Association between sperm mitochondarial DNA copy number and nuclear DNA methylation

Author Department

Ob/Gyn

Document Type

Article, Peer-reviewed

Publication Date

12-2020

Abstract

Aim: Accumulating evidence associates sperm mitochondria DNA copy number (mtDNAcn) with male infertility and reproductive success. However, the mechanism underlying mtDNAcn variation is largely unknown. Patients & methods: Sperm mtDNAcn and genome-wide DNA methylation were assessed using triplex probe-based quantitative PCR and Illumina's 450K array, respectively. Multivariable models assessed the association between sperm mtDNAcn and DNA methylation profiles of 47 men seeking infertility treatment. Results: A priori candidate-gene approach showed sperm mtDNAcn was associated with 16 CpGs located at/near POLG and TWNK genes. Unbiased genome-wide analysis revealed that sperm mtDNAcn was associated with 218 sperm differentially methylated regions (q <0.05), which displayed predominantly (94%) increases in methylation. Conclusion: Findings suggest that DNA methylation may play a role in regulating sperm mtDNAcn.

Keywords: DNA methylation; IVF; copy number; epigenetics; infertility; mitochondria; sperm.

PMID

33320694

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