Short-term diet intervention alters the small non coding RNA (sncRNA) landscape of human sperm

Offspring health outcomes are often linked with epigenetic alterations triggered by maternal nutrition and intrauterine environment. Strong experimental data also link paternal preconception nutrition with pathophysiology in the offspring, but the mechanism(s) routing effects of paternal exposures remain elusive. Animal experimental models have highlighted small non-coding RNAs (sncRNAs) as potential regulators of these effects. This study characterised the baseline sncRNA landscape of human sperm and the effect of a 6 week dietary intervention on their expression profile. 5’tRFs, miRNA and piRNAs were the most abundant sncRNA subtypes identified; their expression was associated with age, BMI and sperm quality. Nutritional intervention with vitamin D and omega-3 fatty acids altered expression of 3 tRFs, 15 miRNAs and 112 piRNAs, targeting genes involved in fatty acid metabolism and transposable elements in the sperm genome. Sperm sncRNA profiling was performed on a subset (N=17) of participants enrolled in the PREconception dietary suPplements in Assisted REproductionin (PREPARE) study in the UK (N=111 recruited and 102 completed the study). Sperm samples were collected twice during the study, i.e. before and 6 weeks after the dietary intervention (visits MV1 and MV4). Of the 17 participants selected for sncRNA analysis, 9 were participants in the control arm, and 8 from the intervention arm of the trial. The intervention group received an olive oil based diet plus a supplemented drink enriched in vitamin D and omega-3 fatty acids for 6 weeks, while the control group received a sunflower oil based diet and a placebo drink for the same duration of time. Small RNA sequencing was performed on the total RNA extracted from the sperm samples.

子代健康结局常与母体营养及宫内环境诱导的表观遗传修饰密切相关。现有大量实验数据表明，父亲孕前营养状况与子代病理生理过程存在关联，但父代暴露产生影响的具体分子机制仍未阐明。动物实验模型已证实，小型非编码RNA（small non-coding RNAs, sncRNAs）是这类效应的潜在调控因子。本研究对人类精子的基线sncRNA表达谱进行了系统表征，并探究了6周膳食干预对其表达特征的影响。本研究鉴定得到的丰度最高的sncRNA亚型为5’端转移RNA片段（5’tRFs）、微小RNA（miRNA）及Piwi互作RNA（piRNAs）；其表达水平与受试者年龄、体重指数（BMI）及精子质量显著相关。补充维生素D与Omega-3脂肪酸的膳食干预可改变3种tRFs、15种miRNA及112种piRNAs的表达，这些RNA的靶基因涉及精子基因组内的脂肪酸代谢通路及转座元件。本研究针对英国辅助生殖领域孕前膳食补充（PREconception dietary suPplements in Assisted REproduction, PREPARE）队列的17名亚组受试者开展精子sncRNA表达谱分析，该队列原招募111名受试者，最终102名完成全部研究流程。研究期间共采集两次精子样本，分别为膳食干预前（访视MV1）及干预6周后（访视MV4）。在纳入sncRNA分析的17名受试者中，9名来自试验对照组，8名来自干预组。干预组受试者接受为期6周的橄榄油基础膳食搭配富含维生素D与Omega-3脂肪酸的补充饮品，对照组则同期接受葵花籽油基础膳食搭配安慰剂饮品。本研究对所有精子样本提取的总RNA进行了小RNA测序。