Aging-Induced Changes in Sperm DNA Methylation are Modified by Low Dose of Perinatal Flame Retardants

Abstract

Aims: Paternal age is increasing in developed countries. Understanding of aging-related epigenetic changes in sperm is needed as well as factors that modify such changes. Materials & methods: Young pubertal and mature rats were exposed perinatally to vehicle or environmental xenobiotic 2,2′,4,4′-tetrabromodiphenyl ether. Epididymal sperm was reduced representation bisulfite sequenced. Differentially methylated regions (DMRs) were identified via MethPipe. Results: In control animals, 5319 age-dependent DMRs were identified. Age-related DMRs were enriched for embryonic development. In exposed rats, DNA methylation was higher in young and lower in mature animals then in controls. Conclusions: Sperm methylome undergoes significant age-dependent changes, which may represent a causal link between paternal age and offspring phenotype. Environmental xenobiotics can interfere with the natural process of epigenetic aging.

Keywords::

• 2,2′,4,4′-tetrabromodiphenyl ether
• advanced paternal age
• aging
• DNA methylation
• environment
• epigenetics
• PBDE
• perinatal
• RRBS
• sperm

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2020-0404

Acknowledgments

The authors gratefully acknowledge the contributions of E Dunaeva, A Esman and K Mironov as research personnel in the production of this work.

Financial & competing interests disclosure

This study was funded by the Russian Science Foundation (#14-45-00065: animal experiment, DNA methylation data and #18-15-00202: validation of RRBS and synergy with sncRNA data). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

All animal protocols were conducted in accordance with the Guide for the Care and Use of Laboratory Animals and approved by the Institutional Animal Care and Use Committee at University of Massachusetts, Amherst.

Data availability

Original data used in this manuscript are available upon request.

Additional information

Funding

This study was funded by the Russian Science Foundation (#14-45-00065: animal experiment, DNA methylation data and #18-15-00202: validation of RRBS and synergy with sncRNA data). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.