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Cited 6 time in webofscience Cited 7 time in scopus
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Redox regulation by TXNRD3 during epididymal maturation underlies capacitation-associated mitochondrial activity and sperm motility in miceopen access

Authors
Wang, HuafengDou, QianhuiJeong, Kyung JoChoi, JungminGladyshev, Vadim N.Chung, Jean-Ju
Issue Date
Jul-2022
Publisher
American Society for Biochemistry and Molecular Biology Inc.
Keywords
thioredoxin glutathione reductase; TXNRD3; redox homeostasis; male fertility; mitochondrial function; ultrastructure
Citation
Journal of Biological Chemistry, v.298, no.7
Indexed
SCIE
SCOPUS
Journal Title
Journal of Biological Chemistry
Volume
298
Number
7
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/61184
DOI
10.1016/j.jbc.2022.102077
ISSN
0021-9258
1083-351X
Abstract
During epididymal transit, redox remodeling protects mammalian spermatozoa, preparing them for survival in the subsequent journey to fertilization. However, molecular mechanisms of redox regulation in sperm development and maturation remain largely elusive. In this study, we report that thioredoxin-glutathione reductase (TXNRD3), a thioredoxin reductase family member particularly abundant in elongating spermatids at the site of mitochondrial sheath formation, regulates redox homeostasis to support male fertility. Using Txnrd3(-/-) mice, our biochemical, ultrastructural, and live cell imaging analyses revealed impairments in sperm morphology and motility under conditions of TXNRD3 deficiency. We find that mitochondria develop more defined cristae during capacitation in wildtype sperm. Furthermore, we show that absence of TXNRD3 alters thiol redox status in both the head and tail during sperm maturation and capacitation, resulting in defective mitochondrial ultrastructure and activity under capacitating conditions. These findings provide insights into molecular mechanisms of redox homeostasis and bioenergetics during sperm maturation, capacitation, and fertilization.
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