Prenatal choline supplementation during mouse pregnancy has differential effects in alcohol-exposed fetal organs

Abstract

Background: Fetal alcohol spectrum disorders (FASD) are preventable adverse outcomes consequent to prenatal alcohol exposure. Supplemental choline confers neuroprotection to the alcohol-exposed offspring, but its actions outside the brain are unclear. We previously reported that prenatal exposure of mice to 4.5 g/kg of alcohol decreased placental weight in females only, but decreased body weight and liver-to-body weight ratio and increased brain-to-body weight ratio in both sexes. Here we test the hypotheses that a lower alcohol dose will elicit similar outcomes, and that concurrent choline treatment will mitigate these outcomes.

Methods: Pregnant C57BL/6J mice were gavaged with alcohol (3 g/kg; Alc) or maltodextrin (MD) from embryonic day (E) 8.5-17.5. Some also received a subcutaneous injection of 100 mg/kg choline chloride (Alc + Cho, MD + Cho). Outcomes were evaluated on E17.5.

Results: Alc dams had lower gestational weight gain than MD; this was normalized by choline. In males, Alc decreased placental weight whereas choline increased placental efficiency, and Alc + Cho (vs. MD) tended to further reduce placental weight and increase efficiency. Despite no significant alcohol effects on these measures, choline increased fetal body weight but not brain weight, thus reducing brain-to-body weight ratio in both sexes. This ratio was also lower in the Alc + Cho (vs. MD) fetuses. Alc reduced liver weight and the liver-to-body weight ratio; choline did not improve these. Placental weight and efficiency correlated with litter size, whereas placental efficiency correlated with fetal morphometric measurements.

Conclusions: Choline prevents an alcohol-induced reduction in gestational weight gain and fetal body weight and corrects fetal brain sparing, consistent with clinical findings of improvements in alcohol-exposed children born to mothers receiving choline supplementation. Importantly, we show that choline enhances placental efficiency in the alcohol-exposed offspring but does not normalize fetal liver growth. Our findings support choline supplementation during pregnancy to mitigate the severity of FASD and emphasize the need to examine choline's actions in different organ systems.

Keywords: Placenta; fetal alcohol syndrome; fetal growth; intervention; sex-specific effects.