Selenoprotein TXNRD3 supports male fertility via the redox regulation of spermatogenesis

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...

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Detalles Bibliográficos
Autores: Dou, Quianhui, Turanov, Anton A., Mariotti, Marco, 1984-, Hwang, Jae Yeon, Wang, Huafeng, Lee, Sang-Goo, Paulo, Joao A., Yim, Sun Hee, Gygi, Stephen P., Chung, Jean-Ju, Gladyshev, Vadim N.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/193974
Acceso en línea:https://hdl.handle.net/2445/193974
Access Level:acceso abierto
Palabra clave:Fecunditat humana
Espermatogènesi
Human fertility
Spermatogenesis
Descripción
Sumario: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.