title: Genome-wide sperm deoxyribonucleic acid methylation is altered in some men with abnormal chromatin packaging or poor in vitro fertilization embryogenesis.
abstract: OBJECTIVE
  To evaluate genome-wide DNA methylation patterns in sperm from men with abnormal sperm chromatin packaging and patients displaying abnormal embryogenesis after IVF in the absence of known female factors.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  University andrology and research laboratory.
  
  
  METHODS
  Men with abnormally high and low protamine 1/protamine 2 ratio (n = 15); patients who have undergone IVF/intracytoplasmic sperm injection resulting in abnormal embryogenesis (n = 13); and normozoospermic, fertile controls (n = 15).
  
  
  METHODS
  Genome-wide sperm DNA methylation was measured using the Illumina Infinium HumanMethylation27 BeadChip assay. Follow-up targeted methylation analysis was performed using bisulfite pyrosequencing.
  
  
  METHODS
  Methylation levels at more than 27,000 CpGs genome-wide were compared between groups.
  
  
  RESULTS
  Of the 43 men analyzed, 40 displayed highly concordant methylation patterns; however, two men with abnormal protamine 1/protamine 2 and one abnormal embryogenesis patient displayed significantly altered methylation patterns across a large number of CpGs. Imprinted regions were more prone to deregulation than the genome at large.
  
  
  CONCLUSIONS
  We have identified three individuals displaying broad disruption of sperm DNA methylation profiles. Although the sample set analyzed is relatively small, these results indicate that broad disruptions in sperm DNA methylation may be an important signature in some infertile men. Functional studies will be necessary to characterize the developmental consequences of such epigenetic disruption.
authors.affiliation: Andrology and IVF Laboratories, Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah 84108, USA.
authors.forename: Kenneth I
authors.initials: KI
authors.lastname: Aston
authors.forename: Vasu
authors.initials: V
authors.lastname: Punj
authors.forename: Lihua
authors.initials: L
authors.lastname: Liu
authors.forename: Douglas T
authors.initials: DT
authors.lastname: Carrell
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D048430:Cell Shape; D002470:Cell Survival; D042002:Chromatin Assembly and Disassembly; D016000:Cluster Analysis; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D005307:Fertilization in Vitro / Q000009:adverse effects*; D055106:Genome-Wide Association Study; D006801:Humans; D007248:Infertility, Male / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D008297:Male; D011247:Pregnancy; D025341:Principal Component Analysis; D011479:Protamines / Q000378:metabolism; D013076:Sperm Count; D020554:Sperm Injections, Intracytoplasmic / Q000009:adverse effects; D013081:Sperm Motility; D013094:Spermatozoa / Q000378:metabolism* / Q000473:pathology; D017211:Treatment Failure
chemical_list: D011479:Protamines