SIRT3 inhibition suppresses hypoxia‐inducible factor 1α signaling and alleviates hypoxia‐induced apoptosis of type B spermatogonia GC‐2 cells

Abstract

Hypoxia has been reported to be an important factor leading to male infertility, and it has been reported that hypoxia can induce the apoptosis of mouse spermatogenic cells. Sirtuin 3 (SIRT3) has been reported to promote the degradation of hypoxia‐inducible factor 1α (HIF‐1α), and thus, we hypothesized that SIRT3 may influence hypoxia‐induced apoptosis of spermatogonia. In this study, we overexpressed or inhibited SIRT3 in mouse type B spermatogonia GC‐2 cells and then subjected the cells to hypoxia or normoxia, before examining hypoxia‐responsive gene expression and cell viability. We report that SIRT3 stabilizes hypoxia‐inducible factor 1α (HIF‐1α) and activates its downstream target gene expression in GC‐2 cells. We also show that the SIRT3 inhibitor 3‐TYP suppresses HIF‐1α target gene expression and alleviates hypoxia‐induced apoptosis of GC‐2 cells. Our study reveals the critical role and underlying mechanisms of SIRT3 in hypoxia‐induced apoptosis of mouse type B spermatogonia GC‐2 cells.

Keywords

• apoptosis
• GC‐2
• HIF‐1α
• hypoxia
• SIRT3
• spermatogonia