Embryologic and cytogenetic effects of ethanol on preimplantation mouse embryos in vitro.
Ethanol and its primary metabolite acetaldehyde were studied in cultured preimplantation mouse embryos with respect to embryotoxicity, embryolethality, chromosome breaking activities, and ability to induce sister chromatid exchange (SCE). Analysis of differentiation and cell number of mouse morulae and blastocysts show that acetaldehyde is three orders of magnitude more toxic than ethanol, indicating that the metabolite is responsible for the embryotoxicity of ethanol in preimplantation embryos. Concentrations of ethanol that do not inhibit growth induce SCEs and chromosome aberrations. The SCE-inducing effect of ethanol disappears in the presence of 4-methylpyrazole (4-MP), an inhibitor of alcohol dehydrogenase (ADH). These data suggest that preimplantation embryos are able to convert ethanol to acetaldehyde and that ADH is the enzyme involved. It is, furthermore, shown histochemically that mouse oocytes as well as morulae and blastocysts are able to oxidize ethanol in the presence of NAD+.
Lau
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CF
Max von Pettenkofer-Institut, Federal Health Office (BGA), Berlin, Germany.
Vogel
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R
Obe
G
G
Spielmann
H
H
D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000818:Animals; D001755:Blastocyst / Q000187:drug effects / Q000648:ultrastructure; D002869:Chromosome Aberrations / Q000502:physiology; D004622:Embryo, Mammalian / Q000187:drug effects*; D047108:Embryonic Development / Q000187:drug effects*; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D000077604:Fomepizole; D006651:Histocytochemistry; D051379:Mice; D009028:Morula / Q000187:drug effects / Q000648:ultrastructure; D009865:Oocytes / Q000201:enzymology; D011247:Pregnancy; D011720:Pyrazoles / Q000494:pharmacology; D012854:Sister Chromatid Exchange / Q000187:drug effects
D011720:Pyrazoles; D000431:Ethanol; D000077604:Fomepizole; D000426:Alcohol Dehydrogenase