The role of meiotic genes in primary ovarian insufficiency and non-obstructive azoospermia: a genetic perspective

Abstract Gonadal dysfunction characterizes both primary ovarian insufficiency (POI) and non-obstructive azoospermia (NOA), manifesting as premature ovarian failure in females and severe spermatogenic impairment in males.Both conditions share fundamental meiotic mechanisms, particularly in homologous recombination (HR), synaptonemal complex (SC) formation, and double-strand breaks (DSBs) repair Genetic disruptions in meiotic pathways can impair oogenesis and spermatogenesis, leading to infertility, and in selected cases, may be associated with increased susceptibility to malignancies.In this study, we reviewed key meiotic genes implicated in POI and NOA, highlighting their potential shared genetic etiology. Establishing these molecular pathways could facilitate genetic screening for individuals at high risk of infertility and associated malignancies. Graphical Abstract Key stages of meiosis, such as the formation of the synaptonemal and cohesion complexes, homologous recombination and repair of DNA DSBs, reveal gene variation identified in POI and NOA patients. Synaptonemal complex formation and sister chromatid cohesion are critical for homologous chromosome segregation in the meiosis. Following processing of the broken DNA ends, ssDNA is generated and covered by 3′ ssDNA as well as RPA. Homologous chromosomes are invaded by single-stranded DNA extensions, a process assisted by the recombinases RAD51 and DMC1. There is a complex protein machinery that enables the uptake of homologous DNA strand and facilitates synthesis of new DNA. When the second end of the break is captured, a dHJ is formed. To resolve the dHJ into crossover or non-crossover products, as needed for proper chromosomal segregation and genetic diversity