Center for Environment, Health and Welfare Research, Cellular and Molecular Toxicology Laboratory, Korea Institute of Science and Technology (KIST), Seoul, Republic of Korea.
Department of Life Science, College of Natural Sciences, Hangyang University, Seoul, South Korea.
Environ Toxicol. 2018 Nov;33(11):1123-1134. doi: 10.1002/tox.22591. Epub 2018 Jul 5.
Particulate matter the environmental toxicant, with a diameter less than or equal to 2.5 μm (PM ) is a common cause of several respiratory diseases. In recent years, several studies have suggested that PM can influence diverse diseases, such as respiratory diseases, cardiovascular diseases, metabolic diseases, dementia, and female reproductive disorders, and unhealthy birth outcomes. In addition, several epidemiological studies have reported that adverse health effects of PM can differ depending on regional variations. In the present study, to evaluate specific adverse health effects of PM , we collected two different PM samples from an underground parking lot and ambient air, and we evaluated cytotoxicity with eight different cell lines originating from human organs. Then, we selected JEG-3 human placenta cells, which show high cytotoxicity to both PM samples. Through RNA sequencing, gene expression profiling, and a gene ontology (GO) analysis of JEG-3 after exposure to two different PM samples, we identified 1021 commonly expressed genes involved in immune responses, the regulation of apoptosis, and so forth, which are known to induce several adverse health effects. In addition, we identified genes related to the calcium-signaling pathway, steroid hormone biosynthesis, and the cytokine-cytokine receptor interaction through a Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Then, we confirmed these gene expressions using qRT-PCR, and the protein levels of mitogen-activated protein kinases and COX-2 with progesterone decreased using western blotting and enzyme-linked immunosorbent assay. In conclusion, this study suggests the possible toxic mechanism of human placenta that might be associated with PM -induced female reproductive disorders.
颗粒物（PM）是一种环境毒物，其直径小于或等于 2.5μm，是多种呼吸道疾病的常见病因。近年来，多项研究表明，PM 可影响多种疾病，如呼吸道疾病、心血管疾病、代谢疾病、痴呆和女性生殖障碍以及不良生育结局。此外，几项流行病学研究报告称，PM 的不良健康影响可能因地区差异而有所不同。在本研究中，为了评估 PM 的特定不良健康影响，我们从地下停车场和环境空气中收集了两种不同的 PM 样本，并使用源自人体器官的八种不同细胞系评估细胞毒性。然后，我们选择了对两种 PM 样本均显示高细胞毒性的 JEG-3 人胎盘细胞。通过对暴露于两种不同 PM 样本后的 JEG-3 进行 RNA 测序、基因表达谱分析和基因本体论（GO）分析，我们鉴定了 1021 个共同表达的基因，这些基因参与免疫反应、细胞凋亡调控等，已知这些基因可引起多种不良健康影响。此外，我们通过京都基因与基因组百科全书（KEGG）分析鉴定了与钙信号通路、甾体激素生物合成和细胞因子-细胞因子受体相互作用相关的基因。然后，我们使用 qRT-PCR 验证了这些基因的表达，并用 Western blot 和酶联免疫吸附试验（ELISA）证实了孕激素诱导的丝裂原活化蛋白激酶和 COX-2 蛋白水平降低。总之，本研究提示了 PM 可能导致女性生殖障碍的胎盘毒性机制。
