DNA double-strand break genetic variants in patients with premature ovarian insufficiency

Premature ovarian insufficiency (POI) is a clinically heterogeneous disease that may seriously affect the physical and mental health of women of reproductive age. POI primarily manifests as ovarian function decline and endocrine disorders in women prior to age 40 and is an established cause of female infertility. It is crucial to elucidate the causative factors of POI, not only to expand the understanding of ovarian physiology, but also to provide genetic counselling and fertility guidance to affected patients. Factors leading to POI are multifaceted with genetic factors accounting for 7% to 30%. In recent years, an increasing number of DNA damage-repair-related genes have been linked with the occurrence of POI. Among them, DNA double-strand breaks (DSBs), one of the most damaging to DNA, and its main repair methods including homologous recombination (HR) and non-homologous end joining (NHEJ) are of particular interest. Numerous genes are known to be involved in the regulation of programmed DSB formation and damage repair. The abnormal expression of several genes have been shown to trigger defects in the overall repair pathway and induce POI and other diseases. This review summarises the DSB-related genes that may contribute to the development of POI and their potential regulatory mechanisms, which will help to further establish role of DSB in the pathogenesis of POI and provide theoretical guidance for the study of the pathogenesis and clinical treatment of this disease.

Automated summary

Premature ovarian insufficiency (POI) is a diverse disease that can greatly impact the health of women of reproductive age. Understanding the causative factors of POI is crucial for genetic counseling and fertility guidance. Recent research has linked DNA damage-repair-related genes, particularly those related to DNA double-strand breaks (DSBs), with the occurrence of POI. This review provides an overview of DSB-related genes and their potential regulatory mechanisms, contributing to the understanding of POI's pathogenesis and clinical treatment.