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Sperm DNA methylation changes after nut supplementation in healthy men consuming a Western-style diet

ABSTRACT: Background Many environmental and lifestyle factors have been implicated in the decline of sperm quality, with diet being one of the most plausible factors identified in recent years. Moreover, several studies have reported a close association between the alteration of specific sperm DNA methylation signatures and semen quality. Objectives To evaluate the effect of tree nuts consumption on sperm DNA methylation patterns in healthy individuals reporting eating a Western‐style diet. Material and Methods This is a post‐hoc analysis conducted in a subset of participants (healthy, non‐smoking, and young) from the FERTINUTS 14‐wk randomized‐controlled, parallel‐trial, recruited between December 2015 and February 2017. The participants included in the current study (n=72) were randomly selected in a proportion 2:1 from the original FERTINUTS trial between the 98 participants that completed the entire dietary intervention (nut group, n=48; control group, n=24). Sperm DNA methylation patterns were examined at baseline and after 14 weeks in 48 individuals consuming 60 g/d of mixed nuts (nuts group) and in 24 individuals following the usual Western‐style diet avoiding consumption of nuts (control group). Results Over the course of the trial, no significant changes in global methylation were observed between groups. However, in the nuts group, we identified 36 genomic regions that were significantly differentially methylated between the baseline and the end of the trial and 97.2% of the regions displayed hypermethylation. We identified no such change in the control group over the same period of time. We also utilized the recently developed germ line age calculator to determine if nut consumption resulted in alterations to the epigenetic age of cells and no significant differences were found. Discussion and Conclusion Adding nuts to a regular Western‐style diet subtly impacts sperm DNA methylation in specific regions, demonstrating that there are some sperm epigenome regions that could respond to diet.

ORGANISM(S): Homo sapiens

PROVIDER: GSE140004 | GEO | 2020/09/24

REPOSITORIES: GEO

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Project description:Interventions: Participants will take 6 brazil nuts a day for four weeks. This four week intervention will be preceded by a 4 week run-in / wash out phase participants will be advised to exclude any selenium rich foods or green tea during the study This Pilot study will confirm the amount of Brazil Nuts we will use in the study comparing with green tea. This follow up study (Effects of combining Selenium (Se) and green tea on biomarkers for colorectal cancer prevention in human subjects). will be registered with ANZCTR in the near future’ At the initial interview dietary advice will be given. This will give an understanding of the nature of the volunteers diet and the likely influence of Se to the diet and suitability to become involved in the study (if intolerant to nuts volunteers will not participate in the study) We will ask participants not to consume, whenever possible, throughout the study:- Any selenium supplement Any selenium enriched foods, such as nuts, sea food (such as tuna or octopus) The Brazil nut is a large nut that comes from the castanheiro de para tree in Brazil’s rainforests. Each serving of about six to eight nuts contains 4 g of protein and 7 grams each of monosaturated and polysaturated fat. Brazil nuts (Berholletia excelas, family Lecythidaceae) are the richest known food source of selenium, with mean concentrations reported in the literature between 8-83 micrograms Se/g 6 Brazil nuts daily provides 48 micrograms Se/day - 53 micrograms Se/day Primary outcome(s): If supplementation of 6 Brazil nuts/day increases plasma Selenium (Se) levels A blood sample (5mls of whole blood taken on 2 occasions) will be collected at baseline and after intervention, testing for plasma Selenium levels[Blood samples collected at commencement of intervention (week 0) and at end of intervention (wk 4)] Study Design: Purpose: Prevention; Allocation: Non-randomised trial; Masking: Open (masking not used);Assignment: Single group;Type of endpoint: Safety

Project description:Fast food diet consumption and sedentary life style leads to energy excess, which elevates risks for obesity, metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), and cancer. Exercise training conveys many health benefits in populations with or without these chronic conditions. Diet and exercise regulate gene expression by mediating epigenetic mechanisms globally and at select loci in an array of human tissues, however, such effects are less well documented in liver tissue. To dissect the epigenetic consequences of diet and exercise in liver, we measured DNA methylation using reduced representation bisulfite sequencing (RRBS) and transcriptome using RNA-seq in mice maintained on a fast food diet with sedentary lifestyle (FFC) or exercise (FFE) compared to control diet with (NCE) and without exercise (NCC). Our analyses demonstrate genome-wide differential DNA methylation at key regulatory regions, including different classes of promoters and enhancers, and differential regulation of gene clusters in each condition group. FFE gene expression is most differentially regulated, with enrichment of carbohydrate/lipid metabolic pathways and skeletal muscle development in altered gene sets. Through evaluation of putative protective effects of exercise on diet-induced DNA methylation and gene expression, we show that hypermethylation is effectively prevented, especially at promoters and enhancers, and hypomethylation is partially attenuated. We assessed diet-induced DNA methylation changes associated with cancer-related epigenetic modifications and identified significant increases at liver-specific enhancers in FFC and FFE, suggesting a repressive effect on the epigenomic signature specifying liver identity. Gaining methylation at a subset of gene promoters was associated with inhibition of tissue development and promotion of carcinogenic process. Taken together, our study demonstrates large-scale diet- and exercise-induced effects on the epigenetic landscape, emphasizing the functional relevance of epigenetic mechanisms as an interface between life-style modifications and phenotypic alterations.

Project description:Interventions: 30 healthy volunteers (>50yrs) at-risk for CRC by virtue of age and /or other standard risk factors will be recruited to participate in a randomised, three cohort dietary intervention study. with a parallel design to test the effects of Se and green tea alone and in combination on molecular biomarkers for CRC prevention in the normal rectal epithelial cells. They will be instructed to maintain their usual diet during the study but to avoid supplementation with any green tea-related food or drink (limited to <3 cups of black tea per day), and Se-rich foods such as octopus, crab and tuna, liver and kidney or additional Brazil nuts or other nuts (except those Brazil nuts and green tea extract prescribed by us). The study will consist of dietary intervention period of 6 weeks, preceded by a run in period of 4 weeks. The volunteers will be randomised (randomisation will be computer generated) into one of three groups of 10, receiving 1) Se, supplied as Brazil nuts (6 Brazil nuts daily will provide 48micrograms Se/day); 2) Green tea, supplied as a green tea extract capsule (4 capsules daily will provide 800mg EGCG/day); and 3) Se + green tea (6 Brazil nuts daily + 4 green tea extract capsules daily (will provide 48micrograms Se/day and 800mg EGCG/day). Six Brazil nuts has been chosen because the average Se concentration (2.7 micrograms Se/g) in Brazil nuts (supplied from Charlesworth, Australia) is relatively low compared to that of the report by Thomson et al, where the Se concentration is 6.4micrograms Se/g, and average weight for one nut is 4g, 2 nuts provided 53 micrograms Se/day (Am J Clin Nutr 2008;87:379-3840). Since the average weight of one Brazil nut (supplied from Charlesworth, Australia) is 3g, 6 Brazil nuts daily will provide 48microgra Primary outcome(s): Effects of combination diet (Se + green tea) on biomarkers of Wnt pathway (catenin), inflammation (COX-2) and DNA repair (MGMT) in rectal epithelium. Rectal biopsies will be collected and examined by RT-PCR and immunohistochemistry for the expression of these biomarkers at gene and protein levels[Commencement of Intervention (Baseline), End of intervention (6 weeks) ] Study Design: Purpose: Prevention; Allocation: Randomised controlled trial; Masking: Open (masking not used);Assignment: Parallel;Type of endpoint: Efficacy

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Sperm DNA methylation changes after nut supplementation in healthy men consuming a Western-style diet

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