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J. Hazard. Mater., Oct 26 2024, 480 S0304-3894(24)02837-1 | https://doi.org/10.1016/j.jhazmat.2024.136258
Maternal exposure to 4-tert-octylphenol causes alterations in the morphology and function of microglia in the offspring mouse brain
Seung Hyun Lee a,b, Hyun Seung Shin a,b, Yun Hee So a,b, Dong Hun Lee a,b, Beum-Soo An c, Geun-Shik Lee d, Eui-Man Jung a,b
aDepartment of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 46241, Republic of Korea
bInstitute for Future Earth, Pusan National University, Busan, Republic of Korea
cDepartment of Biomaterials Science, College of Natural Resources & Life Science, Pusan National University, Miryang, Republic of Korea
dDepartment of Veterinary Medicine, Kangwon National University, Chuncheon, Republic of Korea
Corresponding author : Eui-Man Jung
Abstract
4-tert-Octylphenol (OP), an endocrine disrupting chemical is widely used in the production of industrial products. Prenatal exposure to endocrine-disrupting chemicals negatively affects the brain. However, the influence of OP exposure during neurodevelopment in adult offspring remains unclear. Thus, in the present study, we investigated the effects of maternal OP exposure on brain development in adult offspring by analyzing primary glial cell cultures and mice. Our findings revealed that OP exposure led to a specific increase in the mRNA expression of the ionized calcium-binding adapter molecule 1 (Iba-1) and the proportion of amoeboid microglia in the primary glial cell culture and adult offspring mice. Exposure to OP increased the transcriptional activation of Iba-1 and estrogen response element, which were counteracted by estrogen receptor antagonists ICI 182,780. Moreover, OP exposure increased the nuclear localization of the estrogen receptor. Remarkably, OP exposure decreased the mRNA expression levels of proinflammatory cytokines and genes associated with immune response in the brains of the offspring. OP exposure upregulated actin filament-related genes and altered cytoskeletal gene expression, as demonstrated by microarray analysis. The morphological changes in microglia did not result in an inflammatory response following lipopolysaccharide treatment. Taken together, the effects of OP exposure during neurodevelopment persist into adulthood, resulting in microglial dysfunction mediated by estrogen receptor signaling pathways in the brains of adult offspring mice.
논문정보
- Research article
- 2024년 10월 (BRIC 등록일 2024-10-30)
- 국내 연구진
- 생명과학 > 신경생물학
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