Sperm DNA Methylation Epimutation Biomarkers for Male Infertility and FSH Therapeutic Responsiveness

Sci Rep. 2019 Nov 14;9(1):16786. doi: 10.1038/s41598-019-52903-1.


Male factor infertility is increasing and recognized as playing a key role in reproductive health and disease. The current primary diagnostic approach is to assess sperm quality associated with reduced sperm number and motility, which has been historically of limited success in separating fertile from infertile males. The current study was designed to develop a molecular analysis to identify male idiopathic infertility using genome wide alterations in sperm DNA methylation. A signature of differential DNA methylation regions (DMRs) was identified to be associated with male idiopathic infertility patients. A promising therapeutic treatment of male infertility is the use of follicle stimulating hormone (FSH) analogs which improved sperm numbers and motility in a sub-population of infertility patients. The current study also identified genome-wide DMRs that were associated with the patients that were responsive to FSH therapy versus those that were non-responsive. This novel use of epigenetic biomarkers to identify responsive versus non-responsive patient populations is anticipated to dramatically improve clinical trials and facilitate therapeutic treatment of male infertility patients. The use of epigenetic biomarkers for disease and therapeutic responsiveness is anticipated to be applicable for other medical conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • DNA Methylation* / drug effects
  • Epigenesis, Genetic / drug effects
  • Follicle Stimulating Hormone / administration & dosage*
  • Follicle Stimulating Hormone / analogs & derivatives
  • Follicle Stimulating Hormone / pharmacology
  • Genetic Markers / drug effects
  • Humans
  • Infertility, Male / drug therapy*
  • Infertility, Male / genetics
  • Male
  • Sperm Motility / drug effects
  • Spermatozoa / chemistry*
  • Spermatozoa / drug effects
  • Treatment Outcome
  • Whole Genome Sequencing


  • Genetic Markers
  • Follicle Stimulating Hormone