Effect of dienogest administration on angiogenesis and hemodynamics in a rat endometrial autograft model.
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.
Katayama
Hiroko
H
Department of Obstetrics & Gynecology, Graduate School of Medicine, Ehime University, Shitsukawa Toon, Ehime, Japan.
Katayama
Tomihiro
T
Uematsu
Kazuhiko
K
Hiratsuka
Mie
M
Kiyomura
Masaki
M
Shimizu
Yutaka
Y
Sugita
Atsuro
A
Ito
Masaharu
M
D000818:Animals; D004715:Endometriosis; D004717:Endometrium / Q000098:blood supply* / Q000637:transplantation*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D009277:Nandrolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
C023635:dienogest; D009277:Nandrolone