PD39-01 A DNA METHYLATION SIGNATURE TO PATERNAL GERMLINE AGE AND ASSOCIATION WITH INFERTILITY

Abstract

You have accessJournal of UrologyInfertility: Basic Research & Pathophysiology (PD39)1 Sep 2021PD39-01 A DNA METHYLATION SIGNATURE TO PATERNAL GERMLINE AGE AND ASSOCIATION WITH INFERTILITY Kristin Brogaard, Ryan Miller, Bryce Daines, John Sullivan, Kevin Campbell, and Larry Lipshultz Kristin BrogaardKristin Brogaard More articles by this author , Ryan MillerRyan Miller More articles by this author , Bryce DainesBryce Daines More articles by this author , John SullivanJohn Sullivan More articles by this author , Kevin CampbellKevin Campbell More articles by this author , and Larry LipshultzLarry Lipshultz More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002049.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Epigenetic studies have highlighted the relationship between lifestyle and fertility, including effects of alcohol, smoking, and obesity on DNA methylation profiles within germ cells. We have shown that altered epigenetics have been associated with non-chronological, accelerated sperm aging and reproductive failure. Here we compare the association of chronological and biological sperm age in male patients being treated for reproductive failure. METHODS: DNA methylation from 60 sperm samples was measured using methylation arrays and targeted methylation sequencing. Semen parameters, hormones, medications, health history, fertility treatments and outcomes were provided for each sample. A published machine learning linear regression model capable of predicting biological sperm age with an R2 of 0.89 was then applied to the data. Associations between biological sperm age, chronological age, fertility biomarkers, and comorbidities were examined using supervised and unsupervised learning techniques. RESULTS: Analysis was completed on all samples; however, we chose to sub-stratify samples from patients that were treated with FSH, HCG, anastrozole, or had history of testosterone use. By initially examining oligospermic men considered “truly infertile”, associations were seen between predicted sperm age and semen parameters associated with infertility. The predicted sperm age was observed to be negatively correlated with testosterone levels (R=-0.3) as well as with the % sperm motility (R=-0.31). Higher predicted sperm age was also observed in patients with a high body mass index (BMI) (R=0.5), a factor associated with male infertility. Biological sperm age was more highly correlated with % motility and BMI than chronological age at collection (R=-0.27, R=0.23 respectively). Expanding the sample set to all untreated patients, we still observed a negative correlation between epigenetic sperm age and % motility (R=-0.2), and testosterone (R=-0.2), but the correlations were less pronounced. We also found a statistically significant correlation between hyper-accelerated aging of epigenetic sperm and Cardiovascular risk (p=0.02). CONCLUSIONS: We observed associations between epigenetically-determined sperm age with both semen parameters and BMI. This finding provides further evidence that environmental and epigenetic factors contribute to the health of sperm. If replicated, this use of epigenetic profiling to predict sperm health will become a useful tool in informing discussions with patients regarding the impact of lifestyle and paternal preconception health on fertility success. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e668-e668 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kristin Brogaard More articles by this author Ryan Miller More articles by this author Bryce Daines More articles by this author John Sullivan More articles by this author Kevin Campbell More articles by this author Larry Lipshultz More articles by this author Expand All Advertisement Loading ...