Placental programming in maternal malnutrition as a crucial determinant of offspring health: A critical-interpretative narrative review

Maternal malnutrition during pregnancy is a critical environmental factor that can reprogram placental development and, consequently, influence fetal growth and offspring health across the lifespan. According to the Developmental Origins of Health and Disease (DOHaD) theory, adverse intrauterine conditions - such as nutrient deficiencies or excesses - may induce morphological and functional alterations in the placenta, thereby increasing the risk of chronic noncommunicable diseases (NCDs) in adulthood. This critical-interpretative narrative review compiles evidence on how maternal nutritional disorders, including protein restriction, micronutrient deficiencies, and high-fat diets, compromise placental efficiency by altering nutrient transport, hormonal signaling, and epigenetic regulation. We discuss the interplay between placental dysfunction, impaired fetal development, and increased disease susceptibility in offspring from a sex-specific perspective, highlighting the more adaptive placental responses observed in females and the more pronounced adverse effects and underlying potential pathophysiological pathways in males. Drawing on established studies, we synthesize insights and potential molecular and biochemical mechanisms of placental dysregulation, and propose new directions for research that address not only the consequences for offspring and metabolic programming but also the implications for women's health during critical periods, such as pregnancy. From a DOHaD perspective, this review underscores the central role of the placenta as a mediator between the intrauterine environment and health outcomes, pointing toward preventive strategies and future research approaches.