2. Academic Validation
  3. Maternal DBP exposure promotes synaptic formation in offspring by activating astrocytes via the AKT/NF-κB/IL-6/JAK2/STAT3 signaling pathway

Maternal DBP exposure promotes synaptic formation in offspring by activating astrocytes via the AKT/NF-κB/IL-6/JAK2/STAT3 signaling pathway

  • Sci Total Environ. 2022 Jul 10;829:154437. doi: 10.1016/j.scitotenv.2022.154437.
Yunhui Xia 1,  Junhan Chen 1,  Tan Ma 2,  Xiannan Meng 3,  Xiaodong Han 1,  Dongmei Li 4
Affiliations

Affiliations

  • 1 Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu 210093, China.
  • 2 Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225001, China; Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research, Yangzhou 225001, China.
  • 3 Cancer Institute, Xuzhou Medical University, Xuzhou, China; Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
  • 4 Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu 210093, China. Electronic address: lidm@nju.edu.cn.
PMID: 35278568 DOI: 10.1016/j.scitotenv.2022.154437
Abstract

It has been demonstrated that activated astrocytes in the hypothalamus could disrupt GnRH secretion in offspring after maternal di-n-butyl phthalate (DBP) exposure, indicating that the effect of DBP on astrocyte activation and crosstalk between astrocytes and neurons is still worthy of further investigation. In this study, pregnant mice were intragastrically administered DBP dissolved in corn oil from gestational days (GD) 12.5-21.5. Maternal DBP exposure resulted in hippocampal astrocyte activation, abnormal synaptic formation, and reduced autonomic and exploratory behavior in offspring on postnatal day (PND) 22. Further studies identified that mono-n-butyl phthalate (MBP) induced astrocyte activation and proliferation by activating the Akt/NF-κB/IL-6/JAK2/STAT3 signaling pathway. Moreover, upregulated thrombospondin 1 (TSP1) in activated astrocytes regulated synaptic-related protein expression. This study highlights the neurotoxicity of maternal DBP exposure to offspring, which provides new insights into identifying potential molecular targets for the treatment of diseases related to neurological development disorders in children.

Keywords

Di-n-butyl phthalate (DBP) astrocyte synaptic formation.

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