Peinado F M, Olivas-Martínez A, Iribarne-Durán L M, Ubiña A, León J, Vela-Soria F, Fernández-Parra J, Fernández M F, Olea N, Freire C, Ocón-Hernández O, Artacho-Cordón F
Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), E-18012 Granada, Spain; University of Granada, Centre for Biomedical Research, E-18016 Granada, Spain; Radiology and Physical Medicine Department, University of Granada, E-18016 Granada, Spain.
Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), E-18012 Granada, Spain; University of Granada, Centre for Biomedical Research, E-18016 Granada, Spain; Radiology and Physical Medicine Department, University of Granada, E-18016 Granada, Spain.
Sci Total Environ. 2023 Jun 25;879:163014. doi: 10.1016/j.scitotenv.2023.163014. Epub 2023 Mar 30.
To describe the expression profile in endometriotic tissue of genes involved in four signaling pathways related to the development and progression of endometriosis (cell cycle, apoptosis, cell differentiation and lipid metabolism) and to explore its relationship with the women exposure to chemicals with hormonal activity released from cosmetics and personal care products (PCPs).
This cross-sectional study, encompassed within the EndEA study, comprised a subsample of 33 women with endometriosis. Expression levels of 13 genes (BMI1, CCNB1, CDK1, BAX, BCL2L1, FOXO3, SPP1, HOXA10, PDGFRA, SOX2, APOE, PLCG1 and PLCG2) in endometriotic tissue and urinary concentrations of 4 paraben (PB) and 3 benzophenone (BP) congeners were quantified. Bivariate linear and logistic regression analyses were performed to explore the associations between exposure and gene expression levels.
A total of 8 out 13 genes (61.5 %) were expressed in >75 % of the samples. Exposure to congeners of PBs and/or BPs was associated with the overexpression of CDK1 gene (whose protein drives cells through G2 phase and mitosis), HOXA10 and PDGFRA genes (whose proteins favor pluripotent cell differentiation to endometrial cells), and APOE (whose protein regulates the transport and metabolism of cholesterol, triglycerides and phospholipids in multiple tissues) and PLCG2 genes (whose protein creates 1D-myo-inositol 1,4,5-trisphosphate and diacylglycerol, two important second messengers).
Our findings suggest that women exposure to cosmetic and PCP-released chemicals might be associated with the promotion of cell cycle and cell differentiation as well as with lipid metabolism disruption in endometriotic tissue, three crucial signaling pathways in the development and progression of endometriosis. However, further studies should be accomplished to confirm these preliminary data.
描述参与子宫内膜异位症发生和发展的四个信号通路（细胞周期、细胞凋亡、细胞分化和脂质代谢）相关基因在子宫内膜异位组织中的表达谱，并探讨其与女性接触化妆品和个人护理产品（PCP）释放的具有激素活性的化学物质之间的关系。
本横断面研究是EndEA研究的一部分，包括33例子宫内膜异位症女性的子样本。对13个基因（BMI1、CCNB1、CDK1、BAX、BCL2L1、FOXO3、SPP1、HOXA10、PDGFRA、SOX2、APOE、PLCG1和PLCG2）在子宫内膜异位组织中的表达水平以及4种对羟基苯甲酸酯（PB）和3种二苯甲酮（BP）同系物的尿液浓度进行了定量分析。进行双变量线性和逻辑回归分析以探讨暴露与基因表达水平之间的关联。
13个基因中有8个（61.5%）在超过75%的样本中表达。接触PB和/或BP同系物与CDK1基因（其蛋白质驱动细胞通过G2期和有丝分裂）、HOXA10和PDGFRA基因（其蛋白质有利于多能细胞分化为子宫内膜细胞）以及APOE（其蛋白质调节多种组织中胆固醇、甘油三酯和磷脂的运输和代谢）和PLCG2基因（其蛋白质产生1D-肌醇1,4,5-三磷酸和二酰基甘油，两种重要的第二信使）的过表达相关。
我们的研究结果表明，女性接触化妆品和PCP释放的化学物质可能与子宫内膜异位组织中细胞周期的促进、细胞分化以及脂质代谢紊乱有关，这是子宫内膜异位症发生和发展中的三个关键信号通路。然而，需要进一步研究来证实这些初步数据。
