Regulation of junction dynamics in the testis--transcriptional and post-translational regulations of cell junction proteins

Cell junctions are the sites at which cells attach to the neighboring cells. They do not only maintain tissue integrity, their turnover also plays a crucial role in cell development and morphogenesis. In the testis, tight junctions and adherens junctions are dynamically remodeled to allow the movement of post-meiotic germ cells across the seminiferous epithelium and the timely release of spermatids into the tubular lumen. There is growing evidence that this dynamic remodeling of cell junctions is mediated by several mechanisms at the transcriptional and post-translational levels. This review summarizes what is known about the transcriptional regulation, ubiquitination and endocytosis that are involved in modulating junction dynamics in epithelial cells. It also highlights the recent findings on the regulation of junction dynamics in the testis and the specific areas that require further research for a thorough understanding of the role of junction remodeling in spermatogenesis. Understanding the junction dynamics in the seminiferous epithelium may unfold new targets for non-hormonal male contraceptive development.postprin

The dynamics of Sertoli (SC)-germ cell (GC) anchoring junctions (AJs) are regulated by E-cadherin, N-cadherin and Src

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Thyroid Hormone Function in the Rat Testis

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Coxsackie and adenovirus receptor (CAR) is a product of Sertoli and germ cells in rat testes which is localized at the Sertoli-Sertoli and Sertoli-germ cell interface

The coxsackie and adenovirus receptor (CAR), a putative cell-cell adhesion molecule, has attracted wide interest due to its importance in viral pathogenesis and in mediating adenoviral gene delivery. However, the distribution pattern and physiological function of CAR in the testis is still not clear. Here, we identified CAR in Sertoli cells and germ cells of rats. In vivo studies have shown that CAR resides at the blood-testis barrier as well as at the ectoplasmic specialization. The persistent expression of CAR in rat testes from neonatal period throughout adulthood implicates its role in spermatogenesis. Using primary Sertoli cell cultures, we observed a significant induction of CAR during the formation of Sertoli cell epithelium. Furthermore, CAR was seen to be concentrated at inter-Sertoli cell junctions, co-localizing with tight junction protein marker ZO-1 and adherens junction protein N-cadherin. CAR was also found to be associated with proteins of Src kinase family and its protein level declined after TNFalpha treatment in Sertoli cell cultures. Immunofluorescent staining of isolated germ cells has revealed the presence of CAR on spermatogonia, spermatocytes, round spermatids and elongate spermatids. Taken together, we propose that CAR functions as an adhesion molecule in maintaining the inter-Sertoli cell junctions at the basal compartment of the seminiferous epithelium. In addition, CAR may confer adhesion between Sertoli and germ cells at the Sertoli-germ cell interface. It is possible that the receptor utilized by viral pathogens to breakthrough the epithelial barrier was also employed by developing germ cells to migrate through the inter-Sertoli cell junctions.postprin

Unraveling the molecular targets pertinent to junction restructuring events during spermatogenesis using the Adjudin-induced germ cell depletion model

During spermatogenesis, extensive restructuring takes place at the Sertoli-Sertoli and Sertoli-germ cell interface, which is regulated via intriguing interactions among cytokines, proteases, protease inhibitors, kinases, phosphatases, and transcription factors. This in turn determines the steady-state levels of integral membrane proteins at the cell junctions. We sought to further expand these observations using the Adjudin model. Adjudin is a potential male contraceptive that targets Sertoli-germ cell adhesion, causing exfoliation of spermatids and spermatocytes, but not spermatogonia, from the seminiferous epithelium. This model thus provides the means to identify crucial regulatory molecules and signaling pathways pertinent to junction restructuring events during spermatogenesis. In this study, genome-wide expression profiling of rat testes after treatment with Adjudin at the time of extensive junction restructuring was performed. Differentially regulated genes, such as cytokines, proteases, protease inhibitors, cell junction-associated proteins, and transcription factors pertinent to junction restructuring were identified. These data were consistent with earlier findings; however, much new information was obtained which has been deposited at the Gene Expression Omnibus data repository website: http://www.ncbi.nih.gov/geo/ with Accession number: GSE5131. The primary signaling events pertinent to junction restructuring in the testis induced by Adjudin were also delineated using bioinformatics. These findings were also consistent with recently published reports. The identified molecular signatures or targets pertinent to junction dynamics in the testis as reported herein, many of which have not been investigated, thus offer a framework upon which the regulation of junction restructuring events at the Sertoli-Sertoli and Sertoli-germ cell interface pertinent to spermatogenesis can be further studied.postprin

Rescue of perfluorooctanesulfonate (PFOS)-mediated Sertoli cell injury by overexpression of gap junction protein connexin 43

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N-wasp Is Required For Structural Integrity Of The Blood-testis Barrier.

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Perfluorooctanesulfonate (PFOS)-induced Sertoli cell injury through a disruption of F-actin and microtubule organization is mediated by Akt1/2

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First observations of separated atmospheric nu_mu and bar{nu-mu} events in the MINOS detector

The complete 5.4 kton MINOS far detector has been taking data since the beginning of August 2003 at a depth of 2070 meters water-equivalent in the Soudan mine, Minnesota. This paper presents the first MINOS observations of nuµ and [overline nu ]µ charged-current atmospheric neutrino interactions based on an exposure of 418 days. The ratio of upward- to downward-going events in the data is compared to the Monte Carlo expectation in the absence of neutrino oscillations, giving Rup/downdata/Rup/downMC=0.62-0.14+0.19(stat.)±0.02(sys.). An extended maximum likelihood analysis of the observed L/E distributions excludes the null hypothesis of no neutrino oscillations at the 98% confidence level. Using the curvature of the observed muons in the 1.3 T MINOS magnetic field nuµ and [overline nu ]µ interactions are separated. The ratio of [overline nu ]µ to nuµ events in the data is compared to the Monte Carlo expectation assuming neutrinos and antineutrinos oscillate in the same manner, giving R[overline nu ][sub mu]/nu[sub mu]data/R[overline nu ][sub mu]/nu[sub mu]MC=0.96-0.27+0.38(stat.)±0.15(sys.), where the errors are the statistical and systematic uncertainties. Although the statistics are limited, this is the first direct observation of atmospheric neutrino interactions separately for nuµ and [overline nu ]µ

Management of cryptorchidism: a survey of clinical practice in Italy

<p>Abstract</p> <p>Background</p> <p>An evidence-based Consensus on the treatment of undescended testis (UT) was recently published, recommending to perform orchidopexy between 6 and 12 months of age, or upon diagnosis and to avoid the use of hormones. In Italy, current practices on UT management are little known. Our aim was to describe the current management of UT in a cohort of Italian children in comparison with the Consensus guidelines. As management of retractile testis (RT) differs, RT cases were described separately.</p> <p>Methods</p> <p>Ours is a retrospective, multicenter descriptive study. An online questionnaire was filled in by 140 Italian Family Paediatricians (FP) from <it>Associazione Culturale Pediatri </it>(ACP), a national professional association of FP. The questionnaire requested information on all children with cryptorchidism born between 1/01/2004 and 1/01/2006. Data on 169 children were obtained. Analyses were descriptive.</p> <p>Results</p> <p>Overall 24% of children were diagnosed with RT, 76% with UT. Among the latter, cryptorchidism resolved spontaneously in 10% of cases at a mean age of 21.6 months. Overall 70% of UT cases underwent orchidopexy at a mean age of 22.8 months (SD 10.8, range 1.2-56.4), 13% of whom before 1 year. The intervention was performed by a paediatric surgeon in 90% of cases, with a success rate of 91%. Orchidopexy was the first line treatment in 82% of cases, while preceded by hormonal treatment in the remaining 18%. Hormonal treatment was used as first line therapy in 23% of UT cases with a reported success rate of 25%. Overall, 13 children did not undergo any intervention (mean age at last follow up 39.6 months). We analyzed the data from the 5 Italian Regions with the largest number of children enrolled and found a statistically significant regional difference in the use of hormonal therapy, and in the use of and age at orchidopexy.</p> <p>Conclusions</p> <p>Our study showed an important delay in orchidopexy. A quarter of children with cryptorchidism was treated with hormonal therapy. In line with the Consensus guidelines, surgery was carried out by a paediatric surgeon in the majority of cases, with a high success rate.</p