Analysis of Gene Expression in the Testes of Mice Exposed to Bisphenol A and Nonylphenol

Estrogenic environmental compounds (xenoestrogens) have adverse effects on male reproductive systems, including decreased sperm counts and problems with reproductive development. Although the male reproductive toxicity induced by xenoestrogens has been investigated, the molecular mechanisms by which estrogenic compounds induce toxicity in testes are unclear. This study used a microarray analysis to examine testicular toxicity and gene expression profiles in mice after 30 days of exposure to two estrogenic compounds, bisphenol A (BPA) and nonylphenol (NP). In total, 275 and 729 genes were identified as being either up- or down-regulated, with over 1.5-fold changes, in the testes of the BPA and NP-treated groups, respectively. Differentially expressed genes were classified using a k-means clustering algorithm, and their biological functions and canonical pathways were further analyzed using Ingenuity Pathways Analysis (IPA). Toxicological function analysis characterized the mode of action according to BPA and NP. Pathway analysis identified genes involved in gluconeogenesis and calcium signaling in the BPA-treated group and genes involved in Wnt/beta-catenin and estrogen receptor signaling in the NP-treated group. In addition, several differentially expressed genes that may play a role in spermatogenesis, such as Odf1 and the Sox family, were identified. Collectively, these data help to elucidate the molecular mechanism of reproductive toxicity induced by xenoestrogens.This work was supported by the Ministry of Environment with ail Eco-Technopia 21 Project grant through the Development of Decision Method of Chromosomal Abnormality in Reproductive System by Toxic Substances at the Korea Institute of Toxicology