Hypoxia and cAMP Stimulate Vascular Endothelial Growth Factor (VEGF) in Human Endometrial Stromal Cells: Potential Relevance to Menstruation and Endometrial Regeneration
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Abstract
The human female reproductive tract shows unique cycle-specific changes in vascularization. Vascular endothelial growth factor (VEGF) is a specific vascular endothelial mitogen which is produced by human endometrium and is known to be regulated by steroid hormones. Vasoconstriction during menstruation leads to endometrial hypoxia, a possible stimulus for angiogenesis. In the current study we tested the hypothesis that hypoxia and cAMP, a known stimulus for endometrial decidualization, can induce VEGF in human endometrial stromal cells. Decidualized as well as non decidualized stromal cells from 6 patients were exposed to normoxia (20% oxygen) and hypoxia (2% oxygen) for up to 72h. VEGF levels were assessed by Northern analysis using a 605 bp BamHI fragment of the human VEGF cDNA, and hybridization signals were normalized to levels of 18S RNA. VEGF protein was determined by ELISA. Hypoxia stimulated VEGF in decidualized stromal cells by 10.2 fold at 48h compared to normoxic controls. VEGF protein increased 10 fold by 48h and increased further to 13 fold at 72h. In the presence of 2% oxygen VEGF mRNA in nondecidualized endometrial stromal cells was increased 1.2–8 fold between 2 and 72h of treatment. VEGF protein also increased1.2–9 fold in this time period. cAMP regulated both VEGF mRNA and protein in non decidualized stromal cells. VEGF mRNA increased 2–4 fold in 2–72h and protein production showed a 2–6 fold increase. VEGF was seen to be regulated by both cAMP and hypoxia in an additive manner. These results demonstrate that both non-decidualized and decidualized endometrial stromal cells respond to hypoxia with increasing levels of VEGF. 8Br-cAMP, which is shown to increase VEGF levels in endometrial cells per se, has an additive effect on VEGF production under hypoxic conditions. This effect may have physiologic and pathophysiologic relevance during the process of menstruation and in post menstrual endometrial repair and angiogenesis.
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Cited by (25)
- Circulating Vascular Endothelial Growth Factor and Soluble fms-Like Tyrosine Kinase-1 as Biomarkers for Endometrial Remodeling Across the Menstrual Cycle 2020
- Overexpression of Four Joint Box-I Protein (FJXI) in Eutopic Endometrium From Women With Endometriosis 2017
- Hypoxia-inducible factor-1alpha: A promising therapeutic target in endometriosis 2016
- Quantitative analysis of expression level of estrogen and progesterone receptors and VEGF genes in human endometrial stromal cells after treatment with nicotine 2016
- Hypoxia is not required for human endometrial breakdown or repair in a xenograft model of menstruation 2013
- Alteration in Endometrial Remodeling: A Cause for Implantation Failure in Endometriosis? 2012
- Angiogenesis and Endometriosis 2011
- Best Practice & Research Clinical Obstetrics and Gynaecology 2009
- Abnormal bleeding in postmenopausal hormone users—What do we know today? 2009
- Bleeding with menopausal hormone therapy 2008
- Aberrant Expression of Leptin in Human Endometriotic Stromal Cells Is Induced by Elevated Levels of Hypoxia Inducible Factor-1α 2007
- Regulation of human endometrial function: mechanisms relevant to uterine bleeding 2006
- Assessment of changes in endometrial and subendometrial volume and vascularity during the normal menstrual cycle using three‐dimensional power Doppler ultrasound 2006
- Endocrine Regulation of Menstruation 2005
- Endocrine Regulation of Menstruation 2005
- Changes in vascular endothelial growth factor production associated with decidualization by human endometrial stromal cells <i>in vitro</i> 2004
- VEGF, bFGF, and their receptors in the endometrium of rhesus monkey during menstrual cycle and early pregnancy 2004
- Progestin-regulated expression of tissue factor in decidual cells: implications in endometrial hemostasis, menstruation and angiogenesis 2003
- Differential Effects of Thrombin and Hypoxia on Endometrial Stromal and Glandular Epithelial Cell Vascular Endothelial Growth Factor Expression 2002
- Expression of hypoxia-inducible factors in human endometrium and suppression of matrix metalloproteinases under hypoxic conditions do not support a major role for hypoxia in regulating tissue breakdown at menstruation 2002
- Endometriose und Angiogenese 2002
- Endometrial angiogenesis throughout the human menstrual cycle 2001
- Vascular Repair After Menstruation Involves Regulation of Vascular Endothelial Growth Factor-Receptor Phosphorylation by sFLT-1 2001
- Vascular endothelial growth factor mRNA in eutopic and ectopic endometrium 2001
- Progesterone Withdrawal Up-Regulates Vascular Endothelial Growth Factor Receptor Type 2 in the Superficial Zone Stroma of the Human and Macaque Endometrium: Potential Relevance to Menstruation* 2000
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- last seen: 2026-06-04T00:00:01.174412+00:00
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