• PMID: 27072590
• Gene Name: METTL14
• Condition: Asthenozoospermia, Male infertility
• Association: Associated
• Population size: 52
• Population details: 52 (20 asthenozoospermia patients, 32 healthy controls)
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Asthenozoospermia, Male infertility

Increased N6-methyladenosine in Human Sperm RNA as a Risk Factor for Asthenozoospermia

Yang Y, Huang W, Huang JT, Shen F, Xiong J, Yuan EF, Qin SS, Zhang M, Feng YQ, Yuan BF, Liu SM.

Male infertility is a worldwide medical problem. Asthenozoospermia is a common cause of infertility. Epigenetic modifications of DNA and histones have been shown to influence human infertility, but no research has explored whether N(6)-methyladenosine (m(6)A) level in RNA is associated with asthenozoospermia. Here, we collected a total of 52 semen samples, including 20 asthenozoospermia patients and 32 healthy controls. An LC-ESI-MS/MS method was used to detect m(6)A contents in sperm RNA, and real-time PCR was performed to determine the mRNA expression of demethylase (FTO, ALKBH5), methyltransferase (METTL3, METTL14, WTAP) and an m(6)A-selective-binding protein (YTHDF2). We found that m(6)A content (p = 0.033) and the mRNA expression of METTL3 (p = 0.016) and METTL14 (p = 0.025) in asthenozoospermia patients were significantly higher than those of controls. Increased m(6)A content was a risk factor for asthenozoospermia (odds ratio (OR) 3.229, 95% confidence interval (CI) 1.178 - 8.853, p = 0.023). Moreover, m(6)A content was correlated with the expression of METTL3 (r = 0.303, p = 0.032) and with sperm motility (progressive motility: r = -0.288, p = 0.038; non-progressive motility: r = -0.293, p = 0.037; immotility: r = 0.387, p = 0.005). Our data suggest that increased m(6)A content is a risk factor for asthenozoospermia and affects sperm motility. Methyltransferases, particularly METTL3, play key roles in increasing m(6)A contents in sperm RNA. FAU - Yang, Ying AU - Yang Y AD - Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Donghu Road 169#, Wuhan, 430071, P.R. China. FAU - Huang, Wei AU - Huang W AD - Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), Department of Chemistry, Wuhan University, Wuhan, 430072, P. R. China. FAU - Huang, Jing-Tao AU - Huang JT AD - Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Donghu Road 169#, Wuhan, 430071, P.R. China. FAU - Shen, Fan AU - Shen F AD - Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Donghu Road 169#, Wuhan, 430071, P.R. China. FAU - Xiong, Jun AU - Xiong J AD - Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), Department of Chemistry, Wuhan University, Wuhan, 430072, P. R. China. FAU - Yuan, Er-Feng AU - Yuan EF AD - Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Donghu Road 169#, Wuhan, 430071, P.R. China. FAU - Qin, Shan-shan AU - Qin SS AD - Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), Department of Chemistry, Wuhan University, Wuhan, 430072, P. R. China. FAU - Zhang, Ming AU - Zhang M AD - Reproductive Medicine Center, Zhongnan Hospital of Wuhan University, Donghu Road 169#, Wuhan, 430071, P.R. China. FAU - Feng, Yu-Qi AU - Feng YQ AD - Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), Department of Chemistry, Wuhan University, Wuhan, 430072, P. R. China. FAU - Yuan, Bi-Feng AU - Yuan BF AD - Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), Department of Chemistry, Wuhan University, Wuhan, 430072, P. R. China.