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

ObjectiveTo evaluate in vitro effects of arsenite and of arsenite plus N-acetylcysteine on mouse oocyte meiosis.DesignMorphological study using mouse oocytes submitted to in vitro maturation (IVM).SettingLaboratory of reproductive biology.Animal(s)Six-week-old CD-1 mice superovulated with pregnant mare serum gonadotropin.Intervention(s)During IVM, mouse oocytes were exposed to arsenite alone or to arsenite plus N-acetylcysteine.Main Outcome Measure(s)Meiotic anomalies were assessed using immunofluorescence microscopy and PolScope (Cambridge Research and Instrumentation, Boston, MA) imaging.Result(s)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 μg/mL of arsenite for 12–14 hours or to 8 μg/mL of arsenite for 2 hours arrested oocyte maturation at the germinal vesicle or germinal-vesicle breakdown stage. Exposure to 4 μg/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 μg/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 μg/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.Conclusion(s)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.