The full-length BEND2 protein is dispensable for spermatogenesis but required for setting the ovarian reserve in mice.

Abstract

Infertility affects up to 12% of couples globally, with genetic factors contributing to nearly half of the cases. Advances in genomic technologies have led to the discovery of genes like <i>Bend2</i>, which play a crucial role in gametogenesis. In the testis, <i>Bend2</i> expresses two protein isoforms: full-length and a smaller one. Ablation of both proteins results in an arrested spermatogenesis. Because the <i>Bend2</i> locus is on the X chromosome, and the <i>Bend2^-/y</i> mutants are sterile, BEND2's role in oogenesis remained elusive. In this study, we employed a novel <i>Bend2</i> mutation that blocks the expression of the full-length BEND2 protein but allows the expression of the smaller BEND2 isoform. Interestingly, this mutation does not confer male sterility and mildly affects spermatogenesis. Thus, it allowed us to study the role of BEND2 in oogenesis. Our findings demonstrate that full-length BEND2 is dispensable for male fertility, and its ablation leads to a reduced establishment of the ovarian reserve. These results reveal a critical role for full-length BEND2 in oogenesis and provide insights into the mechanisms underlying the establishment of the ovarian reserve. Furthermore, these findings hold relevance for the diagnostic landscape of human infertility.