Ethanol teratogenicity in mice: an electron microscopic study.

In this study, the neuroepithelium (NE) cells of the mouse embryo were examined with the electron microscope at various intervals after maternal injection of 0.03 ml/g body weight 25% (v/v) ethanol on day 9 of gestation (plug day = day 1), by the intraperitoneal route. Within 1 hour of treatment, the mitochondria of the NE cells became greatly swollen but could recover. Recovery occurred in two phases: a rapid one during the second hour after treatment, followed by a more gradual one that lasted until 12 hours after treatment. About 5 hours after treatment, dying and fragmenting cells were seen in the NE of all embryos examined. The debris from this necrosis was phagocytosed by neighbouring healthy cells. Also at 5 hours after treatment there was an apparent expansion of the intercellular space of the NE and an enlargement of the apical pseudopodial processes of the NE cells. The latter two changes may have been the result of failure of energy-dependent cell fluid homeostasis consequent to mitochondrial dysfunction. All of these changes were reversed by 15 hours after treatment. Although all embryos examined had abnormalities of the NE, including cell necrosis, at 24 hours after treatment only 28% had failed to complete neural tube formation. Hence, either the degree of ethanol-induced damage varies between embryos in the same litter, or the sensitive period is so restricted that variations in stage of development within a litter can account for the lack of concordance between the presence of cellular damage and the subsequent occurrence of a neural tube defect.