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Sexually dimorphic characteristics of the small intestine and colon of prepubescent C57BL/6 mice

ABSTRACT: 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. 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. 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. 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE57516 | GEO | 2015/09/02

SECONDARY ACCESSION(S): PRJNA246578

REPOSITORIES: GEO

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Project description: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. 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. 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. 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. Small intestine and colon were isolated from two-week old pups of dams fed a low-fat diet and subjected to gene expression profiling

Project description:Sexually dimorphic traits are by definition exaggerated in one sex, which may arise from a history of sex-specific selection â in males, females, or both. If this exaggeration comes at a cost, exaggeration is expected to be greater in higher condition individuals (condition-dependent). Although studies using small numbers of morphological traits are generally supportive, this prediction has not been examined at a larger scale. We test this prediction across the trancriptome by determining the condition-dependence of sex-biased (dimorphic) gene expression. We find that high-condition populations are more sexually dimorphic in transcription than low-condition populations. High condition populations have more male-biased genes and more female-biased genes, and a greater degree of sexually dimorphic expression in these genes. Also, condition-dependence in male-biased genes was greater than in a set of unbiased genes. Interestingly, male-biased genes expressed in the testes were not more condition-dependent than those in the soma. By contrast, increased female-biased expression under high condition may be have occurred because of the greater contribution of the ovary-specific transcripts to the entire mRNA pool. We did not find any genomic signatures distinguishing the condition-dependent sex-biased genes. The degree of condition-dependent sexual dimorphism (CDSD) did not differ between the autosomes and the X-chromosome. There was only weak evidence that rates of evolution correlated with CDSD. We suggest that the sensitivity of both female-biased genes and male-biased genes to condition may be akin to the overall heightened sensitivity to condition that life-history and sexually selected traits tend to exhibit. Our results demonstrate that through condition-dependence, early life experience has dramatic effects on sexual dimorphism in the adult transcriptome. There were 8 biologically distinct samples. Each was replicated 6 times for a total of 48 biological samples on 24 arrays. There was no reference or control sample as a loop design was used. Each of the 48 samples are represented separately.

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Sexually dimorphic characteristics of the small intestine and colon of prepubescent C57BL/6 mice

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