Effects of TGF-betas and a specific antagonist on apoptosis of immature rat male germ cells in vitro

Apoptosis : an International Journal on Programmed Cell Death
Lutz KonradR Hofmann

Abstract

Massive apoptosis of pubertal male germ cells is important for the development of functional spermatogenesis in the adult testis. Although the trigger(s) for male germ cell loss at puberty remain undefined, we have hypothesized that transforming growth factor-betas (TGF-betas) play an active role. Here we demonstrate that the three mammalian TGF-beta isoforms, TGF-beta1, TGF-beta2 and TGF-beta3, induce distinct apoptosis of pubertal spermatogonia and spermatocytes in a dose-dependent manner. Induction of male germ cell death by activation of caspase-3 was most pronounced with TGF-beta2 compared to TGF-beta1 and TGF-beta3. Furthermore, we found colocalization of activated caspase-3 with apoptotic protease-activating factor-1 (Apaf-1) in apoptotic germ cells, thus indicating the importance of the intrinsic mitochondrial pathway in TGF-beta-induced apoptosis. The specificity of the TGF-beta effects was proven by addition of recombinant latency-associated peptide against TGF-beta1 (rLAP-TGF-beta1) which completely abolished TGF-beta1-induced and TGF-beta3-induced germ cell apoptosis. Although TGF-beta2-triggered germ cell death also was significantly reduced by rLAP-TGF-beta1, inhibition was not maximal. Our results suggest that th...Continue Reading

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Citations

May 7, 2009·Zygote : the Biology of Gametes and Early Embryos·A SokolowskaF J Peña
Dec 4, 2010·Reproductive Biology and Endocrinology : RB&E·Candela R GonzalezSilvia I Gonzalez-Calvar
Aug 8, 2009·Reproduction : the Official Journal of the Society for the Study of Fertility·Vinali L DiasKate Lakoski Loveland
Sep 18, 2007·Stem Cell Reviews·Amander T Clark
Sep 16, 2008·Molecular and Cellular Endocrinology·Mushtaq A MemonMichael K Skinner
Mar 24, 2009·Birth Defects Research. Part C, Embryo Today : Reviews·Martine Culty
Jan 24, 2017·Asian-Australasian Journal of Animal Sciences·ZhiMing ZhuNenZhu Zheng
Jan 12, 2019·Human Fertility : Journal of the British Fertility Society·Attila MokánszkiIstván Balogh
Sep 29, 2011·Molecular Biology Reports·Yun-Shu FanWan-Xi Yang
Dec 15, 2019·International Journal of Molecular Sciences·Pradeep K KudipudiLutz Konrad
Aug 19, 2021·Journal of Gynecology Obstetrics and Human Reproduction·Neda SaebniaAhmad Reza Bahrami

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