Maternal Thalidomide Treatment and Cell Division in Cultured Rabbit Embryos: Automated Image Analysis of Autoradiographs. (thalidomide/autoradiography/rabbit embryo culture.)

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Abstract
To determine whether thalidomide dysmorphogenesis was preceded by a changed pattern of cell division, embryos from thalidomide-treated rabbits were cultured for 4 h in a medium containing 3H-thymidine. Automated image analysis of serial autoradiographs of the embryos revealed no focus of increased or decreased cell division in the neural tube or limb bud. Thalidomide pretreatment caused a general decrease in cell division at 10 days postcoitum. A similar effect was observed only in those 10 3/4-day embryos whose status in culture was low. Unlike methotrexate, the dysmorphogenic effect of thalidomide could not be attributed to a generally suppressed mitotic rate. This teratogen preprograms dysmorphogenesis before the onset of the limb bud outgrowth (10 days), with the result that teratogenesis is manifest only during limb development after 11 days.