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 Loss of stra8 Increases Germ Cell Apoptosis but Is Still Compatible With Sperm Production in Atlantic Salmon (Salmo salar)

2021 ◽  
Vol 9 ◽  
Author(s):  
Kai O. Skaftnesmo ◽  
Diego Crespo ◽  
Lene Kleppe ◽  
Eva Andersson ◽  
Rolf B. Edvardsen ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Atlantic Salmon ◽  
Germ Cell ◽  
Fish Species ◽  
Germ Cells ◽  
Cell Apoptosis ◽  
Cell Loss ◽  
Sperm Production ◽  
Wild Type ◽  
Germ Cell Apoptosis

Entering meiosis strictly depends on stimulated by retinoic acid 8 (Stra8) gene function in mammals. This gene is missing in a number of fish species, including medaka and zebrafish, but is present in the majority of fishes, including Atlantic salmon. Here, we have examined the effects of removing stra8 on male fertility in Atlantic salmon. As in mammals, stra8 expression was restricted to germ cells in the testis, transcript levels increased during the start of puberty, and decreased when blocking the production of retinoic acid. We targeted the salmon stra8 gene with two gRNAs one of these were highly effective and produced numerous mutations in stra8, which led to a loss of wild-type (WT) stra8 expression in F0 salmon testis. In maturing stra8 crispants, the spermatogenetic tubuli were partially disorganized and displayed a sevenfold increase in germ cell apoptosis, in particular among type B spermatogonia and spermatocytes. The production of spermatogenic cysts, on the other hand, increased in maturing stra8 crispants. Gene expression analysis revealed unchanged (lin28a, ret) or reduced levels (egr1, dusp4) of transcripts associated with undifferentiated spermatogonia. Decreased expression was recorded for some genes expressed in differentiating spermatogonia including dmrt1 and ccnd2 or in spermatocytes, such as ccna1. Different from Stra8-deficient mammals, a large number of germ cells completed spermatogenesis, sperm was produced and fertilization rates were similar in WT and crispant males. While loss of stra8 increased germ cell apoptosis during salmon spermatogenesis, crispants compensated this cell loss by an elevated production of spermatogenic cysts, and were able to produce functional sperm. It appears that also in a fish species with a stra8 gene in the genome, the critical relevance this gene has attained for mammalian spermatogenesis is not yet given, although detrimental effects of the loss of stra8 were clearly visible during maturation.

scholarly journals Transient Testicular Warming Enhances the Suppressive Effect of Testosterone on Spermatogenesis in Adult Cynomolgus Monkeys (Macaca fascicularis)

2006 ◽  
Vol 91 (2) ◽  
pp. 539-545 ◽  
Author(s):  
Yanhe Lue ◽  
Christina Wang ◽  
Yi-Xun Liu ◽  
Amiya P. Sinha Hikim ◽  
Xue-Sen Zhang ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Apoptosis ◽  
Synergistic Effects ◽  
Recovery Period ◽  
Heat Exposure ◽  
Suppressive Effect ◽  
Controlled Study ◽  
Cynomolgus Monkeys ◽  
Germ Cell Apoptosis ◽  
Sperm Counts

Context: The context of the study was to examine whether combined testosterone (T) and heat (H) treatment have additive or synergistic effects on suppression of spermatogenesis. Objective: The objective of the study was to determine whether T+H induces a greater suppression of spermatogenesis than either treatment alone in monkeys. Design: The study was a randomized, placebo-controlled study. Setting: The study was conducted at a primate center in China. Participants: The study population was comprised of 32 adult cynomolgus monkeys. Interventions: Groups of eight adult monkeys were treated for 12 wk with: 1) two empty implants (C); 2) two T implants (T); 3) daily testicular heat exposure (43 C for 30 min) for 2 consecutive days (H); or 4) two T implants plus testicular heat exposure (T+H). Treatment was followed by an 8-wk recovery period. Main Outcome Measures: Measures included sperm counts and germ cell apoptosis. Results: Serum T levels were elevated in both the T and T+H groups during treatment but not in the C or H group. Sperm counts were transiently suppressed after heat to 16.4% of baseline at 4 wk and then returned to pretreatment levels. Sperm counts were suppressed slowly after T treatment to nadir of 6.4% of pretreatment levels at 12 wk. T+H rapidly suppressed sperm output as early as 4 wk to 3.9% of pretreatment levels that was maintained throughout treatment. The decreased sperm counts were due to increased germ cell apoptosis in all treatment groups. Sperm counts recovered to the pretreatment levels in all groups by 8 wk after treatment. Conclusion: This proof-of-concept study demonstrates that transient testicular warming enhances and hastens the effect of T implant on the suppression of spermatogenesis in monkeys.

Prepubertal male rats with high rates of germ-cell apoptosis present exacerbated rates of germ-cell apoptosis after serotonin depletion

2016 ◽  
Vol 28 (6) ◽  
pp. 806 ◽  
Author(s):  
Néstor Méndez Palacios ◽  
María Elena Ayala Escobar ◽  
Maximino Méndez Mendoza ◽  
Rubén Huerta Crispín ◽  
Octavio Guerrero Andrade ◽  
...  
Keyword(s):  
Gene Expression ◽  
Germ Cell ◽  
Mrna Expression ◽  
Cell Apoptosis ◽  
Differential Sensitivity ◽  
Male Rats ◽  
Mrna Levels ◽  
Germ Cell Apoptosis ◽  
Expression Of Genes ◽  
Prepubertal Rats

Male germ-cell apoptosis occurs naturally and can be increased by exposure to drugs and toxic chemicals. Individuals may have different rates of apoptosis and are likely to also exhibit differential sensitivity to outside influences. Previously, we reported that p-chloroamphetamine (pCA), a substance that inhibits serotonin synthesis, induced germ-cell apoptosis in prepubertal male rats. Here, we identified prepubertal rats with naturally high or low rates of germ-cell apoptosis and evaluated gene expression in both groups. Bax and Shbg mRNA levels were higher in rats with high rates of germ-cell apoptosis. Rats were then treated with pCA and the neuro-hormonal response and gene expression were evaluated. Treatment with pCA induced a reduction in serotonin concentrations but levels of sex hormones and gonadotrophins were not changed. Rats with initially high rates of germ-cell apoptosis had even higher rates of germ-cell apoptosis after treatment with pCA. In rats with high rates of germ-cell apoptosis Bax mRNA expression remained high after treatment with pCA. On the basis of category, an inverse relationship between mRNA expression of Bax and Bcl2, Bax and AR and Bax and Hsd3b2 was found. Here we provide evidence that innate levels of germ-cell apoptosis could be explained by the level of mRNA expression of genes involved with apoptosis and spermatogenesis.

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.

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.

Panax ginseng ameliorate toxic effects of cadmium on germ cell apoptosis, sperm quality, and oxidative stress in male Wistar rats

Toxin Reviews ◽  
2021 ◽  
pp. 1-13
Author(s):  
Saeedeh Shojaeepour ◽  
Fariba Sharififar ◽  
Tahereh Haghpanah ◽  
Maryam Iranpour ◽  
Masoud Imani ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Germ Cell ◽  
Panax Ginseng ◽  
Cell Apoptosis ◽  
Wistar Rats ◽  
Sperm Quality ◽  
Toxic Effects ◽  
Germ Cell Apoptosis ◽  
Male Wistar Rats ◽  
And Oxidative Stress

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.

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