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

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

Author information

1
Urology Department, Hospital Universitari i Politècnic La Fe & Instituto de Investigación Sanitaria La Fe, Valencia, Spain.
2
Department of Maternal and Child Health, Reproductive and IVF Unit, Asl Bari, Conversano, Italy.
3
Department of Urology, University of Illinois Chicago, Chicago, IL, USA.
4
Ferring Pharmaceuticals, 100 Interpace Parkway, Parsippany, NJ, 07054, USA.
5
Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA, 99164-4236, USA.
6
Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA, 99164-4236, USA. skinner@wsu.edu.

Abstract

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.

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