Claudin-11 expression increased in spermatogenic defect in human testes

Nah, Won Heum; Lee, Jae Eun; Park, Hyun Jun; Park, Nam Cheol; Gye, Myung Chan

doi:10.1016/j.fertnstert.2010.08.023

Cited by 29 publications

(17 citation statements)

References 26 publications

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“…It is possible that the up-regulated occludin and claudin-11 proteins were mislocalized as revealed by the unusual thickening and diffusion of the fluorescence from the BTB site based on dual-labelled immunofluorescence analysis. Mislocalization of BTB proteins can be a sign of spermatogenic and BTB malfunction as demonstrated by studies showing that claudin-11 expression was also induced, but mislocalized in testes from infertile men with Sertoli cell only syndrome (Nah et al, 2010), as well as in testes of testicular intraepithelial neoplasia patients with loss of BTB function (Fink et al, 2009). Besides, there was also a study reporting that patients with carcinoma in situ having a perturbed BTB, which was manifested by a mis-localization of ZO-1, diffusing from the BTB site in the seminiferous epithelium (Fink et al, 2006), analogous to our findings in this report.…”

Section: Discussionmentioning

confidence: 99%

Spermatogonial stem cells alone are not sufficient to re‐initiate spermatogenesis in the rat testis following adjudin‐induced infertility

Mok

Lee

et al. 2011

Int J of Andrology

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The blood-testis barrier (BTB) is a unique ultrastructure in the testis which creates a specialized microenvironment in the seminiferous epithelium for post-meiotic germ cell development and to maintain an immunological barrier. In this report, we have demonstrated unequivocally that a functional and intact BTB is crucial for initiation of spermatogenesis in particular differentiation of spermatogonial stem cells (SSCs). It was shown that adult rats (~300 gm body weight, b.w.) treated with adjudin at 50 (low-dose) or 250 (high-dose) mg/kg b.w. by gavage led to germ cell depletion from the seminiferous tubules and >98% of the tubules were devoid of germ cells by ~2-week and rats became infertile in both groups after the sperm reserve in the epididymis was exhausted. While the population of SSC/spermatogonia in the seminiferous tubules from both groups was similar to normal rats, only rats from the low-dose group were capable of re-initiating spermatogenesis by 20-week and by 30-week, greater than 75% of the tubules displayed normal spermatogenesis and the fertility of these rats rebounded. Detailed analysis by dual-labeled immunofluorescence analysis and a functional BTB integrity assay revealed that in both treatment groups, the BTB was disrupted from 6- to 12-week. However, the disrupted BTB “resealed” in the low, but not in the high, dose group. Our findings illustrate that that SSC/spermatogonia failed to differentiate into spermatocytes beyond Aaligned spermatogonia in the high-dose group with a disrupted BTB. In short, these findings illustrate the critical significance of BTB for re-initiation of spermatogenesis besides SSC and spermatogonia.

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Section: Discussionmentioning

confidence: 99%

Spermatogonial stem cells alone are not sufficient to re‐initiate spermatogenesis in the rat testis following adjudin‐induced infertility

Mok

Lee

et al. 2011

Int J of Andrology

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“…The tight junction, constituted by Sertoli cells, is the key structure of the blood-testis barrier (BTB) to ensure the stabilization of the microenvironment or niche of the testis. Tight junction proteins, e.g., zona occludens 1 (ZO1), claudin 11 (CLDN11) [2], and occluding (OCLN), are produced by Sertoli cells, and they play vital roles in controlling the function of BTB [3]. In addition to structural support, Sertoli cells play significant roles in promoting the self-renewal, differentiation, and apoptosis of spermatogonial stem cells via secreting a number of growth factors, including bone morphogenetic protein 4 (BMP4), stem cell factor (SCF), leukemia inhibitory factor (LIF), glial cell derived neurotrophic factor (GDNF), fibroblast growth factor 2 (FGF2), and epidermal growth factor (EGF) [1].…”

Section: Introductionmentioning

confidence: 99%

Generation and characteristics of human Sertoli cell line immortalized by overexpression of human telomerase

et al. 2017

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Sertoli cells are required for normal spermatogenesis and they can be reprogrammed to other types of functional cells. However, the number of primary Sertoli cells is rare and human Sertoli cell line is unavailable. In this study, we have for the first time reported a stable human Sertoli cell line, namely hS1 cells, by overexpression of human telomerase. The hS1 cells expressed a number of hallmarks for human Sertoli cells, including SOX9, WT1, GDNF, SCF, BMP4, BMP6, GATA4, and VIM, and they were negative for 3β-HSD, SMA, and VASA. Higher levels of AR and FSHR were observed in hS1 cells compared to primary human Sertoli cells. Microarray analysis showed that 70.4% of global gene profiles of hS1 cells were similar to primary human Sertoli cells. Proliferation assay demonstrated that hS1 cells proliferated rapidly and they could be passaged for more than 30 times in 6 months. Neither Y chromosome microdeletion nor tumorgenesis was detected in this cell line and 90% normal karyotypes existed in hS1 cells. Collectively, we have established the first human Sertoli cell line with phenotype of primary human Sertoli cells, an unlimited proliferation potential and high safety, which could offer sufficient human Sertoli cells for basic research as well as reproductive and regenerative medicine.

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“…compromised, mis-localization of claudin-11 33,34 or ZO-1 32 was detected by immunohistochemistry. Moreover, a recent study has shown that although occludin and claudin-11 were induced significantly at the BTB after acute doses of adjudin in adult rats, BTB was still disrupted because the significantly induced occludin and claudin-11 were mis-localized, 10 illustrating proper localization of proteins at the BTB is crucial to maintain its integrity.…”

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confidence: 99%

A study to assess the assembly of a functional blood-testis barrier in developing rat testes

et al. 2011

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the blood-testis barrier (BtB) is an important ultrastructure in the seminiferous tubule of the mammalian testis that segregates the events of spermatogenesis, in particular post-meiotic germ cell development, from the harmful substances in the environment including toxicants and drugs, as well as from the unwanted hormones and biomolecules in the systemic circulation. It is known that the BtB is assembled by ~15-21 days postpartum (dpp) in rats coinciding with the onset of late cell cycle progression, namely the formation of zygotene and pachytene spermatocytes by day 15-18 dpp. this is to prepare for: (1) the differentiation/transformation of pachytene spermatocytes to diplotene and dictyate spermatocytes and (2) meiosis I and II, which take place by 23-26 and 26 dpp, respectively. Recent findings have shown spermatogonia/spermatogonial stem cells (SSC) in the tubules failed to re-initiate spermatogenesis by differentiating spermatogonia beyond type A spermatogonia in the absence of a functional BtB, leading to meiotic arrest. these studies thus illustrate that a functional BtB is crucial to the initiation and/or re-initiation of spermatogenesis. Herein, we sought to examine the precise time window when a functional and intact BtB is established in the developing rat testis during the final stage of cell cycle progression and meiosis. Using the techniques of: (1) dual-labeled immunofluorescence analysis to assess the distribution of integrated proteins at the tight junction (tJ), basal ectoplasmic specialization [basal eS, a testis-specific atypical adherens junction (AJ) type] and gap junction (GJ) at the BtB, (2) functional assay to assess the BtB integrity in vivo, (3) immunoblot analysis to monitor changes in steady-state levels of adhesion proteins at the BtB, and (4) co-immunoprecipitation to assess changes in protein-protein interactions at the BtB, it was shown that a BtB was being assembled by day 15-20 dpp, but a functional BtB was not fully established until day 25 dpp in Sprague-Dawley rats, tightly associated with the onset of meiosis I and II. these findings thus illustrate the significance of the BtB on cell cycle progression and the preparation for meiosis, such as germ cell differentiation beyond type A spermatogonia.

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Claudin-11 expression increased in spermatogenic defect in human testes

Cited by 29 publications

References 26 publications

Spermatogonial stem cells alone are not sufficient to re‐initiate spermatogenesis in the rat testis following adjudin‐induced infertility

Spermatogonial stem cells alone are not sufficient to re‐initiate spermatogenesis in the rat testis following adjudin‐induced infertility

Generation and characteristics of human Sertoli cell line immortalized by overexpression of human telomerase

A study to assess the assembly of a functional blood-testis barrier in developing rat testes

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