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Open AccessArticle

Paternal Methyl Donor Supplementation in Rats Improves Fertility, Physiological Outcomes, Gut Microbial Signatures and Epigenetic Markers Altered by High Fat/High Sucrose Diet

1
Faculty of Kinesiology, University of Calgary, Calgary, AB T2N 1N4, Canada
2
International Microbiome Centre, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada
3
Division of Medical Science, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada
4
Division of Psychosocial Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada
5
Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(2), 689; https://doi.org/10.3390/ijms22020689
Received: 11 December 2020 / Revised: 8 January 2021 / Accepted: 9 January 2021 / Published: 12 January 2021
(This article belongs to the Section Molecular Endocrinology and Metabolism)
Increased consumption of high fat/sucrose (HF/S) diets has contributed to rising rates of obesity and its co-morbidities globally, while also negatively impacting male reproductive health. Our objective was to examine whether adding a methyl donor cocktail to paternal HF/S diet (HF/S+M) improves health status in fathers and offspring. From 3–12 weeks of age, male Sprague Dawley rats consumed a HF/S or HF/S+M diet. Offspring were followed until 16 weeks of age. Body composition, metabolic markers, gut microbiota, DNA methyltransferase (DNMT) and microRNA expression were measured in fathers and offspring. Compared to HF/S, paternal HF/S+M diet reduced fat mass in offspring (p < 0.005). HF/S+M fathers consumed 16% fewer kcal/day, which persisted in HF/S+M female offspring and was explained in part by changes in serum glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) levels. Compared to HF/S, HF/S+M fathers had a 33% improvement in days until conception and 300% fewer stillbirths. In fathers, adipose tissue DNMT3a and hepatic miR-34a expression were reduced with HF/S+M. Adult male offspring showed upregulated miR-24, -33, -122a and -143 expression while females exhibited downregulated miR-33 expression. Fathers and offspring presented differences in gut microbial signatures. Supplementing a paternal HF/S diet with methyl-donors improved fertility, physiological outcomes, epigenetic and gut microbial signatures intergenerationally. View Full-Text
Keywords: paternal nutritional programming; one-carbon metabolism; gut microbiota; DNMT; microRNA; insulin resistance paternal nutritional programming; one-carbon metabolism; gut microbiota; DNMT; microRNA; insulin resistance
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MDPI and ACS Style

Chleilat, F.; Schick, A.; Deleemans, J.M.; Reimer, R.A. Paternal Methyl Donor Supplementation in Rats Improves Fertility, Physiological Outcomes, Gut Microbial Signatures and Epigenetic Markers Altered by High Fat/High Sucrose Diet. Int. J. Mol. Sci. 2021, 22, 689.

AMA Style

Chleilat F, Schick A, Deleemans JM, Reimer RA. Paternal Methyl Donor Supplementation in Rats Improves Fertility, Physiological Outcomes, Gut Microbial Signatures and Epigenetic Markers Altered by High Fat/High Sucrose Diet. International Journal of Molecular Sciences. 2021; 22(2):689.

Chicago/Turabian Style

Chleilat, Faye; Schick, Alana; Deleemans, Julie M.; Reimer, Raylene A. 2021. "Paternal Methyl Donor Supplementation in Rats Improves Fertility, Physiological Outcomes, Gut Microbial Signatures and Epigenetic Markers Altered by High Fat/High Sucrose Diet" Int. J. Mol. Sci. 22, no. 2: 689.

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