Identification of gene expression changes in postnatal rat foreskin after in utero anti-androgen exposure

• Rat foreskin was found to be a useful tissue to detect gene expression changes caused by DBP exposure, both pre- and post-natally.
• DBP and flutamide chemical exposures caused different gene expression changes.
• Gene expression changes persisted to PND5 after in utero DBP treatment.
• A dose-dependent disruption in gene expression was observed at PND5 after DBP treatment.
• Reproductive malformations were consistent with insufficient androgen signaling.

In utero human phthalate exposure has been associated with male reproductive disorders in epidemiological studies, but discovering relationships is hindered by the lack of identifying markers. This study identified gene expression changes following in utero dibutyl phthalate (DBP) and flutamide exposures in Sprague-Dawley rat foreskin. Dams were exposed to 100 or 500 mg/kg/day dibutyl phthalate or 5 mg/kg/day flutamide from gestational days 16–20. Microarray analysis was performed on foreskin tissue from gestational day 20 and postnatal day 5. Expression changes found following DBP exposure were not present following flutamide treatment, indicating that expression changes were specific to DBP exposure and not caused by altered androgen signaling. Genes that were expressed at lower levels in tissue from pups treated with the low dose of DBP were reduced more in pups treated with the high dose of DBP, demonstrating a dose response effect of this compound. Changes in expression of Marcks, Pum1, Nupr1, and Penk caused by in utero phthalate exposure were confirmed by qRT-PCR. Changes in expression of these genes were maintained after birth and consequently their expression could serve as markers of chemical exposure and biological response.