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Assessment of Phthalate-induced Changes in Fetal Rat Testis Gene Expression using an rt-PCR Drug Metabolism Array.
Citation:
Sampson, H., C. R. LAMBRIGHT, J. R. FURR, N. Evans, L. E. GRAY, V. S. WILSON, AND B. Hannas. Assessment of Phthalate-induced Changes in Fetal Rat Testis Gene Expression using an rt-PCR Drug Metabolism Array. Presented at Triangle Consortium for Reproductive Biology, Research Triangle Park, NC, March 03, 2012.
Impact/Purpose:
Based on numerous studies, phthalates such as diethyl hexyl phthalate (DEHP) produce reproductive malformations in male rodents through reduction of testosterone production and gene expression when gestating dams are exposed during the critical period of sexual differentiation. The SABiosciencesDrug Metabolism Arrays test for 84 genes involved in phase one drug metabolism, including Cytochrome P450, Alcohol Dehydrogenases, Esterases,etc. This study investigated the effects of seven phthalate esters known to reduce fetal testosterone production and gene expression.
Description:
Phthalate esters are a large family of compounds used in many industrial and commercial products. Based on numerous studies, phthalates such as diethyl hexyl phthalate (DEHP) produce reproductive malformations in male rodents through reduction of testosterone production and gene expression when gestating dams are exposed during the critical period of sexual differentiation. The SABiosciencesDrug Metabolism Arrays test for 84 genes involved in phase one drug metabolism, including Cytochrome P450, Alcohol Dehydrogenases, Esterases,etc. This study investigated the effects of seven phthalate esters known to reduce fetal testosterone production and gene expression. Timed pregnant Sprague-Dawley rats were orally dosed with individual phthalates from gestational day 14-18. On gestational day 18, testes were collected from three fetuses per dam and cultured for 3 hours. Medium was collected and testosterone values measured. The remaining testes were pooled by litter and, evaluated for gene expression using Drug Metabolism phase 1 PCR arrays. Evaluated were DiHP(750 mg/kg), Dihexyl (750 rng/kg), DPP (100 mg/kgL DiBP(900 mg/kg), DiNP (1500 mg/kg), DCHP (0, 100, 300, 600, or 900 mg/kg), and DEHP (750 mg/kg). Of the 84 genes, four were significantly reduced: Cypllbl, Cypllal, Cyp17al, and ALDH2. Three genes code for steroidogenic enzymes: Cypl1bl, Cypllal, and Cyp17al. Cypllal and Cyp17al are involved in testosterone synthesis, while Cypllbl aids in the production of cortisol and corticosterone. Mitochondrial aldehyde dehydrogenase (ALDH2Lhas a role in the metabolism of aldehydes. Additional gene pathways are being analyzed to identify additional key gene changes in the testis following phthalate exposure. Disclaimer: This abstract does not necessarily reflect USEPA policy. Supported in part by NTPINIEHS