Proteomics

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The selenoprotein TXNRD3 supports male fertility via the redox regulation of spermatogenesis


ABSTRACT: Thioredoxin/glutathione reductase (TGR, TXNRD3) is a selenoprotein composed of thioredoxin reductase and glutaredoxin domains; the function of this enzyme remains unknown. This NADPH-dependent thiol oxidoreductase evolved by gene duplication within the Txnrd family, is expressed in the testes and can reduce both thioredoxin and glutathione in vitro. To characterize the function of TXNRD3 in vivo, we generated a strain of mice with the deletion of Txnrd3 gene. We show that Txnrd3 knockout mice are viable and without discernable gross phenotypes, but TXNRD3 deficiency leads to fertility impairment in male mice. Txnrd3 knockout animals exhibit a lower fertilization rate in vitro, a sperm movement phenotype and an altered redox status of thiols. Proteomic analyses revealed a broad range of substrates reduced by TXNRD3 during sperm maturation, presumably as a part of quality control. The results show that TXNRD3 plays a critical role in male reproduction via the thiol redox control of spermatogenesis.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Joao Paulo  

LAB HEAD: Vadim Gladyshev

PROVIDER: PXD033872 | Pride | 2022-10-13

REPOSITORIES: Pride

Dataset's files

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Action DRS
394655_j40861_NEM_IAA.mzIdentML Mzid
394656_j40854_NEM_IAA.mzIdentML Mzid
394657_j40854_190518105614_NEM_IAA.mzIdentML Mzid
394658_j40855_NEM_IAA.mzIdentML Mzid
394659_j40857_NEM_IAA.mzIdentML Mzid
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Publications

Selenoprotein TXNRD3 supports male fertility via the redox regulation of spermatogenesis.

Dou Qianhui Q   Turanov Anton A AA   Mariotti Marco M   Hwang Jae Yeon JY   Wang Huafeng H   Lee Sang-Goo SG   Paulo Joao A JA   Yim Sun Hee SH   Gygi Stephen P SP   Chung Jean-Ju JJ   Gladyshev Vadim N VN  

The Journal of biological chemistry 20220623 8


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 k  ...[more]

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