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A cross-species analysis of the rodent uterotrophic program: elucidation of conserved responses and targets of estrogen signaling

¹ Departments of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan
² Departments of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan
³ Departments of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, Michigan
⁴ Center for Integrative Toxicology and National Food Safety and Toxicology Center, Michigan State University, East Lansing, Michigan

Physiological, morphological, and transcriptional alterations elicited by ethynyl estradiol in the uteri of Sprague-Dawley rats and C57BL/6 mice were assessed using comparable study designs, microarray platforms, and analysis methods to identify conserved estrogen signaling networks. Comparative analysis identified 153 orthologous gene pairs that were positively correlated, suggesting conserved transcriptional targets important in uterine proliferation. Functional annotation for these responses were associated with angiogenesis, water and solute transport, cell cycle control, redox control, DNA replication, protein synthesis and transport, xenobiotic metabolism, cell-cell communication, energetics, and cholesterol and fatty acid regulation. The identification of conserved temporal expression patterns of these orthologs provides experimental support for the transfer of functional annotation from mouse orthologs to 44 previously unannotated rat expressed sequence tags based on their homology and co-expression patterns. The identification of comparable temporal phenotypic responses linked to related gene expression profiles demonstrates the ability of systematic comparative genomic assessments to elucidate important conserved mechanisms in rodent estrogen signaling during uterine proliferation.

uterotrophic assay; microarray; species comparison; ethynyl estradiol

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