Arsenite induces aberrations in meiosis that can be prevented by coadministration of N-acetylcysteine in mice

Abstract

To evaluate in vitro effects of arsenite and of arsenite plus N-acetylcysteine on mouse oocyte meiosis. Morphological study using mouse oocytes submitted to in vitro maturation (IVM). Laboratory of reproductive biology. Six-week-old CD-1 mice superovulated with pregnant mare serum gonadotropin. During IVM, mouse oocytes were exposed to arsenite alone or to arsenite plus N-acetylcysteine. Meiotic anomalies were assessed using immunofluorescence microscopy and PolScope (Cambridge Research and Instrumentation, Boston, MA) imaging. In vitro arsenite administration produced dose-dependent and time-dependent meiotic anomalies, characterized by spindle disruption or chromosome misalignment. After 12-14 hours of IVM, exposure to 2 microg/mL of arsenite for 12-14 hours or to 8 microg/mL of arsenite for 2 hours arrested oocyte maturation at the germinal vesicle or germinal-vesicle breakdown stage. Exposure to 4 microg/mL of arsenite for 2 hours arrested oocyte maturation at metaphase I stage in 95% of exposed oocytes (80% exhibiting abnormalities) after 12-14 hours in IVM. After 12-14 hours in IVM, of the oocytes exposed to 2 microg/mL of arsenite for 2 hours, only 15% reached the meiosis II stage (5% exhibiting abnormalities). After 15-17 hours in IVM, however, of the oocytes exposed to 2 microg/mL of arsenite for 2 hours, 65.2% reached the meiosis II stage (43.5% exhibiting abnormalities). Co-administration of N-acetylcysteine prevented the arsenite-induced meiotic abnormalities and the delayed IVM. In vitro arsenite exposure caused meiotic abnormalities that were prevented by co-administration of N-acetylcysteine, suggesting that arsenite-induced meiotic aberrations are mediated by reactive oxygen species.