Sperm DNA methylation mediates the association of male age on reproductive outcomes among couples undergoing infertility treatment
Abstract Parental age at time of offspring conception is increasing in developed countries. Advanced male age is associated with decreased reproductive success and increased risk of adverse neurodevelopmental outcomes in offspring. Mechanisms for these male age effects remain unclear, but changes in...
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doaj-50b7bf75636b4391815a202020e339922021-02-07T12:38:13ZengNature Publishing GroupScientific Reports2045-23222021-02-0111111410.1038/s41598-020-80857-2Sperm DNA methylation mediates the association of male age on reproductive outcomes among couples undergoing infertility treatmentOladele A. Oluwayiose0Haotian Wu1Hachem Saddiki2Brian W. Whitcomb3Laura B. Balzer4Nicole Brandon5Alexander Suvorov6Rahil Tayyab7Cynthia K. Sites8Lisa Hill9Chelsea Marcho10J. Richard Pilsner11Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts AmherstDepartment of Environmental Health Sciences, Columbia University Mailman School of Public HealthDepartment of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts AmherstDepartment of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts AmherstDepartment of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts AmherstDepartment of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts AmherstDepartment of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts AmherstDivision of Reproductive Endocrinology and Infertility, Baystate Medical CenterDivision of Reproductive Endocrinology and Infertility, Baystate Medical CenterDivision of Reproductive Endocrinology and Infertility, Baystate Medical CenterDepartment of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts AmherstDepartment of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts AmherstAbstract Parental age at time of offspring conception is increasing in developed countries. Advanced male age is associated with decreased reproductive success and increased risk of adverse neurodevelopmental outcomes in offspring. Mechanisms for these male age effects remain unclear, but changes in sperm DNA methylation over time is one potential explanation. We assessed genome-wide methylation of sperm DNA from 47 semen samples collected from male participants of couples seeking infertility treatment. We report that higher male age was associated with lower likelihood of fertilization and live birth, and poor embryo development (p < 0.05). Furthermore, our multivariable linear models showed male age was associated with alterations in sperm methylation at 1698 CpGs and 1146 regions (q < 0.05), which were associated with > 750 genes enriched in embryonic development, behavior and neurodevelopment among others. High dimensional mediation analyses identified four genes (DEFB126, TPI1P3, PLCH2 and DLGAP2) with age-related sperm differential methylation that accounted for 64% (95% CI 0.42–0.86%; p < 0.05) of the effect of male age on lower fertilization rate. Our findings from this modest IVF population provide evidence for sperm methylation as a mechanism of age-induced poor reproductive outcomes and identifies possible candidate genes for mediating these effects.https://doi.org/10.1038/s41598-020-80857-2 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Oladele A. Oluwayiose Haotian Wu Hachem Saddiki Brian W. Whitcomb Laura B. Balzer Nicole Brandon Alexander Suvorov Rahil Tayyab Cynthia K. Sites Lisa Hill Chelsea Marcho J. Richard Pilsner |
spellingShingle |
Oladele A. Oluwayiose Haotian Wu Hachem Saddiki Brian W. Whitcomb Laura B. Balzer Nicole Brandon Alexander Suvorov Rahil Tayyab Cynthia K. Sites Lisa Hill Chelsea Marcho J. Richard Pilsner Sperm DNA methylation mediates the association of male age on reproductive outcomes among couples undergoing infertility treatment Scientific Reports |
author_facet |
Oladele A. Oluwayiose Haotian Wu Hachem Saddiki Brian W. Whitcomb Laura B. Balzer Nicole Brandon Alexander Suvorov Rahil Tayyab Cynthia K. Sites Lisa Hill Chelsea Marcho J. Richard Pilsner |
author_sort |
Oladele A. Oluwayiose |
title |
Sperm DNA methylation mediates the association of male age on reproductive outcomes among couples undergoing infertility treatment |
title_short |
Sperm DNA methylation mediates the association of male age on reproductive outcomes among couples undergoing infertility treatment |
title_full |
Sperm DNA methylation mediates the association of male age on reproductive outcomes among couples undergoing infertility treatment |
title_fullStr |
Sperm DNA methylation mediates the association of male age on reproductive outcomes among couples undergoing infertility treatment |
title_full_unstemmed |
Sperm DNA methylation mediates the association of male age on reproductive outcomes among couples undergoing infertility treatment |
title_sort |
sperm dna methylation mediates the association of male age on reproductive outcomes among couples undergoing infertility treatment |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-02-01 |
description |
Abstract Parental age at time of offspring conception is increasing in developed countries. Advanced male age is associated with decreased reproductive success and increased risk of adverse neurodevelopmental outcomes in offspring. Mechanisms for these male age effects remain unclear, but changes in sperm DNA methylation over time is one potential explanation. We assessed genome-wide methylation of sperm DNA from 47 semen samples collected from male participants of couples seeking infertility treatment. We report that higher male age was associated with lower likelihood of fertilization and live birth, and poor embryo development (p < 0.05). Furthermore, our multivariable linear models showed male age was associated with alterations in sperm methylation at 1698 CpGs and 1146 regions (q < 0.05), which were associated with > 750 genes enriched in embryonic development, behavior and neurodevelopment among others. High dimensional mediation analyses identified four genes (DEFB126, TPI1P3, PLCH2 and DLGAP2) with age-related sperm differential methylation that accounted for 64% (95% CI 0.42–0.86%; p < 0.05) of the effect of male age on lower fertilization rate. Our findings from this modest IVF population provide evidence for sperm methylation as a mechanism of age-induced poor reproductive outcomes and identifies possible candidate genes for mediating these effects. |
url |
https://doi.org/10.1038/s41598-020-80857-2 |
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