MicroRNA‐Mediated Placental Maladaptation in Preeclampsia Pathogenesis

Abstract

Preeclampsia (PE) is a pregnancy‐specific disorder characterized by maternal hypertension and proteinuria, typically manifesting in the late second or third trimester. It affects approximately 5%–8% of pregnancies worldwide and accounts for nearly 10%–15% of maternal deaths. PE is also associated with adverse neonatal outcomes, including preterm birth, fetal growth restriction, and low birth weight, with long‐term cardiovascular and metabolic consequences for both mother and offspring. Although clinical symptoms appear in the latter half of pregnancy, substantial evidence indicates that PE originates earlier during placental development. Impaired trophoblast invasion and defective spiral artery remodeling result in placental insufficiency, compromised uteroplacental perfusion, and a hypoxic placental microenvironment, which are hallmark features of the disease. Despite extensive research, PE remains a heterogeneous disorder lacking reliable early diagnostic markers or effective targeted therapies, with placental delivery remaining the only definitive treatment. MicroRNAs (miRNAs) have emerged as critical regulators of placental development and function. Owing to their abundance, evolutionary conservation, and ability to modulate multiple gene networks, miRNAs regulate trophoblast proliferation, migration, invasion, angiogenesis, and apoptosis, processes that are profoundly disrupted in PE. Genome‐wide expression studies have revealed widespread dysregulation of placental miRNAs in PE, frequently associated with hypoxia and angiogenic imbalance. This review summarizes current advances in miRNA expression and function in the preeclamptic placenta, focusing on their roles in trophoblast dysfunction and disease pathogenesis. We highlight differentially expressed placental miRNAs, their targets, and the regulatory pathways they influence, emphasizing the central role of miRNA‐mediated gene regulation in the development and progression of PE.