Placental secretome: uncovering the vast signals shaping fetal metabolic health trajectory

Predisposition to metabolic disease may start during pregnancy, when the intrauterine environment profoundly influences fetal development. The placenta secretes an array of proteins, hormones, metabolites, and extracellular vesicles that coordinate maternal adaptation and fetal development. Beyond classical hormones, emerging evidence reveals a broader placental secretome that regulates metabolic tissue maturation and programming. Maternal health dynamically shapes placental signaling, influencing fetal growth and long-term health trajectory. Advances in proteomics, organoids, and maternal–fetal sampling uncover secretion patterns and networks critical for fetal health programming. Understanding how the placental secretome shapes offspring health trajectories provides a crucial window for intervention to stop the intergenerational cycle of metabolic disease.