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Rho guanosine exchange factor 15 (ARHGEF15) is a member of the guanosine exchange factors, which are involved in cell migration, cell polarity, and cell cycle progression via activation of Rho GTPases. This study investigated the functional role of ARHGEF15 in SCs during spermatogenesis using SC\u2013specific Arhgef15 knockout mice. The results revealed that Arhgef15 deficiency in SCs affected the localization of SC nuclei, disrupted BTB integrity, and led to premature shedding of germ cells. In Arhgef15flox\/flox\/Amh-Cre+ mice, the ultrastructure of the round spermatids was impaired, accompanied by acrosome degeneration, acrosomal vesicle shedding, and atrophic nuclei. Consequently, the percentage of abnormal sperm in the Arhgef15flox\/flox\/Amh-Cre+ epididymis was markedly elevated. RNA-sequencing analysis revealed that most of the differentially expressed genes in SCs of Arhgef15flox\/flox\/Amh-Cre+ mice were associated with immunity. Further study revealed that the sera of Arhgef15flox\/flox\/Amh-Cre+ mice showed immunoreactivity against testicular lysate of wild-type mice, indicating the production of antibodies against testicular autoantigens in Arhgef15flox\/flox\/Amh-Cre+ mice. In conclusion, the specific deletion of Arhgef15 in SCs\u00a0of mice leads to sperm abnormality, probably by disrupting the testicular immune homeostasis.<\/jats:p>","DOI":"10.1093\/biolre\/ioac166","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T18:06:54Z","timestamp":1661364414000},"page":"1565-1579","source":"Crossref","is-referenced-by-count":14,"title":["ARHGEF15 in Sertoli cells contributes to germ cell development and testicular immune privilege"],"prefix":"10.1093","volume":"107","author":[{"given":"Feng","family":"Chen","sequence":"first","affiliation":[{"name":"National Engineering Laboratory for Animal Breeding , College of Animal Science and Technology, , Beijing , China"},{"name":"China Agricultural University , College of Animal Science and Technology, , Beijing , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjie","family":"Wu","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Animal Breeding , College of Animal Science and Technology, , Beijing , China"},{"name":"China Agricultural University , College of Animal Science and Technology, , Beijing , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Ke","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Animal Breeding , College of Animal Science and Technology, , Beijing , China"},{"name":"China Agricultural University , College of Animal Science and Technology, , Beijing , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Lin","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Animal Breeding , College of Animal Science and Technology, , Beijing , China"},{"name":"China Agricultural University , College of Animal Science and Technology, , Beijing , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengchao","family":"Wang","sequence":"additional","affiliation":[{"name":"National Institute of Biological Sciences , Beijing , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinghe","family":"Qin","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Animal Breeding , College of Animal Science and Technology, , Beijing , China"},{"name":"China Agricultural University , College of Animal Science and Technology, , Beijing , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,8,24]]},"reference":[{"key":"2022121508064379700_ref1","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.1210\/me.2009-0184","article-title":"Retinoblastoma protein plays multiple essential roles in the terminal differentiation of Sertoli cells","volume":"23","author":"Nalam","year":"2009","journal-title":"Mol 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