ToxSci Advance Access originally published online on June 15, 2009
Toxicological Sciences 2009 111(1):163-178; doi:10.1093/toxsci/kfp129
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Published by Oxford University Press 2009.
Pubertal Administration of DEHP Delays Puberty, Suppresses Testosterone Production, and Inhibits Reproductive Tract Development in Male Sprague-Dawley and Long-Evans Rats
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* Division of Neuroscience, Oregon National Primate Research Center, 505 NW 185th Avenue, Beaverton, Oregon 97006
United States Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratories, Reproductive Toxicology Division, Endocrinology Branch, Research Triangle Park, North Carolina 27711
1 To whom correspondence should be addressed at United States Environmental Protection Agency, MD-72, Office of Research and Development, National Health and Environmental Effects Research Laboratories, Reproductive Toxicology Branch, TAD, Research Triangle Park, NC 27711. Fax: (919) 541-9017. E-mail: Gray.Earl{at}EPA.gov.
Received April 23, 2009; accepted May 27, 2009
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Abstract |
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Although is clear that exposure to high dosage levels of some phthalates delays the onset of puberty in the male rat, it has been hypothesized that low levels of di(2-ethylhexyl) phthalate (DEHP) accelerate puberty by enhancing testicular androgen synthesis. The current study was designed to determine if the dose response to DEHP was nonmonotonic, as hypothesized. Pubertal administration of DEHP delayed the onset of puberty and reduced androgen-dependent tissue weights in both Long-Evans (LE) and Sprague-Dawley (SD) male rats 300 and 900 mg DEHP/kg/day. These effects were generally of greater magnitude in LE than SD rats. By contrast, alterations in testis histopathology (300 and 900 mg/kg/day) were more severe in SD than in LE rats. Taken together, these results suggest that DEHP may be acting on the pubertal male rat testis via two modes of action; one via the Leydig cells and the other via the Sertoli cells. Treatment with DEHP generally reduced serum testosterone and increased serum luteinizing hormone (LH) levels, demonstrating that the reduction in testosterone was due to the effect of DEHP on the testis and not via an inhibition of LH from hypothalamic-pituitary axis. Testosterone production ex vivo (with and without human chorionic gonadotropin stimulation) was consistently reduced in males at the time of puberty and shortly thereafter. DEHP treatment did not accelerate the age at puberty or enhance testosterone levels at 10 or 100 mg/kg/day in either LE or SD rats, as some have hypothesized. Taken together, these results do not provide any evidence of a nonmonotonic dose response to DEHP during puberty.
Key Words: Phthalates; male puberty; androgens; testis pathology.
Disclaimer: The research described in this article has been reviewed by the National Health and Environmental Effects Research Laboratory, ORD, U. S. Environmental Protection Agency, and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the Agency nor does the mention of trade names or commercial products constitute endorsement or recommendation for use.