Abnormal expression of Hippo–YAP1 signalling pathway and progesterone resistance mechanism in endometrial polyps

Endometrial polyps (EPs) are a localised hyperproliferative disorder of the endometrium, and its pathogenesis remains unclear. Progesterone resistance may influence the recurrence rate of progesterone-treated EPs. Expression of the Hippo–YAP1 signalling pathway has been studied in various diseases. However, few studies have explored their expression in EPs and association with progesterone resistance. Prolactin (PRL), a molecular marker of endometrial mesenchymal cell metaplasia, indirectly reflects progesterone action <i>in vivo</i>. This study aimed to explore the role of Hippo–YAP1 signalling pathway in EPs. Endometrial tissue specimens obtained by surgical resection from 35 patients with a normal endometrium and 35 with EPs were collected between July 2023 and July 2024. Immunohistochemically, the expressions of mammalian STE20-like kinase 1 (MST1), Yes-associated protein 1 (YAP1), progesterone receptor (PR) and PRL in the normal endometrium and EPs tissues were detected. Compared to normal endometrial tissues, the expression of MST1 was relatively low in EPs (<i>p</i> &lt; .05), while the total and nuclear expression of YAP1 was relatively high in EPs (<i>p</i> &lt; .0001). The expression of PR in EPs tissues was significantly lower than that in normal endometrial tissues (<i>p</i> &lt; .05), and the expression level of PRL was lower than that of normal endometrium in EPs tissues (<i>p</i> &lt; .001). EPs have progesterone resistance, and the Hippo–YAP1 signalling pathway may be involved in the development and progression of EPs by acting on the progesterone resistance mechanism. Endometrial polyps (EPs) is a common benign gynaecological disease, formed by the overgrowth of local endometrial tissue. Its main clinical manifestations are abnormal uterine bleeding or infertility, which seriously affects the physical and mental health of patients. In addition, during progesterone therapy, some patients have poor efficacy, which may be related to progesterone resistance, and it becomes an important challenge for clinical treatment. The aim of this study was to investigate the possible pathogenesis of EPs and their progesterone resistance mechanism. Our study found that the Hippo signalling pathway, which regulates cell growth, may be involved in the process of polyp formation and mediate the development of progesterone resistance. This finding may provide a new perspective for understanding the pathogenesis of EPs and may provide a theoretical basis for the development of new therapeutic targets.

子宫内膜息肉（Endometrial polyps, EPs）是一种局限性子宫内膜增生性疾病，其发病机制目前仍未明确。孕酮抵抗可能影响接受孕酮治疗的EPs患者的复发率。Hippo–YAP1信号通路（Hippo–YAP1 signalling pathway）的表达已在多种疾病中得到研究，但鲜有探讨其在EPs中的表达以及与孕酮抵抗关联的研究。催乳素（Prolactin, PRL）作为子宫内膜间质细胞化生的分子标志物，可在体内间接反映孕酮的作用。本研究旨在探讨Hippo–YAP1信号通路在EPs中的作用。

本研究收集了2023年7月至2024年7月期间，经手术切除获取的35例正常子宫内膜组织标本与35例EPs组织标本。采用免疫组化法检测正常子宫内膜组织与EPs组织中哺乳动物STE20样激酶1（mammalian STE20-like kinase 1, MST1）、Yes相关蛋白1（Yes-associated protein 1, YAP1）、孕酮受体（progesterone receptor, PR）以及PRL的表达水平。

与正常子宫内膜组织相比，EPs组织中MST1的表达相对较低（p < 0.05），而YAP1的总表达及核表达水平均显著升高（p < 0.0001）。EPs组织中的PR表达水平显著低于正常子宫内膜组织（p < 0.05），且PRL的表达水平也较正常子宫内膜组织更低（p < 0.001）。

EPs存在孕酮抵抗现象，Hippo–YAP1信号通路可能通过调控孕酮抵抗机制参与EPs的发生与发展。子宫内膜息肉是一类常见的妇科良性疾病，由局部子宫内膜组织过度增生所形成，主要临床表现为异常子宫出血或不孕，严重影响患者的身心健康。此外，在孕酮治疗过程中，部分患者疗效不佳，这可能与孕酮抵抗相关，也成为临床治疗的重要挑战。

本研究旨在探究EPs的潜在发病机制及其孕酮抵抗机制。本研究发现，调控细胞生长的Hippo信号通路可能参与息肉形成过程，并介导孕酮抵抗的发生。该研究结果可为阐明EPs的发病机制提供新视角，也可为新型治疗靶点的开发提供理论依据。