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Mitochondrial deoxyguanosine kinase is required for female fertility in mice

Authors :
Gao Yake
Dong Rui
Yan Jiacong
Chen Huicheng
Sang Lei
Yao Xinyi
Fan Die
Wang Xin
Zuo Xiaoyuan
Zhang Xu
Yang Shengyu
Wu Ze
Sun Jianwei
Source :
Acta Biochimica et Biophysica Sinica, Vol 56, Pp 427-439 (2024)
Publication Year :
2024
Publisher :
China Science Publishing & Media Ltd., 2024.

Abstract

Mitochondrial homeostasis plays a pivotal role in oocyte maturation and embryonic development. Deoxyguanosine kinase (DGUOK) is a nucleoside kinase that salvages purine nucleosides in mitochondria and is critical for mitochondrial DNA replication and homeostasis in non-proliferating cells. Dguok loss-of-function mutations and deletions lead to hepatocerebral mitochondrial DNA deletion syndrome. However, its potential role in reproduction remains largely unknown. In this study, we find that Dguok knockout results in female infertility. Mechanistically, DGUOK deficiency hinders ovarian development and oocyte maturation. Moreover, DGUOK deficiency in oocytes causes a significant reduction in mitochondrial DNA copy number and abnormal mitochondrial dynamics and impairs germinal vesicle breakdown. Only few DGUOK-deficient oocytes can extrude their first polar body during in vitro maturation, and these oocytes exhibit irregular chromosome arrangements and different spindle lengths. In addition, DGUOK deficiency elevates reactive oxygen species levels and accelerates oocyte apoptosis. Our findings reveal novel physiological roles for the mitochondrial nucleoside salvage pathway in oocyte maturation and implicate DGUOK as a potential marker for the diagnosis of female infertility.

Details

Language :
English
ISSN :
16729145
Volume :
56
Database :
Directory of Open Access Journals
Journal :
Acta Biochimica et Biophysica Sinica
Publication Type :
Academic Journal
Accession number :
edsdoj.5e3d7d6d3a8c4123a0eec018d6ed8984
Document Type :
article
Full Text :
https://doi.org/10.3724/abbs.2024003