Alcohol consumption amongst women of reproductive age is widespread. Given that ~50% of pregnancies are unplanned, there is potential to expose the early embryo to alcohol before pregnancy detection. In rats, we have demonstrated that alcohol exposure during the periconceptional period (PCE) leads to fetal growth restriction and sex-specific changes in the placenta. Maternal choline supplementation can ameliorate specific neurological and behavioural abnormalities caused by alcohol exposure during pregnancy. We aimed to test whether mid-gestational choline supplementation could ameliorate the adverse effects of PCE on the late-gestation placenta and fetus.
Sprague-Dawley dams were given 12.5% ethanol (PCE) or 0% ethanol (control) liquid diet from 4 days prior to 4 days after conception. At embryonic day 10 (E10), dams were given choline enriched (2.5X-4X) or standard chow (8-10 litters/group). Late in gestation (E20), fetuses and placentas were collected and measured/weighed. All fetuses/placentas were sexed; only one of each sex/litter was used per analysis. Placentas were separated into labyrinth and junctional zones for molecular analysis or left whole and prepared for histology.
Placental efficiency was reduced by PCE but improved by choline supplementation in a sex-specific manner. Fetal growth restriction due to PCE was restored in both sexes by supplemental choline. Placental depth was increased by PCE but other placental dimensions were altered by choline, independent of PCE. Placental glycogen deposition was increased in the junctional zone in response to PCE, specifically in females, but there was no effect of choline. The glycogen cell marker, protocadherin 12 (Pcdh12), and glycogen synthase kinase 3 beta (Gsk3B), showed altered expression due to PCE and choline in a sex-specific manner.
Therefore, both PCE and choline supplementation resulted in sex-specific changes in the late-gestation placenta. Importantly, our results suggest that choline has the potential to improve placental efficiency and restore fetal growth following prenatal alcohol exposure.