title: Idiopathic male infertility is strongly associated with aberrant promoter methylation of methylenetetrahydrofolate reductase (MTHFR).
abstract: BACKGROUND
  Abnormal germline DNA methylation in males has been proposed as a possible mechanism compromising spermatogenesis of some men currently diagnosed with idiopathic infertility. Previous studies have been focused on imprinted genes with DNA methylation in poor quality human sperms. However, recent but limited data have revealed that sperm methylation abnormalities may involve large numbers of genes or shown that genes that are not imprinted are also affected.
  
  
  RESULTS
  Using the methylation-specific polymerase chain reaction and bisulfite sequencing method, we examined methylation patterns of the promoter of methylenetetrahydrofolate reductase (MTHFR) gene (NG_013351: 1538-1719) in sperm DNA obtained from 94 idiopathic infertile men and 54 normal fertile controls. Subjects with idiopathic infertility were further divided into groups of normozoospermia and oligozoospermia. Overall, 45% (41/94) of idiopathic infertile males had MTHFR hypermethylation (both hemimethylation and full methylation), compared with 15% of fertile controls (P<0.05). Subjects with higher methylation level of MTHFR were more likely to have idiopathic male infertility (P-value for trend  = 0.0007). Comparing the two groups of idiopathic infertile subjects with different sperm concentrations, a higher methylation pattern was found in the group with oligozoospermia.
  
  
  CONCLUSIONS
  Hypermethylation of the promoter of MTHFR gene in sperms is associated with idiopathic male infertility. The functional relevance of hypermathylation of MTHFR to male fertility warrants further investigation.
authors.affiliation: Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Ouxi
authors.initials: O
authors.lastname: Shen
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Qin
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Niu
authors.forename: Chuncheng
authors.initials: C
authors.lastname: Lu
authors.forename: Yankai
authors.initials: Y
authors.lastname: Xia
authors.forename: Ling
authors.initials: L
authors.lastname: Song
authors.forename: Shoulin
authors.initials: S
authors.lastname: Wang
authors.forename: Xinru
authors.initials: X
authors.lastname: Wang
mesh_terms: D000328:Adult; D019175:DNA Methylation; D020022:Genetic Predisposition to Disease; D006801:Humans; D007248:Infertility, Male / Q000201:enzymology / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D009845:Oligospermia / Q000235:genetics; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013094:Spermatozoa / Q000378:metabolism
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2)