Novel variants in YTHDC2 cause non-obstructive azoospermia by disrupting the mitotic-to-meiotic transition in humans and mice

The authors investigate whether variants in the YTHDC2 gene contribute to male infertility, specifically non-obstructive azoospermia (NOA) and severe oligozoospermia, and the underlying mechanisms involved. They identify biallelic pathogenic missense variants in YTHDC2 that disrupt the mitotic-to-meiotic transition, leading to meiotic arrest in both humans and a knock-in mouse model. This study provides clinical evidence linking YTHDC2 variants to male infertility and highlights the gene's critical role in regulating the transition from mitosis to meiosis.