Metformin protects against mouse oocyte apoptosis defects induced by arecoline

Abstract

Objectives: Arecoline is the main bioactive substance extracted from Areca catechu L, which has cell, neural and genetic toxicity. The function of arecoline in reproductive system has not been well explored. Materials and Methods: To investigate the toxic effects of arecoline on oocyte development, immunofluorescence staining, qPCR, Western blotting, sperm binding assays and in vitro fertilization were performed to evaluate oocyte meiosis competence and embryo development. Results: Our data revealed that arecoline exposure disrupts actin filament dynamics, spindle assembly and kinetochore-microtubule attachment stability in mouse oocytes, leading to aneuploidy and oocyte meiosis arrest. In addition, arecoline treatment disturbs the distribution of mitochondria, reduces ATP production and increases the level of oxidative stress, which ultimately induces oocyte apoptosis. Supplementation with metformin, a medicine for type 2 diabetes in the clinic, partially alleviates these damages. Conclusions: Metformin has a protective effect on arecoline-induced mouse oocytes apoptosis.