Maternal choline supplementation in a rat model of periconceptional alcohol exposure: Impacts on the fetus and placenta

Abstract

Background: Maternal choline supplementation in rats can ameliorate specific neurological and behavioral abnormalities caused by alcohol exposure during pregnancy.We tested whether choline supplementation ameliorates fetal growth restriction and molecular changes in the placenta associated with periconceptional ethanol exposure (PCE) in the rat.Methods: Sprague Dawley dams were given either 12.5% ethanol (PCE) or 0% ethanol (Con) in a liquid diet from 4 days prior to 4 days after conception. At day 5 of pregnancy, dams were either placed on a standard chow (1.6 g choline/kg chow) or an intermediate chow (2.6 g choline/kg chow). On day 10 of pregnancy, a subset of the intermediate dams were placed on a chow further supplemented with choline (7.2 g choline/kg chow), resulting in 6 groups. Fetuses and placentas were collected on day 20 of pregnancy for analysis.Results: Choline supplementation resulted in increased fetal weight at late gestation, ameliorating the deficits due to PCE. This was most pronounced in litters on a standard chow during pregnancy. Choline also increased fetal liver weight and decreased fetal brain:liver ratio, independent of alcohol exposure. Placental weight was reduced as choline levels in the chow increased, particularly in female placentas. This resulted in a greater ratio of fetal:placental weight, suggesting increased placental efficiency.Global DNA methylation in the placenta was altered in a sex-specific manner by both PCE and choline. However, the increased glycogen deposition in female placentas, previously reported in this PCE model, was not prevented by choline supplementation. Conclusions:Our results suggest that choline has the potential to ameliorate fetal growth restriction associated with PCE and improve placental efficiency following prenatal alcohol exposure. Our study highlights the importance of maternal nutrition in moderating the severity of adverse fetal and placental outcomes that may arise from prenatal alcohol exposure around the time of conception.

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

“…As such, the alcohol-exposed fetus may still prioritize the choline supply to support brain development. This argument is further supported by a recent study in a rat model of periconceptional alcohol exposure, which reports improved fetal liver growth in offspring whose mothers receive choline supplementation at 2× and 4× the recommended intake level (Steane et al, 2021). Choline uptake between fetal brain and liver may also differ because the ubiquitous choline transporter SLC44A1, which encodes the choline transporter-like protein 1 (CTL1), is highly abundant in the fetal brain but is expressed in lower amounts in fetal liver (Yuan et al, 2004).…”

Paternal alcohol exposures program intergenerational hormetic effects on offspring fetoplacental growth

“…Recent studies examining periconceptional maternal exposures suggest that EtOH may impact brain weights in the developing offspring ( Steane et al, 2021 ). Further, increased proportional brain to body weight is a reliable indicator of intrauterine growth restriction (IUGR) ( Cortes-Araya et al, 2022 ).…”

Untargeted Metabolome Analysis Reveals Reductions in Maternal Hepatic Glucose and Amino Acid Content That Correlate with Fetal Organ Weights in a Mouse Model of Fetal Alcohol Spectrum Disorders

“…Pathways involving choline, methionine, and folate metabolism are also essential to healthy fetal brain development, and deficits during pregnancy are associated with impaired memory and learning in the offspring [58]. We and others recently reported that choline supplementation improves fetal body, liver, and brain weights in rodent models of FASD [59,60], and consistent with this, we find here that the maternal hepatic content of the one-carbon metabolites methionine and S-adenosylhomocysteine (SAH) are positively correlated with fetal brain weight. Similarly, although alcohol affected the hepatic content of far fewer metabolites in the fetus, the methyl donor S-adenosylmethionine (SAM) and its catabolite 5-methylthioadenosine are negatively correlated with fetal brain weight.…”