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

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.

Maternal exposure to a Western‐style diet causes differences in intestinal microbiota composition and gene expression of suckling mouse pups

“…A. Physiological and molecular effects observed in the liver of these mice and sexually dimorphic characteristics in the SI and colon under low‐fat conditions have been reported previously.…”

The microgenderome revealed: sex differences in bidirectional interactions between the microbiota, hormones, immunity and disease susceptibility

“…On the other hand, Lactobacilliaceae (Firmicutes) are absent or occur at low levels in the healthy human GIT but are highly prevalent in the murine GIT. Indeed, while Bacteroidetes and Firmicutes dominate in the microbiota of many laboratory rodents (e.g., mice, rats, hamsters) [35–37], marked differences between the rodent and human GIT microbiota at the genus level indicate that rodent studies may not be generalizable to humans [38]. Furthermore, individual rodents may vary greatly in their microbiota even when co-housed; thus, rigorous experimental techniques are required to ensure consistency in experiments [39].…”

“…However, investigations of the GIT microbiota in young animals suggest that these microbial sex differences do not appear until after puberty [37]. For example, deep sequencing of the colonic luminal contents from pre-pubescent C57BL/6 mice show no effect of sex on colonic bacterial community composition [37]. In this study, however, whole-genome profiling of colonic and small intestinal tissue from pre-pubertal mice revealed multiple genes that exhibit sexually dimorphic expression, many of which were autosomal and involved in infection, immunity and inflammatory pathways, particularly in the small intestine [37].…”

“…For example, deep sequencing of the colonic luminal contents from pre-pubescent C57BL/6 mice show no effect of sex on colonic bacterial community composition [37]. In this study, however, whole-genome profiling of colonic and small intestinal tissue from pre-pubertal mice revealed multiple genes that exhibit sexually dimorphic expression, many of which were autosomal and involved in infection, immunity and inflammatory pathways, particularly in the small intestine [37]. Thus, even in the absence of high levels of circulating sex hormones, mice with identical microbiota have intrinsic sex-specific gene regulation in the GIT.…”

The impact on the activity of acetylcholinesterase of a polylysine-ApoE peptide carrier targeting the blood brain barrier

“…Sexual dimorphism in structure and physiological processes, including with AChE response, in mice is recognized throughout the scientific literature (Haizlip et al, 2015;Steegenga et al, 2014;Loy and Sheldon, 1987). The observed statistically significant (p < 0.05) interaction between sex and dose ( Fig.…”