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Assessment of phthalate-induced changes in fetal rat testis gene expression using an rt-PCR array
Citation:
Lambright, C., H. Sampson, J. Furr, N. Evans, B. Hannas, E. Gray, AND V. Wilson. Assessment of phthalate-induced changes in fetal rat testis gene expression using an rt-PCR array. Presented at Society of Toxicology Meeting, March 10 - 14, 2013.
Impact/Purpose:
This abstract will be presented at the Society of Toxicology meeting March 10-14, 2013, San Antonio, TX
Description:
Lambright, CS’, Sampson, H2, Furr, i1, Evans, N’, Hannas, B’, Gray, LE, Jr.’, VS Wilson1. 1USEPA, NHEERL, RTP, NC, 2USEPA, NHEERL, RTP, NC, ORISE Fellow. Phthalate esters (PE) such as diethyl hexyl phthalate (DEHP) produce reproductive malformations in male rodents by reduction of testosterone (T) production and gene expression after dams are exposed during the critical period of sexual differentiation. We investigated the effects of seven PE known to reduce fetal T production and further evaluated gene expression in testis using novel SABiosciences PCR arrays. Each array tests for 84 genes either involved in phase one drug or lipoprotein transport and cholesterol metabolism/synthesis. Timed pregnant Sprague-Dawley rats were orally dosed with individual phthalates from gestational day (GD) 14-18. On GD 18, testes were collected from 3 fetuses per dam and cultured for 3 hours. Medium was collected and T values measured by RIA. Remaining testes were pooled by litter, RNA extracted, purified, quantified, and evaluated for gene expression using PCR arrays. PE were DiHP (750 mg/kg), Dihexyl (750 mg/kg), DPP (100 mg/kg), 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 on the Drug Metabolism arrays, four were significantly reduced: Cypilbi, Cyplial, Cypl7al, and ALDH2. Cypilal and Cypl7al are involved in T synthesis, while Cypilbi aids in the production of cortisol and corticosterone. Using the lipoprotein/cholesterol arrays, 10 genes were significantly altered which are involved in cholesterol biosynthesis (such as APOc3, Dhcr24/7, EBP, MVK, Tm7sf2). These data support that PE effects in the fetal testis are not limited to alterations in androgen synthesis and include genes for other hormones (lnsl3), growth factors, steroid transport proteins, and multiple genes involved in cholesterol synthesis. Disclaimer: This abstract does not necessarily reflect USEPA policy. Supported in part by NTP/NIEHS IA# RW-75- 9228550 1-1 and fellowship administered jointly between EPA/DOE and the Oak Ridge Institute for Science and Education.