Premature ovarian insufficiency (POI) is a heterogeneous condition characterized by cessation of ovarian function in women before the age of 40 years, infertility, and the systemic consequences of estrogen deficiency. Large-scale implementation of molecular genetic techniques resulted in that the knowledge about the genetic etiology of POI has considerably expanded in recent years. In particular, monogenic disorders account for up to 30% of POI cases. This review systematizes data on genes involved in gonadogenesis (NR5A1, SOX8, AR, ESR1), folliculogenesis (FOXL2, FSHR, BNC1, GDF9, BMP15, BMPR1A, BMPR1B, BMPR2, GNAS, TGFBR3, AIRE, POF1B), meiosis (SYCE1, STAG3, HFM1), DNA replication and repair (MCM8, MCM9, MEIOB, SPATA22, MSH4, MSH5, EXO1, RAD51, DMC1, HSF2BP, ERCC6, SPIDR, RECQL4, FANC gene family), and metabolism (POLG, GALT, PMM2, HSD17B4), the variants in which are associated with the development of POI. Particular attention is paid to the molecular mechanisms underlying ovarian dysfunction. Key processes, the disruption of which leads to depletion of ovarian reserve are examined, including folliculogenesis defects, meiotic arrest, replication fork instability, and decreased DNA repair efficiency. Data on genetic variants affecting hormonal regulation, mitochondrial metabolism, and chromosomal stability are highlighted. The presented material emphasizes the importance of molecular diagnostics of POI for clarifying the etiology, early identification of at-risk patients, and substantiating recommendations for fertility preservation.
Pavlova et al. (Wed,) studied this question.