cdk2 is essential for synapsis completion and gametogenesis in zebrafish

Cyclin-dependent kinase 2 (CDK2), encoded by the cdk2 gene, facilitates the G1/S transition, a pivotal phase for DNA replication during cell proliferation. While cdk2 is widely expressed in mice, its global deletion is not lethal but results in infertility in both sexes due to meiotic defects. In zebrafish, it remains unknown whether and how cdk2 regulates gametogenesis and gonadal development. In this study, we found that cdk2 was predominantly expressed in the spermatocytes and oocytes of zebrafish, and we generated cdk2 mutants through CRISPR/Cas9 technology. All the cdk2 mutants developed ovarian-like structures during juvenile stages akin to wild-type counterparts, but they eventually developed into infertile males in adulthood. Further study showed that in the ovaries, cdk2 deficiency resulted in the failure of oogenesis, triggering Tp53-dependent apoptosis and causing sex reversal. In the testes, cdk2 deficiency disrupted synaptonemal complex assembly, leading to abnormalities at the zygotene stage and impaired DNA damage repair, ultimately culminating in failed spermatogenesis. Introducing tp53 mutations mitigated oocyte apoptosis and the sex reversal phenotype in cdk2 mutants; however, the rescued cdk2 -/- ; tp53 -/- females exhibited reduced egg quality. Collectively, our study underscores the critical role of cdk2 in regulating synapsis completion and gametogenesis in zebrafish. • Cdk2 was predominantly expressed in the spermatocytes and oocytes of zebrafish. • Cdk2 mutants developed into infertile males. • Introducing tp53 mutations mitigated oocyte apoptosis and the sex reversal phenotype in cdk2 mutants. • Deficiency of cdk2 disrupted synapsis completion. • Deficiency of cdk2 caused abnormal formation or repair of DNA double-strand breaks.