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Paternal B Vitamin Intake Is a Determinant of Growth, Hepatic Lipid Metabolism and Intestinal Tumor Volume in Female Apc1638N Mouse Offspring
Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, United States of America: Friedman School of Nutrition Science and Policy at Tufts University, Boston, Massachusetts, United States of America.
Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, United States of America: Friedman School of Nutrition Science and Policy at Tufts University, Boston, Massachusetts, United States of America.
Tufts Center for Neuroscience Research, Neuroscience Department, Tufts University School of Medicine, Boston, Massachusetts, United States of America; Molecular Cardiology Research Institute, Tufts Medical Center, Boston, Massachusetts, United States of America.
Tufts Center for Neuroscience Research, Neuroscience Department, Tufts University School of Medicine, Boston, Massachusetts, United States of America, Molecular Cardiology Research Institute, Tufts Medical Center, Boston, Massachusetts, United States of America.
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2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 3, e0151579Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The importance of maternal nutrition to offspring health and risk of disease is well established. Emerging evidence suggests paternal diet may affect offspring health as well.

OBJECTIVE: In the current study we sought to determine whether modulating pre-conception paternal B vitamin intake alters intestinal tumor formation in offspring. Additionally, we sought to identify potential mechanisms for the observed weight differential among offspring by profiling hepatic gene expression and lipid content.

METHODS: Male Apc1638N mice (prone to intestinal tumor formation) were fed diets containing replete (control, CTRL), mildly deficient (DEF), or supplemental (SUPP) quantities of vitamins B2, B6, B12, and folate for 8 weeks before mating with control-fed wild type females. Wild type offspring were euthanized at weaning and hepatic gene expression profiled. Apc1638N offspring were fed a replete diet and euthanized at 28 weeks of age to assess tumor burden.

RESULTS: No differences in intestinal tumor incidence or burden were found between male Apc1638N offspring of different paternal diet groups. Although in female Apc1638N offspring there were no differences in tumor incidence or multiplicity, a stepwise increase in tumor volume with increasing paternal B vitamin intake was observed. Interestingly, female offspring of SUPP and DEF fathers had a significantly lower body weight than those of CTRL fed fathers. Moreover, hepatic trigylcerides and cholesterol were elevated 3-fold in adult female offspring of SUPP fathers. Weanling offspring of the same fathers displayed altered expression of several key lipid-metabolism genes. Hundreds of differentially methylated regions were identified in the paternal sperm in response to DEF and SUPP diets. Aside from a few genes including Igf2, there was a striking lack of overlap between these genes differentially methylated in sperm and differentially expressed in offspring.

CONCLUSIONS: In this animal model, modulation of paternal B vitamin intake prior to mating alters offspring weight gain, lipid metabolism and tumor growth in a sex-specific fashion. These results highlight the need to better define how paternal nutrition affects the health of offspring.

Place, publisher, year, edition, pages
an Francisco, CA, USA: Public Library of Science , 2016. Vol. 11, no 3, e0151579
National Category
Nutrition and Dietetics
Identifiers
URN: urn:nbn:se:oru:diva-61183DOI: 10.1371/journal.pone.0151579ISI: 000371989200064PubMedID: 26968002Scopus ID: 2-s2.0-84962530085OAI: oai:DiVA.org:oru-61183DiVA: diva2:1145572
Note

Funding Agencies:

NCI (National Cancer Institute, Projektnr. 1 R03CA162505-1 

USDA-ARS, Projektnr. 58-1950-0-014, 58-1950-4-003 

Available from: 2017-09-29 Created: 2017-09-29 Last updated: 2017-09-29Bibliographically approved

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