Dataset Information

Customized MethylC-Capture Sequencing to Evaluate Variation in the Human Sperm DNA Methylome Representative of Altered Folate Metabolism.

ABSTRACT:

Background

The sperm DNA methylation landscape is unique and critical for offspring health. If gamete-derived DNA methylation escapes reprograming in early embryos, epigenetic defects in sperm may be transmitted to the next generation. Current techniques to assess sperm DNA methylation show bias toward CpG-dense regions and do not target areas of dynamic methylation, those predicted to be environmentally sensitive and tunable regulatory elements.

Objectives

Our goal was to assess variation in human sperm DNA methylation and design a targeted capture panel to interrogate the human sperm methylome.

Methods

To characterize variation in sperm DNA methylation, we performed whole genome bisulfite sequencing (WGBS) on an equimolar pool of sperm DNA from a wide cross section of 30 men varying in age, fertility status, methylenetetrahydrofolate reductase (MTHFR) genotype, and exposures. With our targeted capture panel, in individual samples, we examined the effect of MTHFR genotype ([Formula: see text] 677CC, [Formula: see text] 677TT), as well as high-dose folic acid supplementation ([Formula: see text], per genotype, before and after supplementation).

Results

Through WGBS we discovered nearly 1 million CpGs possessing intermediate methylation levels (20-80%), termed dynamic sperm CpGs. These dynamic CpGs, along with 2 million commonly assessed CpGs, were used to customize a capture panel for targeted interrogation of the human sperm methylome and test its ability to detect effects of altered folate metabolism. As compared with MTHFR 677CC men, those with the 677TT genotype (50% decreased MTHFR activity) had both hyper- and hypomethylation in their sperm. High-dose folic acid supplement treatment exacerbated hypomethylation in MTHFR 677TT men compared with 677CC. In both cases, [Formula: see text] of altered methylation was found in dynamic sperm CpGs, uniquely measured by our assay.

Discussion

Our sperm panel allowed the discovery of differential methylation following conditions affecting folate metabolism in novel dynamic sperm CpGs. Improved ability to examine variation in sperm DNA methylation can facilitate comprehensive studies of environment-epigenome interactions. https://doi.org/10.1289/EHP4812.

SUBMITTER: Chan D

PROVIDER: S-EPMC6792365 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Publications

Customized MethylC-Capture Sequencing to Evaluate Variation in the Human Sperm DNA Methylome Representative of Altered Folate Metabolism.

Chan Donovan D Shao Xiaojian X Dumargne Marie-Charlotte MC Aarabi Mahmoud M Simon Marie-Michelle MM Kwan Tony T Bailey Janice L JL Robaire Bernard B Kimmins Sarah S San Gabriel Maria C MC Zini Armand A Librach Clifford C Moskovtsev Sergey S Grundberg Elin E Bourque Guillaume G Pastinen Tomi T Trasler Jacquetta M JM

Environmental health perspectives 20190808 8

<h4>Background</h4>The sperm DNA methylation landscape is unique and critical for offspring health. If gamete-derived DNA methylation escapes reprograming in early embryos, epigenetic defects in sperm may be transmitted to the next generation. Current techniques to assess sperm DNA methylation show bias toward CpG-dense regions and do not target areas of dynamic methylation, those predicted to be environmentally sensitive and tunable regulatory elements.<h4>Objectives</h4>Our goal was to assess ...[more]

PMID: 31393794

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Dataset Information

Customized MethylC-Capture Sequencing to Evaluate Variation in the Human Sperm DNA Methylome Representative of Altered Folate Metabolism.

Background

Objectives

Methods

Results

Discussion

Publications

Customized MethylC-Capture Sequencing to Evaluate Variation in the Human Sperm DNA Methylome Representative of Altered Folate Metabolism.

Similar Datasets

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