[Research of fenvalerate induced neurodevelopmental toxicity by interfering with the action of estrogen]
Zhen Lyu1, Qunan Wang1, Linling Lu1
1Department of Toxicology, School of Public Health, Anhui Medical University, Hefei 230032, China.
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).
Conclusion:
The interference with circulating estrogen is an important mechanism underlying the neurodevelopmental toxicity of fenvalerate.
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