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Hum. Reprod. Advance Access originally published online on June 9, 2009
Human Reproduction 2009 24(9):2217-2224; doi:10.1093/humrep/dep203
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© The Author 2009. 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

Mixed origin of neovascularization of human endometrial grafts in immunodeficient mouse models

M.-L. Alvarez Gonzalez1, F. Frankenne1, C. Galant2, E. Marbaix2, J.-M. Foidart1,3, M. Nisolle1,3,{dagger} and A. Béliard1,3,4,{dagger}

1 Laboratory of Tumor and Development Biology, GIGA-Research, University de Liège, Tour de Pathologie (B23), Sart-Tilman, B-4000 Liège, Belgium 2 Cell Biology Unit and Department of Pathology, Catholic University of Louvain, B-1200 Brussels, Belgium 3 Department of Gynecology, CHU, University of Liège, B-4000 Liège, 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: In vivo mouse models have been developed to study the physiology of normal and pathologic endometrium. Although angiogenesis is known to play an important role in endometrial physiology and pathology, the origin of neovasculature in xenografts remains controversial. The aim of this study was to assess the origin of the neovasculature of endometrial grafts in different mouse models.

METHODS: Human proliferative endometrium (n = 19 women) was grafted s.c. in two immunodeficient mouse strains: nude (n = 8) and severely compromised immunodeficient (SCID; n = 20). Mice were also treated with estradiol, progesterone or levonorgestrel. Fluorescence in-situ hybridization using a centromeric human chromosome X probe, immunohistochemistry (von Willebrand factor and collagen IV) and lectin perfusion were performed to identify the origin of the vessels.

RESULTS: More than 90% of vessels within xenografts were of human origin 4 weeks after implantation. Some vessels (9.67 ± 2.01%) were successively stained by human or mouse specific markers, suggesting the presence of chimeric vessels exhibiting a succession of human and murine portions. No difference in staining was observed between the two strains of mouse or different hormone treatments. Furthermore, erythrocytes were found inside human vessels, confirming their functionality.

CONCLUSION: This article shows that human endometrial grafts retain their own vessels, which connect to the murine vasculature coming from the host tissue and become functional.

Key words: endometrium/chimeric vessels/fluorescence in-situ hybridization/lectin/angiogenesis

{dagger} Equal senior authors.

Submitted on December 16, 2008; resubmitted on May 11, 2009; accepted on May 12, 2009.


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