Knockout of glutathione peroxidase 5 down-regulates the piRNAs in the caput epididymidis of aged mice
Autor: | Joël R. Drevet, Joelle Henry-Berger, Minjie Ni, Lu Yu, Chen Chu, Ayhan Kocer, Yun-Li Guo, Alexandre Champroux, Yuchuan Zhou, Mo-Fang Liu, Andrew L. Eamens, Zimei Ni, Lan-Tao Gou, Yonglian Zhang, Charlie Degui Chen, Yu Zhou, Brett Nixon, Zhao-Liang Fei, Samanta Sharma, Zhi-Tong Li, Wubin Ma, Qiang Liu, Miao He, Yanfei Ru, Shengsong Xie |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Male
endocrine system Aging Somatic cell Urology 030232 urology & nephrology Piwi-interacting RNA Down-Regulation piRNA Biology lcsh:RC870-923 medicine.disease_cause GPX5 Transcriptome 03 medical and health sciences Gene Knockout Techniques Mice 0302 clinical medicine Downregulation and upregulation medicine oxidative stress Animals RNA Small Interfering chemistry.chemical_classification Epididymis Mice Knockout Reactive oxygen species Glutathione Peroxidase 030219 obstetrics & reproductive medicine urogenital system Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling General Medicine lcsh:Diseases of the genitourinary system. Urology small noncoding RNA PIWI-interacting RNA Cell biology Mice Inbred C57BL medicine.anatomical_structure chemistry Original Article epididymis gpx5 pirna piwi-interacting rna small noncoding rna Oxidative stress |
Zdroj: | Asian Journal of Andrology Asian Journal of Andrology, Vol 22, Iss 6, Pp 590-601 (2020) |
ISSN: | 1745-7262 1008-682X |
Popis: | 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. |
Databáze: | OpenAIRE |
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