Disruption of Usp26 gene causes male subfertility associated with spermatogenesis defects in mice.

Ubiquitin-specific protease 26 (USP26) is an X-linked gene exclusively expressed in the testis and codes for the USP26, a peptidase enzyme that belongs to the deubiquitinating enzyme (DUB) family. Recent studies have indicated that mutations in USP26 affect spermatogenesis and are associated with male infertility in humans and mice. However, the exact role of USP26 in spermatogenesis and how it affects male reproduction remains unknown. In this study, we generated a conventional Usp26 knockout (KO) mouse model and found that deletion of Usp26 in male mice (Usp26-/Y) leads to significantly reduced pup numbers per litter and significantly increased intervals between two consecutive offspring. We also found that the serum FSH and T levels of adult Usp26-/Y mice were significantly decreased compared to Usp26+/Y mice. Histological examination results showed that Usp26-/Y mice had significantly increased percentage of abnormal seminiferous tubules at different ages. Flow cytometry results exhibited that Usp26-/Y mice had significantly reduced percentage of mature haploid cells in the testes compared to Usp26+/Y mice. Sperm counts in epididymis were also significantly declined in Usp26-/Y mice compared to Usp26+/Y mice. IHC and IF staining and immunoprecipitation (IP) analysis results showed that USP26 and androgen receptor (AR) co-localized in mouse testicular cells at different ages and they both had physiological interactions. All these results demonstrated that loss of Usp26 affects spermatogenesis and hormone secretion and causes male subfertility. Our study also provides the evidence on the interactions between USP26 and AR in mouse testis, whereby pointing to a potential mechanism.

Biology of reproduction. 2018 Dec 18 [Epub ahead of print]

Hong Tian, Yongwei Huo, Jie Zhang, Shangshu Ding, Zhiyong Wang, Hecheng Li, Lirong Wang, Ming Lu, Sen Liu, Shudong Qiu, Qiuyang Zhang

Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China., Dalian Municipal Women and Children's Medical Center, Dalian, Liaoning, China., Research Center of Reproductive Medicine, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China., Department of Structural & Cellular Biology, Tulane University School of Medicine, New Orleans, LA, USA.

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