Aberrant expression of angiopoietins-1 and -2 and vascular endothelial growth factor-A in peri-implantation endometrium after gonadotrophin stimulation.
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.
Lee
Yin-Lau
YL
Department of Obstetrics and Gynaecology, The University of Hong Kong, Queen Mary Hospital, 5/F, Block K, Pokfulam Road, Pokfulam, Hong Kong, China.
Liu
Yunao
Y
Ng
Pak-Yiu
PY
Lee
Kai-Fai
KF
Au
Chak-Leung
CL
Ng
Ernest Hung-Yu
EH
Ho
Pak-Chung
PC
Yeung
William Shu-Biu
WS
D000328:Adult; D042683:Angiopoietin-1 / Q000378:metabolism*; D042702:Angiopoietin-2 / Q000378:metabolism*; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D010064:Embryo Implantation / Q000235:genetics; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008183:Luteal Phase; D010062:Ovulation Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D006063:Chorionic Gonadotropin; D042461:Vascular Endothelial Growth Factor A