Title: Association between sperm mitochondarial DNA copy number and nuclear DNA methylation.

Authors: Oluwayiose, Oladele A; Josyula, Srinihaari; Houle, Emily; Marcho, Chelsea; Brian W Whitcomb; Rahil, Tayyab; Sites, Cynthia K; Pilsner, J Richard

Published In Epigenomics, (2020 12)

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.

PubMed ID: 33320694

MeSH Terms: Adult; Biomarkers; Cell Nucleus/genetics; CpG Islands; DNA Copy Number Variations*; DNA Methylation*; DNA, Mitochondrial/genetics*; Genomic Imprinting; Humans; Infertility, Male/genetics*; Male; Spermatozoa*