Peroxisome Proliferator-Activated Receptor Alpha (PPARα) in Human Placenta: Molecular Architecture, Feto-Maternal Metabolic Integration, and Pathophysiological Significance

The peroxisome proliferator-activated receptor alpha (PPARα) is a ligand-activated nuclear transcription factor belonging to the nuclear receptor superfamily. Although classically characterised as the master regulator of hepatic fatty acid oxidation (FAO) and lipid catabolism, accumulating evidence positions PPARα as an indispensable molecular conductor at the feto-maternal interface. Within the human placenta, PPARα is expressed in both cytotrophoblast and syncytiotrophoblast layers throughout gestation, where it governs mitochondrial and peroxisomal β-oxidation, orchestrates pro-resolution inflammatory signalling, modulates trophoblast differentiation and invasion, and participates in epigenetic programming of the developing fetus. Derangements of placental PPARα activity are increasingly identified in major obstetric complications, including preeclampsia, gestational diabetes mellitus, and intrauterine growth restriction, where aberrant lipid accumulation, heightened oxidative stress, and amplified pro-inflammatory cytokine signalling converge. This review synthesises current knowledge on the molecular biology and genomic targets of PPARα in the placenta, its integration with maternal metabolic adaptations of pregnancy, its role in nutrient sensing and fetal programming, and the consequences of its dysregulation in pregnancy pathology. We further discuss emerging therapeutic implications of PPARα modulation and outstanding questions in this rapidly evolving field.