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Published on: October 13, 2018
Otud6a Knockout Leads to Male Subfertility in Mice
Fulin Yang1, Zhuangfei Wang1, Danyang Li2
1Department of Basic Medical Sciences, Zunyi Medical University, Zunyi, China.
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.
Insights
The deubiquitinating enzyme OTUD6A is crucial for male fertility. Knocking out Ovarian tumor ubiquitinating 6A (OTUD6A) in mice led to subfertility, decreased sperm counts, and motility issues.
Area of Science:
- Reproductive Biology
- Molecular Biology
- Genetics
Background:
- Deubiquitinating enzymes (DUBs) are vital for spermatogenesis in mice.
- The specific role of Ovarian tumor ubiquitinating 6A (OTUD6A) in male reproduction is not well understood.
- OTUD6A's aberrant expression is linked to diseases like prostate cancer.
Purpose of the Study:
- To investigate the function of OTUD6A in mouse spermatogenesis.
- To determine the impact of OTUD6A deficiency on male fertility.
Main Methods:
- Generation of Otud6a-knockout mice using CRISPR/Cas9 gene editing.
- Analysis of testicular morphology, germ cell apoptosis, sperm count, and motility.
- Localization studies of OTUD6A protein in testicular tissues.
Main Results:
- OTUD6A is primarily expressed in the testis, localized in spermatogonia and spermatocytes.
- Otud6a-knockout mice showed no significant changes in testicular size or morphology.
- Knockout mice exhibited increased germ cell apoptosis, reduced sperm counts, impaired motility, and subfertility.
Conclusions:
- OTUD6A plays a critical role in maintaining male fertility in mice.
- OTUD6A deficiency results in male subfertility due to germ cell apoptosis and sperm dysfunction.
- Targeting OTUD6A may offer therapeutic potential for male infertility.
