1-alpha,25-dihydroxyvitamin D3 Regresses Endometriotic Implants in Rats by Inhibiting Neovascularization and Altering Regulation of Matrix Metalloproteinase

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Basak Yildirim, MD; Tolga Guler, MD; Metin Akbulut, MD; Ozer Oztekin, MD; Gulcin Sariiz, MD

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Postgraduate Medicine:

Volume 126 No. 1

Category:

Clinical Features

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DOI: 10.3810/pgm.2014.01.2730
Abstract: Background:The exact pathogenesis of endometriosis has not been completely discerned. 1-alpha,25-dihydroxyvitamin D3 (1,25[OH][2]D[3]) has been shown to have an anti-angiogenic effect and extracellular matrix-proteases-degrading properties. We hypothesized that 1,25(OH)(2)D(3) may have therapeutic value in the treatment of endometriosis.Methods:Endometrial tissue was implanted into the abdominal peritoneum of 21 Wistar albino rats; the rats were randomized into 3 groups. In Group A (simultaneous group), we simultaneously induced endometriosis and began 1,25(OH)(2)D(3) treatment. Group B rats (sequential group) were treated after endometriosis was documented. Animals in Group C (control group) were followed without any treatment after the development of endometriosis.Results:Histologic score, mean volume, and weight of the explants in Group A and B were found to be significantly lower than those of the control group. Levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) immunoreactivities in Group A and B were also significantly lower compared with Group C. In contrast, intensities of immunoreactivity staining for tissue inhibitor of metalloproteinase-2 (TIMP-2) in Group A and B were significantly higher than that of the control group.Conclusion:1,25(OH)(2)D(3) regresses endometriotic implants in rat models by altering implant levels of VEGF, TIMP-2, and MMP-9.

Keywords: 1-alpha,25-dihydroxyvitamin D3; endometriosis; vascular endothelial growth factor; tissue inhibitor of metalloproteinase-2; metalloproteinase-9