Hypoxia-induced deacetylation is required for tetraploid differentiation in response to testicular ischemia-reperfusion (IR) injury

Journal of Andrology
Wugang HouWei Li

Abstract

Accumulated understanding of epigenetic modifications during ischemia-reperfusion (IR) injury suggests that additional targeted approaches and novel mechanisms that have not been explored in the reproductive system underlie the pathogenesis. Here we show, with a standard murine model of testicular IR, ischemia-induced histone deacetylase (HDAC) activity in the testis with concomitant reduction in histone acetyl transferase activity in vivo. Pretreatment with chemical HDAC inhibitors significantly induced apoptosis in tetraploid pachytene spermatocytes during ischemic insult and thereafter resulted in attenuated meiotic differentiation. We also identified the distinct HDACs involved in primary spermatocytes upon hypoxic stress. In vitro, elevated expression of HDAC2 was physiologically associated with p53, a master regulator believed to be a guardian of genome integrity during spermatogenesis. p53-mediated apoptosis was inhibited by deacetylation of p53 in differentiating pachytene spermatocytes in response to ischemic stress. Overall, the current data suggest that hypoxia-induced deacetylation may operate as an indispensible defensive mechanism for meiotic differentiation during the ischemic period of IR testis, thus pointing t...Continue Reading

Citations

Mar 4, 2014·Biochemical and Biophysical Research Communications·Chao-Juan ZhuWei Li
Dec 18, 2012·Reproduction : the Official Journal of the Society for the Study of Fertility·Shun ZhangWei Li
Feb 18, 2016·Oxidative Medicine and Cellular Longevity·Thais Rose Dos Santos HamiltonMayra Elena Ortiz D'Ávila Assumpção
May 25, 2016·International Journal of Urology : Official Journal of the Japanese Urological Association·Shogo ShimizuMotoaki Saito
May 17, 2018·Oxidative Medicine and Cellular Longevity·Thais Rose Dos Santos HamiltonMayra Elena Ortiz D Ávila Assumpção

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