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Womens Health

Women's Health - Poster Session B

Poster L25 - Diabetes Induces Abnormal Vessel Remodeling in the Vagina: Implications in Urogynecologic Surgeries

Thursday, October 24, 2024
2:45 PM - 3:45 PM EST
Location: Exhibit Hall E, F & G

Introduction:  Pelvic floor disorders (PFD) are common conditions in aging women. Among this population, diabetes mellitus (DM) is prevalent with ~14% affected. Urogynecologic surgeries in women with DM are associated with increased complications, the mechanism of which remains to be elucidated. DM is known to impact vessel remodeling and vascularization in a tissue-specific manner. However, little data are available regarding its impact on the vaginal wall, which is a key surgical route and a primary organ receiving PFD surgical repairs. In this study, we aimed to investigate the independent and combined impacts of DM, postmenopausal status, and urogynecologic surgeries with/without polypropylene mesh implantation on vessel remodeling and neovascularization in the vagina.

Materials and

Methods:  A streptozotocin-induced diabetic rat model (female Wistar, 8 - 9 months) was used. Nondiabetic and diabetic rats received no surgery (control) or underwent supra-cervical hysterectomy with or without mesh implantation, with or without bilaterial ovariectomy (OVX) (n ≥4 per subgroup). At 42 days post-surgery, Masson’s Trichrome staining and immunofluorescence labeling of alpha smooth muscle actin, which is specific to smooth muscle cells, were performed in vaginal tissue cryosections (7μm). Vascular density (total vessel area/tissue area), vessel wall thicknesses (μm), and ratio of wall thickness to lumen radius (T/Lr) were quantified in the subepithelium and muscularis layers (subE/M) using QuPath. Vessel types (lymph vessel, capillary, vein, or artery) were quantified using a customized MATLAB-based random forest classification algorithm trained on nondiabetic control and hysterectomy only samples (~90.5% cross-validation accuracy). Mesh-induced neovascularization and morphology of artery-associated smooth muscle were evaluated in mesh regions (350μm radially from each mesh fiber) in the adventitia. Data were analyzed using Mann-Whitney, and Kruskal-Wallis, and unpaired t tests (p < 0.05).

Results, Conclusions, and Discussions: Under normoglycemic conditions without OVX, surgery (hysterectomy and mesh implantation) did not significantly affect vascular density in the subE/M compared to no-surgery controls (p=0.5475). However, vascular density was significantly elevated in mesh-impacted areas compared to the subE/M (p=0.0159), indicating localized neovascularization induced by mesh.

With OVX, vascular density in the subE/M in surgery groups was increased ~3-fold when compared to groups without OVX (p=0.0014). Yet, vessel T/Lr was decreased in the OVX’ed samples (p < 0.0001, Figure 1). Similar findings were observed in mesh-impacted areas, with increased vascular density (~3-fold, p=0.0159) and decreased artery T/Lr (p=0.0034) in samples with vs. without OVX (Figure 2). These findings indicate that baseline vessel remodeling and mesh-induced neovascularization in the vagina are estrogen-dependent in an antagonistic manner.

Under diabetic conditions, the effect of OVX on subE/M vascular density, mesh-impacted area vascular density, and vessel T/Lr disappeared (p=0.4363, p=0.5476, p>0.9999, Figure 1). Interestingly, OVX otherwise demonstrated significantly decreased artery T/Lr in the adventitia (p=0.0345, Figure 2), indicating that DM and postmenopausal status may interact synergistically in vessel remodeling. Vascular density within mesh-impacted regions was also significantly elevated compared to subE/M with and without OVX (p=0.0159, p=0.0159), demonstrating that mesh consistently induces neovascularization.

When comparing diabetic vs. nondiabetic groups, vascular density in the subE/M and in mesh-impacted areas was increased ~2-fold without OVX (p=0.0006, p=0.0317), yet no differences in these parameters were detected with OVX (p=0.2110, p=0.0556). While the random forest classification algorithm did not show differences in vessel type quantity (p=0.1297), vessel T/Lr was decreased in diabetic vs. nondiabetic non-OVX samples (p=0.0005, Figure 1), and artery T/Lr, which was particularly affected, was lower in diabetic vs. nondiabetic samples with and without OVX (p=0.0001, p=0.0002, Figure 2). Potential fibrosis and irregularities in smooth muscle organization were also noted in diabetic groups with and without OVX (Figure 3G, 3H). These findings suggest that despite increased vascularity, vessel quality was compromised with vessel wall thinning under diabetic conditions.

In conclusion, our study shows abnormal vessel remodeling as a potential mechanism for elevated risks of surgical complications in women with DM and may inform design of therapies to mitigate these risks.

Acknowledgements (Optional):