Mitochondrial deoxyguanosine kinase is required for female fertility in mice  

作　　者：Yake Gao Rui Dong Jiacong Yan Huicheng Chen Lei Sang Xinyi Yao Die Fan Xin Wang Xiaoyuan Zuo Xu Zhang Shengyu Yang Ze Wu Jianwei Sun 

机构地区：[1]Center for Life Sciences,Yunnan Key Laboratory of Cell Metabolism and Diseases,State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan,School of Life Sciences,Yunnan University,Kunming 650091,China [2]Department of Reproductive Medicine,the First People’s Hospital of Yunnan Province,NHC Key Laboratory of Preconception Health Birth in Western China,Kunming 650100,China [3]Department of Cellular and Molecular Physiology,The Penn State University College of Medicine,Hershey,PA 17033,USA

出　　处：《Acta Biochimica et Biophysica Sinica》2024年第3期427-439,共13页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grants from the National Natural Science Foundation of China(Nos.82273460,32260167,82360305 and 32270981);the Yunnan Applied and Basic Research Program(No.202101AV070002);the Major Science and Technique Programs in Yunnan Province(Nos.202102AA310055 and 202302AA310044);grants from Yunnan University(Nos.KC-22221062,ZC-22223104,ZC-23236296 and TM-23236924);the Excellent Doctor Program(No.XDYC-MY-2022-0055).

摘　　要：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.

关 键 词：DGUOK INFERTILITY MITOCHONDRIA nucleoside salvage pathway oocyte maturation 

分 类 号：Q953[生物学—动物学]