title: Increased N6-methyladenosine in Human Sperm RNA as a Risk Factor for Asthenozoospermia.
abstract: 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.
authors.affiliation: Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Donghu Road 169#, Wuhan, 430071, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), Department of Chemistry, Wuhan University, Wuhan, 430072, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Donghu Road 169#, Wuhan, 430071, P.R. China.
authors.forename: Jing-Tao
authors.initials: JT
authors.lastname: Huang
authors.affiliation: Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Donghu Road 169#, Wuhan, 430071, P.R. China.
authors.forename: Fan
authors.initials: F
authors.lastname: Shen
authors.affiliation: Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), Department of Chemistry, Wuhan University, Wuhan, 430072, P. R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xiong
authors.affiliation: Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Donghu Road 169#, Wuhan, 430071, P.R. China.
authors.forename: Er-Feng
authors.initials: EF
authors.lastname: Yuan
authors.affiliation: Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), Department of Chemistry, Wuhan University, Wuhan, 430072, P. R. China.
authors.forename: Shan-shan
authors.initials: SS
authors.lastname: Qin
authors.affiliation: Reproductive Medicine Center, Zhongnan Hospital of Wuhan University, Donghu Road 169#, Wuhan, 430071, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), Department of Chemistry, Wuhan University, Wuhan, 430072, P. R. China.
authors.forename: Yu-Qi
authors.initials: YQ
authors.lastname: Feng
authors.affiliation: Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), Department of Chemistry, Wuhan University, Wuhan, 430072, P. R. China.
authors.forename: Bi-Feng
authors.initials: BF
authors.lastname: Yuan
authors.affiliation: Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Donghu Road 169#, Wuhan, 430071, P.R. China.
authors.forename: Song-Mei
authors.initials: SM
authors.lastname: Liu
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D053627:Asthenozoospermia / Q000378:metabolism*; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D006801:Humans; D008297:Male; D012313:RNA / Q000737:chemistry*; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D021241:Spectrometry, Mass, Electrospray Ionization; D013094:Spermatozoa / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: D012313:RNA; D000241:Adenosine