Knockout of glutathione peroxidase 5 down-regulates the piRNAs in the caput epididymidis of aged mice.
Knockout of glutathione peroxidase 5 down-regulates the piRNAs in the caput epididymidis of aged mice.
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敲除谷胱甘肽过氧化物酶 5 下调老年小鼠头附睾中的 piRNA
DOI：
10.4103/aja.aja_3_20
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发表时间：
2020-11
影响因子：
2.9
通讯作者：
Zhang YL
中科院分区：
文献类型：
--
作者：
Chu C;Yu L;Henry-Berger J;Ru YF;Kocer A;Champroux A;Li ZT;He M;Xie SS;Ma WB;Ni MJ;Ni ZM;Guo YL;Fei ZL;Gou LT;Liu Q;Sharma S;Zhou Y;Liu MF;Chen CD;Eamens AL;Nixon B;Zhou YC;Drevet JR;Zhang YL
哺乳动物附睾不仅在精子成熟过程中起着基础性的作用，而且对各种应激源也具有保护作用。其中最重要的是氧化应激造成的威胁，氧化应激由活性氧物种的不平衡引起，可导致细胞脂类、蛋白质和核酸的损害。在小鼠中，精子氧化损伤的风险通过表达和分泌谷胱甘肽过氧化物酶5(GPX5)来减轻，谷胱甘肽过氧化物酶5(GPX5)是附睾头近端的主要管腔清除剂。因此，丧失GPX5介导的保护会导致老年Gpx5-/-小鼠精子DNA完整性受损。为了探索其潜在的机制，我们对老年(13个月大)Gpx5-/-小鼠的附睾头上皮细胞进行了转录转录分析。这项分析揭示了老年Gpx5-/-小鼠附睾部几千个mRNA转录的异常，包括piRNA途径基因亚群的下调。与这些发现一致，我们还观察到了piRNAs的丢失，它可能与P元素诱导的弱睾丸(PIWI)样蛋白PIWIL1和PIWIL2结合。在Gpx5-/-小鼠附睾头中，这些piRNAs的缺失与其推测的基因靶标的mRNA水平升高有关。重要的是，氧化应激反应基因往往具有更多的靶向piRNAs，其中许多基因是GPX5缺失后最高水平的基因之一。综上所述，我们的研究结果表明，哺乳动物附睾体细胞中存在一条先前未被描述的piRNA途径，它可能参与了衰老和氧化应激介导的反应。
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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影响因子：
10.5
作者：
Goh WS;Falciatori I;Tam OH;Burgess R;Meikar O;Kotaja N;Hammell M;Hannon GJ
通讯作者：
Hannon GJ
影响因子：
3.6
作者：
Johnston, DS;Jelinsky, SA;Turner, TT
通讯作者：
Turner, TT
影响因子：
9.8
作者：
John B;Enright AJ;Aravin A;Tuschl T;Sander C;Marks DS
通讯作者：
Marks DS
影响因子：
5.8
作者：
Feng, Jianxing;Meyer, Clifford A.;Zhang, Yong
通讯作者：
Zhang, Yong
影响因子：
12.3
作者：
Langmead B;Trapnell C;Pop M;Salzberg SL
通讯作者：
Salzberg SL