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Knockout of glutathione peroxidase 5 down-regulates the piRNAs in the caput epididymidis of aged mice


1 State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China
2 Genetics Reproduction and Development Laboratory, CNRS UMR 6293 - INSERM U1103 - Universitι Clermont Auvergne, Clermont-Ferrand 63001, France
3 Institute of Neuroscience, State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
4 Key Laboratory of Agricultural Animal Genetics, Breeding, and Reproduction of the Ministry of Education and Key Laboratory of Swine Genetics and Breeding of the Ministry of Agriculture, Huazhong Agricultural University, Wuhan 430070, China
5 Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093-0651, USA
6 Department of Anatomy, Histology and Embryology, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Reproductive Medicine, Shanghai 200025, China
7 Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA
8 Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
9 Priority Research Centre for Reproductive Sciences, School of Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW 2308, Australia

Correspondence Address:
Joël R Drevet,
Genetics Reproduction and Development Laboratory, CNRS UMR 6293 - INSERM U1103 - Universitι Clermont Auvergne, Clermont-Ferrand 63001, France

Yu-Chuan Zhou,
State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China

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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/aja.aja_3_20

PMID: 32270769

The mammalian epididymis not only plays a fundamental role in the maturation of spermatozoa, but also provides protection against various stressors. The foremost among these is the threat posed by oxidative stress, which arises from an imbalance in reactive oxygen species and can elicit damage to cellular lipids, proteins, and nucleic acids. In mice, the risk of oxidative damage to spermatozoa is mitigated through the expression and secretion of glutathione peroxidase 5 (GPX5) as a major luminal scavenger in the proximal caput epididymidal segment. Accordingly, the loss of GPX5-mediated protection leads to impaired DNA integrity in the spermatozoa of aged Gpx5-/- mice. To explore the underlying mechanism, we have conducted transcriptomic analysis of caput epididymidal epithelial cells from aged (13 months old) Gpx5-/- mice. This analysis revealed the dysregulation of several thousand epididymal mRNA transcripts, including the downregulation of a subgroup of piRNA pathway genes, in aged Gpx5-/- mice. In agreement with these findings, we also observed the loss of piRNAs, which potentially bind to the P-element-induced wimpy testis (PIWI)-like proteins PIWIL1 and PIWIL2. The absence of these piRNAs was correlated with the elevated mRNA levels of their putative gene targets in the caput epididymidis of Gpx5-/- mice. Importantly, the oxidative stress response genes tend to have more targeting piRNAs, and many of them were among the top increased genes upon the loss of GPX5. Taken together, our findings suggest the existence of a previously uncharacterized somatic piRNA pathway in the mammalian epididymis and its possible involvement in the aging and oxidative stress-mediated responses.


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