We examined the time course of changes in gene expression in detail using cDNA microarray analysis of mouse Sertoli TTE3 cells treated with bisphenol A (BPA). A subtoxic dose of BPA (200 microM) transiently increased intracellular Ca(2+) concentration and time-dependently induced an increase in mRNA level of 78-kDa glucose-regulated protein, indicating that BPA induces endoplasmic reticulum stress. Of the 865 genes analyzed, 31 genes showed increased levels of expression. TaqMan analysis confirmed that the mRNA levels of chop-10, fra-2, c-myc, and ornithine decarboxylase were increased, and showed that chop-10 is the most sensitive gene. The expression level of chop-10 protein and cell injury induced by BPA were significantly reduced in stable TTE3 cells overexpressing full-length chop-10 antisense RNA. We conclude that chop-10 plays a key role in Sertoli cell injury induced by BPA.