Testicular gene expression profiling following prepubertal rat mono(2-ethylhexyl)phthalate exposure suggests a common initial genetic response at fetal and prepubertal stages

Phthalate chemical plasticizers can damage the fetal and post-natal mammalian testis, but several aspects of the injury mecha-nism remain unknown. Using a genome-wide microarray, the profile of testicular gene expression changes was examined following exposure of postnatal day 28 rats to a single, high dose (1000 mg/kg) of mono-(2-ethylhexyl) phthalate (MEHP). By microarray analysis, approximately 1675 nonredundant genes exhibited significant expression changes; the vast majority were observed at 12 h. Among the 36 genes significantly altered up to the 3-h time point, prominent functional categories were secreted, transcription, and signaling factors. Using quantitative PCR (qPCR), the dose-response of 24 genes was determined after a single MEHP exposure of 10, 100, or 1000 mg/kg. Increasing 114-fold by 12 h at 1000 mg/kg, Thbs1 (thrombospondin 1) showed the highest level of gene induction. The vast majority of genes analyzed b