title: Decreased fecundity and sperm DNA methylation patterns.
abstract: OBJECTIVE
  To evaluate the relationship between epigenetic patterns in sperm and fecundity.
  
  
  METHODS
  Prospective study.
  
  
  METHODS
  Academic andrology and in vitro fertilization laboratory.
  
  
  METHODS
  Twenty-seven semen samples from couples who conceived within 2 months of attempting a pregnancy and 29 semen samples from couples unable to achieve a pregnancy within 12 months.
  
  
  METHODS
  None.
  
  
  METHODS
  Genomewide assessment of differential sperm DNA methylation and standard semen analysis.
  
  
  RESULTS
  We analyzed DNA methylation alterations associated with fecundity in 124 semen samples, and identified regions of interest in 27 semen samples from couples who conceived within 2 months of attempting a pregnancy and a total of 29 semen samples from couples who were unable to achieve a pregnancy within 12 months. No differences in sperm count, sperm morphology, or semen volume were observed between the patients achieving a pregnancy within 2 months of study time and those not obtaining a pregnancy within 12 months. However, using data from the human methylation 450k array analysis we did identify two genomic regions with statistically significantly decreased (false discovery rate <0.01) methylation and three genomic regions with statistically significantly increased methylation in the failure-to-conceive group. The only two sites where decreased methylation was associated with reduced fecundity are at closely related genes known to be expressed in sperm, HSPA1L and HSPA1B.
  
  
  CONCLUSIONS
  Our data suggest that there are genomic loci where DNA methylation alterations are associated with decreased fecundity. We have thus identified candidate loci for future study to verify these results and investigate the causative or contributory relationship between altered sperm methylation and decreased fecundity.
authors.affiliation: Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah.
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Jenkins
authors.affiliation: Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah.
authors.forename: Kenneth I
authors.initials: KI
authors.lastname: Aston
authors.affiliation: Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah.
authors.forename: Tyson D
authors.initials: TD
authors.lastname: Meyer
authors.affiliation: Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah.
authors.forename: James M
authors.initials: JM
authors.lastname: Hotaling
authors.affiliation: Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah.
authors.forename: Monis B
authors.initials: MB
authors.lastname: Shamsi
authors.affiliation: Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, Utah.
authors.forename: Erica B
authors.initials: EB
authors.lastname: Johnstone
authors.affiliation: Department of Family and Preventive Medicine, University of Utah School of Medicine, Salt Lake City, Utah.
authors.forename: Kyley J
authors.initials: KJ
authors.lastname: Cox
authors.affiliation: Department of Family and Preventive Medicine, University of Utah School of Medicine, Salt Lake City, Utah.
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Stanford
authors.affiliation: Department of Family and Preventive Medicine, University of Utah School of Medicine, Salt Lake City, Utah.
authors.forename: Christina A
authors.initials: CA
authors.lastname: Porucznik
authors.affiliation: Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah; Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, Utah; Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah. Electronic address: douglas.carrell@hsc.utah.edu.
authors.forename: Douglas T
authors.initials: DT
authors.lastname: Carrell
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005298:Fertility / Q000235:genetics*; D055106:Genome-Wide Association Study; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D007248:Infertility, Male / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D008297:Male; D011247:Pregnancy; D055101:Semen Analysis; D013094:Spermatozoa / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D061685:Time-to-Pregnancy
chemical_list: D018840:HSP70 Heat-Shock Proteins; C525621:HSPA1B protein, human; C543454:HSPA1L protein, human
keywords: DNA methylation; HSP; epigenetics; male infertility; sperm