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

Description: 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 infertility using genome wide alterations in sperm DNA methylation. A signature of differential DNA methylation regions (DMRs) was identified to be associated with male 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.Overall design: Twenty-two patients were enrolled which included nine patients in the fertile control group and thirteen in the infertility treatment group. Initial semen analysis and basal hormone determination to assess eligibility criteria were performed. Sperm samples were processed and stored for the subsequent epigenetic analysis. The infertility group received 150 IU of urinary or recombinant FSH three times per week for 12 weeks and the fertile control group did not received treatment. After three months of treatment, semen analysis and hormone profiles were retested in both groups. MeDIP-seq was performed on the pre treatment samples. An additional eighteen patients were enrolled and contributed samples that were not used for the DMR analysis. Samples from these patients were processed in an identical manner as the samples in the treatment groups and were used as a validation dataset.

Data type: Epigenomics

Sample scope: Multiisolate

Relevance: Medical

Last updated: 2019-08-14