Multiple reproductive tract-specific whey acidic protein four-disulfide core genes demonstrate functional requirement for sperm differentiation and function in mice

Our research defines the pivotal roles of the WFDC locus genes in male fertility, particularly in the regulation of sperm development and function. By employing CRISPR/Cas9 mediated gene editing strategy to study this gene family, we provided robust genetic evidence confirming their interconnected functions, which are crucial for sperm differentiation and maturation. Disruptions within these genes can result in infertility, highlighting their regulatory significance. These findings substantiate the potential of targeting EPPIN and related genes for male contraceptive development. Moreover, our study suggests that mutations in the WFDC locus could be instrumental in diagnosing and treating idiopathic male infertility, thereby presenting new therapeutic prospects for reproductive health.本研究明确了WFDC基因座（WFDC locus）相关基因在男性生育能力中的核心作用，尤其参与精子发生与功能的调控。本研究采用CRISPR/Cas9介导的基因编辑技术对该基因家族开展研究，获得了可靠的遗传学证据，证实这些基因之间存在协同调控的功能，而该功能对精子分化与成熟至关重要。此类基因的功能异常可引发男性不育，进一步凸显了其调控的重要意义。本研究结果证实，靶向EPPIN及其相关基因可作为男性避孕药物开发的潜在方向。此外，本研究表明WFDC基因座的突变可用于特发性男性不育的诊断与治疗，为生殖健康领域带来了全新的治疗前景。