Advances in the Study of Noncoding RNAs in the Pathogenesis of Pregnancy-related Diseases.

Abstract

Noncoding RNAs (ncRNAs) are a heterogeneous group of RNA molecules that lack protein-coding capability. The major classes of ncRNAs are long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs). Numerous studies have confirmed that ncRNAs are essential regulators of placental development and maternal-fetal homeostasis. By modulating trophoblast proliferation, apoptosis, migration, invasion, and vascularization, ncRNAs critically regulate the onset and trajectory of gestational disorders. Herein, we summarize studies on the aberrant expression and functional significance of lncRNAs, miRNAs, and circRNAs in pregnancy disorders, including preeclampsia, recurrent spontaneous abortion, fetal growth restriction, and gestational diabetes mellitus. Several ncRNAs, including lncRNAs TUG1 and MALAT1, miRNAs miR-155 and miR-143, hsa_circ_0002348, and circVEGFC, have been experimentally implicated in disease pathogenesis through modulation of key signaling cascades, epigenetic remodeling, and stress-responsive cellular programs. Although current research has provided initial insights into the regulatory functions and expression profiles of ncRNAs in pregnancy-related disorders, most findings are derived from samples collected during mid- and late gestation. The dynamic expression patterns and precise functional roles of ncRNAs during early pregnancy remain poorly understood. Future studies should prioritize longitudinal investigations spanning the entire gestational period, implement standardized validation across large-scale clinical cohorts, and further elucidate the mechanistic involvement of ncRNAs in placental development and disease pathogenesis. This article provides a comprehensive assessment of the substantial potential of ncRNAs in the prevention and treatment of pregnancy-related diseases, and outlines future translational applications and research directions.