Aims, patients & methods: Dietary factors may regulate the epigenome. We aimed to explore whether a diet intervention, including excess sugar, affects the methylome in human sperm, and to describe the sperm methylome. We used Whole Genome Bisulfite Sequencing (WGBS) to analyze DNA methylation in sperm taken at three time points from 15 males during a diet intervention; i) at baseline, ii) after one week on a standardized diet, and iii) after an additional week on a high-sugar diet providing 150% of their estimated total energy expenditure.
Results: We identified seven nominal diet-associated differentially methylated regions in sperm (p < 0.05). The diet was nominally associated with methylation of 143 sites linked to fertility (e.g. AHRR, GNAS, and HDAC4), 313 sites in imprinted genes (e.g. GLIS3, PEG10, PEG3, and SNURF), and 42 sites in top 1%-expressed genes (e.g. CHD2) (p < 0.05). In sperm, 3'UTRs and introns had the highest levels of methylation, while 5'UTRs and CpG islands had the lowest levels. Non-expressed genes in human sperm were hypomethylated in exons compared with transcribed genes.
Conclusions: In human sperm, DNA methylation levels were linked to gene expression, and excess sugar had modest effects on methylation on imprinted and highly expressed genes, and genes affecting fertility.
Keywords: DMR; DNA methylation; Human; WGBS; diet intervention; epigenetics; sperm; sugar.
Diet can influence the way genes are regulated in the body. Using a method called Whole Genome Bisulfite Sequencing, we examined changes in DNA methylation, which can affect how genes are turned on or off. Our findings showed that, in human sperm, DNA methylation was linked to how genes are expressed. In this study, we also looked more specifically at whether consuming high amounts of sugar could affect DNA methylation levels in human sperm. We found that one week of excess sugar intake had small effects on DNA methylation, also in genes that are important for fertility and in genes that are usually highly active. More research is needed to confirm these findings.