In vitro exposure of preimplantation mouse embryos to cocaine and benzoylecgonine inhibits subsequent development.
Cocaine is used by over 20% of women of reproductive age. Although there have been numerous studies focusing on its effects on reproductive processes, none has evaluated its direct effect on preimplantation development. We have investigated the effect of cocaine and its major metabolite, benzoylecgonine, on in vitro preimplantation mouse embryogenesis. One-cell embryos were exposed at the one-, two-, four-, or eight-cell stage for 24 hr to medium containing 0-400 micrograms/ml cocaine or benzoylecgonine and then cultured to the blastocyst stage. Cocaine had its strongest inhibitory effect at the earliest stages of development. At the one- and two-cell stages, there was a significant inhibition of blastocyst formation following exposure to cocaine concentrations of 25-400 micrograms/ml, and at the four-cell stage there was an inhibitory effect at 100 and 400 micrograms/ml cocaine. Benzoylecgonine inhibited the development of embryos to blastocyst only at the one- and two-cell stages, at concentrations of 100-400 micrograms/ml. These findings suggest that cocaine is capable of blocking preimplantation embryogenesis, particularly following exposure at the earliest stages, and that this toxicity may abate as cocaine is biotransformed to benzoylecgonine.
Kaufmann
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C. S. Mott Center for Human Growth and Development, Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan 48201.
Armant
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D000818:Animals; D003042:Cocaine / Q000031:analogs & derivatives* / Q000633:toxicity*; D004622:Embryo, Mammalian / Q000187:drug effects*; D047108:Embryonic Development / Q000187:drug effects*; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D051379:Mice; D011247:Pregnancy; D013480:Superovulation
C005618:benzoylecgonine; D003042:Cocaine