Developing a safe and effective male contraceptive remains a challenge in the field of medical science. Molecules that selectively target the male reproductive tract and whose targets are indispensable for male reproductive function serve among the best candidates for a novel non-hormonal male contraceptive method. To determine the function of these genes in vivo, mutant mice carrying disrupted testis- or epididymis-enriched genes were generated by zygote microinjection or electroporation of the CRISPR/Cas9 components. Male fecundity was determined by consecutively pairing knockout males with wild-type females and comparing the fecundity of wild-type controls. Phenotypic analyses of testis appearance and weight, testis and epididymis histology, and sperm movement were further carried out to examine any potential spermatogenic or sperm maturation defect in mutant males. In this study, we uncovered 13 testis- or epididymis-enriched evolutionarily conserved genes that are individually dispensable for male fertility in mice. Owing to their dispensable nature, it is not feasible to use these targets for the development of a male contraceptive.

中文翻译：

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小鼠中基于 CRISPR/Cas9 的基因组编辑揭示了 13 个富含睾丸或附睾的基因，这些基因对于雄性生殖来说是可有可无的†。

开发安全有效的男性避孕药仍然是医学领域的一个挑战。选择性靶向男性生殖道且其靶标对男性生殖功能必不可少的分子是新型非激素男性避孕方法的最佳候选者之一。为了确定这些基因在体内的功能，携带被破坏的睾丸或附睾富集基因的突变小鼠是通过合子显微注射或 CRISPR/Cas9 组件的电穿孔产生的。通过将敲除雄性与野生型雌性连续配对并比较野生型对照的繁殖力来确定雄性繁殖力。进一步进行睾丸外观和重量、睾丸和附睾组织学以及精子运动的表型分析，以检查突变男性中任何潜在的生精或精子成熟缺陷。在这项研究中，我们发现了 13 个富含睾丸或附睾的进化保守基因，这些基因对于小鼠的雄性生育能力来说是可有可无的。由于其可有可无的性质，将这些目标用于开发男性避孕药具是不可行的。