This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Walter, L. M Articles by Girling, J. E Search for Related Content PubMed PubMed Citation Articles by Walter, L. M Articles by Girling, J. E

The role of progesterone in endometrial angiogenesis in pregnant and ovariectomised mice

Centre for Women’s Health Research, Monash University Department of Obstetrics and Gynaecology, Monash Medical Centre, 246 Clayton Rd, Clayton, Victoria, Australia 3168

Correspondence should be addressed to J Girling; Email: jane.girling{at}med.monash.edu.au

The role of progesterone (and oestrogen) in endometrial angiogenesis remains controversial. The aims of this study were to quantify endometrial angiogenesis in pregnant mice and to investigate the role of progesterone in promoting endothelial cell proliferation in ovariectomized mice. Uteri were collected on days 1 to 4 of pregnancy when circulating progesterone concentrations were increasing, prior to implantation. Before dissection, mice were injected with bromodeoxyuridine (BrdU) enabling proliferating endothelial cells to be quantified with CD31/BrdU double-immunohistochemistry. There was a significant increase in proliferating endothelial cells on day 3 of pregnancy when plasma progesterone also increased. To determine if this endothelial cell proliferation was due to progesterone, an experiment was performed on ovariectomised mice. One group was treated with a single oestradiol injection on day 8 after ovariectomy, followed by a no-treatment day and three consecutive daily injections of progesterone. Other groups were treated with either the vehicle, oestradiol or progesterone injections only; all were dissected on day 13 following ovariectomy. Unexpectedly, mice treated with progesterone-only had the highest amount of endothelial cell proliferation and oestrogen priming was found to significantly reduce this progesterone-induced endothelial cell proliferation. To determine if this proliferation is mediated by vascular endothelial growth factor (VEGF), a further experiment in which VEGF anti-serum was administered concurrently with the progesterone injections was performed. Endothelial cell proliferation was reduced but not abolished suggesting progesterone-induced endometrial angiogenesis is only partly mediated by VEGF. Results indicate that oestrogen priming is not required for progesterone to stimulate endometrial endothelial cell proliferation and that oestrogen inhibits progesterone-induced angiogenesis in ovariectomised mice.

This article has been cited by other articles:

				J. E Girling and P. A W Rogers Regulation of endometrial vascular remodelling: role of the vascular endothelial growth factor family and the angiopoietin-TIE signalling system Reproduction, December 1, 2009; 138(6): 883 - 893. [Abstract] [Full Text] [PDF]

				R.G. Craythorn, J.E. Girling, M.P. Hedger, P.A.W. Rogers, and W.R. Winnall An RNA spiking method demonstrates that 18S rRNA is regulated by progesterone in the mouse uterus Mol. Hum. Reprod., November 1, 2009; 15(11): 757 - 761. [Abstract] [Full Text] [PDF]

				N. C. Douglas, H. Tang, R. Gomez, B. Pytowski, D. J. Hicklin, C. M. Sauer, J. Kitajewski, M. V. Sauer, and R. C. Zimmermann Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2) Functions to Promote Uterine Decidual Angiogenesis during Early Pregnancy in the Mouse Endocrinology, August 1, 2009; 150(8): 3845 - 3854. [Abstract] [Full Text] [PDF]

				P. A. W. Rogers, J. F. Donoghue, L. M. Walter, and J. E. Girling Endometrial Angiogenesis, Vascular Maturation, and Lymphangiogenesis Reproductive Sciences, February 1, 2009; 16(2): 147 - 151. [Abstract] [PDF]

				J. E. Girling, F. L. Lederman, L. M. Walter, and P. A. W. Rogers Progesterone, But Not Estrogen, Stimulates Vessel Maturation in the Mouse Endometrium Endocrinology, November 1, 2007; 148(11): 5433 - 5441. [Abstract] [Full Text] [PDF]

				J. Luther, J. Milne, R. Aitken, M. Matsuzaki, L. Reynolds, D. Redmer, and J. Wallace Placental Growth, Angiogenic Gene Expression, and Vascular Development in Undernourished Adolescent Sheep Biol Reprod, August 1, 2007; 77(2): 351 - 357. [Abstract] [Full Text] [PDF]

				V L Bosquiazzo, J G Ramos, J Varayoud, M Munoz-de-Toro, and E H Luque Mast cell degranulation in rat uterine cervix during pregnancy correlates with expression of vascular endothelial growth factor mRNA and angiogenesis Reproduction, May 1, 2007; 133(5): 1045 - 1055. [Abstract] [Full Text] [PDF]