Formin INF2 supplementation alleviates cytoskeleton-based mitochondria defects for oocyte quality under obesity

Abstract

Obesity is one main cause of reproductive disorders in female, and oocytes show meiotic maturation defects under obesity, which leads to infertility. However, the molecular characterization for the obese oocytes remains largely unclear. Inverted-formin 2 (INF2) is a formin family member which is involved in actin-based multiple cellular events including vesicle transport and oxidative stress-induced apoptosis. In present study, we reported that INF2 deficiency linked with declined oocyte quality of obesity. Our results showed that INF2 expression decreased in the oocytes of obese mice. INF2 deficiency caused the failure of polar body extrusion and induced large polar bodies. We showed that INF2 depletion disturbed mitochondrial distribution and function, which might be due to the association with mitochondria fission factor DRP1. INF2 co-localized with cytoplasmic actin and its depletion reduced actin polymerization, which further caused the failure of spindle migration in both mouse and porcine oocytes. In addition, we also found that INF2 interacted with HDAC6 and further affected tubulin acetylation for microtubule stability, which disturbed mitochondrial transport. Exogenous INF2 mRNA supplement rescued the meiotic maturation defects of oocytes from obese mice. Thus, our study demonstrated that INF2 is responsible for both mouse and porcine oocyte maturation through its regulation on actin polymerization and tubulin acetylation for mitochondrial function, and its deficiency might be one cause for obesity-induced oocyte defects.