Abstract
Spermatogenesis is a reproductive system process that produces sperm. Ubiquitin specific peptidase 26 (USP26) is an X chromosome-linked deubiquitinase that is specifically expressed in the testes. It has long been controversial whether USP26 variants are associated with human male infertility. Thus, in the present study, we introduced a mutation into the Usp26 gene in mice and found that Usp26 mutant males backcrossed to a DBA/2 background, but not a C57BL/6 background, were sterile or subfertile and had atrophic testes. These findings indicate that the effects of the Usp26 mutation on male reproductive capacity were influenced by genetic background. Sperm in the cauda epididymis of Usp26 mutant mice backcrossed to a DBA/2 background were decreased in number and showed a malformed head morphology compared to those of wild-type mice. Additionally, histological examinations of the testes revealed that the number of round and elongated spermatids were dramatically reduced in Usp26 mutant mice. The mutant mice exhibited unsynapsed chromosomes in pachynema and defective chiasma formation in diplonema, which presumably resulted in apoptosis of metaphase spermatocytes and subsequent decrease of spermatids. Taken together, these results indicate that the deficiencies in fertility and spermatogenesis caused by mutation of Usp26 were dependent on genetic background.
Highlights
Spermatogenesis is a complex system of differentiation that involves the self-renewal of spermatogonial stem cells, the differentiation of spermatogonia into meiotic spermatocytes, and morphogenesis of haploid spermatids[1]
The present results clearly demonstrate that the effects of the Usp[26] mutation on murine spermatogenesis were dependent on genetic background, which may account for the conflicting findings regarding the relationship between Ubiquitin specific peptidase 26 (USP26) variants/Usp[26] mutations and male infertility
Fertilized eggs collected from mating pairs of B6D2F1 mice, F1 hybrids crossed between C57BL/6 females and DBA/2 males, were electroporated with Cas[9] mRNA and guide RNA (gRNA) corresponding to the N-terminal of ubiquitin carboxyl-terminal hydroxylase domain (UCH_N; Fig. 1A,B) and transferred to pseudopregnant females
Summary
Spermatogenesis is a complex system of differentiation that involves the self-renewal of spermatogonial stem cells, the differentiation of spermatogonia into meiotic spermatocytes, and morphogenesis of haploid spermatids[1] These differentiation processes are strictly regulated by transcriptional, translational, and post-translational mechanisms, and alterations in these processes may be causative factors for male infertility and subfertility[2]. Mice with a mutation of Usp[26] were generated and backcrossed to either a DBA/2 background or a C57BL/6 background to investigate genetic effects. The present results clearly demonstrate that the effects of the Usp[26] mutation on murine spermatogenesis were dependent on genetic background, which may account for the conflicting findings regarding the relationship between USP26 variants/Usp[26] mutations and male infertility
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
