Pyridoxal 5′-phosphate alleviates prenatal pyridaben exposure-induced anxiety-like behaviors in offspring

Pyridaben (PY) is a widely used organochlorine acaricide, which can be detected in the peripheral blood of pregnant women. Available evidence suggests that PY has reproductive toxicity. However, it remains uncertain whether prenatal PY exposure impacts neurobehavioral development in offspring. Here,...

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Main Authors: Xingwang Ding, Ya Wen, Xuan Ma, Yuepei Zhang, Yuting Cheng, Zhaofeng Liu, Weiyue Hu, Yankai Xia
Format: Article
Language:English
Published: Elsevier 2023-01-01
Series:Environmental Science and Ecotechnology
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2666498422000801
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author Xingwang Ding
Ya Wen
Xuan Ma
Yuepei Zhang
Yuting Cheng
Zhaofeng Liu
Weiyue Hu
Yankai Xia
author_facet Xingwang Ding
Ya Wen
Xuan Ma
Yuepei Zhang
Yuting Cheng
Zhaofeng Liu
Weiyue Hu
Yankai Xia
author_sort Xingwang Ding
collection DOAJ
description Pyridaben (PY) is a widely used organochlorine acaricide, which can be detected in the peripheral blood of pregnant women. Available evidence suggests that PY has reproductive toxicity. However, it remains uncertain whether prenatal PY exposure impacts neurobehavioral development in offspring. Here, we administered PY to pregnant mice at a dose of 0.5 and 5 mg kg−1 day−1 via gavage and observed anxiety-like behaviors in PY offspring aged five weeks. We then integrated the metabolome and transcriptome of the offspring's brain to explore the underlying mechanism. Metabolome data indicated that the vitamin B6 metabolism pathway was significantly affected, and the pyridoxal 5′-phosphate (PLP) concentration and the active form of vitamin B6 was significantly reduced. Moreover, the transcriptome data showed that both PLP generation-related Pdxk and anxiety-related Gad1 were significantly down-regulated. Meanwhile, there was a decreasing trend in the concentration of GABA in the hippocampal DG region. Next, we supplemented PLP at a dose of 20 mg kg−1 day−1 to the PY offspring via intraperitoneal injection at three weeks. We found up-regulated expression of Pdxk and Gad1 and restored anxiety-like behaviors. This study suggests that prenatal exposure to PY can disrupt vitamin B6 metabolism, reduce the concentration of PLP, down-regulate the expression levels of Pdxk and Gad1, inhibit the production of GABA, and ultimately lead to anxiety-like behaviors in offspring.
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spelling doaj.art-8c7ae4e80a904cc48ab17405837021e52023-03-05T04:25:48ZengElsevierEnvironmental Science and Ecotechnology2666-49842023-01-0113100224Pyridoxal 5′-phosphate alleviates prenatal pyridaben exposure-induced anxiety-like behaviors in offspringXingwang Ding0Ya Wen1Xuan Ma2Yuepei Zhang3Yuting Cheng4Zhaofeng Liu5Weiyue Hu6Yankai Xia7State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, ChinaState Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China; Department of Chronic Non-Communicable Disease Control, Wuxi Liangxi District Center for Disease Control and Prevention, Wuxi, 214011, ChinaState Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, ChinaState Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, ChinaState Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, ChinaState Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, ChinaState Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China; Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China; Corresponding author. Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China; Corresponding author. State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, No.101 Longmian, Road, Nanjing, 211166, China.Pyridaben (PY) is a widely used organochlorine acaricide, which can be detected in the peripheral blood of pregnant women. Available evidence suggests that PY has reproductive toxicity. However, it remains uncertain whether prenatal PY exposure impacts neurobehavioral development in offspring. Here, we administered PY to pregnant mice at a dose of 0.5 and 5 mg kg−1 day−1 via gavage and observed anxiety-like behaviors in PY offspring aged five weeks. We then integrated the metabolome and transcriptome of the offspring's brain to explore the underlying mechanism. Metabolome data indicated that the vitamin B6 metabolism pathway was significantly affected, and the pyridoxal 5′-phosphate (PLP) concentration and the active form of vitamin B6 was significantly reduced. Moreover, the transcriptome data showed that both PLP generation-related Pdxk and anxiety-related Gad1 were significantly down-regulated. Meanwhile, there was a decreasing trend in the concentration of GABA in the hippocampal DG region. Next, we supplemented PLP at a dose of 20 mg kg−1 day−1 to the PY offspring via intraperitoneal injection at three weeks. We found up-regulated expression of Pdxk and Gad1 and restored anxiety-like behaviors. This study suggests that prenatal exposure to PY can disrupt vitamin B6 metabolism, reduce the concentration of PLP, down-regulate the expression levels of Pdxk and Gad1, inhibit the production of GABA, and ultimately lead to anxiety-like behaviors in offspring.http://www.sciencedirect.com/science/article/pii/S2666498422000801PyridabenPrenatal exposurePyridoxal 5′-phosphateAnxiety-like behaviors
spellingShingle Xingwang Ding
Ya Wen
Xuan Ma
Yuepei Zhang
Yuting Cheng
Zhaofeng Liu
Weiyue Hu
Yankai Xia
Pyridoxal 5′-phosphate alleviates prenatal pyridaben exposure-induced anxiety-like behaviors in offspring
Environmental Science and Ecotechnology
Pyridaben
Prenatal exposure
Pyridoxal 5′-phosphate
Anxiety-like behaviors
title Pyridoxal 5′-phosphate alleviates prenatal pyridaben exposure-induced anxiety-like behaviors in offspring
title_full Pyridoxal 5′-phosphate alleviates prenatal pyridaben exposure-induced anxiety-like behaviors in offspring
title_fullStr Pyridoxal 5′-phosphate alleviates prenatal pyridaben exposure-induced anxiety-like behaviors in offspring
title_full_unstemmed Pyridoxal 5′-phosphate alleviates prenatal pyridaben exposure-induced anxiety-like behaviors in offspring
title_short Pyridoxal 5′-phosphate alleviates prenatal pyridaben exposure-induced anxiety-like behaviors in offspring
title_sort pyridoxal 5 phosphate alleviates prenatal pyridaben exposure induced anxiety like behaviors in offspring
topic Pyridaben
Prenatal exposure
Pyridoxal 5′-phosphate
Anxiety-like behaviors
url http://www.sciencedirect.com/science/article/pii/S2666498422000801
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