title: Sexually dimorphic characteristics of the small intestine and colon of prepubescent C57BL/6 mice.
abstract: BACKGROUND
  There is increasing appreciation for sexually dimorphic effects, but the molecular mechanisms underlying these effects are only partially understood. In the present study, we explored transcriptomics and epigenetic differences in the small intestine and colon of prepubescent male and female mice. In addition, the microbiota composition of the colonic luminal content has been examined.
  
  
  METHODS
  At postnatal day 14, male and female C57BL/6 mice were sacrificed and the small intestine, colon and content of luminal colon were isolated. Gene expression of both segments of the intestine was analysed by microarray analysis. DNA methylation of the promoter regions of selected sexually dimorphic genes was examined by pyrosequencing. Composition of the microbiota was explored by deep sequencing.
  
  
  RESULTS
  Sexually dimorphic genes were observed in both segments of the intestine of 2-week-old mouse pups, with a stronger effect in the small intestine. Amongst the total of 349 genes displaying a sexually dimorphic effect in the small intestine and/or colon, several candidates exhibited a previously established function in the intestine (i.e. Nts, Nucb2, Alox5ap and Retnlγ). In addition, differential expression of genes linked to intestinal bowel disease (i.e. Ccr3, Ccl11 and Tnfr) and colorectal cancer development (i.e. Wt1 and Mmp25) was observed between males and females. Amongst the genes displaying significant sexually dimorphic expression, nine genes were histone-modifying enzymes, suggesting that epigenetic mechanisms might be a potential underlying regulatory mechanism. However, our results reveal no significant changes in DNA methylation of analysed CpGs within the selected differentially expressed genes. With respect to the bacterial community composition in the colon, a dominant effect of litter origin was found but no significant sex effect was detected. However, a sex effect on the dominance of specific taxa was observed.
  
  
  CONCLUSIONS
  This study reveals molecular dissimilarities between males and females in the small intestine and colon of prepubescent mice, which might underlie differences in physiological functioning and in disease predisposition in the two sexes.
authors.affiliation: Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: Wilma T
authors.initials: WT
authors.lastname: Steegenga
authors.affiliation: Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: Mona
authors.initials: M
authors.lastname: Mischke
authors.affiliation: Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: Carolien
authors.initials: C
authors.lastname: Lute
authors.affiliation: Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: Mark V
authors.initials: MV
authors.lastname: Boekschoten
authors.affiliation: Center for Liver, Digestive and Metabolic Diseases, Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Maurien Gm
authors.initials: MG
authors.lastname: Pruis
authors.affiliation: Center for Liver, Digestive and Metabolic Diseases, Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Agnes
authors.initials: A
authors.lastname: Lendvai
authors.affiliation: Center for Liver, Digestive and Metabolic Diseases, Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Henkjan J
authors.initials: HJ
authors.lastname: Verkade
authors.affiliation: NIZO food Research BV, Ede, The Netherlands.
authors.forename: Jos
authors.initials: J
authors.lastname: Boekhorst
authors.affiliation: NIZO food Research BV, Ede, The Netherlands.
authors.forename: Harro M
authors.initials: HM
authors.lastname: Timmerman
authors.affiliation: Department of Obstetrics and Gynaecology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Torsten
authors.initials: T
authors.lastname: Plösch
authors.affiliation: Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands ; Norwich Medical School, University of East Anglia, Norwich, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Müller
keywords: Chromosomes; Colon; DNA methylation; Epigenetics; Gene expression; Histone modification; Microbiota; Prepubescent; Sexually dimorphism; Small intestine