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Differential expression of the phthalate syndrome in male Sprague-Dawley and Wistar rats after in utero DEHP exposure
Citation:
WILSON, V. S., K. HOWDESHELL, C. R. LAMBRIGHT, J. R. FURR, AND L. E. GRAY. Differential expression of the phthalate syndrome in male Sprague-Dawley and Wistar rats after in utero DEHP exposure . TOXICOLOGY LETTERS. Elsevier Science Ltd, New York, NY, 170:177-184, (2007).
Impact/Purpose:
This original research demonstrates for the first time that a phthalate, DEHP, known to interfere with steroidogenesis, insl3 peptide mRNA levels and reproductive development in male rats. This research is the first to demonstrate that two commonly used rats strains, the SD and Wistar, display very different epididymal and gubernacular effects after in utero DEHP administration. The strain differences in reproductive malformation rates are related to strain differences in both control and treated fetal rat endocrine alterations. These results will enhance our ability to identify the mechanisms and modes of action by which phthalates alter reproductive function and studying the molecular basis of such differences will aide in understanding how other species, including humans, might respond to fetal phthalate exposures.
Description:
Exposure to phthalate esters during sexual differentiation disrupts testosterone and insulin-like three hormones resulting in malformations of androgen- and insulin-like three-dependent tissues. The current study was designed to test the hypothesis that gubernacular lesions would be more prevalent in the DEHP-treated (750 mg/kg/day, gestational days 14-18) Wistar male than in the SD rat offspring, whereas the SD rat would display a higher incidence of epididymal agenesis. As hypothesized, striking differences were seen in the incidences of epididymal (67% in SD versus 8% in Wistar) and gubernacular lesions (0% in SD versus 64% in Wistar) among the two strains. In addition, fetal androgen and insl3 mRNA levels differed among the strains. SD fetal males had higher insl3 mRNA and lower T levels than Wistar males. The ratio of insl3 mRNA to T differed among DEHP-treated SD and Wistar fetal males, indicating that the steroidogenic pathway was more affected in the SD strain than in the Wistar strain. Taken together, these results suggest 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.
URLs/Downloads:
Differential Expression of the Phthalate Syndrome in Male Sprague-Dawley and Wistar Rats after In Utero DEHP Exposure