1-alpha,25-dihydroxyvitamin D3 regresses endometriotic implants in rats by inhibiting neovascularization and altering regulation of matrix metalloproteinase.

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.