Abstract
BackgroundThere 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.MethodsAt 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.ResultsSexually 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.ConclusionsThis 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.
Highlights
There is increasing appreciation for sexually dimorphic effects, but the molecular mechanisms underlying these effects are only partially understood
Gene expression in the small intestine and colon of prepubescent mice is sexually dimorphic To determine differences in gene expression in the intestine between male and female mice, whole-genome expression profiling was performed on the small intestine (SI) and colon of 2-week-old male and female C57BL/6 mice using microarray analysis (MA)
All of them are located on the Y chromosome and reveal, as expected, strong differential expression since these genes are not expressed by females
Summary
There is increasing appreciation for sexually dimorphic effects, but the molecular mechanisms underlying these effects are only partially understood. We explored transcriptomics and epigenetic differences in the small intestine and colon of prepubescent male and female mice. The male Y chromosome is relatively small (60 Mb) and contains only a limited number of genes (~60 in humans and 12 in mice) [6,7]. Even though these genes are exclusively expressed in males, a female variant for some of them has been identified [8]. The X chromosome, which is present as one copy in males and as two copies in females, is much larger in size (155 Mb) and contains a much larger number of genes (~1,500). Some genes located on the X chromosome escape silencing in female somatic cells, including a number of genes containing a homologue on the Y chromosome such as the well-known escapee Kdm5c [15,16]
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