Paternal preconception phthalate exposure alters sperm methylome and embryonic programming.
Oladele A Oluwayiose1, Chelsea Marcho2, Haotian Wu3
1Department of Environmental Health Sciences, University of Massachusetts Amherst, Amherst, MA, USA.
Environment International
|June 13, 2021
Summary
Male exposure to di(2-ethylhexyl) phthalate (DEHP) alters sperm epigenetics, impacting offspring development. This study reveals DEHP-induced changes in DNA methylation and gene expression in both fathers and developing embryos.
Area of Science:
- Environmental epigenetics
- Reproductive toxicology
- Developmental biology
Background:
- Preconception environmental exposures can influence offspring health via epigenetic modifications in sperm.
- Previous human studies linked anti-androgenic phthalates to altered sperm methylation and embryo development.
Purpose of the Study:
- To investigate the effects of preconception di(2-ethylhexyl) phthalate (DEHP) exposure on genome-wide DNA methylation and gene expression in mice.
- To determine if paternal DEHP exposure impacts the epigenetics and gene expression of developing embryos.
Main Methods:
- Adult male mice were exposed to DEHP or vehicle control for 67 days before mating.
- Reduced representation bisulfite sequencing (RRBS) was used to analyze DNA methylation in sperm and gastrulation-stage embryos (embryonic and extra-embryonic tissues).
- Transcriptome analysis was performed on E7.5 embryos.
Main Results:
- DEHP exposure induced significant changes in DNA methylation in sperm (704 differentially methylated regions), embryonic (1,716 DMRs), and extra-embryonic tissues (3,181 DMRs).
- Twenty-nine DMRs overlapped between sperm and F1 embryo tissues, with half showing concordant methylation changes.
- F1 embryo transcriptomes showed alterations in key developmental gene families (Hox, Gata, Sox), and gene ontology analysis revealed enrichment in developmental processes.
Conclusions:
- Paternal preconception exposure to DEHP alters the sperm methylome.
- DEHP-induced epigenetic changes in sperm are associated with altered DNA methylation and gene expression in developing embryos.
- Spermatogenesis represents a sensitive window for environmental exposures like DEHP to impact offspring epigenetics and development.
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