Resveratrol reliefs DEHP-induced defects during human decidualization.
Resveratrol reliefs DEHP-induced defects during human decidualization.
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DOI：
10.1016/j.ecoenv.2023.114931
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发表时间：
2023-04
影响因子：
6.8
通讯作者：
Chenghong Long;Zhenru Li;Shijin Liang;Sitong Yao;Songqi Zhu;Lin Lu;Rui Cao;Yingni Chen;Yuxin Huang;Yongjiang Ma;Wei-Xiang Lei;Xiaohuan Liang
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文献类型：
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作者：
Chenghong Long;Zhenru Li;Shijin Liang;Sitong Yao;Songqi Zhu;Lin Lu;Rui Cao;Yingni Chen;Yuxin Huang;Yongjiang Ma;Wei-Xiang Lei;Xiaohuan Liang
邻苯二甲酸二（2-乙基己基）酯（DEHP）被广泛用作许多塑料产品的添加剂。研究显示，DEHP持续暴露会影响胚胎发育，并导致女性生殖障碍。妊娠的建立涉及子宫内膜组织的广泛变化，包括大量的细胞外基质（ECM）重塑。子宫内膜的蜕膜化通过引起子宫间质细胞形态的改变，为后续的生长提供适宜的环境，是人类妊娠的关键过程。白藜芦醇（Resveratrol，RSV）是一种天然多酚类植物抗毒素，具有广泛的药理作用。越来越多的证据表明RSV对某些女性生殖疾病具有治疗作用。在这项研究中，DEHP对细胞活力的影响进行了研究，通过细胞增殖试验。在体外诱导细胞蜕膜化，并通过定量实时PCR和蛋白质印迹分析证实与蜕膜化相关的分子的下调。免疫荧光分析显示细胞形态发生改变，并发现给予DEHP足以诱导ERα进入细胞核。通过RNA-seq分析充分验证了DEHP对细胞的影响。有趣的是，在用RSV拯救后观察到蜕膜分子的上调，这通过RNA-seq转录组分析和定量实时PCR测定证实。此外，通过RSV施用，ECM重塑相关基因的表达显著恢复。该研究揭示了DEHP诱导的蜕膜化缺陷的潜在机制和RSV的功能缓解作用，同时为缓解DEHP诱导的蜕膜化缺陷提供了有前景的治疗候选物。
Di-(2-Ethylhexyl) phthalate (DEHP) is widely used as an additive in many plastic products. Studies have revealed that DEHP persistent exposure can affect embryonic development and lead to adverse female reproductive disorders. The establishment of pregnancy involves extensive changes in the endometrial tissue, including massive extracellular matrix (ECM) remodeling. Decidualization of the endometrium provides a suitable environment for subsequent growth by causing changes in the morphology of the uterine stromal cells, is a key process in human pregnancy. Resveratrol (RSV) is a natural polyphenolic plant antitoxin with a wide range of pharmacological effects. Growing evidence indicates that RSV has therapeutic effects on certain female reproductive disorders. In this study, the effect of DEHP on cell viability was investigated by cell proliferation assay. Cell decidualization was induced in vitro, and the downregulation of molecules associated with decidualization was confirmed through quantitative real-time PCR and western blot analysis. Immunofluorescence analysis revealed alteration in cell morphology, and found that administration of DEHP sufficiently induced ERα entry into the nucleus. The effect of DEHP on cells was fully verified by RNA-seq analysis. Interestingly, an upregulation of decidual molecules was observed after rescue with RSV, which was confirmed by RNA-seq transcriptome analysis and quantitative real-time PCR assay. Additionally, the expression of ECM remodeling-related genes was significantly restored by RSV administration. The study revealed the potential mechanisms of DEHP-induced decidualization defects and the functional relieving roles of RSV while providing a perspective therapeutic candidate for alleviating the DEHP-induced deficiencies in decidualization.