Comparative Analysis of Sperm DNA Methylation Supports Evolutionary Acquired Epigenetic Plasticity for Organ Speciation

Abstract

Aim: To perform a comparative epigenomic analysis of DNA methylation in spermatozoa from humans, mice, rats and mini-pigs. Materials & methods: Genome-wide DNA methylation analysis was used to compare the methylation profiles of orthologous CpG sites. Transcription profiles of early embryo development were analyzed to provide insight into the association between sperm methylation and gene expression programming. Results: We identified DNA methylation variation near genes related to the central nervous system and signal transduction. Gene expression dynamics at different time points of preimplantation stages were modestly associated with spermatozoal DNA methylation at the nearest promoters. Conclusion: Conserved genomic regions subject to epigenetic variation across different species were associated with specific organ functions, suggesting their potential contribution to organ speciation and long-term adaptation to the environment.

Keywords::

• comparative epigenomics
• DNA methylation
• embryo development
• epigenetics
• evolution
• spermatozoa

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-2022-0168

Author contributions

R Barrès conceived and designed the study. F Moharrek performed all the bioinformatics and statistical analyses with contributions from C Workman, L Ingerslev, A Altıntaş and L Lundell. A Hansen and L Small contributed to the material preparation. F Moharrek and R Barrès wrote the manuscript. All authors have reviewed and approved the final version of the manuscript.

Acknowledgments

The authors acknowledge the Single-Cell Omics platform at the Centre for Basic Metabolic Research (CBMR) for the technical expertise and support, and also thank X Wang for his constructive feedback on statistical matters.

Financial & competing interests disclosure

This research was funded by a Challenge Programme Grant from the Novo Nordisk Foundation under grant agreement NNF18OC0033754. The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent research center at the University of Copenhagen, partially funded by an unrestricted donation from the Novo Nordisk Foundation (NNF18CC0034900). 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

For human WGBS data, samples were obtained from men attending the University of Utah Andrology laboratory consented for research (IRB approved protocol # 7790). For mouse WGBS data, the study was done under an approved Institutional Animal Care and Use Committee protocol at University of Utah School of Medicine, USA. For rat WGBS data, part of the study was approved by the Zoos scientific review committee and also by the Institutional Animal Care and Use Committee at University of Southern California, USA. For human RRBS data, the study was approved by the Ethics Committee from the Capital Region of Denmark (reference H-1-2013-064) and informed consent was obtained from all participants. For mouse RRBS data, all procedures followed the guidelines of the National Institutes of Health Guide for the Care and Use of Laboratory Animals and the approval for the study was received from the Institutional Animal Care and Use Committee at University of Massachusetts, Amherst, USA. For rat RRBS data, the study was performed following the National Institutes of Health guidelines for the care and use of laboratory animals and approved by the Institutional Animal Care and Use Committee at The Lundquist Institute for Biomedical Innovation at Harbor–UCLA Medical Center, CA, USA. For mini-pig data, all animal procedures were performed following the National Institutes of Health guidelines for the care and use of laboratory animals at Bionea Lab and approved by the French Ministry of Education and Research (reference APAFIS#22853-201911212455784v1).

Additional information

Funding

This research was funded by a Challenge Programme Grant from the Novo Nordisk Foundation under grant agreement NNF18OC0033754. The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent research center at the University of Copenhagen, partially funded by an unrestricted donation from the Novo Nordisk Foundation (NNF18CC0034900). 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.