title: Paternal B Vitamin Intake Is a Determinant of Growth, Hepatic Lipid Metabolism and Intestinal Tumor Volume in Female Apc1638N Mouse Offspring.
abstract: 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.
authors.affiliation: 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.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Sabet
authors.affiliation: 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.
authors.forename: Lara K
authors.initials: LK
authors.lastname: Park
authors.affiliation: 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.
authors.forename: Lakshmanan K
authors.initials: LK
authors.lastname: Iyer
authors.affiliation: Tufts University Core Facility, Tufts University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Albert K
authors.initials: AK
authors.lastname: Tai
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, United States of America.
authors.forename: Gar Yee
authors.initials: GY
authors.lastname: Koh
authors.affiliation: 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.
authors.forename: Anna C
authors.initials: AC
authors.lastname: Pfalzer
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, United States of America.
authors.forename: Laurence D
authors.initials: LD
authors.lastname: Parnell
authors.affiliation: 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.
authors.forename: Joel B
authors.initials: JB
authors.lastname: Mason
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, United States of America.|School of Public Health and Health Sciences, UMass Amherst, Amherst, Massachusetts, United States of America.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, United States of America.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Byun
authors.affiliation: 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.
authors.forename: Jimmy W
authors.initials: JW
authors.lastname: Crott
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects; D005220:Fathers; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D048788:Growth and Development / Q000187:drug effects*; D006801:Humans; D007414:Intestinal Neoplasms / Q000473:pathology*; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D009154:Mutation; D012098:Reproduction / Q000187:drug effects; D012727:Sex Characteristics; D013094:Spermatozoa / Q000187:drug effects / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects*; D014803:Vitamin B Complex / Q000097:blood / Q000494:pharmacology*
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D014803:Vitamin B Complex