The teratogenic effect of dilantin on preimplantation mouse embryo development : an honors thesis (HONRS 499)

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Clouser, Pamela J.
Chatot, Clare L.
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Thesis (B.?.)
Honors College
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Dilantin, diphenylhydantoin (DPH), is an anticonvulsant drug used to control the disorder known as epilepsy. Dilantin, however, is a known human teratogen and pregnant females taking this drug have an increased risk of spontaneous miscarriages and of giving birth to babies with fetal hydantoin syndrome. To study the effects of Dilantin at preimplantation stages, varying concentrations of the drug were added directly to cultures of 2-cell mouse embryos. After two days of culture, the embryos were analyzed for percent development beyond the two cell stage. Although effects of Dilantin were observed, no true dosage response curve was found in the therapeutic range in the cultures where Dilantin was added directly. Cultures containing 5 pg/ml DPH promoted normal development to morula and blastocyst stages (46%). DPH at 10 and 20 gg/ml concentrations promoted development to the 4-8 cell stage but morula and blastocyst stages were reduced (40.5% and 53%). This effect became more severe at 50 and 100 µg/ml levels. Further studies that investigate whether the teratogenic agent is the parent drug or actually a metabolic intermediate of DPH were performed by addition of a microsomal S9 fraction to cultures of two cell mouse embryos. The S9 fraction alone was found to not be teratogenic to the embryos itself, however, the addition of DPH and S9 fraction increased the toxic effect of the drug.