Gene and Protein Expression of Placental Nutrient-Stress Sensor Proteins in Fetal Growth Restriction

Abstract

Fetal growth restriction (FGR) and low birth weight increase the risk of non-communicable diseases such as type 2 diabetes and heart failure in adulthood. Placental insufficiency is widely considered a major contributor to FGR. Two crucial placental proteins involved in nutrient and stress sensing—O-linked N-acetylglucosamine transferase (OGT) and mechanistic target of rapamycin (mTOR) kinase—play roles in post-translational protein modification and protein translation, influencing cellular growth and metabolism in response to maternal stress, hypoxia, and nutritional status in the placenta. In our study, we examined the gene and protein profiles of OGT and mTOR in FGR and control placentae, comparing those appropriate for gestational age (AGA), while also considering potential confounding effects of fetal sex and delivery mode. Our findings revealed no significant differences in gene expression, protein levels, or activity of OGT, OGA, mTOR, or their associated markers between female AGA and FGR cesarean placentae, nor between female AGA and male AGA cesarean placentae. Additionally, the mode of delivery in female AGA placentae did not affect the levels or activity of these proteins. Overall, our study did not observe significant differences in nutrient sensor protein expression after stratifying by FGR, sex, and delivery mode. Nevertheless, these unbiased results provide a more comprehensive understanding of the complexities of placental gene expression involving OGT and mTOR.