Toxicological Sciences 67, 264-274 (2002)
Copyright © 2002 by the Society of Toxicology
REPRODUCTIVE AND DEVELOPMENTAL TOXICOLOGY |
2,3,7,8-Tetrachlorodibenzo-p-dioxin Interacts with Endogenous Estradiol to Disrupt Prostate Gland Morphogenesis in Male Rat Fetuses
* Division of Basic Biomedical Sciences, School of Medicine, University of South Dakota, 414 East Clark Street, Vermillion, South Dakota 57069;
School of Pharmacy, University of Wisconsin, Madison, Wisconsin 53705; and
Division of Biological Sciences, University of Missouri–Columbia, Columbia, Missouri 65211
Fetal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) interferes with normal development of the male reproductive system in rats and mice. We examined the effects of TCDD on the initial development of the urogenital system (urethra, prostate, and seminal vesicles) in male rat fetuses on gestation day (GD) 20. The number of prostatic buds and size of prostate glands as well as seminal vesicle size was determined by computer-assisted 3D reconstruction. Pregnant Holtzman rats received a single oral dose of TCDD (1 µg/kg) on GD 15. The intrauterine position (IUP) of male fetuses was identified based on the sex of adjacent fetuses: 2F males were located between 2 females and 2M males were located between 2 males. Control 2F males had elevated serum estradiol and larger prostates than control 2M males, which had elevated serum testosterone and larger seminal vesicles, confirming prior findings. There was no effect of TCDD on serum testosterone. TCDD significantly decreased the number of buds in the dorsocranial and dorsolateral regions of the urogenital sinus and overall prostate size, and was associated with a significant decrease in serum estradiol only in 2F males. In contrast, in 2M males both serum estradiol and the number and size of prostatic buds in these same regions of the prostate were unaffected by TCDD, although seminal vesicle size was reduced. These findings show that individual differences in gonadal steroid levels influence the response of the developing prostate to TCDD in male fetuses. In addition, these TCDD effects may be mediated in part by a decrease in serum estradiol levels.
Key Words: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); prostate development; intrauterine position; testosterone; estrogen; rat.
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