PMID- 33445606
OWN - NLM
STAT- MEDLINE
DCOM- 20210402
LR  - 20210402
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 2
DP  - 2021 Jan 12
TI  - Paternal Methyl Donor Supplementation in Rats Improves Fertility, Physiological 
      Outcomes, Gut Microbial Signatures and Epigenetic Markers Altered by High 
      Fat/High Sucrose Diet.
LID - 10.3390/ijms22020689 [doi]
LID - 689
AB  - 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.
FAU - Chleilat, Faye
AU  - Chleilat F
AUID- ORCID: 0000-0002-0804-1611
AD  - Faculty of Kinesiology, University of Calgary, Calgary, AB T2N 1N4, Canada.
FAU - Schick, Alana
AU  - Schick A
AD  - International Microbiome Centre, Cumming School of Medicine, University of 
      Calgary, Calgary, AB T2N 4N1, Canada.
FAU - Deleemans, Julie M
AU  - Deleemans JM
AUID- ORCID: 0000-0001-8645-0990
AD  - Division of Medical Science, Cumming School of Medicine, University of Calgary, 
      Calgary, AB T2N 4N1, Canada.
AD  - Division of Psychosocial Oncology, Cumming School of Medicine, University of 
      Calgary, Calgary, AB T2N 4N1, Canada.
FAU - Reimer, Raylene A
AU  - Reimer RA
AUID- ORCID: 0000-0001-5088-7947
AD  - Faculty of Kinesiology, University of Calgary, Calgary, AB T2N 1N4, Canada.
AD  - Department of Biochemistry and Molecular Biology, Cumming School of Medicine, 
      University of Calgary, Calgary, AB T2N 4N1, Canada.
LA  - eng
GR  - RGPIN/03773-2016/Natural Sciences and Engineering Research Council of Canada/
PT  - Journal Article
DEP - 20210112
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Biomarkers)
RN  - 0 (MicroRNAs)
RN  - 106388-42-5 (Peptide YY)
RN  - 57-50-1 (Sucrose)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
SB  - IM
MH  - Animals
MH  - Biomarkers/*metabolism
MH  - Body Composition/genetics
MH  - Diet, High-Fat
MH  - Dietary Supplements
MH  - Epigenesis, Genetic/*genetics
MH  - Fathers
MH  - Female
MH  - Fertility/genetics
MH  - Gastrointestinal Microbiome/*genetics
MH  - Glucagon-Like Peptide 1/genetics
MH  - Male
MH  - MicroRNAs/genetics
MH  - Obesity/genetics
MH  - Peptide YY/genetics
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/genetics
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sucrose/*metabolism
PMC - PMC7826956
OTO - NOTNLM
OT  - DNMT
OT  - gut microbiota
OT  - insulin resistance
OT  - microRNA
OT  - one-carbon metabolism
OT  - paternal nutritional programming
COIS- The authors declare no conflict of interest.
EDAT- 2021/01/16 06:00
MHDA- 2021/04/07 06:00
PMCR- 2021/01/12
CRDT- 2021/01/15 01:01
PHST- 2020/12/11 00:00 [received]
PHST- 2021/01/08 00:00 [revised]
PHST- 2021/01/09 00:00 [accepted]
PHST- 2021/01/15 01:01 [entrez]
PHST- 2021/01/16 06:00 [pubmed]
PHST- 2021/04/07 06:00 [medline]
PHST- 2021/01/12 00:00 [pmc-release]
AID - ijms22020689 [pii]
AID - ijms-22-00689 [pii]
AID - 10.3390/ijms22020689 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Jan 12;22(2):689. doi: 10.3390/ijms22020689.