title: Hypoxia-induced deacetylation is required for tetraploid differentiation in response to testicular ischemia-reperfusion (IR) injury.
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 to a novel therapeutic  target for future medical intervention.
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi’an, China.
authors.forename: Wugang
authors.initials: W
authors.lastname: Hou
authors.forename: Yushu
authors.initials: Y
authors.lastname: Dong
authors.forename: Jinshan
authors.initials: J
authors.lastname: Zhang
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Yin
authors.forename: Hua
authors.initials: H
authors.lastname: Wen
authors.forename: Lize
authors.initials: L
authors.lastname: Xiong
authors.forename: Wei
authors.initials: W
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000187:drug effects / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019319:Okadaic Acid / Q000494:pharmacology; D015427:Reperfusion Injury / Q000503:physiopathology*; D013737:Testis / Q000201:enzymology / Q000293:injuries*; D057891:Tetraploidy; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D016159:Tumor Suppressor Protein p53; D019319:Okadaic Acid; C012589:trichostatin A; D006655:Histone Deacetylases