A Novel BIRC6 Variant Impairs Apoptotic Regulation in Familial Premature Ovarian Insufficiency: Functional Validation in a CRISPR/Cas9 Zebrafish Model

zebrafish model recapitulated POI phenotypes: homozygous females exhibited reduced fecundity, aberrant oocyte morphology, and elevated embryonic death. Transcriptional analysis revealed dysregulation of apoptotic (badb, sortilin, apc) and fertility-related (nanos1, vtg1) genes, alongside unaltered estradiol levels, implicating apoptosis-driven follicular atresia rather than endocrine dysfunction. Compensatory increase in egg production in mutants mirrored human POI progression, where initial irregular cycles culminate in follicular depletion. This study establishes BIRC6 as a novel POI candidate, links its anti-apoptotic function to ovarian homeostasis, and highlights zebrafish as a tractable model for dissecting POI mechanisms. Our findings expand the genetic landscape of infertility and suggest therapeutic potential for apoptosis modulation in fertility preservation.