Analysis of toxicogenomic response to endocrine disruptors in the mouse testis

Abstract

In order to evaluate the feasibility of cDNA microarrays for the risk assessment of endocrine disruptors (EDs), alteration of gene expression profiles was analyzed in adult mouse testes after neonatal exposure to diethylstilbestrol (DES), bisphenol A (BPA) or genistein (Gen), using cDNA microarrays. Analysis with Mouse GEM I revealed that the expression levels of 34, 38 and 12 genes were changed in testes of DES-, Gen- and BPA-treated 12-week old mice, respectively. Gene expression profiles were very similar between DES- and Gen-treated mice, but that of the BPA-treated mice was quite different. These results suggest that gene expression profiles might be feasible for the grouping of EDs in terms of their effects. Further, it is suggested that mechanisms of BPA action may be different from those of DES and Gen, although they are all estrogen-like compounds. Next, we investigated the transition of the expression profiles in testes of DES-treated mice using in-house cDNA microarrays. Many of the genes affected by DES were up- or down-regulated at restricted periods, but some genes were continuously up-regulated or shifted from the down-regulated state to the up-regulated state. These results suggest that the transition patterns may represent the gene expression cascades that were affected by EDs. We propose that the cDNA microarray is a useful tool, which provides us a bird’s eye view of the global effects of EDs on gene expression.