Mei4 deficiency induces sexual dimorphism in early meiosis and promotes production of unreduced eggs in zebrafish.

Polyploidy frequently originates from meiotic failure, with mis-segregation of homologous chromosomes commonly arising from impaired formation of programmed DNA double-strand breaks (DSBs). Meiotic double-stranded break formation protein 4 (Mei4) is essential for recruiting the Sporulation-specific protein 11 (Spo11) nuclease to chromosome axes to initiate DSB formation in yeast and mice, yet its role in fish remains uncharacterized. In this study, mei4 -/- zebrafish mutants were generated and exhibited severe defects in synapsis, DSB formation, homologous recombination, and crossover (CO) formation during meiosis in both male and female germ cells. Notably, pronounced sexual dimorphism in responses to Mei4 deficiency was observed during meiotic prophase I, with males exhibiting complete sterility due to meiotic arrest, while females produced numerous aneuploid oocytes and a minority of unreduced eggs due to defective chromosome segregation. Remarkably, crosses between mei4 -/- females and wild-type males yielded a substantial number of viable triploid progeny. These findings demonstrate functional conservation of Mei4 in mediating meiotic DSB formation across vertebrates, reveal sex-specific divergence in meiotic responses to recombination failure in this vertebrate model, and highlight a critical role for DSB-dependent crossover failure in the genesis of polyploidy.