Abstract
Dlx3 (distal-less homeobox 3) haploinsufficiency in mice has been shown to result in restricted fetal growth and placental defects. We previously showed that maternal choline supplementation (4X versus 1X choline) in the Dlx3+/− mouse increased fetal and placental growth in mid-gestation. The current study sought to test the hypothesis that prenatal choline would modulate indicators of placenta function and development. Pregnant Dlx3+/− mice consuming 1X (control), 2X, or 4X choline from conception were sacrificed at embryonic (E) days E10.5, E12.5, E15.5, and E18.5, and placentas and embryos were harvested. Data were analyzed separately for each gestational day controlling for litter size, fetal genotype (except for models including only +/− pups), and fetal sex (except when data were stratified by this variable). 4X choline tended to increase (p < 0.1) placental labyrinth size at E10.5 and decrease (p < 0.05) placental apoptosis at E12.5. Choline supplementation decreased (p < 0.05) expression of pro-angiogenic genes Eng (E10.5, E12.5, and E15.5), and Vegf (E12.5, E15.5); and pro-inflammatory genes Il1b (at E15.5 and 18.5), Tnfα (at E12.5) and Nfκb (at E15.5) in a fetal sex-dependent manner. These findings provide support for a modulatory effect of maternal choline supplementation on biomarkers of placental function and development in a mouse model of placental insufficiency.
Highlights
Abnormal placental development underlies many pathologies of pregnancy including preeclampsia, intrauterine growth restriction (IUGR), and spontaneous abortion [1]
We previously reported that maternal choline supplementation increased placental and fetal weights at E10.5 in offspring of Dlx3+/− dams regardless of fetal genotype [14]
Because the Dlx3 model is associated with labyrinth abnormalities, we sought to determine whether choline treatment increased placental weight by increasing the size of the labyrinth
Summary
Abnormal placental development underlies many pathologies of pregnancy including preeclampsia, intrauterine growth restriction (IUGR), and spontaneous abortion [1]. Anti-angiogenic factors in the maternal circulation, including soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), may contribute to the pathogenesis of preeclampsia symptoms including hypertension and proteinuria, and can be used as biomarkers or predictors of risk when measured in early gestation [5,6]. Together, these dysregulated processes interact to contribute to the pathogenesis of placental disorders such as preeclampsia and IUGR
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