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RETRACTED ARTICLE: Impact of Prenatal Acetaminophen Exposure for Hippocampal Development Disorder on Mice

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This article was retracted on 30 April 2024

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Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used as analgesic agents. They have been detected in various environmental matrices. The degradation of environmental contaminants and the long-term adverse effects have become a major public concern. Prenatal exposure to acetaminophen can cause damage to the developing hippocampus. However, the molecular mechanisms behind hippocampal damage following prenatal acetaminophen exposure (PAcE) remain unclear. The present study shows an increased risk of adverse neurodevelopmental outcomes in offspring following exposure to acetaminophen during pregnancy on mice. The results revealed that different doses, timings, and duration of exposure to acetaminophen during pregnancy were associated with dose-dependent changes in the hippocampus of the offspring. Furthermore, exposure to high doses, multiple-treatment courses, and late pregnancy induced pathological changes, such as wrinkling and vacuolation, inhibited hippocampal proliferation and increased apoptosis. In addition, PAcE significantly decreased the expression of genes related to synaptic development in fetal hippocampal neurons and hippocampal astrocyte and microglia were also damaged to varying degrees. The significant reduction either in SOX2, an essential gene in regulating neural progenitor cell proliferation, and reduction of genes related to the SOX2/Notch pathway may suggest that the role of SOX2/Notch pathway in impaired hippocampal development in the offspring due to PAcE. In general, PAcE at high doses, multiple-treatment courses, and mid- and late gestation were associated with neurodevelopmental toxicity to the offspring.

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Acknowledgements

We thank Yu Guo for technical support.

Funding

This work was supported by grants from the National Key Research and Development Program of China (No. 2020YFA0803900), the National Natural Science Foundation of China (Nos. 82122071, 81973405, 82030111), and Joint Foundation of Translational Medicine and Interdisciplinary Research, Zhongnan Hospital, Wuhan University (No. ZNJC202230).

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Author notes

  1. Lulu Xie and Jiaxin Qin contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacology, Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan, China

    Lulu Xie, Jiaxin Qin, Tingting Wang, Shuai Zhang, Mingcui Luo, Xinrui Cao & Hui Wang

  2. Department of Pediatrics, Renmin Hospital of Wuhan University, Wuhan, China

    Lulu Xie, Jiaxin Qin & Baozhen Yao

  3. Department of Physiology, Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan, China

    Xuelei Cheng & Biwen Peng

  4. Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, China

    Hui Wang, Baozhen Yao, Dan Xu & Biwen Peng

  5. Department of Pharmacy, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan, China

    Dan Xu

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  1. Lulu Xie
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Contributions

Lulu Xie and Jiaxin Qin performed the research; Lulu Xie and Jiaxin Qin wrote and revised the paper; Dan Xu, Biwen Peng and Baozhen Yao designed the research study; Jiaxin Qin, Lulu Xie, Tingting Wang, Shuai Zhang, Mingcui Luo, Xuelei Cheng, Xinrui Cao, Dan Xu, Biwen Peng, and Baozhen Yao wrote and revised the paper; all authors approved the final manuscript.

Corresponding authors

Correspondence to Baozhen Yao, Dan Xu or Biwen Peng.

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The protocol was approved by the Committee on the Ethics of Animal Experiments of the Wuhan University School of Medicine (permit number: WG2020-0001).

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This article has been retracted. Please see the retraction notice for more detail: https://doi.org/10.1007/s12035-024-04202-8

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Xie, L., Qin, J., Wang, T. et al. RETRACTED ARTICLE: Impact of Prenatal Acetaminophen Exposure for Hippocampal Development Disorder on Mice. Mol Neurobiol 60, 6916–6930 (2023). https://doi.org/10.1007/s12035-023-03515-4

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