Effect of antiangiogenic treatment on peritoneal endometriosis-associated nerve fibers
Edurne Novella-Maestre1, Sonia Herraiz, José María Vila-Vives
1Unidad de Genética, Hospital Universitario y Politécnico La Fe, Valencia, Spain. edurnenovella@yahoo.es
Objective:
To investigate the effect of antiangiogenic treatment on experimental endometriotic lesion nerve fibers.
Design:
Heterologous mouse model of endometriosis.
Setting:
University Institute IVI, University Hospital La Fe.
Animal(S):
Ovariectomized nude mice (n = 16) receiving human endometrial fragments from oocyte donors (n = 4).
Intervention(S):
Endometrium fragments stuck in the peritoneum of 5-week-old female nude mice treated with vehicle (n = 8) and antiangiogenic agent cabergoline (n = 8; Cb(2,) 0.05 mg/kg/day) for 14 days.
Main Outcome Measure(S):
Immunofluorescence analysis of von-Willebrand factor (vWF) and vascular smooth muscle cells (αSMA) for evaluating the number of immature blood vessels (IBV) and microvascular density (MVD); immunochemical analysis of protein-gene product 9.5 (PGP 9.5) to assess nerve fibers density (NFD), and blue toluidine staining to confirm presence of mast cells and macrophages in endometriotic lesions.
Result(S):
All the results were quantified by morphometric techniques. The IBV, NFD, and number of macrophages and mast cells were statistically significantly decreased in the Cb2-treated group when compared with controls.
Conclusion(S):
Antiangiogenic treatment statistically significantly diminishes new blood vessel formation after macrophage, mast cell, and nerve fiber reduction, providing a rationale to test antiangiogenic agents as a novel therapeutic approach to severe pelvic pain associated with human peritoneal endometriosis.
Insights
Antiangiogenic treatment with cabergoline reduced new blood vessel formation, nerve fibers, and inflammatory cells in experimental endometriosis. This suggests antiangiogenic agents may treat pelvic pain in endometriosis.
Area of Science:
- Reproductive Medicine
- Vascular Biology
- Pain Management
Background:
- Endometriosis is a condition characterized by endometrial tissue outside the uterus, often associated with severe pelvic pain.
- Nerve fibers and neovascularization within endometriotic lesions are implicated in endometriosis-associated pain.
- Current treatments for endometriosis pain have limitations, necessitating novel therapeutic strategies.
Purpose of the Study:
- To investigate the impact of antiangiogenic treatment on nerve fibers within experimental endometriosis lesions.
- To evaluate the effect of cabergoline, an antiangiogenic agent, on lesion vascularity and associated cellular components.
Main Methods:
- A heterologous mouse model of endometriosis was established using ovariectomized nude mice implanted with human endometrial fragments.
- Mice were treated with either vehicle or cabergoline (0.05 mg/kg/day) for 14 days.
- Immunofluorescence and immunochemical analyses were performed to quantify immature blood vessels (IBV), microvascular density (MVD), nerve fiber density (NFD), and inflammatory cells (macrophages, mast cells).
Main Results:
- Cabergoline treatment led to a statistically significant decrease in immature blood vessels (IBV) and nerve fiber density (NFD) in endometriotic lesions.
- A significant reduction in the number of macrophages and mast cells was observed in the cabergoline-treated group compared to controls.
- Quantification was performed using morphometric techniques.
Conclusions:
- Antiangiogenic treatment with cabergoline effectively reduces neovascularization and nerve fiber proliferation in experimental endometriosis.
- The observed reduction in inflammatory cells suggests a potential mechanism for the antiangiogenic effect.
- These findings support the investigation of antiangiogenic agents as a novel therapeutic approach for managing severe pelvic pain in human peritoneal endometriosis.
