title: Mechanism of nonylphenol-induced neurotoxicity in F1 rats during sexual maturity.
abstract: OBJECTIVE
  The purpose of this study was to examine whether gestational and lactational exposure to environmental endocrine disrupting chemical, nonylphenol (NP), in pregnant dams would lead to the alterations in hormone levels in the body, apoptosis and glial fibrillary acidic protein (GFAP) in hippocampus during weaning and sexual maturity periods in pups of rats.
  
  
  METHODS
  Dams were gavaged with NP at dose levels of 25 mg/kg/day (low dose), 50 mg/kg/day (middle dose), 100 mg/kg/day (high dose) and groundnut oil alone (vehicle control) respectively from gestational day 6 to postnatal day (PND) 21.
  
  
  RESULTS
  At PND 21, serum testosterone (TT) level significantly decreased in the 50, 100 mg/kg NP-treated groups compared with the control (p < 0.01). Serum estradiol (E2) level was increased with the increase in the NP concentration; a dose-effect relationship was revealed (r = 0.462, p < 0.01). At both PND 21 and PND 60, pups exposed to 100 mg/kg/day NP had an obviously higher apoptotic rate than control did. We observed a significant positive correlation between the dose of NP and the apoptotic rate (r = 0.836, p < 0.05). The number of GFAP-positive cells in rat hippocampus and integral optical density (IOD) of 100 mg/kg/day NP-treated group were much higher than the control group. GFAP mRNA expressions increased at high dose (100 mg/kg/day) (p < 0.05), and positive correlations between the GFAP mRNA expressions and NP level was observed (r = 0.586, 0.737, p < 0.05). Both the number of growth-associated protein (GAP)-43 positive cells and IOD were much lower at high dose (100 mg/kg/day) than the control at both PND 21 and PND 60 (p < 0.05). The number of GAP-43 positive cells was negatively correlated with the NP exposure dose (r = - 0.562, - 0.649, p < 0.05) at these two time points. GAP-43 mRNA expressions in the hippocampus of pups decreased dramatically at high dose (100 mg/kg/day) at both PND 21 and PND 60 compared with the control (p < 0.05).
  
  
  CONCLUSIONS
  High exposure to NP might inhibit neuronal development and differentiation as indicated by the reduction of the neurotrophic factor GAP-43.
authors.affiliation: School of Public Health, Zunyi Medical University, 563000, Zunyi, Guizhou, P.R. of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Jie
authors.affiliation: Department of Gastrointestinal Surgery, Affiliated Hospital of Zunyi Medical University, 563000, Zunyi, Guizhou, P.R. of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xuefeng
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Zunyi Medical University, 563000, Zunyi, Guizhou, P.R. of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Mengxue
authors.affiliation: School of Public Health, Zunyi Medical University, 563000, Zunyi, Guizhou, P.R. of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xuesong
authors.affiliation: School of Public Health, Zunyi Medical University, 563000, Zunyi, Guizhou, P.R. of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Jing
authors.affiliation: School of Public Health, Zunyi Medical University, 563000, Zunyi, Guizhou, P.R. of China.
authors.forename: Tang
authors.initials: T
authors.lastname: Yin
authors.affiliation: School of Public Health, Zunyi Medical University, 563000, Zunyi, Guizhou, P.R. of China. Xujie360@sina.com.
authors.forename: Xu
authors.initials: X
authors.lastname: Jie
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood; D008297:Male; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D012741:Sexual Maturation / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D052244:Endocrine Disruptors; D012739:Gonadal Steroid Hormones; D010636:Phenols; C025256:nonylphenol
keywords: Hippocampus; Neurotoxicity; Nonylphenol; Offspring rat