuharu; Saavedra-Mendoza, Ana G; Guzmán-Romero, Ana K; Canto, Patricia; Coral-Vázquez, Ramón M

    2015-10-01

    This study aimed to identify the isotype of human papillomavirus (HPV) in fresh tissue samples of 35 male adults with adult recurrent adult respiratory papillomatosis which may be important to define the precise etiology of the disease, and determine the therapeutic and prophylactic measures. A total of 35 adult male patients diagnosed with active RRP who have been treated for several years were included in the study. DNA of patients was extracted from fresh biological samples and analyzed by PCR and a Linear Array® HPV Genotyping system. Most cases (95%) corresponded to adult-onset of RRP. A questionnaire was applied to obtain demographic and clinical data. Using a PCR-based detection system all patients showed the presence of HPV; 80% were positive for HPV-6, 8% for HPV-11 and one for HPV-16. Most patients presented HPV-6 and consequently it was not feasible to correlate clinical and demographic characteristics with viral type. Besides, co-infections were not evident. This knowledge may be relevant to delineate therapeutic and preventive measures. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. A seroprevalence survey for human immunodeficiency virus antibody in mentally retarded adults.

    PubMed

    Pincus, S H; Schoenbaum, E E; Webber, M

    1990-03-01

    The prevalence of human immunodeficiency virus (HIV) infection among adults who are mentally retarded is not known. Policies for those in residential settings are being established despite incomplete information. Knowledge regarding HIV seroprevalence would enable administrators to make more effective policy decisions concerning testing and HIV prevention. Discarded sera from mentally retarded adults were anonymously tested for HIV antibody. Sera were collected from a health facility in Westchester County, NY, that provides car