help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sharkey, A. M.
Right arrow Articles by Charnock-Jones, D. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sharkey, A. M.
Right arrow Articles by Charnock-Jones, D. S.
The Journal of Clinical Endocrinology & Metabolism Vol. 85, No. 1 402-409
Copyright © 2000 by The Endocrine Society

Original Studies

Vascular Endothelial Growth Factor Expression in Human Endometrium Is Regulated by Hypoxia1

A. M. Sharkey, K. Day, A. McPherson, S. Malik, D. Licence, S. K. Smith and D. S. Charnock-Jones

Reproductive Molecular Research Group, Department of Obstetrics and Gynecology, University of Cambridge, Rosie Hospital, Cambridge, United Kingdom CB2 2SW

Address all correspondence and requests for reprints to: Dr. Andrew Sharkey, Department of Obstetrics and Gynecology, University of Cambridge, Box 223, Rosie Maternity Hospital, Robinson Way, Cambridge, United Kingdom CB2 2SW. E-mail: ams{at}mole.bio.cam.ac.uk

Endometrial growth and repair after menstruation are associated with profound angiogenesis. Abnormalities in these processes result in excessive or unpredictable bleeding patterns and are common in many women. It is therefore important to understand which factors regulate normal endometrial angiogenesis. Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen that plays an important role in normal and pathological angiogenesis. In this study we show that expression of VEGF is regulated by hypoxia in human endometrium. Culture in vitro for 24 h under hypoxic conditions resulted in a 2- to 6-fold increase in VEGF secretion by both stromal and epithelial cells isolated from human endometrium. Quantitative RT-PCR was used to measure VEGF messenger ribonucleic acid (mRNA) levels in these cells. After hypoxia, VEGF mRNA levels increased 1.8-fold in stromal cells and 3.4-fold in glandular epithelial cells. The mRNA for each VEGF splice variant increased to an equal extent. The increase in VEGF secretion by stromal and epithelial cells in response to hypoxia was not altered by treatment at the same time with estradiol or progesterone. In situ hybridization of human endometrium during menstruation, when steroid levels are low but the tissue is subject to ischemia, showed strong hybridization to VEGF mRNA in both stromal and glandular cells. These results show that local factors, such as hypoxia, can regulate VEGF expression in the endometrium. This may play an important part in normal endometrial repair after menstruation. The secretion of VEGF by endometrial cells under hypoxic conditions may also be important in the pathogenesis of endometriosis, because it would be predicted to assist revascularization of desquamated endometrial explants when they attach at ectopic sites.




This article has been cited by other articles:


Home page
 Hum ReprodHome page
E. W. S. So, E. H. Y. Ng, Y. Y. Wong, E. Y. L. Lau, W. S. B. Yeung, and P. C. Ho
A randomized double blind comparison of real and placebo acupuncture in IVF treatment
Hum. Reprod., November 12, 2008; (2008) den380v3.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
M. Plaisier, I. Dennert, E. Rost, P. Koolwijk, V.W.M. van Hinsbergh, and F.M. Helmerhorst
Decidual vascularization and the expression of angiogenic growth factors and proteases in first trimester spontaneous abortions
Hum. Reprod., October 14, 2008; (2008) den296v1.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
X. Fan, S. Krieg, C. J. Kuo, S. J. Wiegand, M. Rabinovitch, M. L. Druzin, R. M. Brenner, L. C. Giudice, and N. R. Nayak
VEGF blockade inhibits angiogenesis and reepithelialization of endometrium
FASEB J, October 1, 2008; 22(10): 3571 - 3580.
[Abstract] [Full Text] [PDF]

Home page
 Reproductive SciencesHome page
M. Plaisier, E. Streefland, P. Koolwijk, V.W.M. van Hinsbergh, F.M. Helmerhorst, and J.J.H.M. Erwich
Angiogenic Growth Factors and Their Receptors in First-Trimester Human Decidua of Pregnancies Further Complicated By Preeclampsia or Fetal Growth Restriction
Reproductive Sciences, September 1, 2008; 15(7): 720 - 726.
[Abstract] [PDF]

Home page
 Am. J. Pathol.Home page
M. L. Hull, C. R. Escareno, J. M. Godsland, J. R. Doig, C. M. Johnson, S. C. Phillips, S. K. Smith, S. Tavare, C. G. Print, and D. S. Charnock-Jones
Endometrial-Peritoneal Interactions during Endometriotic Lesion Establishment
Am. J. Pathol., September 1, 2008; 173(3): 700 - 715.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
I. Gashaw, S. Stiller, C. Boing, R. Kimmig, and E. Winterhager
Premenstrual Regulation of the Pro-Angiogenic Factor CYR61 in Human Endometrium
Endocrinology, May 1, 2008; 149(5): 2261 - 2269.
[Abstract] [Full Text] [PDF]

Home page
 Hum Reprod UpdateHome page
P.G. Groothuis, H.H.N.M. Dassen, A. Romano, and C. Punyadeera
Estrogen and the endometrium: lessons learned from gene expression profiling in rodents and human
Hum. Reprod. Update, July 1, 2007; 13(4): 405 - 417.
[Abstract] [Full Text] [PDF]

Home page
 Hum Reprod UpdateHome page
M. W. Laschke and M. D. Menger
In vitro and in vivo approaches to study angiogenesis in the pathophysiology and therapy of endometriosis
Hum. Reprod. Update, July 1, 2007; 13(4): 331 - 342.
[Abstract] [Full Text] [PDF]

Home page
 ReproductionHome page
V Bourlev, N Volkov, S Pavlovitch, N Lets, A Larsson, and M Olovsson
The relationship between microvessel density, proliferative activity and expression of vascular endothelial growth factor-A and its receptors in eutopic endometrium and endometriotic lesions.
Reproduction, September 1, 2006; 132(3): 501 - 509.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. Hickey, G. Krikun, P. Kodaman, F. Schatz, C. Carati, and C. J. Lockwood
Long-Term Progestin-Only Contraceptives Result in Reduced Endometrial Blood Flow and Oxidative Stress
J. Clin. Endocrinol. Metab., September 1, 2006; 91(9): 3633 - 3638.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
S. Malik, K. Day, I. Perrault, D.S. Charnock-Jones, and S. K. Smith
Reduced levels of VEGF-A and MMP-2 and MMP-9 activity and increased TNF-{alpha} in menstrual endometrium and effluent in women with menorrhagia
Hum. Reprod., August 1, 2006; 21(8): 2158 - 2166.
[Abstract] [Full Text] [PDF]

Home page
 Mol Hum ReprodHome page
C. Punyadeera, V.L. Thijssen, S. Tchaikovski, R. Kamps, B. Delvoux, G.A.J. Dunselman, A.F.P.M. de Goeij, A.W. Griffioen, and P.G. Groothuis
Expression and regulation of vascular endothelial growth factor ligands and receptors during menstruation and post-menstrual repair of human endometrium
Mol. Hum. Reprod., June 1, 2006; 12(6): 367 - 375.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
E. H. Y. Ng, C. C. W. Chan, O. S. Tang, W. S. B. Yeung, and P. C. Ho
The role of endometrial and subendometrial vascularity measured by three-dimensional power Doppler ultrasound in the prediction of pregnancy during frozen-thawed embryo transfer cycles
Hum. Reprod., June 1, 2006; 21(6): 1612 - 1617.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
N. J. Davie, E. V. Gerasimovskaya, S. E. Hofmeister, A. P. Richman, P. L. Jones, J. T. Reeves, and K. R. Stenmark
Pulmonary Artery Adventitial Fibroblasts Cooperate with Vasa Vasorum Endothelial Cells to Regulate Vasa Vasorum Neovascularization: A Process Mediated by Hypoxia and Endothelin-1
Am. J. Pathol., June 1, 2006; 168(6): 1793 - 1807.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
I. Gashaw, J. M. Hastings, K. S. Jackson, E. Winterhager, and A. T. Fazleabas
Induced Endometriosis in the Baboon (Papio anubis) Increases the Expression of the Proangiogenic Factor CYR61 (CCN1) in Eutopic and Ectopic Endometria
Biol Reprod, June 1, 2006; 74(6): 1060 - 1066.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
H. N. Jabbour, R. W. Kelly, H. M. Fraser, and H. O. D. Critchley
Endocrine Regulation of Menstruation
Endocr. Rev., February 1, 2006; 27(1): 17 - 46.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
H. O. D. Critchley, J. Osei, T. A. Henderson, L. Boswell, K. J. Sales, H. N. Jabbour, and N. Hirani
Hypoxia-Inducible Factor-1{alpha} Expression in Human Endometrium and Its Regulation by Prostaglandin E-Series Prostanoid Receptor 2 (EP2)
Endocrinology, February 1, 2006; 147(2): 744 - 753.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
E. H. Y. Ng, C. C. W. Chan, O. S. Tang, W. S. B. Yeung, and P. C. Ho
The role of endometrial and subendometrial blood flows measured by three-dimensional power Doppler ultrasound in the prediction of pregnancy during IVF treatment
Hum. Reprod., January 1, 2006; 21(1): 164 - 170.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
M. Tesone, R. L. Stouffer, S. M. Borman, J. D. Hennebold, and T. A. Molskness
Vascular Endothelial Growth Factor (VEGF) Production by the Monkey Corpus Luteum During the Menstrual Cycle: Isoform-Selective Messenger RNA Expression In Vivo and Hypoxia-Regulated Protein Secretion In Vitro
Biol Reprod, November 1, 2005; 73(5): 927 - 934.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
H. Koshiba, J. Kitawaki, M. Teramoto, Y. Kitaoka, H. Ishihara, H. Obayashi, M. Ohta, H. Hara, T. Adachi, and H. Honjo
Expression of Allograft Inflammatory Factor-1 in Human Eutopic Endometrium and Endometriosis: Possible Association with Progression of Endometriosis
J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 529 - 537.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
N.J. Raine-Fenning, B.K. Campbell, N.R. Kendall, J.S. Clewes, and I.R. Johnson
Endometrial and subendometrial perfusion are impaired in women with unexplained subfertility
Hum. Reprod., November 1, 2004; 19(11): 2605 - 2614.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
E.S. Hayes, E.C. Curnow, A.O. Trounson, L.A. Danielson, and E.N. Unemori
Implantation and Pregnancy Following In Vitro Fertilization and the Effect of Recombinant Human Relaxin Administration in Macaca fascicularis
Biol Reprod, November 1, 2004; 71(5): 1591 - 1597.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
P D Taylor, S G Hillier, and H M Fraser
Effects of GnRH antagonist treatment on follicular development and angiogenesis in the primate ovary
J. Endocrinol., October 1, 2004; 183(1): 1 - 17.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
C. Print, R. Valtola, A. Evans, K. Lessan, S. Malik, and S. Smith
Soluble factors from human endometrium promote angiogenesis and regulate the endothelial cell transcriptome
Hum. Reprod., October 1, 2004; 19(10): 2356 - 2366.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
A. W. Nap, A. W. Griffioen, G. A. J. Dunselman, J. C. A. Bouma-Ter Steege, V. L. J. L. Thijssen, J. L. H. Evers, and P. G. Groothuis
Antiangiogenesis Therapy for Endometriosis
J. Clin. Endocrinol. Metab., March 1, 2004; 89(3): 1089 - 1095.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
C. J. Lockwood, P. Kumar, G. Krikun, S. Kadner, P. Dubon, H. Critchley, and F. Schatz
Effects of Thrombin, Hypoxia, and Steroids on Interleukin-8 Expression in Decidualized Human Endometrial Stromal Cells: Implications for Long-Term Progestin-Only Contraceptive-Induced Bleeding
J. Clin. Endocrinol. Metab., March 1, 2004; 89(3): 1467 - 1475.
[Abstract] [Full Text] [PDF]

Home page
 Mol Hum ReprodHome page
J. Hirchenhain, I. Huse, A. Hess, P. Bielfeld, F. De Bruyne, and J. S. Krussel
Differential expression of angiopoietins 1 and 2 and their receptor Tie-2 in human endometrium
Mol. Hum. Reprod., November 1, 2003; 9(11): 663 - 669.
[Abstract] [Full Text] [PDF]

Home page
 Mol Hum ReprodHome page
B. Malette, E. Cherry, M. Lagace, M. Bernard, D. Gosselin, P. Hugo, and K. Shazand
Large scale validation of human N-myc Downstream-Regulated Gene (NDRG)-1 expression in endometrium during the menstrual cycle
Mol. Hum. Reprod., November 1, 2003; 9(11): 671 - 679.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
E. D. Albrecht, J. S. Babischkin, Y. Lidor, L. D. Anderson, L. C. Udoff, and G. J. Pepe
Effect of estrogen on angiogenesis in co-cultures of human endometrial cells and microvascular endothelial cells
Hum. Reprod., October 1, 2003; 18(10): 2039 - 2047.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. L. Hull, D. S. Charnock-Jones, C. L. K. Chan, K. L. Bruner-Tran, K. G. Osteen, B. D. M. Tom, T.-P. D. Fan, and S. K. Smith
Antiangiogenic Agents Are Effective Inhibitors of Endometriosis
J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2889 - 2899.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
A. L. Niklaus, G. W. Aberdeen, J. S. Babischkin, G. J. Pepe, and E. D. Albrecht
Effect of Estrogen on Vascular Endothelial Growth/Permeability Factor Expression by Glandular Epithelial and Stromal Cells in the Baboon Endometrium
Biol Reprod, June 1, 2003; 68(6): 1997 - 2004.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
J.B. Laoag-Fernandez, T. Maruo, P. Pakarinen, I.M. Spitz, and E. Johansson
Effects of levonorgestrel-releasing intra-uterine system on the expression of vascular endothelial growth factor and adrenomedullin in the endometrium in adenomyosis
Hum. Reprod., April 1, 2003; 18(4): 694 - 699.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
J.C. Martinez-Chequer, R.L. Stouffer, T.M. Hazzard, P.E. Patton, and T.A. Molskness
Insulin-Like Growth Factors-1 and -2, but not Hypoxia, Synergize with Gonadotropin Hormone to Promote Vascular Endothelial Growth Factor-A Secretion by Monkey Granulosa Cells from Preovulatory Follicles
Biol Reprod, April 1, 2003; 68(4): 1112 - 1118.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
J. M. Hastings, D. R. Licence, G. J. Burton, D. S. Charnock-Jones, and S. K. Smith
Soluble Vascular Endothelial Growth Factor Receptor 1 Inhibits Edema and Epithelial Proliferation Induced by 17{beta}-Estradiol in the Mouse Uterus
Endocrinology, January 1, 2003; 144(1): 326 - 334.
[Abstract] [Full Text] [PDF]

Home page
 Mol Hum ReprodHome page
M. von Wolff, S. Stieger, K. Lumpp, J. Bucking, T. Strowitzki, and C.J. Thaler
Endometrial interleukin-6 in vitro is not regulated directly by female steroid hormones, but by pro-inflammatory cytokines and hypoxia
Mol. Hum. Reprod., December 1, 2002; 8(12): 1096 - 1102.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. L. Niklaus, J. S. Babischkin, G. W. Aberdeen, G. J. Pepe, and E. D. Albrecht
Expression of Vascular Endothelial Growth/Permeability Factor by Endometrial Glandular Epithelial and Stromal Cells in Baboons during the Menstrual Cycle and after Ovariectomy
Endocrinology, October 1, 2002; 143(10): 4007 - 4017.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
C. J. Lockwood, G. Krikun, A. B. C. Koo, S. Kadner, and F. Schatz
Differential Effects of Thrombin and Hypoxia on Endometrial Stromal and Glandular Epithelial Cell Vascular Endothelial Growth Factor Expression
J. Clin. Endocrinol. Metab., September 1, 2002; 87(9): 4280 - 4286.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
G. Krikun, H. Critchley, F. Schatz, L. Wan, R. Caze, R. N. Baergen, and C. J. Lockwood
Abnormal Uterine Bleeding during Progestin-Only Contraception May Result from Free Radical-Induced Alterations in Angiopoietin Expression
Am. J. Pathol., September 1, 2002; 161(3): 979 - 986.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
N. R. Nayak and R. M. Brenner
Vascular Proliferation and Vascular Endothelial Growth Factor Expression in the Rhesus Macaque Endometrium
J. Clin. Endocrinol. Metab., April 1, 2002; 87(4): 1845 - 1855.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
K. S. Mark and T. P. Davis
Cerebral microvascular changes in permeability and tight junctions induced by hypoxia-reoxygenation
Am J Physiol Heart Circ Physiol, April 1, 2002; 282(4): H1485 - H1494.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
R. Kats, C. N. Metz, and A. Akoum
Macrophage Migration Inhibitory Factor Is Markedly Expressed in Active and Early-Stage Endometriotic Lesions
J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 883 - 889.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
J. Zhang and L.A. Salamonsen
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
Hum. Reprod., February 1, 2002; 17(2): 265 - 274.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
S. A. Milne, G. B. Perchick, S. C. Boddy, and H. N. Jabbour
Expression, Localization, and Signaling of PGE2 and EP2/EP4 Receptors in Human Nonpregnant Endometrium across the Menstrual Cycle
J. Clin. Endocrinol. Metab., September 1, 2001; 86(9): 4453 - 4459.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
M. D. Graubert, M. Asuncion Ortega, B. Kessel, J. F. Mortola, and M. L. Iruela-Arispe
Vascular Repair After Menstruation Involves Regulation of Vascular Endothelial Growth Factor-Receptor Phosphorylation by sFLT-1
Am. J. Pathol., April 1, 2001; 158(4): 1399 - 1410.
[Abstract] [Full Text] [PDF]

Home page
 Mol Hum ReprodHome page
B. Moller, C. Rasmussen, B. Lindblom, and M. Olovsson
Expression of the angiogenic growth factors VEGF, FGF-2, EGF and their receptors in normal human endometrium during the menstrual cycle
Mol. Hum. Reprod., January 1, 2001; 7(1): 65 - 72.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
N. R. Nayak, H. O. D. Critchley, O. D. Slayden, A. Menrad, K. Chwalisz, D. T. Baird, and R. M. Brenner
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
J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3442 - 3452.
[Abstract] [Full Text]

Home page
 Mol Hum ReprodHome page
L.L. Nikitenko, I.Z. MacKenzie, M.C.P. Rees, and R. Bicknell
Adrenomedullin is an autocrine regulator of endothelial growth in human endometrium
Mol. Hum. Reprod., September 1, 2000; 6(9): 811 - 819.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2000 by The Endocrine Society