Sex-Differential Effect On Placental Choline Metabolism And Impaired Angiogenesis Associated mTOR pathway In Pregnancy Complicated by Maternal Obesity

Objectives Maternal obesity impairs placental angiogenesis and increases inflammation, affecting nutrient metabolism and transfer to the developing fetus. Choline is an essential nutrient involved in lipid metabolism. Maternal intake of choline was showed to improving angiogenesis in placenta. We investigated whether fetal sex differently affects placental angiogenesis associated with altered nutrient sensing mTOR pathway and altered choline metabolism in obesity. Methods Placentas were collected at birth from women with pre-gravid obesity (OB, BMI=33.6 ± 4.1 kg/m2, 12 females/15 males) and normal BMI (N, BMI=21.5 ± 2.1 kg/m2, 13 females/19 males). Key genes that regulate mTOR signaling, HIF1a (hypoxia response) and VEGFa, FLT1, (angiogenesis) were quantified by RTqPCR. Western Blot was used for AMPKa, mTOR, rpS6, 4E-BP1, Akt and matched phosphorylated proteins. Changes in placental choline associated metabolites (betaine, acetylcholine, sphingomyelins (SM) were determined by LC-MS/MS. Gene expression encoding for choline transporter-like protein SLC44A1 (CTL1) was quantified by RTqPCR (unpaired t test, *P