• PMID: 31835093
• Gene Name: SOX30
• Condition: Male infertility, Non-obstructive Azoospermia
• Association: Associated
• Sex: Male
• Infertility type: Male infertility

Epigenetic Inactivation of SOX30 Is Associated with Male Infertility and Offers a Therapy Target for Non-obstructive Azoospermia

Han F, Jiang X, Li ZM, Zhuang X, Zhang X, Ouyang WM, Liu WB, Mao CY, Chen Q, Huang CS, Gao F, Cui ZH, Ao L, Li YF, Cao J, Liu JY.

Non-obstructive azoospermia (NOA) is the most severe form of male infertility. However, the etiology of NOA is largely unknown, resulting in a lack of clinical treatments. Here, we performed a comparative genome-wide profiling of DNA methylation and identified SOX30 as the most notably hyper-methylated gene at promoter in testicular tissues from NOA patients. This hyper-methylation at promoter of SOX30 directly causes its silencing of expression in NOA. The reduced levels of SOX30 expression are correlated with severity of NOA disease. Deletion of Sox30 in mice uniquely impairs testis development and spermatogenesis with complete absence of spermatozoa in testes leading to male infertility, but does not influence ovary development and female fertility. The pathology and testicular size of Sox30 null mice highly simulate those of NOA patients. Re-expression of Sox30 in Sox30 null mice at adult age reverses the pathological damage of testis and restores the spermatogenesis. The re-presented spermatozoa after re-expression of Sox30 in Sox30 null mice have the ability to start a pregnancy. Moreover, the male offspring of Sox30 re-expression Sox30 null mice still can father children, and these male offspring and their children can live normally more than 1 year without significant difference of physical appearance compared with wild-type mice. In summary, methylated inactivation of SOX30 uniquely impairs spermatogenesis, probably causing NOA disease, and re-expression of SOX30 can successfully restore the spermatogenesis and actual fertility. This study advances our understanding of the pathogenesis of NOA, offering a promising therapy target for NOA disease. CI - Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Han, Fei AU - Han F AD - Institute of Toxicology, College of Preventive Medicine, Army Medical University, Chongqing, China. FAU - Jiang, Xiao AU - Jiang X AD - Institute of Toxicology, College of Preventive Medicine, Army Medical University, Chongqing, China. FAU - Li, Zhi-Ming AU - Li ZM AD - Institute of Reproductive Health, Tongji College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Zhuang, Xuan AU - Zhuang X AD - Department of Urology, The First Affiliated Hospital, Xiamen University, Xiamen, Fujian, China. FAU - Zhang, Xi AU - Zhang X AD - Institute of Toxicology, College of Preventive Medicine, Army Medical University, Chongqing, China. FAU - Ouyang, Wei-Ming AU - Ouyang WM AD - Office of Biotechnology Products, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA. FAU - Liu, Wen-Bin AU - Liu WB AD - Institute of Toxicology, College of Preventive Medicine, Army Medical University, Chongqing, China. FAU - Mao, Cheng-Yi AU - Mao CY AD - Department of Pathology, Daping Hospital, Army Medical University, Chongqing, China. FAU - Chen, Qing AU - Chen Q AD - Institute of Toxicology, College of Preventive Medicine, Army Medical University, Chongqing, China. FAU - Huang, Chuan-Shu AU - Huang CS AD - Nelson Institute of Environmental Medicine, NYU School of Medicine, New York, NY, USA. FAU - Gao, Fei AU - Gao F AD - Comparative Pediatrics and Nutrition, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark. FAU - Cui, Zhi-Hong AU - Cui ZH AD - Institute of Toxicology, College of Preventive Medicine, Army Medical University, Chongqing, China; College of Pharmaceutical Sciences, Southwest University, Chongqing, China. FAU - Ao, Lin AU - Ao L AD - Institute of Toxicology, College of Preventive Medicine, Army Medical University, Chongqing, China. FAU - Li, Yan-Feng AU - Li YF AD - Department of Urology, Daping Hospital, Army Medical University, Chongqing, China. FAU - Cao, Jia AU - Cao J AD - Institute of Toxicology, College of Preventive Medicine, Army Medical University, Chongqing, China. Electronic address: caojia1962@126.com.