Prenatal high-fat diet alters placental morphology, nutrient transporter expression, and mtorc1 signaling in rat

Objective: This study aimed to determine how the rat placenta and fetus respond to maternal high-fat (HF) diet during gestation and to identify the possible mechanisms. Methods: Pregnant Sprague-Dawley rats were fed with standard chow (13.5% fat) or HF (60% fat) diet during gestation. Placentas were collected on gestation day 21. Results: HF dams had greater fat mass, higher plasma leptin, lower plasma adiponectin, and impaired glucose tolerance during pregnancy. The placental labyrinth thickness was reduced in both male and female fetuses of HF dams. In HF male placentas, glucose transporter 3 gene expression, system A amino acid transporter (SNAT) 2 gene expression, and SNAT2 protein expression were increased through the activation of the mTORC1 4EBP1 branch. In HF female placentas, gene expression of insulin-like growth factor 2 (IGF2) and IGF2 receptor was elevated compared to placentas of females fed standard chow. Although male and female placentas responded differently to prenatal HF diet exposure, both male and female fetal weight was not altered by maternal HF diet. Conclusions: Placenta responds and adapts to maternal metabolic changes by altering placental layer thickness, mTORC1 signaling, expression of nutrient transporters, and growth factors in a sex-specific manner.