Abstract
Impairments in placental development can adversely affect pregnancy outcomes. The bioactive nutrient choline may mitigate some of these impairments, as suggested by data in humans, animals, and human trophoblasts. Herein, we investigated the effects of maternal choline supplementation (MCS) on parameters of fetal growth in a Dlx3+/− (distal-less homeobox 3) mouse model of placental insufficiency. Dlx3+/− female mice were assigned to 1X (control), 2X, or 4X choline intake levels during gestation. Dams were sacrificed at embryonic days E10.5, 12.5, 15.5, and 18.5. At E10.5, placental weight, embryo weight, and placental efficiency were higher in 4X versus 1X choline. Higher concentrations of hepatic and placental betaine were detected in 4X versus 1X choline, and placental betaine was positively associated with embryo weight. Placental mRNA expression of Igf1 was downregulated by 4X (versus 1X) choline at E10.5. No differences in fetal growth parameters were detected at E12.5 and 15.5, whereas a small but significant reduction in fetal weight was detected at E18.5 in 4X versus 1X choline. MCS improved fetal growth during early pregnancy in the Dlx3+/− mice with the compensatory downregulation of Igf1 to slow growth as gestation progressed. Placental betaine may be responsible for the growth-promoting effects of choline.
Highlights
The placenta mediates the delivery of nutrients to the fetus and is a major determinant of fetal growth [1]
No differences in fetal growth parameters were detected at E12.5 and 15.5, whereas a small but significant reduction in fetal weight was detected at E18.5 in 4X versus 1X choline
Impairments in placental development can lead to placental insufficiency, an inability of the placenta to provide adequate nutrients for the fetus, and contribute to adverse pregnancy outcomes, including intrauterine growth restriction (IUGR), miscarriage, and preeclampsia [2,3]
Summary
The placenta mediates the delivery of nutrients to the fetus and is a major determinant of fetal growth [1]. Impairments in placental development can lead to placental insufficiency, an inability of the placenta to provide adequate nutrients for the fetus, and contribute to adverse pregnancy outcomes, including intrauterine growth restriction (IUGR), miscarriage, and preeclampsia [2,3]. Choline is a water-soluble essential nutrient that is necessary for the synthesis of acetylcholine (a neurotransmitter), phosphatidylcholine (a membrane phospholipid), and betaine (a methyl donor and osmolyte) [5]. During pregnancy, these molecules support rapid cell division, govern genomic methylation patterns, and modulate placental and fetal development [6]
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