https://elsevier.proofcentral.com/en-us/landing-page.html?token=baf280639f2773e07701834b1c13daInhibition of spermatogenesis by hypoxia is mediated by V-ATPase via the JNK/c-Jun pathway in mice

Abstract

Spermatocyte apoptosis is the primary cause of a poor outcome after hypoxia-triggered spermatogenesis reduction (HSR). Vacuolar H⁺-ATPase (V-ATPase) is involved in the regulation of hypoxia-induced spermatocyte apoptosis; however, the underlying mechanism remains to be elucidated. The aim of this study was to investigate the effect of V-ATPase deficiency on spermatocyte apoptosis and the relationship between c-Jun and apoptosis in primary spermatocytes induced by hypoxia. We found that mice under hypoxia exposure for 30 days demonstrated a marked spermatogenesis reduction and downregulation of V-ATPase expression, which were assessed by a TUNEL assay and western blotting, respectively. V-ATPase deficiency resulted in more severe spermatogenesis reduction and spermatocyte apoptosis after hypoxia exposure. We also observed that silencing V-ATPase expression enhanced JNK/c-Jun activation and death receptor-mediated apoptosis in primary spermatocytes. However, inhibition of c-Jun attenuated V-ATPase deficiency-induced spermatocyte apoptosis in primary spermatocytes. In conclusion, the data in this study suggest that V-ATPase deficiency aggravated hypoxia-induced spermatogenesis reduction by promoting spermatocyte apoptosis in mice via the JNK/c-Jun pathway.

Keywords: C-Jun; DR(5); Hypoxia; JNK; V-ATPase.