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In utero exposure to dietheylhexyl phthalate differentially affects fetal testosterone and insl3 levels in the testes of male Sprague Dawley and Wistar rats: A dose response study
Citation:
WILSON, V. S., K. L. HOWDESHELL, C. R. LAMBRIGHT, J. R. FURR, AND L. E. GRAY. In utero exposure to dietheylhexyl phthalate differentially affects fetal testosterone and insl3 levels in the testes of male Sprague Dawley and Wistar rats: A dose response study. Presented at Society for the Study of Reproduction, Kona, HI, May 27 - 30, 2008.
Impact/Purpose:
Presentation at SSR
Description:
We previously reported that 750 mg/kg/day of diethylhexyl phthalate (DEHP) administered in utero during the period of sex differentiation resulted in a higher prevalence of gubernacular lesions in male Wistar offspring than in the male Sprague Dawley (SD) rat offspring, whereas DEHP induced a higher incidence of epididymal agenesis in SD males (Wilson et al, 2007. Tox Let). In addition, on gestation day (GD)18, fetal testes from SD males had lower testosterone (T) 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 T production and insl3 mRNA levels in the fetal testes of these two rat strains. Dams were dosed with 0, 100, 300, 500, 625, or 750 mg DEHP/kg/d on GD14-18 (day of sperm positive = GD1) and fetal testis T production and insl3 mRNA were assessed on GD 18. DEHP significantly reduced T in both strains at 300 mg/kg/d and above, but SD rats had significantly lower T production at 0 and 100 mg DEHP dose groups, indicating that there is an inherent strain difference in Leydig cell function. Initial quantification of insl3 mRNA expression from 2-3 litters per dose group indicates that the opposite situation exists for the peptide hormone insl3. DEHP reduces insl3 mRNA in both strains but generally SD males have higher insl3 mRNA levels than Wistar males. Taken together, these results suggest that the Leydig cells of the Wistar produce proportionally more T than insl3 as compared the Leydig cells of the SD strain. Future studies will be conducted to increase the sample size and quantify the expression of key genes in the steroidogenic pathway. Results of the current study are consistent with our previous observations and 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.