scholarly journals TACE/ADAM17 is involved in germ cell apoptosis during rat spermatogenesis

Reproduction ◽  
2010 ◽  
Vol 140 (2) ◽  
pp. 305-317 ◽  
Author(s):  
Carlos Lizama ◽  
Diego Rojas-Benítez ◽  
Marcelo Antonelli ◽  
Andreas Ludwig ◽  
Ximena Bustamante-Marín ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Cell Apoptosis ◽  
Ex Vivo ◽  
Extracellular Domain ◽  
Germ Cell Apoptosis ◽  
Protein Levels ◽  
Kit Receptor ◽  
Membrane Bound

The pathways leading to male germ cell apoptosisin vivoare poorly understood, but are highly relevant for the comprehension of sperm production regulation by the testis. In this work, we show the evidence of a mechanism where germ cell apoptosis is induced through the inactivation and shedding of the extracellular domain of KIT (c-kit) by the protease TACE/a disintegrin and metalloprotease 17 (ADAM17) during the first wave of spermatogenesis in the rat. We show that germ cells undergoing apoptosis lacked the extracellular domain of the KIT receptor. TACE/ADAM17, a membrane-bound metalloprotease, was highly expressed in germ cells undergoing apoptosis as well. On the contrary, cell surface presence of ADAM10, a closely related metalloprotease isoform, was not associated with apoptotic germ cells. Pharmacological inhibition of TACE/ADAM17, but not ADAM10, significantly prevented germ cell apoptosis in the male pubertal rat. Induction of TACE/ADAM17 by the phorbol-ester phorbol 12-myristate 13-acetate (PMA) induced germ cell apoptosis, which was prevented when an inhibitor of TACE/ADAM17 was present in the assay.Ex-vivorat testis culture showed that PMA induced the cleavage of the KIT extracellular domain. Isolation of apoptotic germ cells showed that even though protein levels of TACE/ADAM17 were higher in apoptotic germ cells than in nonapoptotic cells, the contrary was observed for ADAM10. These results suggest that TACE/ADAM17 is one of the elements triggering physiological germ cell apoptosis during the first wave of spermatogenesis.

scholarly journals The IL-27 Component EBI-3 and Its Receptor Subunit IL-27Rα Are Essential for the Cytoprotective Action of Humanin on Male Germ Cells

2020 ◽  
Author(s):  
Yue Jia ◽  
Ronald S Swerdloff ◽  
YanHe Lue ◽  
Jenny Dai-Ju ◽  
Prasanth Surampudi ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Cell Apoptosis ◽  
Ex Vivo ◽  
Direct Interaction ◽  
Seminiferous Tubules ◽  
Receptor Subunit ◽  
Dot Blot ◽  
Germ Cell Apoptosis ◽  
Stat3 Phosphorylation

Abstract Humanin (HN) is a mitochondrial-derived peptide that protects many cells/tissues from damage. We previously demonstrated that HN reduces stress-induced male germ cell apoptosis in rodents. HN action in neuronal cells is mediated through its binding to a trimeric cell membrane receptor composed of glycoprotein 130 (gp130), IL-27 receptor subunit α (IL-27Rα, also known as WSX-1/TCCR), and ciliary neurotrophic factor receptor subunit α (CNTFRα). However, the mechanisms of HN action in testis remain unclear. Here, we demonstrated in ex-vivo seminiferous tubules culture that HN prevented heat-induced germ cell apoptosis that was blocked by specific anti-IL-27Rα, anti-gp130, and anti-EBI-3, but not significantly reduced by anti-CNTFRα antibodies. We further studied the cytoprotective action of HN on groups of il-27rα−/− or ebi-3−/− knockout mice administered the following treatment: 1) vehicle; 2) a single intra-peritoneal (IP) injection of HN peptide; 3) testicular hyperthermia; and 4) testicular hyperthermia plus HN. We demonstrated that HN inhibited heat-induced germ cell apoptosis in wildtype (wt) but not in il-27rα−/− or ebi-3−/− mice. HN restored heat-suppressed STAT3 phosphorylation in wt but not il-27rα−/− or ebi-3−/− mice. Dot blot analyses showed the direct interaction of HN with IL-27Rα or EBI-3 peptide. Immunofluorescence staining showed co-localization of IL-27Rα with HN and gp130 in Leydig cells and germ cells. We conclude that the anti-apoptotic effects of HN in mouse testes are mediated through interaction with EBI-3, IL-27Rα, and activation of gp130, whereas the role of CNTFRα in HN action needs further studies. This suggests a multi-component tissue-specific receptor for HN in the testis and linking HN action with the IL-12/IL-27 family of cytokines.

scholarly journals Testosterone regulates granzyme K expression in rat testes

2017 ◽  
Vol 51 (4) ◽  
pp. 193-204 ◽  
Author(s):  
Dibyendu Dutta ◽  
In Park ◽  
Hiwot Guililat ◽  
Samuel Sang ◽  
Arpita Talapatra ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Cell Apoptosis ◽  
Seminiferous Tubule ◽  
Serine Proteases ◽  
Leydig Cells ◽  
Seminiferous Tubules ◽  
Germ Cell Apoptosis ◽  
Tubule Lumen ◽  
Premature Release

Abstract Objective. Testosterone depletion induces increased germ cell apoptosis in testes. However, limited studies exist on genes that regulate the germ cell apoptosis. Granzymes (GZM) are serine proteases that induce apoptosis in various tissues. Multiple granzymes, including GZMA, GZMB and GZMN, are present in testes. Th us, we investigated which granzyme may be testosterone responsive and possibly may have a role in germ cell apoptosis aft er testosterone depletion. Methods. Ethylene dimethane sulfonate (EDS), a toxicant that selectively ablates the Leydig cells, was injected into rats to withdraw the testosterone. The testosterone depletion effects after 7 days post-EDS were verified by replacing the testosterone exogenously into EDS-treated rats. Serum or testicular testosterone was measured by radioimmunoassay. Using qPCR, mRNAs of granzyme variants in testes were quantified. The germ cell apoptosis was identified by TUNEL assay and the localization of GZMK was by immunohistochemistry. Results. EDS treatment eliminated the Leydig cells and depleted serum and testicular testosterone. At 7 days post-EDS, testis weights were reduced 18% with increased germ cell apoptosis plus elevation GZMK expression. GZMK was not associated with TUNEL-positive cells, but was localized to stripped cytoplasm of spermatids. In addition, apoptotic round spermatids were observed in the caput epididymis. Conclusions. GZMK expression in testes is testosterone dependent. GZMK is located adjacent to germ cells in seminiferous tubules and the presence of apoptotic round spermatids in the epididymis suggest its role in the degradation of microtubules in ectoplasmic specializations. Thus, overexpression of GZMK may indirectly regulate germ cell apoptosis by premature release of round spermatids from seminiferous tubule lumen.

Vanadocene-Mediated in Vivo Male Germ Cell Apoptosis

2000 ◽  
Vol 166 (3) ◽  
pp. 186-195 ◽  
Author(s):  
Osmond J. D'Cruz ◽  
Fatih M. Uckun
Keyword(s):  
Germ Cell ◽  
Cell Apoptosis ◽  
Male Germ Cell ◽  
Germ Cell Apoptosis

scholarly journals Adult-only exposure of male rats to a diet of high phytoestrogen content increases apoptosis of meiotic and post-meiotic germ cells

Reproduction ◽  
2007 ◽  
Vol 133 (1) ◽  
pp. 11-19 ◽  
Author(s):  
Stephen Assinder ◽  
Ryan Davis ◽  
Mark Fenwick ◽  
Amy Glover
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Cell Apoptosis ◽  
Critical Role ◽  
Male Rats ◽  
Male Rat ◽  
Sperm Production ◽  
Germ Cell Apoptosis ◽  
Sperm Counts ◽  
Male Wistar Rats

Apoptosis plays a critical role in regulating sperm production. Removal of androgens and gonadotropins, or estrogen administration induces germ cell apoptosis. It is hypothesized that dietary phytoestrogens increase apoptosis of developing germ cells, decreasing sperm production. This study aimed to test this in rats fed a high phytoestrogen diet only during adulthood. Male Wistar rats used in this study were offspring of females maintained on a low phytoestrogen diet prior to conception through to weaning. After weaning, juveniles were fed the same low phytoestrogen diet into adulthood. A cohort of males were transferred to a high phytoestrogen diet for 24 days and subsequently testes were collected from all animals. In the high phytoestrogen fed group, homogenization-resistant sperm counts were significantly decreased, as were epididymal sperm counts. Morphometric analysis determined round and elongated spermatid volumes to be significantly decreased, but seminiferous tubule lumen diameters to be significantly increased. TUNEL analysis determined that apoptosis of spermatocytes and round spermatids was significantly greater in the high phytoestrogen fed rats. Neither plasma gonadotropin concentrations nor testicular testosterone were altered. In conclusion, exposure of the adult male rat to a high phytoestrogen diet disrupts spermatogenesis, increasing germ cell apoptosis. This effect is independent of the hypothalamo–pituitary–testicular axis and is likely due to disruption of estrogen’s actions in the testis.

scholarly journals Gliadin Intake Causes Disruption of the Intestinal Barrier and an Increase in Germ Cell Apoptosis in A Caenorhabditis Elegans Model

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2587 ◽  
Author(s):  
Hyemin Min ◽  
Ji-Sun Kim ◽  
Jiyun Ahn ◽  
Yhong-Hee Shim
Keyword(s):  
Caenorhabditis Elegans ◽  
Germ Cell ◽  
Germ Cells ◽  
Cell Apoptosis ◽  
Mapk Pathway ◽  
Intestinal Barrier ◽  
Mitogen Activated Protein Kinase ◽  
Major Protein ◽  
Ros Production ◽  
Germ Cell Apoptosis

Gliadin is a major protein component of gluten and causes gluten toxicity through intestinal stress. We previously showed that gliadin intake induces oxidative stress in the intestine and reduces fertility in a Caenorhabditis elegans model. To elucidate the possible link between intestinal stress and reproduction, changes in the intestine and germ cells of C. elegans after gliadin intake were examined at the molecular level. Gliadin intake increased reactive oxygen species (ROS) production in the intestine, decreased intestinal F-actin levels, and increased germ cell apoptosis. These gliadin-triggered effects were suppressed by antioxidant treatment. These results suggest that ROS production in the intestine induced by gliadin intake causes disruption of intestinal integrity and increases germ cell apoptosis. Gliadin-induced germ cell apoptosis (GIGA) was suppressed by depletion of cep-1, ced-13, egl-1, or mpk-1. However, HUS-1 was not activated, suggesting that GIGA is activated through the mitogen-activated protein kinase (MAPK) pathway and is CEP-1-dependent but is a separate pathway from that controlling the DNA damage response. Taken together, our results suggest that gliadin causes intestinal barrier disruption through ROS production and interacts with the germ cells to reduce fertility through GIGA.

scholarly journals Androgen-dependent apoptosis in male germ cells is regulated through the proto-oncoprotein Cbl

2005 ◽  
Vol 171 (4) ◽  
pp. 651-661 ◽  
Author(s):  
Nisrine El Chami ◽  
Fouziha Ikhlef ◽  
Krisztian Kaszas ◽  
Sadok Yakoub ◽  
Eric Tabone ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Cell Apoptosis ◽  
Knockout Mouse ◽  
Inhibitor Of Apoptosis ◽  
Male Germ Cells ◽  
Germ Cell Apoptosis ◽  
Androgen Withdrawal ◽  
Hypophysectomized Rats ◽  
Pachytene Spermatocytes

The proto-oncoprotein Cbl is known to control several signaling processes. It is highly expressed in the testis, and because spermatogenesis is androgen dependent, we investigated the androgen dependency expression of Cbl through its testicular sublocalization and its expression levels in rats that were exposed to the antiandrogen flutamide or were hypophysectomized. We report the androgen dependency of Cbl as it localizes in pachytene spermatocytes during androgen-dependent stages, is down-regulated upon flutamide exposure, and is up-regulated with testosterone in hypophysectomized rats. Coculture experiments showed the key control exerted by the Sertoli cell on Cbl activity. As flutamide induces germ cell apoptosis, we investigate members of the Bcl-2 family upon flutamide exposure. We show that the proapoptotic Bcl-2 family member Bim mirrored Cbl expression through a posttranscriptional process. We also show that in Cbl knockout mouse testes, the imbalance between the high expression of Bim and Smac/Diablo and antiapoptotic factors such as cellular inhibitor of apoptosis 2 favors a survival process, which makes these mice unresponsive to androgen withdrawal and could explain their hypofertility.

scholarly journals C-X-C motif chemokine ligand 10 produced by mouse Sertoli cells in response to mumps virus infection induces male germ cell apoptosis

2017 ◽  
Vol 8 (10) ◽  
pp. e3146-e3146 ◽  
Author(s):  
Qian Jiang ◽  
Fei Wang ◽  
Lili Shi ◽  
Xiang Zhao ◽  
Maolei Gong ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Mumps Virus ◽  
Male Germ Cell ◽  
Male Germ Cells ◽  
Germ Cell Apoptosis ◽  
Chemokine Ligand

Abstract Mumps virus (MuV) infection usually results in germ cell degeneration in the testis, which is an etiological factor for male infertility. However, the mechanisms by which MuV infection damages male germ cells remain unclear. The present study showed that C-X-C motif chemokine ligand 10 (CXCL10) is produced by mouse Sertoli cells in response to MuV infection, which induces germ cell apoptosis through the activation of caspase-3. CXC chemokine receptor 3 (CXCR3), a functional receptor of CXCL10, is constitutively expressed in male germ cells. Neutralizing antibodies against CXCR3 and an inhibitor of caspase-3 activation significantly inhibited CXCL10-induced male germ cell apoptosis. Furthermore, the tumor necrosis factor-α (TNF-α) upregulated CXCL10 production in Sertoli cells after MuV infection. The knockout of either CXCL10 or TNF-α reduced germ cell apoptosis in the co-cultures of germ cells and Sertoli cells in response to MuV infection. Local injection of MuV into the testes of mice confirmed the involvement of CXCL10 in germ cell apoptosis in vivo. These results provide novel insights into MuV-induced germ cell apoptosis in the testis.

scholarly journals Germ cell apoptosis is critical to maintain Caenorhabditis elegans offspring viability in stressful environments

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260573
Author(s):  
Sarah Fausett ◽  
Nausicaa Poullet ◽  
Clotilde Gimond ◽  
Anne Vielle ◽  
Michele Bellone ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Environmental Stress ◽  
Germ Cell ◽  
Germ Cells ◽  
Cell Apoptosis ◽  
Environmental Stressors ◽  
Embryonic Survival ◽  
Germ Cell Apoptosis ◽  
Offspring Fitness ◽  
Stressful Environments

Maintaining reproduction in highly variable, often stressful, environments is an essential challenge for all organisms. Even transient exposure to mild environmental stress may directly damage germ cells or simply tax the physiology of an individual, making it difficult to produce quality gametes. In Caenorhabditis elegans, a large fraction of germ cells acts as nurse cells, supporting developing oocytes before eventually undergoing so-called physiological germ cell apoptosis. Although C. elegans apoptosis has been extensively studied, little is known about how germline apoptosis is influenced by ecologically relevant environmental stress. Moreover, it remains unclear to what extent germline apoptosis contributes to maintaining oocyte quality, and thus offspring viability, in such conditions. Here we show that exposure to diverse environmental stressors, likely occurring in the natural C. elegans habitat (starvation, ethanol, acid, and mild oxidative stress), increases germline apoptosis, consistent with previous reports on stress-induced apoptosis. Using loss-of-function mutant alleles of ced-3 and ced-4, we demonstrate that eliminating the core apoptotic machinery strongly reduces embryonic survival when mothers are exposed to such environmental stressors during early adult life. In contrast, mutations in ced-9 and egl-1 that primarily block apoptosis in the soma but not in the germline, did not exhibit such reduced embryonic survival under environmental stress. Therefore, C. elegans germ cell apoptosis plays an essential role in maintaining offspring fitness in adverse environments. Finally, we show that ced-3 and ced-4 mutants exhibit concomitant decreases in embryo size and changes in embryo shape when mothers are exposed to environmental stress. These observations may indicate inadequate oocyte provisioning due to the absence of germ cell apoptosis. Taken together, our results show that the central genes of the apoptosis pathway play a key role in maintaining gamete quality, and thus offspring fitness, under ecologically relevant environmental conditions.

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