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. Overall design: 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.