title: Methylation changes in mature sperm deoxyribonucleic acid from oligozoospermic men: assessment of genetic variants and assisted reproductive technology outcome.
abstract: OBJECTIVE
  To characterize a potential genetic cause for methylation errors described in oligozoospermia.
  
  
  METHODS
  Analysis of PEG1/MEST-DMR and H19-DMR methylation level in sperm, in parallel with the study of several genes on the Y chromosome, DNMT3A, and DNMT3L. Clinical outcome was also looked at regarding PEG1/MEST-DMR and H19-DMR methylation level in sperm.
  
  
  METHODS
  Research and diagnostic laboratories.
  
  
  METHODS
  One hundred nineteen normospermic and 175 oligozoospermic men consulting for couple infertility.
  
  
  METHODS
  We studied PEG1/MEST-DMR and H19-DMR methylation profiles in 294 men. We searched for Y chromosome gene aberrations and for mutations in both DNMT3A and DNMT3L genes in men showing epimutations. Assisted reproductive technology (ART) outcomes were also investigated.
  
  
  METHODS
  Sperm samples were collected from 294 volunteers for genomic DNA isolation that was used to study methylation profiles in imprinted loci and Y chromosome SMCY, DNMT3A, and DNMT3L genes. Pregnancy rate was also studied after ART treatment using sperm showing epimutations.
  
  
  RESULTS
  Epimutations in H19-DMR and PEG1/MEST-DMR were found in 20% and 3% of oligozoospermic men, respectively. We identified an amino acid change in DNMT3A in one case and in DNMT3L in eight men with altered methylation profiles. No mutations were detected in SMCY or in selected Y chromsome genes. No correlation between ART outcome and epimutations was found.
  
  
  CONCLUSIONS
  We observed epimethylations in spermatozoa of oligozoospermic individuals, but no association was found with genetic variants or in the ART outcome.
authors.affiliation: Institut Pasteur, Unité de Génétique du Développement Humain, Paris, France; Laboratoire d'Eylau, Unilabs, Paris, France. Electronic address: debbie_montjean@hotmail.com.
authors.forename: Debbie
authors.initials: D
authors.lastname: Montjean
authors.forename: Célia
authors.initials: C
authors.lastname: Ravel
authors.forename: Moncef
authors.initials: M
authors.lastname: Benkhalifa
authors.forename: Paul
authors.initials: P
authors.lastname: Cohen-Bacrie
authors.forename: Isabelle
authors.initials: I
authors.lastname: Berthaut
authors.forename: Anu
authors.initials: A
authors.lastname: Bashamboo
authors.forename: Kenneth
authors.initials: K
authors.lastname: McElreavey
mesh_terms: D016022:Case-Control Studies; D016009:Chi-Square Distribution; D041322:Chromosomes, Human, Y; D004247:DNA / Q000378:metabolism*; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D005260:Female; D005298:Fertility; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D016017:Odds Ratio; D009845:Oligospermia / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D010641:Phenotype; D011247:Pregnancy; D018873:Pregnancy Rate; D011506:Proteins / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics; D027724:Reproductive Techniques, Assisted; D012307:Risk Factors; D013094:Spermatozoa / Q000378:metabolism* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: C000717967:DNMT3A protein, human; C094335:H19 long non-coding RNA; D011506:Proteins; D062085:RNA, Long Noncoding; C103637:mesoderm specific transcript protein; D004247:DNA; C412484:DNMT3L protein, human; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A
keywords: DNMTs; Sperm DNA methylation; Y chromosome; genetic variants; oligozoospermia