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Hum. Reprod. Advance Access originally published online on December 17, 2008
Human Reproduction 2009 24(3):697-704; doi:10.1093/humrep/den437
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© The Author 2008. 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@oxfordjournals.org
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed: the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given: if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative word this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

Development of an animal experimental model to study the effects of levonorgestrel on the human endometrium

M.-L. Alvarez Gonzalez1, C. Galant3, F. Frankenne1, M. Nisolle1,2, S. Labied1, J.-M. Foidart1,2, E. Marbaix3,{dagger} and A. Béliard1,2,4,{dagger}

1 Laboratory of Tumor and Development Biology, GIGA-Research, B23, University de Liège, Sart-Tilman, B-4000 Liège, Belgium 2 Department of Gynecology, CHU, University of Liège, B-4000 Liège, Belgium 3 Cell Biology Unit and Department of Pathology, Université Catholique de Louvain, B-1200 Bruxelles, Belgium

4 Correspondence address. Tel +32-4-366-25-69; Fax: +32-4-366-29-36; E-mail: abeliard{at}chu.ulg.ac.be

BACKGROUND: This study was designed to develop an animal model to test the response of endometrium to local progestin delivery.

METHODS: Proliferative human endometrium was subcutaneously grafted in two groups of SCID mice that received, 2 days before, a subcutaneous estradiol (E2) pellet and, for half of them, an additional implant of levonorgestrel (LNG). Mice were sacrificed 1, 2, 3 or 4 weeks after endometrial implantation and grafts were histologically analysed. Proliferation, steroid hormone receptors, blood vessels and stromal decidualization in both groups (E2 and LNG) were immunohistologically evaluated and compared with proliferative endometrium and endometrium from women with an LNG intrauterine device.

RESULTS: Grafts presented normal morphological endometrial characteristics. The expression of progesterone receptors was significantly decreased in glands and stroma of the LNG group as compared with the E2 group at all times. A significant decrease was also observed in the stromal expression of estrogen receptor-{alpha} in the LNG group. At 4 weeks, the mean cross-sectional area of vessels was significantly higher after LNG treatment.

CONCLUSIONS: These morphological and immunohistochemical characteristics are similar to those observed in women treated with local LNG. This mouse model might facilitate further investigations needed to understand the mechanisms responsible for the breakthrough bleeding frequently observed in progestin users.

Key words: levonorgestrel/endometrium/mouse model/endometrial transplants

{dagger} Equal senior authors.

Submitted on September 25, 2008; resubmitted on September 25, 2008; accepted on November 12, 2008.


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