Maternal Choline Supplementation Modulates Fetal Growth Patterns in a Mouse Model of Placental Insufficiency

Impairments in placental development can result in intrauterine growth restriction, miscarriage, and preeclampsia. The bioactive nutrient choline has previously been shown to modulate various aspects of placental function in healthy third trimester pregnant women and human trophoblast cell culture. To further explore the role of choline intake in placental function and fetal development, we investigated the effects of maternal choline supplementation (MCS) in a mouse model of placental insufficiency. Dlx3 +/‐ female mice were assigned to control, 2X or 4X intake levels of choline during gestation and were sacrificed at embryonic days E10.5, E12.5, E15.5, and E18.5. Data was analyzed using linear mixed models with dam as a random factor. At E10.5 the 4x choline treatment increased embryo weight by 70% in wildtype (WT) pups (P<.001) and by 60% in heterozygous (HET) pups (P=.013) compared to controls. Similarly, placental efficiency (ratio of embryo weight to placental weight) was increased by 44% in HET pups (P=.044) on 4X choline. However, by E12.5, neither 2X or 4X choline group pups weighed more than controls. At E18.5, both WT (P=.024) and HET (P=.024) 4X pups showed 10% lower weight as compared to controls. Placental weight and fetal crown‐rump length did not differ significantly between groups at any gestational time point. Overall, these data suggest that MCS improves fetal growth in early pregnancy in the Dlx3 +/‐ mouse with potential compensatory adjustments to slow growth as gestation progresses. The molecular mechanisms yielding these effects of MCS are under investigation. Funding provided by USDA