Jiang Sun, Yonggang Lu, Kaori Nozawa, Zoulan Xu, Akane Morohoshi, Julio M. Castaneda, Taichi Noda, Haruhiko Miyata, Ferheen Abbasi, Hossam H. Shawki, Satoru Takahashi, Darius J. Devlin, Zhifeng Yu, Ryan M. Matzuk, Thomas X. Garcia, Martin M. Matzuk, Masahito Ikawa
Biology of Reproduction 103 (2), 183-194, (26 May 2020) https://doi.org/10.1093/biolre/ioaa083
KEYWORDS: male contraceptive, CRISPR/Cas9, knockout mice, Male infertility, testis, epididymis
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.
Summary sentence
Thirteen testis- or epididymis-enriched genes are individually dispensable for male fertility based on phenotypic analyses of mutant mice produced by the CRISPR/Cas9 system.