期刊
FOOD AND CHEMICAL TOXICOLOGY
卷 163, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2022.112967
关键词
DEHP; Neurotoxicity; Long-term effects; TH signaling
资金
- National Natural Science Foundation of China [81872662]
- National Key R&D Program of China [2016YFC1305900]
- Anhui Innovative and Entrepreneurship Support Program [2021LCX013]
This study found that prenatal DEHP exposure can have lasting effects on offspring neurobehavior, including anxiety, depression, and cognitive impairment. The results suggest that these effects may be caused by damage to the fetal brain's thyroid hormone signaling system due to DEHP exposure.
Prenatal DEHP exposure can cause offspring neurodevelopmental toxicity, but the persistent effects of such exposure window are unclear. This study aimed to investigate the lasting neurobehavioral impact of DEHP on offspring following early exposure from GD9.5 (fetal neural tube closure) to GD16.5 (fetal thyroxin, TH, synthesis). Data showed maternal exposure to DEHP during the thyroid hormone-dependent stage induced a range of neurobehavioral phenotypic changes in adult and middle-aged mice, including anxiety, depression and cognitive impairment. Significant reductions in free TH, TH transporters, and TH metabolic enzyme deiodinase II (D2) were observed in the fetal brain, whereas D3 was elevated, indicating that TH signaling disruption was caused by in utero exposure. Gene expression analyses suggested the expression levels of the TH receptors Tr alpha 1, Tr beta 1 and their downstream target, brain-derived neurotrophic factor, were significantly attenuated, which may partially explain the mechanisms of neurodevelopmental impairment. This study provides new evidence of the persistent effects of sex-specific neurodevelopmental impairment due to in utero DEHP exposure, possibly through damage to the fetal brain TH signaling systems that causes lifelong brain damage. These results further suggest a profound neurobehavioral toxicity of DEHP that may be programmed during early developmental stage exposure and manifested later in life.
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