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Updated: Feb 21, 2026
Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
Notch signaling controls sprouting angiogenesis of endometriotic lesions
Christina Körbel1, Miriam D Gerstner1, Michael D Menger1
1Institute for Clinical and Experimental Surgery, Saarland University, 66421, Homburg/Saar, Germany.
Abstract:
Angiogenesis is essential for the engraftment and growth of endometriotic lesions. In this study, we analyzed whether this process is regulated by Notch signaling. Endometriotic lesions were induced by endometrial tissue transplantation into dorsal skinfold chambers of C57BL/6 mice, which were treated with the γ-secretase inhibitor DAPT or vehicle. Vascularization, morphology, and proliferation of the newly developing lesions were analyzed using intravital fluorescence microscopy, histology, and immunohistochemistry over 14 days. Inhibition of Notch signaling by DAPT significantly increased the number of angiogenic sprouts within the endometrial grafts during the first days after transplantation when compared to vehicle-treated controls. This was associated with an accelerated vascularization, as indicated by a higher functional microvessel density of DAPT-treated lesions on day 6. However, inhibition of Notch signaling did not affect the morphology and proliferating activity of the lesions, as previously described for tumors. Both DAPT- and vehicle-treated lesions finally consisted of cyst-like dilated glands, which were surrounded by a well-vascularized stroma and contained comparable numbers of proliferating cell nuclear antigen-positive cells. These findings demonstrate that sprouting angiogenesis in endometriotic lesions is controlled by Notch signaling. However, inhibition of Notch signaling does not have beneficial therapeutic effects on lesion development.
Insights
Notch signaling controls blood vessel growth in endometriosis. Inhibiting this pathway accelerated early lesion vascularization but did not improve overall lesion development or morphology, suggesting it is not a viable therapeutic target.
Area of Science:
- Reproductive biology
- Vascular biology
- Cell signaling
Background:
- Angiogenesis is critical for endometriosis lesion establishment and growth.
- Notch signaling is a key regulator of angiogenesis in various physiological and pathological processes.
- The role of Notch signaling in endometriosis-driven angiogenesis remains largely unexplored.
Purpose of the Study:
- To investigate the role of Notch signaling in regulating angiogenesis within endometriotic lesions.
- To determine the therapeutic potential of inhibiting Notch signaling in a mouse model of endometriosis.
Main Methods:
- Endometriotic lesions were induced in C57BL/6 mice using endometrial tissue transplantation.
- Mice were treated with DAPT (a γ-secretase inhibitor) or vehicle control.
- Vascularization, morphology, and proliferation were assessed over 14 days using intravital fluorescence microscopy, histology, and immunohistochemistry.
Main Results:
- DAPT treatment significantly increased the number of angiogenic sprouts in early-stage lesions compared to controls.
- Accelerated vascularization was observed in DAPT-treated lesions by day 6.
- Notch inhibition did not alter lesion morphology or proliferation rates, with both groups showing similar gland dilation and cell proliferation markers by day 14.
Conclusions:
- Sprouting angiogenesis in endometriotic lesions is regulated by Notch signaling.
- Inhibition of Notch signaling accelerates early vascularization but does not provide therapeutic benefits for overall lesion development in endometriosis.
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