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环境暴露于持久性有机污染物及其与子宫内膜异位症风险的关联:上皮-间质转化过程中的影响

Environmental Exposure to Persistent Organic Pollutants and Its Association with Endometriosis Risk: Implications in the Epithelial-Mesenchymal Transition Process.

作者信息

Martín-Leyva Ana, Peinado Francisco M, Ocón-Hernández Olga, Olivas-Martínez Alicia, Luque Antonio, León Josefa, Lendínez Inmaculada, Cardona Jesús, Lara-Ramos Ana, Olea Nicolás, Fernández Mariana F, Artacho-Cordón Francisco

机构信息

Radiology and Physical Medicine Department, University of Granada, E-18016 Granada, Spain.

Biohealth Research Institute in Granada (ibs.GRANADA), E-18012 Granada, Spain.

出版信息

Int J Mol Sci. 2024 Apr 17;25(8):4420. doi: 10.3390/ijms25084420.

Abstract

We aimed to explore the relationship of adipose tissue concentrations of some persistent organic pollutants (POPs) with the risk of endometriosis and the endometriotic tissue expression profile of genes related to the endometriosis-related epithelial-mesenchymal transition (EMT) process. This case-control study enrolled 109 women (34 cases and 75 controls) between January 2018 and March 2020. Adipose tissue samples and endometriotic tissues were intraoperatively collected to determine concentrations of nine POPs and the gene expression profiles of 36 EMT-related genes, respectively. Associations of POPs with endometriosis risk were explored with multivariate logistic regression, while the relationship between exposure and gene expression profiles was assessed through Spearman correlation or Mann-Whitney U tests. After adjustment, increased endometriosis risk was associated with -DDT, PCB-180, and ΣPCBs. POP exposure was also associated with reduced gene expression levels of the CLDN7 epithelial marker and increased levels of the ITGB2 mesenchymal marker and a variety of EMT promoters (HMGA1, HOXA10, FOXM1, DKK1, CCR1, TNFRSF1B, RRM2, ANG, ANGPT1, and ESR1). Our findings indicate that exposure to POPs may increase the risk of endometriosis and might have a role in the endometriosis-related EMT development, contributing to the disease onset and progression. Further studies are warranted to corroborate these findings.

摘要

我们旨在探讨某些持久性有机污染物(POPs)在脂肪组织中的浓度与子宫内膜异位症风险之间的关系,以及与子宫内膜异位症相关的上皮-间质转化(EMT)过程相关基因在异位内膜组织中的表达谱。这项病例对照研究在2018年1月至2020年3月期间招募了109名女性(34例病例和75名对照)。术中分别采集脂肪组织样本和异位内膜组织,以测定9种POPs的浓度和36个EMT相关基因的基因表达谱。采用多因素logistic回归探讨POPs与子宫内膜异位症风险的关联,通过Spearman相关性分析或Mann-Whitney U检验评估暴露与基因表达谱之间的关系。调整后,子宫内膜异位症风险增加与滴滴涕、多氯联苯-180和多氯联苯总量有关。POP暴露还与紧密连接蛋白7(CLDN7)上皮标志物的基因表达水平降低、整合素β2(ITGB2)间质标志物水平升高以及多种EMT促进因子(高迁移率族蛋白A1(HMGA1)、同源框A10(HOXA10)、叉头框蛋白M1(FOXM1)、 dickkopf 相关蛋白1(DKK1)、趋化因子受体1(CCR1)、肿瘤坏死因子受体超家族成员1B(TNFRSF1B)、核糖核苷酸还原酶M2(RRM2)、血管生成素(ANG)、血管生成素1(ANGPT1)和雌激素受体1(ESR1))水平升高有关。我们的研究结果表明,接触POPs可能会增加子宫内膜异位症的风险,并且可能在与子宫内膜异位症相关的EMT发展中起作用,促进疾病的发生和发展。有必要进行进一步的研究来证实这些发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38d2/11050161/632f4c2e5548/ijms-25-04420-g001.jpg

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