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Hum. Reprod. Advance Access originally published online on March 17, 2005
Human Reproduction 2005 20(6):1447-1455; doi:10.1093/humrep/deh841
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© The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions{at}oupjournals.org

Progesterone induces the fibulin-1 expression in human endometrial stromal cells

T. Nakamoto1, H. Okada, T. Nakajima, A. Ikuta, K. Yasuda and H. Kanzaki

Department of Obstetrics and Gynecology, Kansai Medical University, 10–15 Fumizono-cho, Moriguchi, Osaka, 570-8507, Japan

1 To whom correspondence should be addressed. Email: nakamott{at}takii.kmu.ac.jp

BACKGROUND: By using microarray analysis with human endometrial stromal cells (ESCs), we previously reported that the mRNA for fibulin-1, an extracellular matrix as well as a plasma glycoprotein, is up-regulated by progesterone. In the present study, we tried to clarify the spatial and temporal regulation mechanism of fibulin-1 in the human endometrium. METHODS AND RESULTS: Quantitative analysis with real-time PCR experiments on human endometrial tissues showed significantly higher fibulin-1 mRNA expressions in secretory phase endometria than in proliferative phase. Immunohistochemical studies revealed that the fibulin-1 protein is expressed in the glandular epithelium in proliferative phase endometria, and that expression switched to the stroma in secretory phase endometria. In culture experiments with ESCs, a significant increase of fibulin-1 mRNA expression was observed in cells treated with 6{alpha}-methyl-17{alpha}-hydroxy-progesterone acetate (MPA) or 8 bromoadenosine 3':5'-cyclic monophosphate (8-Br-cAMP). MPA stimulated the fibulin-1 mRNA expression in a dose-dependent manner, and a progesterone antagonist, RU-486, inhibited the stimulatory effect almost completely. By contrast, {beta}-estradiol alone did not increase the fibulin-1 mRNA expression. CONCLUSIONS: These results suggest that fiblin-1 is an important molecule that mediates progesterone action in human ESC differentiation towards implantation.

Key words: endometrial stromal cell culture/fibulin-1/human endometrium/progesterone


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