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Fetal Phthalate Screen: Assessment of Several Phthalate Esters on Fetal Rodent Testosterone Production and Gene Expression Following In Utero Exposure
Citation:
LAMBRIGHT, C. R., J. R. FURR, M. C. CARDON, B. Hannas, D. Bermudez, N. WRENCH, P. Foster, L. E. GRAY, AND V. S. WILSON. Fetal Phthalate Screen: Assessment of Several Phthalate Esters on Fetal Rodent Testosterone Production and Gene Expression Following In Utero Exposure . Presented at Society of Toxicology (SOT) Annual Meeting, Washington, DC, March 06 - 10, 2011.
Impact/Purpose:
Historically, it has been proposed that di-n-alkyl phthalates with straight side chains of C4 to C6 are likely reproductive toxicants but C3 or shorter and C7 or longer are not. The goal of the present study was to test this assumption using a relatively rapid in vivo screen to evaluate a suite of PE for their potential reproductive toxicities.
Description:
Phthalate esters(PE) are a large family of compounds used in a wide array of common products from medical tubing to pharmaceuticals to cables, and wall/floor coverings. Laboratory studies have demonstrated that in utero treatment with PE such as di-ethyl hexyl phthalate (DEHP) during the critical period of fetal reproductive development produced male reproductive malformations by reducing fetal testosterone (T) production and gene expression of Ins13 (Wilson et al, Tox Lett, 146(3):207-15,2004). Historically, it has been proposed that di-n-alkyl phthalates with straight side chains of C4 to C6 are likely reproductive toxicants but C3 or shorter and C7 or longer are not. The goal of the present study was to test this assumption using a relatively rapid in vivo screen to evaluate a suite of PE for their potential reproductive toxicities. Using this screen, we investigated the effects of 12 individual phthalates on fetal testes T production and gene expression ofIns13, STAR and Cyplla by exposing timed pregnant Sprague-Dawley rats via oral gavage (750 mg/kg/day) from gestational day (GD) 14-18. On GD 18, individual testes from three fetuses were collected and incubated for 3 hours. Medium was collected and T levels measured by RIA. The remaining testes were pooled by litter, mRNA extracted and gene expression for Ins13, STAR and Cyplla was measured. Fetal testes T production was significantly reduced compared to control following treatment with BBP, DBP, DIBP, DPP, DiHP, DHeP(diheptyl-), DHP (dihexyl-), DCHP (dicyclo-), and DINP. No effect on fetal Twas seen with DEP, BrDEHP, DOTP or DiNCH. In addition, gene expression of Ins13, STAR and Cyplla was significantly reduced as compared to control by some of the above phthalates that also reduced T production. In summary, we demonstrate that some phthalates are able to reduce both fetal testes T production and expression of three genes involved in steroid hormone production and that some phthalates with straight chains less than C4 or longer than C6 also can disrupt fetal hormone synthesis. Disclaimer: This is an abstract of a proposed presentation and does not necessarily reflect U.S. EPA policy.