Bi-allelic MEI1 variants cause meiosis arrest and non-obstructive azoospermia

doi:10.1038/s10038-023-01119-3

	Bi-allelic MEI1 variants cause meiosis arrest and non-obstructive azoospermia
	Zhang, Yuxiang 1; Li, Na2,3,4 ; Ji, Zhiyong 5; Bai, Haowei 1; Ou, Ningjing 6; Tian, Ruhui 1; Li, Peng 1; Zhi, Erlei 1; Huang, Yuhua 1; Zhao, Jingpeng 6; Han, Yaqin 7; Zhang, Jing 8; Zhou, Yuchuan 9; Li, Zheng 1; Yao, Chencheng 1
	2023
发表期刊	JOURNAL OF HUMAN GENETICS; (IF:2.6[JCR-2023],2.6[5-Year])
ISSN	1434-5161
EISSN	1435-232X
DOI	10.1038/s10038-023-01119-3
摘要	Non-obstructive azoospermia (NOA) is characterized by the failure of sperm production due to testicular disorders and represents the most severe form of male infertility. Growing evidences have indicated that gene defects could be the potential cause of NOA via genome-wide sequencing approaches. Here, bi-allelic deleterious variants in meiosis inhibitor protein 1 (MEI1) were identified by whole-exome sequencing in four Chinese patients with NOA. Testicular pathologic analysis and immunohistochemical staining revealed that spermatogenesis is arrested at spermatocyte stage, with defective programmed DNA double-strand breaks (DSBs) homoeostasis and meiotic chromosome synapsis in patients carrying the variants. In addition, our results showed that one missense variant (c.G186C) reduced the expression of MEI1 and one frameshift variant (c.251delT) led to truncated proteins of MEI1 in in vitro. Furthermore, the missense variant (c.T1585A) was assumed to affect the interaction between MEI1 and its partners via bioinformatic analysis. Collectively, our findings provide direct genetic and functional evidences that bi-allelic variants in MEI1 could cause defective DSBs homoeostasis and meiotic chromosome synapsis, which subsequently lead to meiosis arrest and male infertility. Thus, our study deepens our knowledge of the role of MEI1 in male fertility and provides a novel insight to understand the genetic aetiology of NOA.
学科门类	Genetics ; Genetics (clinical)
URL	查看原文
收录类别	SCOPUS
语种	英语
原始文献类型	Article
Scopus 记录号	2-s2.0-85147782595
来源库	SCOPUS
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/286470
专题	生命科学与技术学院生命科学与技术学院_PI研究组_朱焕乎组
作者单位	1.Department of Andrology,Center for Men’s Health,Department of ART,Institute of Urology,Urologic Medical Center,Shanghai Key Laboratory of Reproductive Medicine,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,200080,China; 2.School of Life Science and Technology,ShanghaiTech University,Shanghai,201210,China; 3.CAS Center for Excellence in Molecular Cell Science,Shanghai Institute of Biochemistry and Cell Biology,Chinese Academy of Sciences,Shanghai,200031,China; 4.University of Chinese Academy of Sciences,Beijing,100049,China; 5.Reproductive Medical Department,The First Affiliated Hospital of Xiamen University,School of Medicine,Xiamen University,Xiamen,China; 6.State Key Lab of Reproductive Medicine,Nanjing Medical University,Nanjing,211100,China; 7.Pathology Center,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,200080,China; 8.The Reproductive Medicine Research Center,the Sixth Affiliated Hospital of Sun Yat-sen University,17 Shougouling Road,Guangzhou,510620,China; 9.The International Peace Maternity and Child Health Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,200030,China
推荐引用方式 GB/T 7714	Zhang, Yuxiang,Li, Na,Ji, Zhiyong,et al. Bi-allelic MEI1 variants cause meiosis arrest and non-obstructive azoospermia[J]. JOURNAL OF HUMAN GENETICS;,2023.
APA	Zhang, Yuxiang.,Li, Na.,Ji, Zhiyong.,Bai, Haowei.,Ou, Ningjing.,...&Yao, Chencheng.(2023).Bi-allelic MEI1 variants cause meiosis arrest and non-obstructive azoospermia.JOURNAL OF HUMAN GENETICS;.
MLA	Zhang, Yuxiang,et al."Bi-allelic MEI1 variants cause meiosis arrest and non-obstructive azoospermia".JOURNAL OF HUMAN GENETICS; (2023).