Human Reproduction, Vol. 18, No. 10, 2039-2047,
October 2003
© 2003 European Society of Human Reproduction and Embryology
Effect of estrogen on angiogenesis in co-cultures of human endometrial cells and microvascular endothelial cells
1 Departments of Obstetrics, Gynecology and Reproductive Sciences, and Physiology, 2 Department of Anatomy and Neurobiology, Center for Studies in Reproduction; University of Maryland School of Medicine, Baltimore, MD 21201 and 3 Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, VA 23507, USA
4 To whom correspondence should be addressed at: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Bressler Research Laboratories 11-019, 655 West Baltimore Street, Baltimore, MD 21201, USA. e-mail ealbrech{at}umaryland.edu
BACKGROUND: We recently showed that vascular endothelial growth factor (VEGF) expression by endometrial glandular epithelial and stromal cells, and endometrial microvascular endothelial cell permeability, an early step in angiogenesis, were rapidly increased by estradiol (E2) administration to ovariectomized baboons. We proposed that estrogen promotes endometrial angiogenesis by regulating VEGF expression by glandular epithelial and stromal cells. In the present study, we developed a co-culture of human endometrial cells and microvascular endothelial cells to determine whether the regulatory role shown for estrogen on endometrial angiogenesis in vivo in the non-human primate would be demonstrable in vitro in the human. METHODS AND RESULTS: Human endometrial glandular epithelial and stromal cells were co-cultured with human myometrial microvascular endothelial cells (HMMECs) and E2. HMMEC tube formation (means ± SEM, % endothelial tube area/total endothelial cell area), an index of angiogenesis, was 65% (P < 0.05) and 2-fold (P < 0.01) greater in cells co-cultured with human glandular epithelial cells (54 ± 7%) and glandular epithelial cells plus E2 (66 ± 11%), respectively, compared with medium (33 ± 4%). In contrast, endothelial tube formation was not altered in HMMECs incubated with endometrial stromal cells (32 ± 4%), stromal cells plus E2 (36 ± 2%) or E2 (39 ± 3%). CONCLUSIONS: We propose that estrogen, by regulating expression and secretion of angiogenic factors such as VEGF by glandular epithelial cells of the endometrium, regulates endometrial angiogenesis.
Key words: angiogenesis/endometrium/estrogen/glandular/human/
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