Velázquez-Hernández Dora Maria, Vázquez-Martínez Edgar Ricardo, Cruz-Orozco Oliver, Silvestri-Tomassoni José Roberto, Sánchez-Ramírez Brenda, Olguín-Ortega Andrea, Escobar-Ponce Luis F, Rodríguez-Dorantes Mauricio, Camacho-Arroyo Ignacio
Unidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología-Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México 11000, Mexico.
Departamento de Ginecología Quirúrgica, Instituto Nacional de Perinatología, Ciudad de México 11000, Mexico.
Int J Mol Sci. 2025 Jul 28;26(15):7297. doi: 10.3390/ijms26157297.
Endometriosis is a disorder characterized by the presence of endometrial tissue outside the uterus, leading to dyspareunia, chronic pelvic pain, dysuria, and infertility. The latter has been related to implantation failure associated with alterations in decidualization, a process regulated by sex hormones such as progesterone. Membrane progesterone receptor β (mPRβ) exhibits a lower expression in endometriotic tissues than in normal endometrial ones. However, the role of mPRβ in decidualization is unknown. This work aimed to investigate whether mPRβ plays a role in the decidualization of endometrial stromal cells (ESCs) derived from women with and without endometriosis. The mPR agonist OrgOD-2 induced the gene expression of key decidualization markers (insulin-like growth factor binding protein 1, prolactin, transcription factor heart and neural crest derivatives-expressed transcript 2, and fork-head transcription factor) in healthy ESCs, eutopic (uterine cavity), and ectopic (outside of the uterine cavity) ESCs from women with endometriosis. Notably, the expression of the decidualization markers was lower in endometriotic cells than in healthy endometrial ones. An siRNA mediated knockdown of mPRβ reduced the expression of decidualization-associated genes in ESCs treated with a decidualization stimuli, regardless of whether cells were derived from healthy women or those with endometriosis. Our data suggest that progesterone, through mPRβ activation, regulates the decidualization process in endometrial stromal cells from women with and without endometriosis.
子宫内膜异位症是一种以子宫外存在子宫内膜组织为特征的疾病，可导致性交困难、慢性盆腔疼痛、排尿困难和不孕。后者与蜕膜化改变相关的着床失败有关，蜕膜化是一个受孕酮等性激素调节的过程。膜孕酮受体β（mPRβ）在子宫内膜异位组织中的表达低于正常子宫内膜组织。然而，mPRβ在蜕膜化中的作用尚不清楚。这项研究旨在调查mPRβ是否在患有和未患有子宫内膜异位症的女性来源的子宫内膜基质细胞（ESC）的蜕膜化中发挥作用。mPR激动剂OrgOD-2诱导了健康ESC、患有子宫内膜异位症女性的在位（子宫腔）和异位（子宫腔外）ESC中关键蜕膜化标志物（胰岛素样生长因子结合蛋白1、催乳素、转录因子心脏和神经嵴衍生物表达转录本2以及叉头转录因子）的基因表达。值得注意的是，蜕膜化标志物在子宫内膜异位细胞中的表达低于健康子宫内膜细胞。无论细胞是来自健康女性还是患有子宫内膜异位症的女性，siRNA介导的mPRβ敲低都会降低用蜕膜化刺激物处理的ESC中蜕膜化相关基因的表达。我们的数据表明，孕酮通过激活mPRβ，调节患有和未患有子宫内膜异位症的女性子宫内膜基质细胞的蜕膜化过程。
