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 quantitativePCR 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:Apriori 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 differentiallymethylated 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.
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