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FETAL TESTOSTERONE LEVELS ARE DIFFERENTIALLY AFFECTED IN MALE SPRAGUE DAWLEY AND WISTAR RATS AFTER IN UTERO EXPOSURE TO DIETHYLHEXYL PHTHALATE: A DOSE RESPONSE STUDY.
Citation:
WILSON, V. S., K. HOWDESHELL, C. R. LAMBRIGHT, J. R. FURR, AND L. E. GRAY. FETAL TESTOSTERONE LEVELS ARE DIFFERENTIALLY AFFECTED IN MALE SPRAGUE DAWLEY AND WISTAR RATS AFTER IN UTERO EXPOSURE TO DIETHYLHEXYL PHTHALATE: A DOSE RESPONSE STUDY. Presented at SOT Annual Meeting, Seattle, WA, March 16 - 20, 2007.
Impact/Purpose:
To be presented at SOT annual meeting
Description:
Exposure to phthalate esters during sexual differentiation disrupts testosterone resulting in malformations of androgen-dependent tissues. We have found that gubernacular lesions are more prevalent in in utero diethylhexyl phthalate (DEHP)-treated Wistar male than in the SD rat offspring, whereas the SD rat displays a higher incidence of epididymal agenesis (Wilson et al, 2007. Tox Let). In addition, during gestation, fetal SD males had lower testosterone (T) hormone production and higher insl3 mRNA expression levels than Wistar males. The current study was designed to examine the effects of graded doses of DEHP on fetal androgen levels in these two rat strains. Rats were dosed with 0, 500, 625, 750 or 875 mg DEHP/kg/d on gestational days (GD)14-18 and fetal T production was measured on GD 18 (day of sperm positive = GD1). As hypothesized, untreated Wistar fetal males had higher T levels than SD rats and SD rats treated with DEHP at 500 and 625 mg produced 50% less T than did Wistar rats, indicating that the steroidogenic pathway is more affected in the SD strain than in the Wistar strain by phthalate treatment. Future studies will use lower doses of DEHP and examine fetal testis insl3 and steroidogenic gene expression in both strains. Taken together, these results are consistent with our initial observations, which suggested that the different malformation profiles produced by in utero phthalate treatment arise, at least in part, from strain differences in fetal Leydig cell function and the manner in which these cells respond to DEHP treatment.