Effect of dienogest administration on angiogenesis and hemodynamics in a rat endometrial autograft model
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Dienogest administration suppressed angiogenesis in a rat endometrial autograft model, reducing microvascular network size and density, while altering microvessel structure and perivascular smooth muscle actin levels.
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Abstract
BACKGROUND: We aimed to establish an endometrial autograft model in rats that would allow for repetitive in vivo analyses of angiogenesis. Dienogest (DNG) is an orally active progestin used for the treatment of endometriosis. We investigated whether DNG would affect angiogenesis of the ectopic endometrium in our model. METHODS: Mechanically isolated endometrial fragments were transplanted into dorsal skinfold chambers in rats. We analyzed the effect of DNG on angiogenesis of the ectopic endometrium on Days 0, 2, 4, 7, 10 and 14 after transplantation using intravital fluorescence microscopy. RESULTS: The DNG-administered group showed significant suppression of angiogenesis of endometrial autografts, as indicated by the reduced size of the microvascular network and decreased microvessel density compared with those of control animals. The newly formed microvessels of the DNG-administered group showed consistently elevated diameters and centerline red blood cell velocity was decreased. Immunohistochemistry revealed a significant reduction in the level of perivascular α-smooth muscle actin within endometrial grafts of the DNG-administered group. CONCLUSIONS: DNG inhibited angiogenesis of the ectopic endometrium, with confirmed structural changes in the microvessels.
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