Otud6a Knockout Leads to Male Subfertility in Mice

IF 3 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Reproduction and Development Pub Date : 2025-03-25 DOI:10.1002/mrd.70022
Fulin Yang, Zhuangfei Wang, Danyang Li, Fei Gao, Xiaohui Hou
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Abstract

Ovarian tumor ubiquitinating 6A (OTUD6A) is a deubiquitinating enzyme whose aberrant expression has been linked to various diseases, including inflammation and prostate cancer. Research indicates that deubiquitinating enzymes (DUBs) play a significant role in spermatogenesis in mice. However, the role of OTUD6A in spermatogenesis remains unclear. To investigate the function of OTUD6A in mouse spermatogenesis, we generated Otud6a-knockout mice using the CRISPR/Cas9 system. Our results showed that OTUD6A is predominantly expressed in the testis and localized to the cytoplasm of spermatogonia and spermatocytes. Although no significant differences were observed in testicular size or morphology between Otud6a-knockout and wild-type mice, the knockout mice exhibited increased germ cell apoptosis, decreased epididymal sperm counts, abnormalities in sperm motility and subfertility. These findings indicate that Otud6a-knockout leads to male subfertility in mice.

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敲除Otud6a导致小鼠雄性不育
卵巢肿瘤泛素化6A (OTUD6A)是一种去泛素化酶,其异常表达与多种疾病有关,包括炎症和前列腺癌。研究表明,去泛素化酶(DUBs)在小鼠精子发生过程中起着重要作用。然而,OTUD6A在精子发生中的作用尚不清楚。为了研究OTUD6A在小鼠精子发生中的功能,我们使用CRISPR/Cas9系统培养了OTUD6A基因敲除小鼠。结果表明,OTUD6A主要在睾丸中表达,并定位于精原细胞和精母细胞的细胞质中。虽然otud6a基因敲除小鼠和野生型小鼠在睾丸大小和形态上没有显著差异,但敲除小鼠表现出生殖细胞凋亡增加、附睾精子数量减少、精子活力异常和生育能力低下。这些发现表明otud6a基因敲除会导致小鼠雄性不育。
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来源期刊
CiteScore
5.20
自引率
0.00%
发文量
78
审稿时长
6-12 weeks
期刊介绍: Molecular Reproduction and Development takes an integrated, systems-biology approach to understand the dynamic continuum of cellular, reproductive, and developmental processes. This journal fosters dialogue among diverse disciplines through primary research communications and educational forums, with the philosophy that fundamental findings within the life sciences result from a convergence of disciplines. Increasingly, readers of the Journal need to be informed of diverse, yet integrated, topics impinging on their areas of interest. This requires an expansion in thinking towards non-traditional, interdisciplinary experimental design and data analysis.
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