文献类型：期刊文献

英文题名：Mitochondrial DNA mutation exacerbates female reproductive aging via impairment of the NADH/NAD+redox

作者：Yang, Liang[1,2,3];Lin, Xiaobing[1,2,3];Tang, Haite[1,2,3];Fan, Yuting[4];Zeng, Sheng[5];Jia, Lei[4];Li, Yukun[1,2,3];Shi, Yanan[4];He, Shujing[4];Wang, Hao[1,2,3];Hu, Zhijuan[1,2,3];Gong, Xiao[6];Liang, Xiaoyan[4];Yang, Yi[7];Liu, Xingguo[1,2,3]

机构：[1]Guangzhou Med Univ, CAS Key Lab Regenerat Biol, Guangzhou Inst Biomed & Hlth,Chinese Acad Sci, Hefei Inst Stem Cell & Regenerat Med,Joint Sch Li, Guangzhou 510530, Peoples R China;[2]Chinese Acad Sci, Guangzhou Regenerat Med & Hlth Guangdong Lab, Guangdong Prov Key Lab Stem Cell & Regenerat Med, South China Inst Stem Cell Biol & Regenerat Med,I, Beijing, Peoples R China;[3]Univ Chinese Acad Sci, Beijing, Peoples R China;[4]Sun Yat Sen Univ, Affiliated Hosp 6, Guangzhou, Peoples R China;[5]Chinese Acad Sci, State Key Lab Resp Dis, Guangzhou Regenerat Med & Hlth Guangdong Lab, Guangzhou Inst Biomed & Hlth, Guangzhou, Peoples R China;[6]Guangdong Pharmaceut Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Guangzhou, Peoples R China;[7]East China Univ Sci & Technol, Synthet Biol & Biotechnol Lab, State Key Lab Bioreactor Engn, Shanghai Collaborat Innovat Ctr Biomanufacturing, Shanghai, Peoples R China

年份：2020

卷号：19

期号：9

外文期刊名：AGING CELL

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000554561600001)】；

基金：National Key Research and Development Program of China, Grant/Award Number: 2018YFA0107100, 2017YFA0106300, 2017YFA0102900, 2017YFC1001602, 2019YFA09004500 and 2016YFA0100300; Strategic Priority Research Program of the Chinese Academy of Sciences, Grant/Award Number: XDA16030505; National Natural Science Foundation Projects of China, Grant/Award Number: U1601227, 31631163001, 31701281, 31701106, 31801168, 31900614, 31970709 and 81901275; Key Research Program of Frontier Sciences, CAS, Grant/Award Number: QYZDB-SSW-SMC001; CAS STS Program, Grant/Award Number: KFJ-STS-QYZD-125; Guangzhou Health Care and Cooperative Innovation Major Project, Grant/Award Number: 201704020218; Guangdong Province Science and Technology Program, Grant/Award Number: 2017B020230005, 2017A020215056, 2017B030314056, 2018A030313825, 2018GZR110103002, 2020A1515011200, 2020A1515010919 and 2020A1515011410; Guangzhou Science and Technology Program, Grant/Award Number: 201707010178, 201807010067 and 202002030277; Grant from Yangtze River Scholar Bonus Schemes

语种：英文

外文关键词：aging; fertility; mitochondria; mitochondrial DNA; nicotinamide mononucleotide

摘要：Mammals' aging is correlated with the accumulation of somatic heteroplasmic mitochondrial DNA (mtDNA) mutations. Whether and how aging accumulated mtDNA mutations modulate fertility remains unknown. Here, we analyzed oocyte quality of young (<= 30 years old) and elder (>= 38 years old) female patients and show the elder group had lower blastocyst formation rate and more mtDNA point mutations in oocytes. To test the causal role of mtDNA point mutations on infertility, we used polymerase gamma (POLG) mutator mice. We show that mtDNA mutation levels inversely correlate with fertility, interestingly mainly affecting not male but female fertility. mtDNA mutations decrease female mice's fertility by reducing ovarian primordial and mature follicles. Mechanistically, accumulation of mtDNA mutations decreases fertility by impairing oocyte's NADH/NAD(+)redox state, which could be rescued by nicotinamide mononucleotide treatment. For the first time, we answer the fundamental question of the causal effect of age-accumulated mtDNA mutations on fertility and its sex dependence, and show its distinct metabolic controlling mechanism.