Hum. Reprod. Advance Access originally published online on December 16, 2008
Human Reproduction 2009 24(3):608-618; doi:10.1093/humrep/den417
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Anti-angiogenic effects of green tea catechin on an experimental endometriosis mouse model
Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong
1 Correspondence address. Tel: +852-2632-2810; Fax: +852-2636-0008; E-mail: ccwang{at}cuhk.edu.hk (C.C.W.)/msrogers{at}cuhk.edu.hk (M.S.R.)
BACKGROUND: The development of new blood vessels plays an essential role in growth and survival of endometriosis. Epigallocatechin gallate (EGCG) from green tea has powerful anti-angiogenic properties and our aim was to evaluate these properties in experimental endometriosis.
METHODS AND RESULTS: Eutopic endometrium from endometriosis patients was transplanted s.c. to severely compromised immunodeficient mice, randomly treated i.p. with EGCG (anti-angiogenic and -oxidant), Vitamin E (a non-angiogenic antioxidant) or saline for 2 weeks. The endometrial implant, including adjacent host outer skin and subcutaneous layers plus inner abdominal muscle and peritoneum, was collected. New microvessels were determined by species-specific immunohistochemistry. Angiogenic factors in lesions and abdominal muscle were detected by quantitative real-time PCR. Apoptosis was studied by terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling and quantitative real-time PCR. In saline control, endometrial implants developed new blood vessels with proliferating glandular epithelium and were tightly adhered to host subcutaneous and abdominal muscle layers. After EGCG, endometriotic lesions were smaller than control (P < 0.05), and glandular epithelium was smaller and eccentrically distributed. Angiogenesis in lesions from the implant and adjacent tissues was under-developed, and microvessel size and density were lower (both P < 0.01) than control. mRNA for angiogenic vascular endothelial growth factor A, but not hypoxia inducible factor 1, alpha subunit, was significantly down-regulated in lesions after EGCG (P < 0.05). In addition, apoptosis in the lesions was more obvious, and nuclear factor kappa B and mitogen activated protein kinase 1 mRNA levels were up-regulated (P < 0.05) after EGCG treatment. No differences were observed with Vitamin E treatment.
CONCLUSIONS: EGCG significantly inhibits the development of experimental endometriosis through anti-angiogenic effects.
Key words: angiogenesis/vascular endothelial growth factor/green tea/catechin/endometriosis
Submitted on July 27, 2008; resubmitted on October 23, 2008; accepted on October 30, 2008.