Selenoprotein TXNRD3 supports male fertility via the redox regulation of spermatogenesis.
Selenoprotein TXNRD3 supports male fertility via the redox regulation of spermatogenesis.
复制标题
硒蛋白TXNRD3通过对精子发生过程的氧化还原调控来维持雄性生育能力。
DOI：
10.1016/j.jbc.2022.102183
复制
发表时间：
2022-08
影响因子：
4.8
通讯作者：
Gladyshev, Vadim N.
中科院分区：
文献类型：
--
作者：
Dou, Qianhui;Turanov, Anton A.;Mariotti, Marco;Hwang, Jae Yeon;Wang, Huafeng;Lee, Sang -Goo;Paulo, Joao A.;Yim, Sun Hee;Gygi, Stephen P.;Chung, Jean-Ju;Gladyshev, Vadim N.
硫氧还蛋白/谷胱甘肽还原酶(TXNRD3)是由硫氧还蛋白还原酶和谷氧还蛋白结构域组成的一种硒蛋白。这种依赖于NADPH的硫醇氧化还原酶在Txnrd家族内通过基因复制进化而来，在睾丸中表达，在体外可以还原硫氧还蛋白和谷胱甘肽；然而，这种酶的功能尚不清楚。为了研究TXNRD3在体内的功能，我们建立了一株Txnrd3基因缺失的小鼠。我们证明，这些Txnrd3基因敲除小鼠是存活的，没有可辨别的大体表型，而且TXNRD3缺乏会导致雄性小鼠生育能力受损。我们发现，Txnrd3基因敲除动物在体外表现出较低的受精率，精子运动表型，以及精子细胞中硫醇氧化还原状态的改变。蛋白质组学分析进一步表明，在精子成熟过程中，TXNRD3会减少大量底物，这可能是精子质量控制的一部分。综上所述，这些结果表明TXNRD3通过硫醇氧化还原控制精子发生在雄性生殖中起关键作用。
Thioredoxin/glutathione reductase (TXNRD3) is a selenoprotein composed of thioredoxin reductase and glutaredoxin domains. This NADPH-dependent thiol oxidoreductase evolved through gene duplication within the Txnrd family, is expressed in the testes, and can reduce both thioredoxin and glutathione in vitro; however, the function of this enzyme remains unknown. To characterize the function of TXNRD3 in vivo, we generated a strain of mice bearing deletion of Txnrd3 gene. We show that these Txnrd3 knockout mice are viable and without discernable gross phenotypes, and also that TXNRD3 deficiency leads to fertility impairment in male mice. We found that Txnrd3 knockout animals exhibited a lower fertilization rate in vitro, a sperm movement phenotype, and an altered thiol redox status in sperm cells. Proteomic analyses further revealed a broad range of substrates reduced by TXNRD3 during sperm maturation, presumably as a part of sperm quality control. Taken together, these results show that TXNRD3 plays a critical role in male reproduction via the thiol redox control of spermatogenesis.
登录
查看更多内容
DOI：
10.1126/science.1252806
发表时间：
2014-06-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Jiang Y;Xie M;Chen W;Talbot R;Maddox JF;Faraut T;Wu C;Muzny DM;Li Y;Zhang W;Stanton JA;Brauning R;Barris WC;Hourlier T;Aken BL;Searle SMJ;Adelson DL;Bian C;Cam GR;Chen Y;Cheng S;DeSilva U;Dixen K;Dong Y;Fan G;Franklin IR;Fu S;Guan R;Highland MA;Holder ME;Huang G;Ingham AB;Jhangiani SN;Kalra D;Kovar CL;Lee SL;Liu W;Liu X;Lu C;Lv T;Mathew T;McWilliam S;Menzies M;Pan S;Robelin D;Servin B;Townley D;Wang W;Wei B;White SN;Yang X;Ye C;Yue Y;Zeng P;Zhou Q;Hansen JB;Kristensen K;Gibbs RA;Flicek P;Warkup CC;Jones HE;Oddy VH;Nicholas FW;McEwan JC;Kijas J;Wang J;Worley KC;Archibald AL;Cockett N;Xu X;Wang W;Dalrymple BP
通讯作者：
Dalrymple BP
影响因子：
64.5
作者：
Hwang JY;Mannowetz N;Zhang Y;Everley RA;Gygi SP;Bewersdorf J;Lishko PV;Chung JJ
通讯作者：
Chung JJ
影响因子：
4.8
作者：
Bonilla, Mariana;Denicola, Ana;Salinas, Gustavo
通讯作者：
Salinas, Gustavo
影响因子：
5.3
作者：
Conrad, M;Jakupoglu, C;Brielmeier, M
通讯作者：
Brielmeier, M
DOI：
10.1126/science.1262110
发表时间：
2015-05-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
GTEx Consortium
通讯作者：
GTEx Consortium