Novel variants in YTHDC2 cause non-obstructive azoospermia by disrupting the mitotic-to-meiotic transition in humans and mice - PubMed
4 hours ago
- #YTHDC2
- #male infertility
- #meiotic arrest
- Novel biallelic pathogenic missense variants in YTHDC2 cause human male infertility, specifically non-obstructive azoospermia (NOA) or severe oligozoospermia.
- These variants disrupt the mitotic-to-meiotic transition, leading to meiotic prophase arrest during spermatogenesis, as validated in a knock-in mouse model.
- Mechanistically, YTHDC2 variants result in decreased levels of key interacting proteins (MEIOC and RBM46) and aberrant upregulation of mitotic cell cycle regulators, indicating a failure to properly switch from mitotic to meiotic programs.
- The study involved genetic screening of a cohort of infertile men and identified five patients from three families with YTHDC2 variants, though the sample size is limited.
- Findings highlight YTHDC2's conserved role in meiotic transcriptome reprogramming and support its inclusion in genetic screening for male infertility diagnosis.