Genome-Wide Methylation Analyses of Human Sperm Unravel Novel Differentially Methylated Regions in Asthenozoospermia

Abstract

Aims & objectives: To investigate DNA methylation patterns in asthenozoospermic and normozoospermic sperm and to explore the potential roles of differential methylations in the etiology of the disease. Materials & methods: The authors performed whole-genome bisulfite sequencing analysis between normozoospermic controls and asthenozoospermic individuals. Results: The authors identified 238 significant differentially methylated regions. These differentially methylated regions were annotated to 114 protein-coding genes, with many genes showing associations with spermatogenesis, sperm motility etc. Conclusion: There are plenty of genomic regions exhibiting altered DNA methylation in asthenozoospermia, a number of which are located within or adjacent to sperm-related genes, suggesting novel methylation markers of asthenozoospermia and potential epigenetic regulation mechanisms through DNA methylation in the disease.

Keywords::

• asthenozoospermia
• DNA methylation
• epigenetics
• male infertility
• sperm
• WGBS

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-2022-0122

Author contributions

C Fan, F Li and B Shen conceived and supervised the study. J Li performed DNA extraction, library construction and bisulfite sequencing. J Xu, T Yang and F Li performed sperm collection and semen analysis. J Li, J Chen and C Fan performed data and statistical analyses. J Li and C Fan wrote the manuscript. All authors contributed to and approved the final version of the manuscript.

Acknowledgments

The authors thank the participants of the study who made this work possible, the medical staff of West China Second University Hospital of Sichuan University and the members of Institutes for Systems Genetics at West China Hospital, Sichuan University.

Financial & competing interests disclosure

This work was supported and funded by the International Cooperation Initiative grant (no. 139190042) from West China Hospital, Sichuan University, Chengdu, China. 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 used in the creation of this manuscript.

Ethical conduct of research

The authors state that this work has been approved by all respective institutional research and ethics boards (WHO International Clinical Trials Registry ChiCTR2200056153). 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.

Additional information

Funding

This work was supported and funded by the International Cooperation Initiative grant (no. 139190042) from West China Hospital, Sichuan University, Chengdu, China. 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 used in the creation of this manuscript.