title: [Research of fenvalerate induced neurodevelopmental toxicity by interfering with the action of estrogen].
abstract: OBJECTIVE
  To investigate the estrogen interference property of fenvalerate in neurodevelopmental toxicity.
  
  
  METHODS
  Thirty 4-week-old healthy female ICR mice were randomly divided into 6 groups: sham operation group, ovariectomized control group, ovariectomized with estrogen (10 µg/g) group, ovariectomized with fenvalerate (5 µg/g) group, sham operation with fenvalerate group, and ovariectomized with estrogen and fenvalerate group, with 5 mice in each group. Fenvalerate was injected intraperitoneally once a day for 7 consecutive days. Mice were sacrificed at 24 h after the last exposure to separate the hippocampus. Immunofluorescence was used to detect neuron marker (NeuN) and astrocyte marker (GFAP) in hippocampal CA1, CA3, and DG regions.
  
  
  RESULTS
  Compared with the sham operation group (numbers of NeuN-positive cells: CA1 (54.00±1.73), CA3 (59.00 ± 1.73), DG (100.00 ± 4.58)), the sham operation with fenvalerate group (CA1 (37.67 ± 2.08), CA3 (41.33 ± 1.15), DG (80.67±0.58)) and ovariectomized control group (CA1 (44.00 ± 3.00), CA3 (51.00 ± 3.00), DG (83.00 ± 1.72)) showed significant decreases in number of neurons (NeuN-positive cells) in the hippocampus (P < 0.05). Compared with the ovariectomized control group, the ovariectomized with fenvalerate group (CA1 (47.67 ± 3.21), CA3 (49.00 ± 1.73), DG (87.33 ± 4.04)) showed no significant change in number of hippocampal NeuN-positive cells. Compared with the ovariectomized with fenvalerate group (CA1 (47.67 ± 3.21), DG (87.33 ± 4.04)), the sham operation with fenvalerate group and ovariectomized with estrogen and fenvalerate group (CA1 (40.00 ± 1.00), DG (78.67 ± 2.31)) experienced significant decreases in NeuN-positive cells (P < 0.05). Compared with the sham operation group (CA3 (11.00 ± 1.12), DG (10.67 ± 1.15)), the sham operation with fenvalerate group (CA3 (18.67 ± 2.07), DG (16.33 ± 1.53)) showed significant increase in number of astrocytes (GFAP-positive) cells (P < 0.05). Compared with the sham operation with fenvalerate group, the ovariectomized with fenvalerate group (CA3 (12.00 ± 1.00), DG (11.68 ± 1.16)) showed significant decrease in GFAP-positive cells (P < 0.05). Compared with the ovariectomized with fenvalerate group, the sham operation with fenvalerate group and ovariectomized with estrogen and fenvalerate group (CA3 (16.67 ± 2.13), DG (15.38 ± 1.42)) showed significant increases in GFAP-positive cells (P < 0.05).
  
  
  CONCLUSIONS
  The interference with circulating estrogen is an important mechanism underlying the neurodevelopmental toxicity of fenvalerate.
authors.affiliation: Department of Toxicology, School of Public Health, Anhui Medical University, Hefei 230032, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Lyu
authors.affiliation: Department of Toxicology, School of Public Health, Anhui Medical University, Hefei 230032, China. E-mail: wqn@ahmu.edu.cn.
authors.forename: Qunan
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Toxicology, School of Public Health, Anhui Medical University, Hefei 230032, China.
authors.forename: Linling
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Toxicology, School of Public Health, Anhui Medical University, Hefei 230032, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xia
authors.affiliation: Department of Toxicology, School of Public Health, Anhui Medical University, Hefei 230032, China.
authors.forename: Long
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D009570:Nitriles / Q000633:toxicity*; D010052:Ovariectomy; D011722:Pyrethrins / Q000633:toxicity*
chemical_list: D004967:Estrogens; D009570:Nitriles; D011722:Pyrethrins; C017690:fenvalerate