Molecular Biology Department's Jeong Eman Professor Team, Paper in 'Journal of Hazardous Materials'
Neurodevelopmental Exposure to Environmental Hormones Causes Persistent Adverse Effects on Adult Brain Microglia
Researchers at Pusan National University have announced findings that exposure to environmental hormones during the early neurodevelopmental period of pregnancy has lasting adverse effects on the adult brain.
The research team led by Professor Jeong Eeman from the Department of Molecular Biology at Pusan National University (President Choi Jaewon) revealed on the 13th that exposure to "endocrine disrupting chemicals (EDCs)," known as "environmental hormones," during pregnancy and lactation disrupts normal brain development and causes permanent damage lasting into adulthood.
According to the study, endocrine disrupting chemicals are foreign chemicals that can interfere with the normal function of hormones in the body. These chemicals are widely used in everyday life, found in cosmetics, aluminum cans, plastics, pharmaceuticals, and more. Humans are constantly exposed to endocrine disrupting chemicals, which can have harmful effects on the body.
Amid active global research on the toxicity and harmfulness of endocrine disrupting chemicals, Professor Jeong Eeman’s team at Pusan National University investigated the effects of octylphenol (4-tert-octylphenol), a type of alkylphenol endocrine disrupting chemical, on mouse brain development and published their findings.
The research team confirmed that exposure to octylphenol during the neurodevelopmental period causes persistent adverse effects on the morphology and function of microglia in adult offspring mice through the estrogen signaling pathway.
Glial cells not only support the function of neurons but also help ensure the normal migration, generation, and apoptosis of neurons during brain development. Microglia are immune cells that remove damaged cells in the brain to help maintain normal brain function.
The team found that when microglia isolated from mouse brains were exposed to octylphenol, the cell area of microglia increased, and the expression of a specific gene related to microglia (Iba-1) also increased. Furthermore, octylphenol exposure activated the transcription of the Iba-1 gene regulatory region in glial cells and the estrogen response element, which can be regulated by estrogenic environmental hormones.
The Iba-1 gene encodes a calcium-binding protein involved in the normal functions of microglia, such as phagocytosis and regulation of cell membrane morphology.
These findings demonstrate that octylphenol acts like an estrogen mimic, regulating gene expression through the estrogen signaling pathway in microglia and leading to morphological changes in microglia.
To investigate the effects of octylphenol exposure during brain development on the adult mouse brain, the research team exposed pregnant mice to octylphenol from pregnancy through lactation, a period of active brain development, thereby indirectly exposing the offspring mice to octylphenol and raising them to adulthood.
Similar to the experiments with isolated microglia, the team confirmed that octylphenol altered the morphology of microglia in the cerebral cortex of adult offspring mice. Additionally, maternal exposure to octylphenol increased the expression of the Iba-1 gene in the adult mouse brain and altered the expression of genes related to the cytoskeleton.
Microarray analysis revealed that gene expression related to immune responses and cytokines was decreased in the brains of adult mice exposed to octylphenol compared to controls. These results suggest that maternal exposure to octylphenol potentially has lasting effects on microglial function in the adult offspring mouse brain.
This study identified a new mechanism by which endocrine disrupting chemicals affect glial cells during brain development, raising awareness that endocrine disrupting chemicals, to which people are constantly exposed in daily life, may pose potential risks to brain health.
Professor Jeong Eeman, who led the study at Pusan National University’s Department of Molecular Biology, stated, “This research provides new clues to understanding the impact of endocrine disrupting chemicals on brain development. We plan to continue exploring how various environmental factors affect brain development to raise awareness of related risks and contribute to the establishment of relevant policies and regulations.”
The study was published online on October 26 in the internationally renowned journal Journal of Hazardous Materials under the title “Maternal exposure to 4-tert-octylphenol causes alterations in the morphology and function of microglia in the offspring mouse brain.”
This research was conducted with support from the G-LAMP project and the National Research Foundation of Korea. Seunghyun Lee, a master’s student in the Department of Life Systems at Pusan National University, was the first author, and Professor Jeong Eeman, the principal investigator, served as the corresponding author.
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