Visualization of sex-dimorphic changes in the intestinal transcriptome of Fabp2 gene-ablated mice.

BACKGROUND/AIMS:Sex differences in gene expression program have not been effectively explored at the transcriptome level. We aimed to develop a method for the analysis of transcriptome data to identify sex differences and sex-dimorphic responses to experimental conditions in mice. METHODS:Profiling of the small intestine transcriptome of chow-fed C57BL/6J (wild-type, WT) and Fabp2⁻/⁻ mice was carried out by microarray analysis. Sex-specific and androgynous effects of Fabp2 gene ablation were examined using FlexArray V1.6 by comparing WT to Fabp2⁻/⁻ mice. The data generated were exported into a single spreadsheet, collated and transformed to identify the differentially expressed genes for pathway analysis. RESULTS:The method revealed enrichment of 17 sex-dimorphic pathways in the small intestine of WT mice compared to only 4 in Fabp2⁻/⁻ mice. Comparison of the effects of Fabp2 loss in individual sexes revealed a male-specific upregulation of 5 pathways involved in the production of unsaturated fatty acids, and a female-specific downregulation of pathways involved in xenobiotic metabolism. CONCLUSIONS:Our approach detected the common as well as sex-differential pathways that are modified due to the loss of Fabp2. These findings suggest that the pathways involved in nutrient and xenobiotic metabolism in the intestine are regulated by sex-specific mechanisms.

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