Abstract
Epidemiological research suggests that paternal obesity may increase the risk of fathering small for gestational age offspring. Studies in non-human mammals indicate that such associations could be mediated by DNA methylation changes in spermatozoa that influence offspring development in utero. Human obesity is associated with differential DNA methylation in peripheral blood. It is unclear, however, whether this differential DNA methylation is reflected in spermatozoa. We profiled genome-wide DNA methylation using the Illumina MethylationEPIC array in a cross-sectional study of matched human blood and sperm from lean (discovery n = 47; replication n = 21) and obese (n = 22) males to analyse tissue covariation of DNA methylation, and identify obesity-associated methylomic signatures. We found that DNA methylation signatures of human blood and spermatozoa are highly discordant, and methylation levels are correlated at only a minority of CpG sites (~1%). At the majority of these sites, DNA methylation appears to be influenced by genetic variation. Obesity-associated DNA methylation in blood was not generally reflected in spermatozoa, and obesity was not associated with altered covariation patterns or accelerated epigenetic ageing in the two tissues. However, one cross-tissue obesity-specific hypermethylated site (cg19357369; chr4:2429884; P = 8.95 × 10−8; 2% DNA methylation difference) was identified, warranting replication and further investigation. When compared to a wide range of human somatic tissue samples (n = 5,917), spermatozoa displayed differential DNA methylation across pathways enriched in transcriptional regulation. Overall, human sperm displays a unique DNA methylation profile that is highly discordant to, and practically uncorrelated with, that of matched peripheral blood. We observed that obesity was only nominally associated with differential DNA methylation in sperm, and therefore suggest that spermatozoal DNA methylation is an unlikely mediator of intergenerational effects of metabolic traits.
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
