Scholarlink

Background <p>Ovarian endometriosis (OEMs) is a primary cause of female infertility and is driven primarily by fibrosis, which disrupts the ovarian follicular microenvironment. Pirfenidone (PFD), an FDA-approved antifibrotic drug, holds promise for treating OEMs, but its efficacy and underlying mechanisms in a relevant in vivo model remain unexplored.</p> Methods <p>A novel mouse model of OEMs was surgically induced. Model mice were randomized to receive either PFD (200 mg/kg every 2 days, <i>n</i> = 20) or vehicle (<i>n</i> = 20) for 24 days. We assessed lesion size and weight, fibrosis via Masson’s trichrome staining and α-SMA immunohistochemistry (IHC), ovarian function through follicle-stimulating hormone receptor (Fshr) IHC and quantitative PCR, and granulosa cell status via Ki67 IHC and TUNEL assays. An unbiased label-free quantitative proteomic analysis was performed to elucidate the mechanism, with key pathways validated by Prussian blue staining and Western blotting. Statistical significance was determined via Student’s t test.</p> Results <p>The OEMs exhibited characteristic cysts, extensive fibrosis (increased α-SMA and collagen deposition, <i>p</i> &lt; 0.05), impaired fertility, and disrupted ovarian function (downregulated Fshr, reduced granulosa cell proliferation, and increased apoptosis, <i>p</i> &lt; 0.05). PFD treatment significantly reduced lesion size, weight, and fibrosis (<i>p</i> &lt; 0.05) and restored the expression of markers of ovarian reserve and folliculogenesis (<i>p</i> &lt; 0.05). Proteomics revealed 554 differentially expressed proteins. PFD downregulated pathways involved in extracellular matrix (ECM) organization and inflammation and upregulated proteins related to iron ion transport and ferroptosis. These findings were confirmed by a significant reduction in ferric iron deposition (<i>p</i> &lt; 0.05) and collagen I protein expression (<i>p</i> &lt; 0.05) in the PFD group.</p> Conclusions <p>Pirfenidone has strong therapeutic potential for treating ovarian endometriosis by simultaneously alleviating fibrosis and restoring ovarian function. Its efficacy is mediated through a novel mechanism of modulating iron homeostasis and the ferroptosis pathway, alongside its known antifibrotic actions. Our findings provide a compelling rationale for repurposing pirfenidone as a disease-modifying treatment for OEMs.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

The therapeutic potential of pirfenidone in alleviating fibrosis and restoring ovarian function in a novel ovarian endometriosis mouse model

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月5日

查看全文
  • Zhaoyang Gao,
  • Yihao Chen,
  • Xiaomin Xu,
  • Mengjie Yang,
  • Peitong Wei,
  • Xiaohong Que,
  • Youyang Weng,
  • Lemeng Wang,
  • Lulu Ren,
  • Xiaohong Yan,
  • Qionghua Chen,
  • Rongfeng Wu

摘要

Background

Ovarian endometriosis (OEMs) is a primary cause of female infertility and is driven primarily by fibrosis, which disrupts the ovarian follicular microenvironment. Pirfenidone (PFD), an FDA-approved antifibrotic drug, holds promise for treating OEMs, but its efficacy and underlying mechanisms in a relevant in vivo model remain unexplored.

Methods

A novel mouse model of OEMs was surgically induced. Model mice were randomized to receive either PFD (200 mg/kg every 2 days, n = 20) or vehicle (n = 20) for 24 days. We assessed lesion size and weight, fibrosis via Masson’s trichrome staining and α-SMA immunohistochemistry (IHC), ovarian function through follicle-stimulating hormone receptor (Fshr) IHC and quantitative PCR, and granulosa cell status via Ki67 IHC and TUNEL assays. An unbiased label-free quantitative proteomic analysis was performed to elucidate the mechanism, with key pathways validated by Prussian blue staining and Western blotting. Statistical significance was determined via Student’s t test.

Results

The OEMs exhibited characteristic cysts, extensive fibrosis (increased α-SMA and collagen deposition, p < 0.05), impaired fertility, and disrupted ovarian function (downregulated Fshr, reduced granulosa cell proliferation, and increased apoptosis, p < 0.05). PFD treatment significantly reduced lesion size, weight, and fibrosis (p < 0.05) and restored the expression of markers of ovarian reserve and folliculogenesis (p < 0.05). Proteomics revealed 554 differentially expressed proteins. PFD downregulated pathways involved in extracellular matrix (ECM) organization and inflammation and upregulated proteins related to iron ion transport and ferroptosis. These findings were confirmed by a significant reduction in ferric iron deposition (p < 0.05) and collagen I protein expression (p < 0.05) in the PFD group.

Conclusions

Pirfenidone has strong therapeutic potential for treating ovarian endometriosis by simultaneously alleviating fibrosis and restoring ovarian function. Its efficacy is mediated through a novel mechanism of modulating iron homeostasis and the ferroptosis pathway, alongside its known antifibrotic actions. Our findings provide a compelling rationale for repurposing pirfenidone as a disease-modifying treatment for OEMs.