Arsenite induces aberrations in meiosis that can be rescued by co-administration of N-acetylcysteine in mouse

Abstract

Objective: Because of the important role of reactive oxygen species (ROS) on embryo development, we investigated in vivo and in vitro effects of arsenite, an environmental toxicant which uncouples mitochondria, on meiotic progression of germinal vesicle (GV) oocytes. We also investigated the effect of co-administration of an antioxidant, N-acetylcysteine, on arsenite-induced meiotic abnormalities. Design: An experimental study using a mouse model was performed. Materials/Methods: Using immunostaining and fluorescence microscopy, as well as Pol-scope imaging, we imaged spindle and chromosomal distribution of mouse oocytes after in vitro maturation of control and in vivo and in vitro arsenite-treated oocytes. Results: Both in vivo and in vitro arsenite treatments produced oocyte meiotic anomalies, characterized by spindle disruption and/or chromosomal misalignment, which were dose and time dependent. Exposure to 2 ug/ml of arsenite during 12–14 h, or 8 ug/ml for 2 h, arrested oocyte maturation at GV (64.7% and 20%, respectively), or GV breakdown (35.3% and 80%, respectively), after 12–14 h of IVM culture. Exposure to 2 or 4 ug/ml of arsenite for 2 h caused meiotic anomalies, respectively, in 75% and 80% of in vitro treated oocytes (60% and 80% of abnormal MI oocytes, respectively) after 12–14 h in culture. However, after 15–17 h in IVM culture, many oocytes (65.2%) treated with 2 ug/ml of arsenite for 2 h reached MII stage, with 43.5% exhibiting abnormalities. Co-administration of N-acetylcysteine prevented meiotic abnormalities and the delay in in vitro maturation induced by arsenite treatment, producing rates of normal MII oocytes after 12–14 h in IVM culture comparable to control cultures. Conclusions: Our data demonstrate that both in vivo and in vitro arsenite treatments produce meiotic abnormalities, which can be prevented by in vitro co-administration of N-acetylcysteine. These findings also suggest that arsenite-induced meiotic aberrations are mediated by reactive oxygen species. These data open new perspectives about possible arsenite effects on the reproductive system in mammals, and provide a model for evaluating meiotic effects of other heavy metals. Supported by: This projected was supported in part by CAPES-Brazil and NIH.