发育完全停滞的体外受精胚胎线粒体DNA突变研究  

Mitochondrial DNA mutations in women with complete early embryo development arrest in vitro fertilized embryos

作　　者：姚欣怡 王伟[2] 王启航 阮卓琳 游艳琴[3] 赵勇[2] 钟威 商微 YAO Xinyi;WANG Wei;WANG Qihang;RUAN Zhuolin;YOU Yanqin;ZHAO Yong;ZHONG Wei;SHANG Wei(Department of Obstetrics and Gynecology,Chinese PLA General Hospital,Beijing,100853;Department of Obstetrics and Gynecology,Seventh Medical Center of Chinese PLA General Hospital,Beijing,100700;Department of Obstetrics and Gynecology,First Medical Center of Chinese PLA General Hospital,Beijing,100853,China)

机构地区：[1]解放军总医院妇产科,北京100853 [2]解放军总医院第七医学中心妇产科医学部,北京100700 [3]解放军总医院第一医学中心妇产科,北京100853

出　　处：《陆军军医大学学报》2024年第5期477-483,共7页Journal of Army Medical University

基　　金：国家重点研发计划(2018YFC1003003)。

摘　　要：目的 通过探究不明原因早期胚胎发育全部停滞患者线粒体基因的特异性突变。方法 本研究为病例对照研究。收集2021年5月至2022年11月就诊我院的不孕不育女性患者共计46人,均进行外周血全外显子测序及线粒体基因突变检测。经筛选纳入研究组10人,为全部胚胎发育停滞患者;对照组15人,为具有3个以上可移植胚胎的患者,所有入组病例夫妻双方未见染色体异常。统计2组患者临床基线数据、胚胎发育情况,比较2组患者线粒体基因突变位点及其定位基因情况,并对特异性突变位点/基因进行功能注释。结果 研究组发现5个特异线粒体突变位点,分别为:MT-16172(T>C)、MT-12882(C>T)、MT-12406(G>A)、MT-10609(T>C)、MT-16129(G>A)。这些突变点均位于线粒体呼吸链复合物基因和线粒体基因调控区。结论 5个线粒体基因特异性突变位点[MT-16172(T>C)、MT-12882(C>T)、MT-12406(G>A)、MT-10609(T>C)、MT-16129(G>A)]可能与不明原因早期胚胎发育停滞相关。Objective To explore the specific mutations in mitochondrial genes of woman with unexplained complete early embryo development arrest in order to provide new data support for further elucidating the underlying mechanisms.Methods A case-control study was conducted on 46 infertile woman admitted to the Sixth Medical Center of Chinese PLA General Hospital from May 2021 to November 2022.All of them underwent peripheral blood whole exome sequencing and mitochondrial gene mutation detection.Ten patients with complete embryo development arrest were finally subjected and assigned into the study group,and another 15 patients with 3 or more transplantable embryos were enrolled into the control group.No chromosomal abnormalities were observed in both male and female partners of all above cases.Baseline clinical data and embryo development data were collected and compared between the 2 groups of patients.Mitochondrial gene mutation sites and their associated genes were analyzed in the 2 groups,and functional annotation was performed for the specific mutation sites/genes.Results There were 5 specific mitochondrial mutation sites identified in the study group:MT-16172(T>C),MT-12882(C>T),MT-12406(G>A),MT-10609(T>C),and MT-16129(G>A).All these mutation sites are located on the genes of the mitochondrial respiratory chain complex and mitochondrial regulatory genes.Conclusion Five specific mitochondrial mutation sites may be related to unexplained early embryo development arrest.

关 键 词：胚胎发育 生殖技术 线粒体 基因突变 D-loop环 

分 类 号：R321.2[医药卫生—人体解剖和组织胚胎学] R363.25[医药卫生—基础医学] R711.6