Human Reproduction, Vol. 15, No. suppl_3, pp. 67-77, 2000
© 2000 European Society of Human Reproduction and Embryology
Ovarian steroid and cytokine modulation of human endometrial angiogenesis
1 Department of Obstetrics, Gynecology and Reproductive Sciences San Francisco, CA 94143–0556, USA 2 Center for Reproductive Sciences San Francisco, CA 94143–0556, USA 3 San Francisco General Hospital San Francisco, CA 94143–0556, USA 4 Center for Family Planning Research, University of California San Francisco, CA 94143–0556, USA
Correspondence: 6To whom correspondence should be addressed at:Reproductive Endocrinology Center, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco HSE 1689, Box 0556, San Francisco, CA 94143–0556, USA. E-mail: rtaylor{at}socrates.ucsf.edu
A key mechanism underlying the cyclical growth of the endometrium is its ability to regenerate a vascular capillary network. In normal cycling human endometrium, angiogenesis is influenced by both endocrine and paracrine factors. Hormonal manipulation of the endometrium, such as that occurring during the use of steroidal contraception, appears to result in capillary proliferation and fragility. As a consequence of these vascular changes, contraceptive users may be predisposed to unpredictable uterine bleeding, which is responsible for the high frequency of contraceptive discontinuation. In this paper we address mechanisms responsible for vascular endothelial cell proliferation in normal and contraceptive steroid-exposed endometria. We propose that regulation of endometrial angiogenesis is mediated indirectly, via steroid and cytokine actions on vascular endothelial growth factor (VEGF), and we present data indicating that VEGF expression in normal endometrial stromal cells is increased by oestrogens and progestins. Three proinflammatory cytokines with angiogenic effects in other systems (i.e. interleukin-β,tumour necrosis factor-a and interferon-
) do not appear to up-regulate VEGF expression in normal endometrial stromal cells. Well-characterized in-vitro models in conjunction with immunohistochemistry provide usefulexperimental systems to study endometrialne. ovascularization under physiological conditions and in those potentially perturbed via the use of contraceptive steroids.
Key words: bleeding/Norplant/progestins/uterus/VEGF
5 Present address: Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA, USA
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