Ovotoxicity and PPAR-mediated aromatase downregulation in female Sprague-Dawley rats following combined oral exposure to benzo[a]pyrene and di-(2-ethylhexyl) phthalate Article

Xu, C, Chen, JA, Qiu, Z et al. (2010). Ovotoxicity and PPAR-mediated aromatase downregulation in female Sprague-Dawley rats following combined oral exposure to benzo[a]pyrene and di-(2-ethylhexyl) phthalate . TOXICOLOGY LETTERS, 199(3), 323-332. 10.1016/j.toxlet.2010.09.015

cited authors

  • Xu, C; Chen, JA; Qiu, Z; Zhao, Q; Luo, J; Yang, L; Zeng, H; Huang, Y; Zhang, L; Cao, J; Shu, W

authors

abstract

  • 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 10. mg/kg), DEHP (300 and 600. mg/kg) and B[a]P. +. DEHP (at 5. mg/kg and 300. mg/kg respectively, or at 10. mg/kg and 600. mg/kg respectively) on alternate days for 60 days. Relative ovary weight, estrous cycle, 17β-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. © 2010 Elsevier Ireland Ltd.

publication date

  • December 15, 2010

published in

Digital Object Identifier (DOI)

start page

  • 323

end page

  • 332

volume

  • 199

issue

  • 3