Placental gene signatures associated with high neonatal adiposity: role for immune cell activation

Fetal fat accumulation is an important indicator of the nutritional environment in pregnancy and placental function. Excessive fat accretion leading to high adiposity at birth, however, can increase a child's long-term risk for obesity and metabolic disease. While maternal body mass index is associated with neonatal adiposity, there is a wide variation in body composition among babies born to women with and without obesity. The placenta orchestrates a complex exchange of nutrients and signals between the mother and baby. To better understand the molecular mechanisms that govern fetal fat accumulation, we profiled the transcriptomics of 79 placentas collected from mothers with and without obesity. We identified a set of 18 neonatal adiposity-associated genes, common to pregnancies with and without obesity. A coexpressed cluster of these genes is involved in innate immune responses, particularly neutrophil activation. We also identified neonatal adiposity-associated genes unique to mothers with or without obesity, suggesting different biological pathways support high newborn adiposity, and/or are responsive to a common initial immune signal. These findings suggest that placental inflammation may influence fetal fat accumulation. Understanding these pathways may help identify novel ways to support healthy fetal growth and reduce the risk of long-term disease.