Expression and regulation of vascular endothelial growth factor ligands and receptors during menstruation and post-menstrual repair of human endometrium

Punyadeera, C., Thijssen, V.L., Tchaikovski, S., Kamps, R., Delvoux, B., Dunselman, G.A.J., de Goeij, A.F.P.M., Griffioen, A.W., & Groothuis, P.G. (2006) Expression and regulation of vascular endothelial growth factor ligands and receptors during menstruation and post-menstrual repair of human endometrium. Molecular Human Reproduction, 12(6), pp. 367-375.

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Regeneration and growth of the human endometrium after shedding of the functional layer during menstruation depends on an adequate angiogenic response. We analysed the mRNA expression levels of all known vascular endothelial growth factor (VEGF) ligands and receptors in human endometrium collected in the menstrual and proliferative phases of the menstrual cycle. In addition, we evaluated the expression of VEGF-A, VEGF-R2 and NRP-1 at the protein level. Two periods of elevated mRNA expression of ligands and receptors were observed, separated by a distinct drop at cycle days (CDs) 9 and 10. Immunohistochemical staining showed that VEGF and VEGF-R2 were expressed in epithelial, stromal and endothelial cells. NRP-1 was mainly confined to stroma and blood vessels; only in late-proliferative endometrium, epithelial staining was also observed. Except for endothelial VEGF-R2 expression in CDs 6-8, there were no significant differences in the expression of VEGF, VEGF-R2 or NRP-1 in any of the cell compartments. In contrast, VEGF release by cultured human endometrium explants decreased during the proliferative phase. This output was significantly reduced in menstrual and early-proliferative endometrium by estradiol (E2) treatment. Western blot analysis indicated that part of the VEGF-A was trapped in the extracellular matrix (ECM). Changes in VEGF ligands and receptors were associated with elevated expression of the hypoxia markers HIF1 alpha and CA-IX in the menstrual and early proliferative phases. HIF1 alpha was also detected in late-proliferative phase endometrium. Our findings indicate that VEGF-A exerts its actions mostly during the first half of the proliferative phase. Furthermore, VEGF-A production appears to be triggered by hypoxia in the menstrual phase and subsequently suppressed toy estrogen during the late proliferative phase.

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ID Code: 77812
Item Type: Journal Article
Refereed: Yes
Additional Information: Articles free to read on journal website after 12 months
Keywords: angiogenesis, ECM, gene-expression profiling, human endometrium, hypoxia, menstrual cycle, neuropilin, estrogen, VEGF and VEGF receptor, cycling human endometrium, rhesus macaque endometrium, factor vegf, matrix-metalloproteinases, epithelial-cells, gene-expression, messenger-rna, stromal cells, estrogen, angiogenesis
DOI: 10.1093/molehr/ga1027
ISSN: 1360-9947
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Copyright Owner: Copyright 2006 The Author
Copyright Statement: Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.
Deposited On: 19 Oct 2014 23:25
Last Modified: 05 Feb 2015 03:33

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