Maternal exposure to deltamethrin during pregnancy and lactation impairs hippocampal learning and memory function of male offspring by ferroptosis

Deltamethrin (DM), a broad-spectrum insecticide, is widely used in the world. It can exert direct action on the central nervous system to produce neurotoxicity. Exposure to DM can lead to iron metabolism disorder, oxidative stress and learning and memory dysfunction. In our study, pregnant Wistar ra...

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Main Authors: Shasha Huang, Wanqi Li, Dengke Wang, Huiwen Feng, Bo Wang, Xinyu Dong, Wei Zhao, Dan Liu, Yuan Wang
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Ecotoxicology and Environmental Safety
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Online Access:http://www.sciencedirect.com/science/article/pii/S014765132500065X
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author Shasha Huang
Wanqi Li
Dengke Wang
Huiwen Feng
Bo Wang
Xinyu Dong
Wei Zhao
Dan Liu
Yuan Wang
author_facet Shasha Huang
Wanqi Li
Dengke Wang
Huiwen Feng
Bo Wang
Xinyu Dong
Wei Zhao
Dan Liu
Yuan Wang
author_sort Shasha Huang
collection DOAJ
description Deltamethrin (DM), a broad-spectrum insecticide, is widely used in the world. It can exert direct action on the central nervous system to produce neurotoxicity. Exposure to DM can lead to iron metabolism disorder, oxidative stress and learning and memory dysfunction. In our study, pregnant Wistar rats were randomly divided into four groups and gavaged at doses of 0, 1, 4 or 10 mg/kg/d DM from gestational day (GD) 0 to postnatal day (PND) 21. We used behavioral experiments and Nissl staining to observe the hippocampal development and learning and memory function of male offspring. In order to further confirm the regulation mechanisms of DM, we detected ferrous ion, oxidative stress, ferroptosis related proteins, phospholipase C (PL-C)/inositol triphosphate 3 receptor (IP3R) signaling pathway, intracellular Ca2+ and calcineurin (CaN) content in vivo. In vitro,we selected HT-22 cells to be exposed to DM under the intervention of ferrostatin-1 and pifithrin-α. Our results showed that maternal exposure to DM reduced T-maze correctness and the number of hippocampal neurons, and increased shuttle box passive avoidance rate. Moreover, maternal exposure to DM increased the expression of ferrous ion, malondialdehyde (MDA) and prostaglandin-endoperoxide synthase 2 (PTGS2) protein, and decreased the glutathione (GSH) level in the hippocampus, which was contributed to ferroptosis by p53-mediated solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) axis in the male offspring. Furthermore, the ferroptosis caused by DM exposure could active PL-C/IP3R signaling pathway and increase the intracellular Ca2+ and CaN level, leading to an imbalance of calcium homeostasis in the hippocampus. Thus, maternal exposure to DM during pregnancy and lactation could impair hippocampal learning and memory function of male offspring by p53-mediated ferroptosis.
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spelling doaj-art-c43d2ec8bc1d4688a2e19336d5adcd2b2025-02-12T05:30:07ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01290117729Maternal exposure to deltamethrin during pregnancy and lactation impairs hippocampal learning and memory function of male offspring by ferroptosisShasha Huang0Wanqi Li1Dengke Wang2Huiwen Feng3Bo Wang4Xinyu Dong5Wei Zhao6Dan Liu7Yuan Wang8Yongchuan Center for Disease Control and Prevention, Chongqing, China; Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, Liaoning, China; Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning, ChinaKey Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, Liaoning, China; Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning, China; Tai’an Center for Disease Control and Prevention, Shandong, ChinaKey Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, Liaoning, China; Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning, ChinaKey Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, Liaoning, China; Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning, ChinaKey Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, Liaoning, China; Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning, ChinaKey Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, Liaoning, China; Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning, ChinaKey Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, Liaoning, China; Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning, ChinaNHC Key Laboratory of Congenital Malformation, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China; Corresponding author.Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, Liaoning, China; Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning, China; Correspondence to: Department of Occupational and Environmental Health, School of Public Health, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang 110122, PR China.Deltamethrin (DM), a broad-spectrum insecticide, is widely used in the world. It can exert direct action on the central nervous system to produce neurotoxicity. Exposure to DM can lead to iron metabolism disorder, oxidative stress and learning and memory dysfunction. In our study, pregnant Wistar rats were randomly divided into four groups and gavaged at doses of 0, 1, 4 or 10 mg/kg/d DM from gestational day (GD) 0 to postnatal day (PND) 21. We used behavioral experiments and Nissl staining to observe the hippocampal development and learning and memory function of male offspring. In order to further confirm the regulation mechanisms of DM, we detected ferrous ion, oxidative stress, ferroptosis related proteins, phospholipase C (PL-C)/inositol triphosphate 3 receptor (IP3R) signaling pathway, intracellular Ca2+ and calcineurin (CaN) content in vivo. In vitro,we selected HT-22 cells to be exposed to DM under the intervention of ferrostatin-1 and pifithrin-α. Our results showed that maternal exposure to DM reduced T-maze correctness and the number of hippocampal neurons, and increased shuttle box passive avoidance rate. Moreover, maternal exposure to DM increased the expression of ferrous ion, malondialdehyde (MDA) and prostaglandin-endoperoxide synthase 2 (PTGS2) protein, and decreased the glutathione (GSH) level in the hippocampus, which was contributed to ferroptosis by p53-mediated solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) axis in the male offspring. Furthermore, the ferroptosis caused by DM exposure could active PL-C/IP3R signaling pathway and increase the intracellular Ca2+ and CaN level, leading to an imbalance of calcium homeostasis in the hippocampus. Thus, maternal exposure to DM during pregnancy and lactation could impair hippocampal learning and memory function of male offspring by p53-mediated ferroptosis.http://www.sciencedirect.com/science/article/pii/S014765132500065XDeltamethrinHippocampusLearning and memoryFerroptosisP53
spellingShingle Shasha Huang
Wanqi Li
Dengke Wang
Huiwen Feng
Bo Wang
Xinyu Dong
Wei Zhao
Dan Liu
Yuan Wang
Maternal exposure to deltamethrin during pregnancy and lactation impairs hippocampal learning and memory function of male offspring by ferroptosis
Ecotoxicology and Environmental Safety
Deltamethrin
Hippocampus
Learning and memory
Ferroptosis
P53
title Maternal exposure to deltamethrin during pregnancy and lactation impairs hippocampal learning and memory function of male offspring by ferroptosis
title_full Maternal exposure to deltamethrin during pregnancy and lactation impairs hippocampal learning and memory function of male offspring by ferroptosis
title_fullStr Maternal exposure to deltamethrin during pregnancy and lactation impairs hippocampal learning and memory function of male offspring by ferroptosis
title_full_unstemmed Maternal exposure to deltamethrin during pregnancy and lactation impairs hippocampal learning and memory function of male offspring by ferroptosis
title_short Maternal exposure to deltamethrin during pregnancy and lactation impairs hippocampal learning and memory function of male offspring by ferroptosis
title_sort maternal exposure to deltamethrin during pregnancy and lactation impairs hippocampal learning and memory function of male offspring by ferroptosis
topic Deltamethrin
Hippocampus
Learning and memory
Ferroptosis
P53
url http://www.sciencedirect.com/science/article/pii/S014765132500065X
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