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

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.

SUBMITTER: King JH

PROVIDER: S-EPMC5537879 | biostudies-other | 2017 Jul

REPOSITORIES: biostudies-other

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

King Julia H JH Kwan Sze Ting Cecilia STC Yan Jian J Klatt Kevin C KC Jiang Xinyin X Roberson Mark S MS Caudill Marie A MA

Nutrients 20170718 7

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 <i>Dlx3</i>+/- (distal-less homeobox 3) mouse model of placental insufficiency. <i>Dlx3</i>+/- female mice were assigned to 1X (control), 2X, or 4X choline intake levels dur ...[more]

PMID: 28718809

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Project description:BACKGROUND:Individuals exposed to gestational stressors such as alcohol exhibit a spectrum of growth patterns, suggesting individualized responses to the stressors. We hypothesized that intrauterine growth responses to gestational alcohol are modified not only by the stressor's severity but by fetal sex and the placenta's adaptive capacity. METHODS:Pregnant C57BL/6J mice were assigned to one of three groups. Group 1 consumed a normal protein diet (18% protein by weight) and received 4.5?g alcohol/kg body weight (NP-Alc-8) or isocaloric maltodextrin (NP-MD-8) daily from embryonic day (E) 8.5-E17.5. Group 2 consumed the same diet but received alcohol (NP-Alc-13) or maltodextrin (NP-MD-13) daily from E13.5-E17.5. Group 3 consumed the same diet but containing a lower protein content (12% protein by weight) from E0.5 and also received alcohol (LP-Alc-8) or maltodextrin (LP-MD-8) daily from E8.5-E17.5. Maternal, placental, and fetal outcomes were assessed on E17.5 using 2-way ANOVA or mixed linear model. RESULTS:We found that intrauterine growth differed in the alcohol-exposed fetuses depending on sex and insult severity. Both NP-Alc-8 (vs. NP-MD-8) males and females had lower body weight and asymmetrical growth, but only NP-Alc-8 females had lower placental weight (P < 0.05). NP-Alc-13 (vs. NP-MD-13) females, but not their male littermates, had lower body weight (P = 0.019). Alcohol exposure beginning from E8.5 (vs. E13.5) decreased the ratio of fetal liver-to-body weight and increased the ratio of fetal brain-to-liver weight in both sexes (P < 0.05). LP-Alc-8 (vs. NP-MD-8) group had smaller litter size (P = 0.048), but the survivors had normal placental and body weight at E17.5. Nevertheless, LP-Alc-8 fetuses still showed asymmetrical growth. Correlation analyses reveal a relationship between litter size and placental outcomes, which were related to fetal outcomes in a sex-dependent manner, suggesting that the placenta may mediate the consequence of LP-Alc-altered litter size on fetal development. CONCLUSIONS:Our data indicate that the placenta is strongly involved in the fetal stress response and adapts in a sex-dependent fashion to support fetal development under the alcohol stressor. These variables may further influence the spectrum of intrauterine growth outcomes observed in those diagnosed with fetal alcohol spectrum disorder.

Dataset Information

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

Publications

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

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