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ONTOGENY OF CHANGES IN FETAL TESTIS GENE EXPRESSION INDUCED IN MALE OFFSPRING AFTER MATERNAL TREATMENT WITH DEHP (DIETHYLHEXYL PHTHALATE)
Citation:
WILSON, V. S., C. R. LAMBRIGHT, J. FURR, K. L. BOBSEINE, C. R. WOOD, K. HOWDESHELL, AND L. E. GRAY. ONTOGENY OF CHANGES IN FETAL TESTIS GENE EXPRESSION INDUCED IN MALE OFFSPRING AFTER MATERNAL TREATMENT WITH DEHP (DIETHYLHEXYL PHTHALATE). Presented at Society of Toxicology, San Diego, CA, March 05 - 09, 2006.
Description:
Phthalate esters are high production volume, ubiquitous environmental chemicals some of which induce reproductive malformations in rats when administered during sexual differentiation. Recently we have shown that malformations in gubernacular ligament development induced by DEHP are associated with decreased insl3 gene expression, a gene critical for proper gubernacular ligament formation. DEHP (0, 100, 300, 600, or 900 mg/kg/day) administered orally to Sprague Dawley dams on gestation days (GD) 8 through 18 produced dose-dependent decreases in testosterone production and in insl3 gene expression. To investigate the ontogeny of gene changes associated with these effects, dams were dosed orally with 0 (vehicle only) or 750 mg/kg/day DEHP beginning on GD8. Testes RNA was prepared from 3 litters each of control and treated fetuses on GD 16.5, 17, and 18. Microarray analysis was conducted on these samples using Affymetrix gene chips. Preliminary results indicate significant (p< 0.05) changes in several genes associated with Leydig cell steroidogenesis (such as CYP17, StAR) and peptide hormone production (insl3) beginning, in some cases, as early as GD 16.5. Significant changes were also detected in androgen-dependent genes and genes involved in lipid and cholesterol transport and signal transduction. A more thorough analysis and validation of gene chip results is underway and will be presented. These data on gene expression changes are consistent with the malformations previously observed in male offspring after in utero exposure to similar doses of DEHP. Disclaimer: This is an abstract of a proposed presentation and does not necessarily reflect EPA policy.