• PMID: 26453269
• Gene Name: HSPA1B
• Condition: Male infertility
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Associated genes: Methylation array

Decreased fecundity and sperm DNA methylation patterns

Jenkins TG, Aston KI, Meyer TD, Hotaling JM, Shamsi MB, Johnstone EB, Cox KJ, Stanford JB, Porucznik CA, Carrell DT.

OBJECTIVE: To evaluate the relationship between epigenetic patterns in sperm and fecundity. DESIGN: Prospective study. SETTING: Academic andrology and in vitro fertilization laboratory. PATIENT(S): 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. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Genomewide assessment of differential sperm DNA methylation and standard semen analysis. RESULT(S): 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. CONCLUSION(S): 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. CI - Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved. FAU - Jenkins, Timothy G AU - Jenkins TG AD - Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah. FAU - Aston, Kenneth I AU - Aston KI AD - Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah. FAU - Meyer, Tyson D AU - Meyer TD AD - Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah. FAU - Hotaling, James M AU - Hotaling JM AD - Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah. FAU - Shamsi, Monis B AU - Shamsi MB AD - Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah. FAU - Johnstone, Erica B AU - Johnstone EB AD - Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, Utah. FAU - Cox, Kyley J AU - Cox KJ AD - Department of Family and Preventive Medicine, University of Utah School of Medicine, Salt Lake City, Utah. FAU - Stanford, Joseph B AU - Stanford JB AD - Department of Family and Preventive Medicine, University of Utah School of Medicine, Salt Lake City, Utah. FAU - Porucznik, Christina A AU - Porucznik CA AD - Department of Family and Preventive Medicine, University of Utah School of Medicine, Salt Lake City, Utah.