Differential expression of angiopoietins 1 and 2 and their receptor Tie-2 in human endometrium

Abstract

Angiogenesis, the growth of new capillaries from pre-existing blood vessels, is a physiological process involved in both normal menstrual cycling and implantation of the embryo. So far, very little is known about the expression of angiopoietins, growth factors involved in angiogenesis, in human endometrium. Both angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) are ligands for the endothelial cell-specific receptor tyrosine kinase Tie-2. In this study we determined the mRNA expression of Ang-1, Ang-2 and Tie-2 by quantitative competitive RT/(QC)-PCR (including specifically designed competitor cDNA) in biopsied human endometrium throughout the menstrual cycle. We detected the mRNA for the angiopoietins in 30 out of 32 endometrial biopsies (94%), covering early proliferative (n = 4), mid proliferative (n = 12), late proliferative (n = 3), early secretory (n = 3), mid secretory (n = 5) and late secretory (n = 3) phases. Analysis of the target/competitor ratios (QC-PCR) revealed that Ang-1 mRNA expression was significantly up-regulated (P = 0.027) during the secretory phase of the menstrual cycle. In contrast, the expression levels of both Ang-2 mRNA and Tie-2 mRNA showed only minor variations at different cycle stages. These findings were confirmed by the relative expression ratio of Ang-1 versus Ang-2 in a multiplex PCR. The expression of Ang-1, Ang-2 and Tie-2 mRNA was detected in both isolated endometrial epithelial and stromal cell fractions. Immunohistochemical localization of the proteins revealed qualitative differences in both cell type and cycle stage expression. In conclusion, the enhanced Ang-1 expression during the secretory phase might serve to stabilize the newly developed blood vessels.

The study of relationship between the expression of VEGF and Ang-2 and Tie-2 in endometriosis

“…The expression of Tie-2 protein was dominated by glandular epithelial cytoplasm, and a small amount of vascular endothelial cells and cytoplasm of interstitial cells were expressed in varying degrees, but weak. This is consistent with the findings of Hirchenhain et al [9] The experiment also showed that Ang-2 and Tie-2 protein expressions in EMs eutopic endometrium group were higher than that in the normal group. This is consistent with the findings of Hur et al, [7] suggesting that endometrium may carry out stronger angiogenic activity.…”

Localization of angiogenic growth factors and their receptors in the human endometrium throughout the menstrual cycle and in recurrent miscarriage

“…Ang-1 has been immunolocalized to all cell types within endometrium (Blumenthal et al, 2002;Saito et al, 2007) and has been reported to either increase (Hirchenhain et al, 2003;Saito et al, 2007) or not alter (Blumenthal et al, 2002;Hur et al, 2006;Lee et al, 2008) as the menstrual cycle progresses. Ang-2 is also widely expressed in endometrium with levels reported to be decreased (Hirchenhain et al, 2003;Saito et al, 2007), unaltered (Blumenthal et al, 2002;Hewett et al, 2002;Hur et al, 2006) or increased (Lee et al, 2008) as the menstrual cycle progresses. Tie-2 expression is also widespread in the endometrium and has been reported to not alter with the menstrual cycle (Blumenthal et al, 2002;Hewett et al, 2002;Hirchenhain et al, 2003;Hur et al, 2006).…”

“…Ang-2 is also widely expressed in endometrium with levels reported to be decreased (Hirchenhain et al, 2003;Saito et al, 2007), unaltered (Blumenthal et al, 2002;Hewett et al, 2002;Hur et al, 2006) or increased (Lee et al, 2008) as the menstrual cycle progresses. Tie-2 expression is also widespread in the endometrium and has been reported to not alter with the menstrual cycle (Blumenthal et al, 2002;Hewett et al, 2002;Hirchenhain et al, 2003;Hur et al, 2006).…”

Regulation of endometrial vascular remodelling: role of the vascular endothelial growth factor family and the angiopoietin–TIE signalling system

“…Staining has been reported variously in the epithelium, stroma and uterine natural killer cells (reviewed in Rogers & Abberton (2003)). In one study, ANG1 immunostaining was observed in stroma, luminal and glandular epithelium, and endothelial cells, whereas ANG2 was detected in the stroma and glandular epithelium (Hirchenhain et al 2003). TIE2 was observed in glandular epithelium, as well as in endometrial endothelium.…”