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Inflammatory state and autism-like behavioral phenotype of offspring induced by maternal exposure to low-dose chemical mixtures during pregnancy in mice |
SONG Linyang1( ),WEN Wenzhi2,LIU Jing1,JIN Xiaobao3,YANG Junhua1,3,*( ) |
1. Department of Anatomy, School of Biosciences & Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China; 2. Department of Biopharmaceutics, School of Biosciences & Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China; 3. Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou 510006, China |
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Abstract Objective:To investigate the effects of maternal exposure to 13 chemicals mixture (CM) during pregnancy on pregnancy outcome and health status of maternal/offspring mice. Methods:C57BL/6 pregnant mice were given drinking water containing carbaryl?0.0075?mg/kg, dimethoate?0.001?mg/kg, glyphosate?0.5?mg/kg, methomyl 0.0025?mg/kg, methyl parathion 0.003?mg/kg, triadimefon 0.03?mg/kg, aspartame 40?mg/kg, sodium benzoate?5?mg/kg, calcium disodium ethylene diamine tetra-acetate?2.5?mg/kg, ethylparaben 10?mg/kg, butylparaben 0.5?mg/kg, bisphenol A 0.004?mg/kg and acacia gum 34?mg/kg. The effects of CM exposure on pregnancy outcome, health status of dams/offspring, levels of circulating inflammatory cytokines in dams/offspring and emotional related behaviors of offspring were evaluated. Results: CM exposure during pregnancy had no significant effect on pregnancy outcome, liver function, body weight of the dams in late pregnancy and uterine/ovarian weight after delivery, however, it led to an increase in maternal serum IFN-γ level (P<0.05). CM exposure during pregnancy had no significant effect on the liver function of offspring, but increased the serum IFN-γ, prefrontal cortex IFN-γ, IL-6 and TNF-α and hippocampus IFN-γ levels in the offspring(allP<0.01). In addition, the offspring of CM group showed significant abnormal emotion-related (autism-like) behaviors in adulthood, especially in male offspring.Conclusion: Low dose CM exposure during pregnancy may induce inflammation status in dams/offspring, and lead to autism-like behaviors in offspring, indicating the potential effects of low dose CM exposure on human maternal and infant health.
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Received: 31 March 2021
Published: 16 August 2021
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Corresponding Authors:
YANG Junhua
E-mail: 1011986184@qq.com;jhyang2018@gdpu.edu.cn
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孕期多种低剂量化学物质暴露诱发子代炎症状态和自闭症样行为的实验研究
目的:研究孕期暴露于13种混合化学物质的日常饮食对妊娠结局和母代/子代小鼠健康状态的影响。方法:C57BL/6孕鼠饮用含13种混合化学物质的饮用水,日暴露剂量分别为:西维因0.0075?mg/kg、乐果0.001?mg/kg、草甘膦0.5?mg/kg、灭多威0.0025?mg/kg、甲基对硫磷0.003?mg/kg、三唑酮0.03?mg/kg、阿斯巴甜40?mg/kg、苯甲酸钠5?mg/kg、乙二胺四乙酸2.5?mg/kg、对羟基苯甲酸乙酯10?mg/kg、对羟基苯甲酸丁酯0.5?mg/kg、双酚A?0.004?mg/kg、阿拉伯树胶34?mg/kg。评估混合化学物质暴露后的妊娠结局、母代/子代健康状态、母代/子代循环血炎症因子水平和子代的情绪相关行为。结果:孕期混合化学物质暴露对妊娠结局和母鼠肝功能、孕晚期体重及分娩后子宫/卵巢质量无显著影响,但母体血清中γ干扰素水平升高(P<0.05)。孕期混合化学物质暴露对子鼠肝功能无显著影响,但可增加子鼠血清中γ干扰素的水平,前额皮质中γ干扰素、白介素-6和肿瘤坏死因子α的水平,以及海马中γ干扰素的水平(均P<0.01)。另外,混合化学物质暴露导致子鼠在成年期表现出显著的自闭症样情绪相关行为异常,其中雄性小鼠更为严重。结论:孕期混合化学物质暴露可诱发母鼠和子鼠炎症状态,并导致子鼠自闭症样行为。
关键词:
环境毒物,
母婴健康,
发育,
免疫,
自闭症,
小鼠
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