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Mol. Hum. Reprod. Advance Access originally published online on June 4, 2008
Molecular Human Reproduction 2008 14(7):413-421; doi:10.1093/molehr/gan029
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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

Expression of immunomodulatory genes, their protein products and specific ligands/receptors during the window of implantation in the human endometrium

Anahi Franchi, Jessica Zaret, Xiaomei Zhang, Silvina Bocca and Sergio Oehninger1

The Jones Institute for Reproductive Medicine, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, VA, USA

1 Correspondence address. 601 Colley Avenue, Norfolk, VA 23507, USA. E-mail: oehninsc{at}evms.edu

We have demonstrated up-regulation of the immunomodulatory genes decay accelerating factor (DAF), interleukin 15 (IL-15) and osteopontin (OPN) during the window of implantation (WOI). Here, we characterized gene expression and determined the localization of their protein products and respective ligands at the opening and closure of the WOI. In addition, we used laser capture microdissection (LCM) to analyze the cell type-specific gene expression. Human endometrial biopsies from cycle Days 16, 21 and 24 were evaluated by real-time RT–PCR. Purified epithelial and stromal cells were obtained by LCM. Localization of the proteins and their ligands was assessed by immunohistochemistry. mRNA expression of DAF, IL-15 and OPN was significantly increased throughout the WOI. DAF, OPN and {alpha}vβ3 integrin were strongly immunolocalized to the glandular compartment by Days 21 and 24, whereas C3, IL-15 and IL-15R{alpha} were highly stained in both glandular and stromal compartments. After LCM, gene expression of DAF was 4.8-fold increased in epithelium versus stroma, whereas for OPN there was a 2-fold increase. For IL-15, the expression in stroma was 8.7-fold higher than in epithelial cells. The progressive increase of the expression of these immunomodulatory genes, proteins and ligands during the WOI, support a critical role at the time of endometrial receptiveness.

Key words: window of implantation/gene expression/immunomodulatory proteins/laser capture microdissection/human endometrium

Submitted on March 10, 2008; resubmitted on May 7, 2008; accepted on May 9, 2008.


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