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Ovotoxicity and PPAR-mediated aromatase downregulation in female Sprague-Dawley rats following combined oral exposure to benzopyrene and di-(2-ethylhexyl) phthalate.

Authors: Xu, C  Chen, JA  Qiu, Z  Zhao, Q  Luo, J  Yang, L  Zeng, H  Huang, Y  Zhang, L  Cao, J  Shu, W 
Citation: Xu C, etal., Toxicol Lett. 2010 Dec 15;199(3):323-32.
Pubmed: (View Article at PubMed) PMID:20920559
DOI: Full-text: DOI:10.1016/j.toxlet.2010.09.015

The aim of the present study was to determine the ovotoxicity of female Sprague-Dawley (SD) rats exposed to benzo[a]pyrene (B[a]P) and di-(2-ethylhexyl) phthalate (DEHP), either alone or in combination; the molecular mechanism and the combined effects were also evaluated. Female rats were given intragastric administration of control (corn oil), B[a]P (5 and 10mg/kg), DEHP (300 and 600 mg/kg) and B[a]P+DEHP (at 5mg/kg and 300 mg/kg respectively, or at 10mg/kg and 600 mg/kg respectively) on alternate days for 60 days. Relative ovary weight, estrous cycle, 17beta-estradiol blood level, ovarian follicle populations, granulosa cell apoptosis, and gene and protein expression of P450Arom and PPAR were investigated. Our study demonstrated that the combination of B[a]P and DEHP exerts ovotoxicity in female rats and suppression of sex hormone secretion and homeostasis, which is associated with prolonged estrous cycles, decreases in ovarian follicle populations and granulosa cell apoptosis involving a PPAR-mediated signaling pathway of action of the two chemicals. In addition, based on qualitative assessment of the combined toxicity, no interaction effects were observed following combined B[a]P and DEHP administration.

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RGD Object Information
RGD ID: 4890045
Created: 2010-12-14
Species: All species
Last Modified: 2010-12-14
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.