PFOA上调FGF2激活Wnt/β-catenin通路诱导腺肌症纤维化的机制及其病因学诊断价值的研究

全氟辛酸（Perfluorooctanoic acid，PFOA）暴露普遍，可通过内分泌干扰作用产生广泛毒性。子宫腺肌症（Adenomyosis, AM）是一种妇科常见疾病，发病机制不明，无有效诊疗手段。申请者在前期流行病学和体内研究基础上首次发现PFOA能剂量依赖性诱导小鼠AM纤维化。初步机制研究提示PFOA是通过诱导小鼠子宫炎症损伤，上调损伤修复因子FGF2表达，进一步激活Wnt/β-catenin信号诱导上皮间充质转换，引起AM纤维化。本研究拟通过AM类器官体外模型及体内研究进一步明确PFOA诱导AM纤维化的具体分子机制，并通过临床研究探讨利用PFOA构建全新的分子诊断标签用于AM病因学诊断的可行性。本项目的完成将揭示PFOA诱导AM纤维化的病理机制，为AM的病因学筛查及患者的分类管理和特异性治疗提供崭新的方法与理论依据。

Perfluorooctanoic acid (PFOA) is a widely exposed environmental hormone which can produce extensive toxicity through endocrine disruption. Adenomyosis (AM) is a common gynecological disease with unknown pathogenesis and no effective treatment. On the basis of previous epidemiological and in vivo studies, we have firstly verified that PFOA can dose-dependently induce AM fibrosis in mice. Our preliminary mechanism studies suggested that PFOA up-regulated the expression of damage repair factor FGF2 by inducing uterine inflammatory injury in mice, and further activated Wnt/β-catenin signal to induce epithelial mesenchymal transformation and induce AM fibrosis. Based on these previous findings, this study intends to investigate the specific molecular mechanism of AM fibrosis induced by PFOA through the in vitro model of AM organoid and in vivo assays, and explore the feasibility of using PFOA to construct an innovative molecular diagnostic label for the etiological diagnosis of AM through clinical studies. The completion of this investigation will reveal the pathological mechanism of PFOA-induced AM fibrosis, and provide new insights and theoretical basis for the etiological screening, classified management of patients and specific treatment of AM.