在决策化过程中,子宫内膜基质细胞动态变化,为胚胎着床创造了良好的环境。在植入前和妊娠早期,溶酶体活性通常与子宫内膜的生理变化有关。在这项研究中,对壬基酚(p-NP)的作用,内分泌干扰物,研究了人永生化子宫内膜基质细胞(tHESC)。暴露于p-NP(1nM和1pM)后,检测细胞的蜕膜化标记物Connexin-43,胰岛素样生长因子结合蛋白1(IGFBP1)和催乳素.此外,通过检测转录因子EB(TFEB)和溶酶体相关膜蛋白1(LAMP-1)的表达和定位,研究了p-NP对溶酶体生物发生和胞吐作用的影响。最后,我们使用纤连蛋白测定法评估了p-NP对ECM重塑的影响。我们的结果表明,p-NP降低了催乳素蛋白的表达,增加了TFEB的核定位,并诱导溶酶体蛋白LAMP-1的增加和易位到tHESCs的膜上。数据表明蜕膜化受损,并提示溶酶体生物发生和胞吐作用增加,这得到了tHESCs对活性组织蛋白酶D的更高释放的支持。鉴于组织蛋白酶在滋养层侵入和迁移到蜕膜中过程中对ECM的处理和降解的重要性,我们的结果似乎是p-NP对子宫内膜进程的负面影响的明确证据,而这对成功生育和怀孕至关重要.
During the process of decidualization, the stromal cells of the endometrium change dynamically to create a favorable environment for embryo implantation. Lysosome activity has often been associated with physiological changes in the endometrium during the preimplantation period and early pregnancy. In this study, the effect of para-nonylphenol (p-NP), an endocrine disruptor, on human immortalized endometrial stromal cells (tHESCs) was investigated. After exposure to p-NP (1 nM and 1 pM), the cells were examined for the decidualization markers connexin-43, insulin like growth factor binding protein 1 (IGFBP1), and prolactin. In addition, the effect of p-NP on lysosome biogenesis and exocytosis was investigated by examining the expression and localization of the transcription factor EB (TFEB) and that of the lysosomal-associated membrane protein 1 (LAMP-1). Finally, we evaluated the effect of p-NP on extracellular matrix (ECM) remodeling using a fibronectin assay. Our results showed that p-NP reduced the expression of prolactin protein, increased the nuclear localization of TFEB, and induced the increase and translocation of the lysosomal protein LAMP-1 to the membrane of tHESCs. The data indicate an impairment of decidualization and suggest an increase in lysosomal biogenesis and exocytosis, which is supported by the higher release of active cathepsin D by tHESCs. Given the importance of cathepsins in the processing and degradation of the ECM during trophoblast invasiveness and migration into the decidua, our results appear to be clear evidence of the negative effects of p-NP on endometrial processes that are fundamental to reproductive success and the establishment of pregnancy.NEW & NOTEWORTHY Endocrine disruptors, such as para-nonylphenol, affect the decidualization of human endometrial stromal cells with an impact on decidualization itself, lysosome biogenesis and exocytosis, and extracellular matrix remodeling. All these alterations may negatively impact embryo implantation with the success of reproduction and the establishment of pregnancy.