Maternal Choline Supplementation Modulates Placental Markers of Inflammation, Angiogenesis, and Apoptosis in a Mouse Model of Placental Insufficiency.

(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 +/- 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 +/- 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 ( < 0.1) placental labyrinth size at E10.5 and decrease ( < 0.05) placental apoptosis at E12.5. Choline supplementation decreased ( < 0.05) expression of pro-angiogenic genes (E10.5, E12.5, and E15.5), and (E12.5, E15.5); and pro-inflammatory genes (at E15.5 and 18.5), (at E12.5) and (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.