Role of autonomic nervous system in BDE-209 maternal exposure induced immunotoxicity in female offspring.

Guanghua Mao, Junjie Tang, Muge Xu, Emmanuel Sunday Okeke, Fangyuan Dong, Yao Chen, Jinlin Gao, Weiwei Feng, Ting Zhao, Xiangyang Wu, Liuqing Yang

Environmental toxicology 2024 Sep

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Decabrominated diphenyl ether (BDE-209) is a typical persistent organic pollutant that can cross the placental barrier, increasing the exposure risk for offspring. Norepinephrine (NE) from nerve terminals and acetylcholine (Ach) can bind to specific receptors on immune cells, inhibit the immune function of the body then cause immunotoxicity. However, whether maternal exposure to BDE-209 could lead to immunotoxicity in the offspring by acting on the sympathetic and parasympathetic nervous systems remains unclear. In view of this, the pregnancy and lactation rat BDE-209 exposure model was established and the results demonstrated that pregnancy and lactation BDE-209 exposure could induce immunotoxicity to female offspring via affecting immunopathology (hematological and biochemical parameters, organ indices, and spleen histopathological), decreasing humoral immunity (serum hemolysin, immunoglobulins, and cytokine productions), damaging cellular immunity (splenic lymphocytes and spleen cytokine productions), and restraining nonspecific immunity. Moreover, a dramatically significant correlation was observed between spleen nerve indices and immunity indices. Additionally, the mechanism revealed that maternal BDE-209 exposure caused offspring immunotoxicity through (1) activating MHC/PKCθ/NF-κB pathway; (2) promoting sympathetic nervous pathway, by upregulating the expression of β2AR protein, which in turn elevating cAMP, following activate PKA and phosphorylate CREB, ultimately leading to immunotoxicity;(3) activating parasympathetic nerve pathway by reducing the binding with Ach and α7nAchR, upregulating the expression of JAK2 and phosphorylating STAT3, induced immunotoxicity of female offspring. © 2024 Wiley Periodicals LLC.

Citation

Guanghua Mao, Junjie Tang, Muge Xu, Emmanuel Sunday Okeke, Fangyuan Dong, Yao Chen, Jinlin Gao, Weiwei Feng, Ting Zhao, Xiangyang Wu, Liuqing Yang. Role of autonomic nervous system in BDE-209 maternal exposure induced immunotoxicity in female offspring. Environmental toxicology. 2024 Sep;39(9):4397-4416