Epidemiology Research Center, Department of Public Health and Primary Care, Faculty of Medicine, KU Leuven-University, Leuven, Belgium.
Department of Obstetrics and Gynecology, Division of Reproductive Sciences, Duke University Medical Center, Durham, NC, United States.
Front Endocrinol (Lausanne). 2021 Apr 23;12:625204. doi: 10.3389/fendo.2021.625204. eCollection 2021.
Animal experiments have demonstrated that diets high in fats create a harmful environment for developing sperm cells, contributing to impaired reproductive health and induced risk for chronic diseases in the next generation. Changes at the level of the epigenome have been suggested to underlie these observations. Human data are limited to verify this hypothesis. While we earlier demonstrated a link between male obesity and DNA methylation changes at imprinted genes in mature sperm cells and newborns, it is currently unknown if -or how- a paternal eating pattern (related to obesity) is related to indices for epigenetic inheritance. We here aim to examine a yet unexplored link between consumption of healthy (rich in vitamins and fibers) or unhealthy ("fast") foods and methylation at imprint regulatory regions in DNA of sperm. We obtained semen and data from 67 men, as part of a North Carolina-based study: The Influence of the Environment on Gametic Epigenetic Reprogramming (TIEGER) study. Dietary data included intake of fruits/nuts, vegetables/soups, whole grain bread, meat, seafood/fish, and fatty or processed food items. Multiple regression models were used to explore the association between dietary habits and clinical sperm parameters as well as DNA methylation levels, quantified using bisulfite pyrosequencing at 12 differentially methylated regions (DMRs) of the following imprinted genes: , , , , , , , , , and . After adjusting for age, obesity status and recruitment method, we found that Total Motile Count (TMC) was significantly higher if men consumed fruits/nuts (β=+6.9, SE=1.9, p=0.0005) and vegetables (β=+5.4, SE=1.9, p=0.006), whereas consumption of fries was associated with lower TMC (β=-20.2, SE=8.7, p=0.024). Semen volume was also higher if vegetables or fruits/nuts were frequently consumed (β=+0.06, SE=0.03, p=0.03). Similarly, our sperm epigenetic analyses showed opposing associations for healthy fast food items. Frequent consumption of fries was related to a higher chance of sperm being methylated at the CpG4 site (OR=1.073, 95%CI: 1.035-1.112), and high consumption of vegetables was associated with a lower risk of DNA methylation at the CpG3 site (OR=0.941, 95%CI: 0.914-0.968). These results remained significant after adjusting for multiple testing. We conclude that dietary habits are linked to sperm epigenetic outcomes. If carried into the next generation paternal unhealthy dietary patterns may result in adverse metabolic conditions and increased risk for chronic diseases in offspring.
动物实验表明，高脂肪饮食会为精子细胞的发育创造一个有害的环境，导致生殖健康受损，并增加下一代患慢性疾病的风险。表观基因组水平的变化被认为是这些观察结果的基础。人类数据仅限于验证这一假设。虽然我们之前已经证明了男性肥胖与成熟精子和新生儿中印记基因的 DNA 甲基化变化之间存在联系，但目前尚不清楚父亲的饮食模式（与肥胖有关）是否与表观遗传遗传的指标有关。在这里，我们旨在研究一种尚未被探索的联系，即健康食品（富含维生素和纤维）或不健康食品（“快餐”）的消费与精子 DNA 印记调节区域的甲基化之间的联系。我们从北卡罗来纳州的一项研究：环境对配子表观遗传重编程的影响（TIEGER）研究中获得了 67 名男性的精液和数据。饮食数据包括水果/坚果、蔬菜/汤、全麦面包、肉、海鲜/鱼以及高脂肪或加工食品的摄入量。使用亚硫酸氢盐焦磷酸测序在以下 12 个差异甲基化区域（DMR）量化 DNA 甲基化水平，采用多元回归模型来探索饮食习惯与临床精子参数以及 DNA 甲基化水平之间的关系，这些基因的印记： ,,,,,,,,, 和 。在调整年龄、肥胖状况和招募方法后，我们发现如果男性摄入更多的水果/坚果（β=+6.9，SE=1.9，p=0.0005）和蔬菜（β=+5.4，SE=1.9，p=0.006），总活动精子计数（TMC）显著升高，而摄入炸薯条与 TMC 降低有关（β=-20.2，SE=8.7，p=0.024）。如果经常食用蔬菜或水果/坚果，精液量也会更高（β=+0.06，SE=0.03，p=0.03）。同样，我们的精子表观遗传分析也显示出健康的 快餐食品的相反关联。经常食用炸薯条与精子在 CpG4 位点发生甲基化的几率更高有关（OR=1.073，95%CI：1.035-1.112），而大量食用蔬菜与 CpG3 位点的 DNA 甲基化风险降低有关（OR=0.941，95%CI：0.914-0.968）。这些结果在经过多次测试调整后仍然具有统计学意义。我们得出的结论是，饮食习惯与精子的表观遗传结果有关。如果这种情况延续到下一代，父亲不健康的饮食模式可能会导致后代出现代谢不良和慢性疾病风险增加的情况。
