Estrogen stimulates the human endometrium to express a factor(s) that promotes vascular smooth muscle cell migration as
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ORIGINAL PAPER
Estrogen stimulates the human endometrium to express a factor(s) that promotes vascular smooth muscle cell migration as an early step in microvessel remodeling Jeffery S. Babischkin Æ Thomas W. Bonagura Æ Laurence C. Udoff Æ Christine O. Vergara Æ Harry W. Johnson Æ Robert O. Atlas Æ Gerald J. Pepe Æ Eugene D. Albrecht
Received: 15 August 2008 / Accepted: 21 October 2008 / Published online: 19 November 2008 Ó Humana Press Inc. 2008
Abstract Vascular smooth muscle cell (VSMC) migration is a pivotal early step in blood vessel remodeling; however, very little is known about the regulation of this process in the human endometrium during the menstrual cycle. In this study, explants of human endometrium were incubated with estradiol and/or progesterone and the conditioned medium (CM) applied to cultures of VSMC to test the hypothesis that estrogen and progesterone stimulate endometrial cells to secrete a factor(s) that promotes VSMC migration. Endometrial explants were composed of highly organized glands and stroma. VSMC migration (cells migrated in 21 h/mm2 fibronectin-coated semipermeable membrane) in the presence of CM from human endometrial explants obtained in the proliferative phase of the menstrual cycle and incubated for 24 h with estradiol was approximately threefold greater (P \ 0.001) than with medium alone and greater (P \ 0.05) than with CM from explants treated with estradiol plus progesterone or
J. S. Babischkin T. W. Bonagura L. C. Udoff H. W. Johnson E. D. Albrecht (&) Department of Obstetrics, Gynecology and Reproductive Sciences, Center for Studies in Reproduction, University of Maryland School of Medicine, Bressler Research Laboratories 11-019, 655 West Baltimore Street, Baltimore, MD 21201, USA e-mail: [email protected] C. O. Vergara R. O. Atlas Department of Obstetrics and Gynecology, Mercy Medical Center, Baltimore, MD, USA G. J. Pepe Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, VA, USA
progesterone. It is concluded, therefore, that estrogen stimulates endometrial secretion of a factor(s) that promotes VSMC migration as an early step in vessel remodeling within the endometrium. Keywords Vessel remodeling Endometrium Human Estrogen Progesterone
Introduction New capillaries develop, via angiogenesis, and then undergo remodeling and maturation, via investment of vascular smooth muscle cells (VSMC) with endothelial cells, to form a new vascular network during each menstrual cycle to support growth and differentiation of the endometrium for implantation. Improper vascularization of the endometrium may lead to dysfunctional menstrual bleeding [1], implantation failure [2], and infertility [3]. Although ovarian estrogen and progesterone have a pivotal role in establishing the endometrial vascular bed during each menstrual cycle ([4–6]; for reviews), relatively little is known about the mechanisms by which these steroid hormones regulate this fundamentally important process. It is well established that vascular endothelial growth
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