Arsenite induces aberrations in meiosis that can be prevented by coadministration of N-acetylcysteine in mice.
OBJECTIVE
To evaluate in vitro effects of arsenite and of arsenite plus N-acetylcysteine on mouse oocyte meiosis.


METHODS
Morphological study using mouse oocytes submitted to in vitro maturation (IVM).


METHODS
Laboratory of reproductive biology.


METHODS
Six-week-old CD-1 mice superovulated with pregnant mare serum gonadotropin.


METHODS
During IVM, mouse oocytes were exposed to arsenite alone or to arsenite plus N-acetylcysteine.


METHODS
Meiotic anomalies were assessed using immunofluorescence microscopy and PolScope (Cambridge Research and Instrumentation, Boston, MA) imaging.


RESULTS
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.


CONCLUSIONS
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.
Navarro
Paula A A S
PA
Department of Obstetrics and Gynecology, Women and Infants Hospital, Brown University, Providence, Rhode Island, USA. paasnavarro@uol.com.br
Liu
Lin
L
Ferriani
Rui A
RA
Keefe
David L
DL
D000111:Acetylcysteine / Q000008:administration & dosage*; D000818:Animals; D018053:Arsenites / Q000633:toxicity*; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000139:chemically induced*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004785:Environmental Pollutants / Q000633:toxicity*; D008540:Meiosis / Q000187:drug effects*; D051379:Mice; D009865:Oocytes / Q000187:drug effects* / Q000473:pathology*
D018053:Arsenites; D004785:Environmental Pollutants; C015001:arsenite; D000111:Acetylcysteine