Disruption of Placental Immune Privilege by Complications of Pregnancy: Consequences for Maternal and Child Health

Maternal chronic conditions, including obesity, diabetes, hypertensive disorders, and autoimmune diseases, promote a systemic proinflammatory environment characterized by oxidative stress and chronic inflammation. These alterations lead to reduced expressions of human leukocyte antigen-G (HLA-G) and programmed death-ligand 1 (PD-L1), decreased regulatory T (Treg)cell activity, and increased T helper (Th)1/Th17 responses, disrupting placental immune privilege and resulting in increased production of proinflammatory cytokines, oxidative stress, trophoblastic dysfunction, and placental senescence. This change in immune privilege contributes to fetal growth restriction, preterm birth, congenital anomalies, and long-term cardiometabolic programming in offspring. Understanding the mechanisms underlying placental immune dysregulation may facilitate the development of targeted therapeutic strategies aimed at restoring immune tolerance and reducing inflammatory and hypoxic signaling pathways to improve maternal and neonatal outcomes. This review summarizes the current state of the field of placental immunological privilege and how maternal chronic conditions like obesity, diabetes, hypertensive disorders, and autoimmune diseases can disrupt it and its possible consequences on the progeny.