Mei4 deficiency leads to sexual dimorphism of early meiosis and occurrence of unreduced eggs in zebrafish

Polyploids typically arise from meiotic catastrophes, and homologous chromosome mis-segregation, resulting from defects in programmed DNA double-strand breaks (DSBs) formation, is a major cause. Mei4 is known to recruit the Spo11 nuclease onto chromosome axes to catalyze DSB formation in yeast and mice, but its function in fish remains unexplored. Here, we generated mei4-/- zebrafish mutants and observed severe defects in synapsis, DSB formation, homologous repair, and crossover during meiosis in both male and female germ cells. Significantly, distinct sexual dimorphism in responses to Mei4 deficiency was observed in meiotic prophase I between males and females. And, mei4-/- males were sterile, while females produced a lot of aneuploid oocytes and a few of unreduced eggs due to defective chromosome segregation. Strikingly, a considerable number of viable triploid offspring from mei4-/- females × wild type males were produced. Our findings demonstrate the conserved role of Mei4 in DSB formation across vertebrates, provide new insights into sex-specific meiotic behaviors in this vertebrate model, and highlight the critical role of meiotic DSB-based crossover defects in polyploidy occurrence.