Melatonin in Pregnancy-Related Disorders: A Review of Protective Mechanisms and Therapeutic Potential

Melatonin (N-acetyl-5-methoxytryptamine), classically known as a pineal neurohormone regulating circadian rhythms, has emerged as a critical pleiotropic molecule in reproductive physiology. Beyond its role in establishing circadian entrainment, it acts as a potent antioxidant, anti-inflammatory agent, and mitochondrial function modulator. This review synthesizes current knowledge on the multifaceted roles of melatonin in normal pregnancy and its pathophysiological implications in major gestational disorders, including preeclampsia (PE), fetal growth restriction (FGR), gestational diabetes mellitus (GDM), and preterm birth (PTB). Distinct from prior reviews, this work provides a structured, disorder-specific analysis of translational evidence with a critical evaluation of pharmacological optimization strategies, biomarker-driven trial design, and long-term developmental safety considerations. We highlight the dual source of melatonin maternal and placental and its receptor-mediated and receptor-independent actions. Compelling preclinical data and emerging clinical studies suggest that melatonin supplementation may represent a novel, safe, and effective therapeutic strategy for mitigating oxidative stress and inflammation at the maternal-fetal interface. This article reviews the mechanistic underpinnings, summarizes existing evidence in a structured format, and identifies critical gaps for future translational research.