Effect of dienogest administration on angiogenesis and hemodynamics in a rat endometrial autograft model

被引：53

作者：

Katayama, Hiroko ^{[1
]}

Katayama, Tomihiro ^{[1
]}

Uematsu, Kazuhiko ^{[1
]}

Hiratsuka, Mie ^{[2
]}

Kiyomura, Masaki ^{[1
]}

Shimizu, Yutaka ^{[3
]}

Sugita, Atsuro ^{[4
]}

Ito, Masaharu ^{[1
]}

机构：

[1] Ehime Univ, Grad Sch Med, Dept Obstet & Gynecol, Shitsukawa Toon, Ehime 7910295, Japan

[2] Fukui Womens Clin, Matsuyama, Ehime 7900922, Japan

[3] Mochida Pharmaceut Co Ltd, Pharmaceut Res Ctr, Gotemba 4128524, Japan

[4] Ehime Univ Hosp, Div Pathol, Shitsukawa Toon, Ehime 7910295, Japan

来源：

HUMAN REPRODUCTION | 2010年 / 25卷 / 11期

关键词：

dienogest; endometriosis; angiogenesis; dorsal skinfold chamber; intravital fluorescence microscopy; DEPOT MEDROXYPROGESTERONE ACETATE; GROWTH-FACTOR; PROGESTERONE-RECEPTORS; LEUPROLIDE ACETATE; STROMAL CELLS; EXPRESSION; LESIONS; STIMULATION; INHIBITION; MANAGEMENT;

D O I：

10.1093/humrep/deq241

中图分类号：

R71 [妇产科学];

学科分类号：

100211 ;

摘要：

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. 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. 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 alpha-smooth muscle actin within endometrial grafts of the DNG-administered group. DNG inhibited angiogenesis of the ectopic endometrium, with confirmed structural changes in the microvessels.

引用

页码：2851 / 2858

页数：8

共 37 条

[11] Image analysis measurements of the microvascularisation in endometrium, superficial and deep endometriotic tissues [J].

Jondet M. ;

Vacher-Lavenu M.C. ;

Chapron C. ;

Vacher-Lavenu M.C. ;

Chapron C. .

Angiogenesis, 2006, 9 (4) :177-182

[12] ESHRE guideline for the diagnosis and treatment of endometriosis [J].

Kennedy, S ;

Bergqvist, A ;

Chapron, C ;

D'Hooghe, T ;

Dunselman, G ;

Greb, R ;

Hummelshoj, L ;

Prentice, A ;

Saridogan, E .

HUMAN REPRODUCTION, 2005, 20 (10) :2698-2704

[13] Rapamycin induces regression of endometriotic lesions by inhibiting neovascularization and cell proliferation [J].

Laschke, M. W. ;

Elitzsch, A. ;

Scheuer, C. ;

Holstein, J. H. ;

Vollmar, B. ;

Menger, M. D. .

BRITISH JOURNAL OF PHARMACOLOGY, 2006, 149 (02) :137-144

[14] Selective cyclo-oxygenase-2 inhibition induces regression of autologous endometrial grafts by down-regulation of vascular endothelial growth factor-mediated angiogenesis and stimulation of caspase-3-dependent apoptosis [J].

Laschke, Matthias W. ;

Elitzsch, Antje ;

Scheuer, Claudia ;

Vollmar, Brigitte ;

Menger, Michael D. .

FERTILITY AND STERILITY, 2007, 87 (01) :163-171

[15] In vitro and in vivo approaches to study angiogenesis in the pathophysiology and therapy of endometriosis [J].

Laschke, Matthias W. ;

Menger, Michael D. .

HUMAN REPRODUCTION UPDATE, 2007, 13 (04) :331-342

[16] Combined inhibition of vascular endothelial growth factor (VEGF), fibroblast growth factor and platelet-derived growth factor, but not inhibition of VEGF alone, effectively suppresses angiogenesis and vessel maturation in endometriotic lesions [J].

Laschke, MW ;

Elitzsch, A ;

Vollmar, B ;

Vajkoczy, P ;

Menger, MD .

HUMAN REPRODUCTION, 2006, 21 (01) :262-268

[17] In vivo analysis of angiogenesis in endometriosis-like lesions by intravital fluorescence microscopy [J].

Laschke, MW ;

Elitzsch, A ;

Vollmar, B ;

Menger, MD .

FERTILITY AND STERILITY, 2005, 84 :1199-1209

[18] IMMUNOHISTOCHEMICAL ANALYSIS OF HUMAN UTERINE ESTROGEN AND PROGESTERONE RECEPTORS THROUGHOUT THE MENSTRUAL-CYCLE [J].

LESSEY, BA ;

KILLAM, AP ;

METZGER, DA ;

HANEY, AF ;

GREENE, GL ;

MCCARTY, KS .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1988, 67 (02) :334-340

[19] ESTRADIOL AND PROGESTERONE RECEPTORS IN HUMAN-ENDOMETRIUM - NORMAL AND ABNORMAL MENSTRUAL CYCLES AND EARLY-PREGNANCY [J].

LEVY, C ;

ROBEL, P ;

GAUTRAY, JP ;

DEBRUX, J ;

VERMA, U ;

DESCOMPS, B ;

BAULIEU, EE ;

EYCHENNE, B .

AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY, 1980, 136 (05) :646-651

[20] Medical management of endometriosis-associated pain [J].

Mahutte, NG ;

Arici, A .

OBSTETRICS AND GYNECOLOGY CLINICS OF NORTH AMERICA, 2003, 30 (01) :133-+

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