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Hum. Reprod. Advance Access originally published online on February 7, 2008
Human Reproduction 2008 23(4):894-903; doi:10.1093/humrep/den004
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Aberrant expression of angiopoietins-1 and -2 and vascular endothelial growth factor-A in peri-implantation endometrium after gonadotrophin stimulation

Yin-Lau Lee1, Yunao Liu1, Pak-Yiu Ng1, Kai-Fai Lee1, Chak-Leung Au2, Ernest Hung-Yu Ng1, Pak-Chung Ho1 and William Shu-Biu Yeung1,3

1 Department of Obstetrics and Gynaecology, The University of Hong Kong, Queen Mary Hospital, 5/F, Block K, Pokfulam Road, Pokfulam, Hong Kong, China 2 Department of Physiology, The Chinese University of Hong Kong, Shatin, Hong Kong, China

3 Correspondence address. Tel: +852-28553405; Fax: +852-28161947; E-mail: wsbyeung{at}hkucc.hku.hk

BACKGROUND: Ovarian stimulation affects normal endometrial development. The expression of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A) and the vascular state in the peri-implantation endometrium in women with natural and gonadotrophin-stimulated cycles were compared.

METHODS: The expression of these angiogenesis-associated molecules in endometrial biopsies, collected on Day 7 after human chorionic gonadotrophin injection or luteinizing hormone surge in stimulated or natural cycles respectively, or at mid-luteal phase of women undergoing diagnositic laparoscopy, were analysed.

RESULTS: Women with gonadotrophin-stimulation had lower Ang-1, but higher Ang-2, mRNA and protein expression (P < 0.05), and increased concentrations of von Willebrand factor (vWF) and blood vessel density than those with natural cycles (P < 0.05). Although stimulated cycles had higher VEGF-A mRNA expression (P = 0.023), VEGF-A protein expression was similar between the groups. Lower Ang-1/Ang-2 but higher Ang-2/VEGF-A mRNA ratios (P = 0.025) were found after gonadotrophin-stimulation. The ratios were negatively (P < 0.001) and positively correlated (P < 0.001) with estradiol levels, respectively. Cyclical changes in Ang-1 and Ang-2, but not in VEGF-A expression were noted.

CONCLUSIONS: The decreased Ang-1 concentration and Ang-1/Ang-2 ratio and the increased Ang-2 concentration, with the increased vWF concentration and blood vessel density, in stimulated cycles suggests advanced endometrial angiogenesis after gonadotrophin-stimulation.

Key words: angiogenesis/angiopoietin/endometrium/ovarian stimulation/VEGF

Submitted on April 12, 2007; resubmitted on December 15, 2007; accepted on January 2, 2008.


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