Impact of excess sugar on the whole genome DNA methylation pattern in human sperm

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. We identified seven nominal diet-associated differentially methylated regions in sperm (<i>p</i> &lt; 0.05). The diet was nominally associated with methylation of 143 sites linked to fertility (e.g. <i>AHRR</i>, <i>GNAS</i>, and <i>HDAC4</i>), 313 sites in imprinted genes (e.g. <i>GLIS3</i>, <i>PEG10</i>, <i>PEG3</i>, and <i>SNURF</i>), and 42 sites in top 1%-expressed genes (e.g. <i>CHD2</i>) (<i>p</i> &lt; 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. 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. 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.

饮食因素可能调控表观基因组（epigenome）。本研究旨在探究包含过量糖分的饮食干预是否会影响人类精子的甲基化组，并对精子甲基化组进行描述。我们采用全基因组亚硫酸氢盐测序（Whole Genome Bisulfite Sequencing, WGBS）分析了15名男性在饮食干预期间三个时间点采集的精子DNA甲基化情况：i）基线期；ii）标准化饮食一周后；iii）在标准化饮食基础上额外摄入一周高糖饮食后（该高糖饮食提供其预估总能量消耗的150%）。我们在精子中鉴定出7个与饮食相关的名义差异甲基化区域（differentially methylated regions, DMR），其p值小于0.05。该饮食与143个生育相关位点（如AHRR、GNAS和HDAC4）、313个印记基因位点（如GLIS3、PEG10、PEG3和SNURF）以及42个表达量前1%的基因位点（如CHD2）的甲基化存在名义关联（p<0.05）。在精子中，3'非翻译区（3'UTR）和内含子的甲基化水平最高，而5'非翻译区（5'UTR）和CpG岛的甲基化水平最低。与转录基因相比，人类精子中未表达基因的外显子呈低甲基化状态。在人类精子中，DNA甲基化水平与基因表达相关，过量糖分对印记基因、高表达基因及影响生育的基因的甲基化具有轻微作用。饮食可影响体内基因的调控方式。我们通过全基因组亚硫酸氢盐测序（WGBS）检测了DNA甲基化的变化——这一变化会影响基因的开关状态。研究结果表明，人类精子中的DNA甲基化与基因表达相关。本研究还更具体地探究了高糖摄入是否会影响人类精子的DNA甲基化水平，发现一周过量糖分摄入对DNA甲基化存在微小影响，这种影响同样存在于生育相关基因及通常高活性的基因中。需进一步研究以验证这些发现。