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

• Published in: International journal of molecular sciences 2021-01, Vol.22 (2), p.689
• Main Authors: Chleilat, Faye, Schick, Alana, Deleemans, Julie M, Reimer, Raylene A
• Format: Article
• Language: English
• Subjects: Adipose tissue; Animals; Biomarkers - metabolism; Body composition; Body Composition - genetics; Body fat; Carbon; Cell division; Deoxyribonucleic acid; Diet; Diet, High-Fat; Dietary Supplements; DNA; DNA methylation; DNA methyltransferase; DNMT; Epigenesis, Genetic - genetics; Epigenetics; Fathers; Female; Fertility; Fertility - genetics; Gastrointestinal Microbiome - genetics; Gene expression; Glucagon; Glucagon-like peptide 1; Glucagon-Like Peptide 1 - genetics; gut microbiota; High fat diet; Influence; Insulin resistance; Intestinal microflora; Liver; Male; Metabolism; Microbiota; Microorganisms; microRNA; MicroRNAs; MicroRNAs - genetics; miRNA; Obesity; Obesity - genetics; one-carbon metabolism; paternal nutritional programming; Peptide YY - genetics; Peptides; Pregnancy; Prenatal Exposure Delayed Effects - genetics; Rats; Rats, Sprague-Dawley; Reproductive health; Sexes; Sperm; Spermatogenesis; Sucrose; Sucrose - metabolism; Tyrosine; Vitamin B
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22020689

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 ( < 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.