Primary Ovarian Insufficiency: Molecular Mechanisms and the Role of MicroRNAs.

Primary ovarian insufficiency (POI) is a multifactorial disorder marked by ovarian function cessation before age 40, leading to infertility and systemic complications, including osteoporosis, cardiovascular disease, and neurocognitive impairment. It results from accelerated ovarian reserve depletion, impaired folliculogenesis, and hormonal dysregulation. The majority of cases are idiopathic, with known causes including genetic mutations, autoimmune disorders, infections, and iatrogenic factors. Recent RNA sequencing advances highlight microRNAs (miRNAs) as critical regulators of ovarian processes. Dysregulated miRNAs drive granulosa cell apoptosis, oxidative stress, and follicular atresia, with distinct profiles offering potential as biomarkers for early diagnosis and therapeutic targets. This review synthesizes miRNA-mediated mechanisms in POI, integrating their roles in apoptosis, DNA repair, and folliculogenesis, and evaluates miRNA-based diagnostics and therapies, including exosome-mediated delivery, to improve reproductive and clinical outcomes.