Lambright, CR; Wilson, VS; Furr, JR; Wolf, CJ; Noriega, N; Gray, LE
Exposure to EDCs during critical periods of fetal sexual development can have profound effects on the male reproductive system. We examined effects of gestational exposure to eight EDCs on testes testosterone (T) and progesterone (P4) production. Chemicals included fungicides (Procymidone (PD), Vinclozolin (V), Prochloraz (PZ)), phthalate esters (DEHP, DBP, BBP) and herbicides (Linuron (L), Neburon (N)). Doses of 200, 200, 250, 1000, 1000, 1000, 100, 100 mg/kg/day respectively were administered daily GD 14-18 to SD rats and chosen based on previous studies indicating that the majority of fetuses would be affected. PD and V are androgen receptor (AR) antagonists, while the phthalates alter fetal Leydig cell differentiation and reduce fetal T production. L and PZ have been reported to display multiple endocrine activities, including AR antagonism and inhibition of fetal T synthesis. N has been shown to bind AR in vitro, but it is unknown if it alters sexual differentiation. Dams were sacrificed on GD 18 and fetal testes were incubated in M199 medium supplemented with 10% DCC serum for 3 hours. Medium were collected for hormonal analysis. L, N, DEHP, DBP, and BBP all caused a significant reduction in fetal testes T and P4 release. As anticipated, V and PD treatment did not reduce the release of either hormone. PZ exposure resulted in a 10-20 fold increase in P4 and a slight decrease in T versus the control, suggesting a specific inhibition of CYP450 conversion of P4 to the androgens. Other studies are ongoing to examine the direct effects of these chemicals in vitro. Gene expression will also be examined in the testes using microarrays and PCR. These studies provide background from which we can further investigate the mechanisms by which these chemicals affect fetal testes hormone production after gestational exposure.
Pregnancy; Fungicides, Industrial/ TOXICITY; Herbicides/ TOXICITY; Testis/ EMBRYOLOGY; Testis/ METABOLISM; Testosterone/ BIOSYNTHESIS; Progesterone/ BIOSYNTHESIS; Dose-Response Relationship, Drug
