<i>In vivo</i> influence of S-adenosylmethionine supplementation on ethanol teratogenicity in the rat

Abstract

Studies have shown that maternal alcohol consumption during pregnancy negatively impacts on prenatal development. Ethanol-induced alteration in S-adenosylmethionine (SAMe) metabolism and subsequent depletion of SAMe may be a mechanism involved in fetal ethanol effects. The aim of the present study was to determine the teratogenicity of ethanol and to investigate protective effects of SAMe. Pregnant Sprague-Dawley rats, weighing 220-250 g were used. Pregnant animals were treated from day 6 through 12 of gestation with ethanol alone (6.4% ethanol) or ethanol plus SAMe (200 mg/kg). The groups for the day-20 and day-12 experiments included: Group I (ethanol liquid diet: unrestricted-fed); Group II (isocaloric maltose-dextrin liquid diet: restricted-fed); and Group III (ethanol liquid diet + SAMe: unrestricted-fed). Embryos and fetuses were recovered on gestational day-12 or day-20, respectively, and were quantitatively and qualitatively assessed for developmental anomalies. The data on continuous variables were analyzed using paired T-Test and categorical embryonic development data were processed using Chi-Square Analysis. In the present study, prenatal growth and developmental retardations such as significantly reduced crown-rump length, anomalies of the central nervous system, the heart, limbs and the skeleton were observed in embryos and fetuses of ethanol treated rats. SAMe supplementation of the ethanol treated pregnant rats significantly improved litter weight, from 20.9 + 1.6 g to 23.6 + 0.8 g, and crown-rump length from 25.8 + 0.8 mm  to 27.6 + 0.4 mm, and decreased the incidence of resorptions from 1.9 + 0.6 to 0.5 + 0.8 in day-20 fetuses. It also significantly increased embryonic protein content from 173 + 36 μg to 251 + 29 μg and significantly improved the development of brain vesicles and closure of the posterior neuropore in day-12 embryos. The present study clearly showed that ethanol is teratogenic in vivo. SAMe supplementation of ethanol treated pregnant rats partially ameliorated the teratogenic effects of ethanol. This indicated that the observed ethanol related growth and developmental abnormalities may have been, at least partly, due to ethanol-induced SAMe deficiency. Further studies should consider extending the treatment period to the entire gestational period instead of limiting it to only the days covering the period of organogenesis.

Keywords: ethanol teratogenicity, Sprague-Dawley rats, S-adenosylmethionine, embryos, fetuses