Association between sperm mitochondarial DNA copy number and nuclear DNA methylation.
Oladele A OluwayioseSrinihaari JosyulaEmily HouleChelsea MarchoBrian W WhitcombTayyab RahilCynthia K SitesJ Richard PilsnerPublished in: Epigenomics (2020)
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.
Keyphrases
- genome wide
- dna methylation
- copy number
- mitochondrial dna
- gene expression
- end stage renal disease
- genome wide analysis
- mental health
- single cell
- chronic kidney disease
- newly diagnosed
- single molecule
- skeletal muscle
- circulating tumor
- prognostic factors
- high resolution
- polycystic ovary syndrome
- metabolic syndrome
- quantum dots