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Submitted on February 6, 2006
Accepted on June 14, 2006
Department of Developmental and Molecular Biology and Obstetrics & Gynecology and Women's Health, Center for the Study of Reproductive Biology and Women's Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, 10461, USA
* To whom correspondence should be addressed. E-mail: pollard{at}aecom.yu.edu.
In mice, the uterus becomes transiently receptive to the hatched blastocyst on the day of implantation to allow its attachment to the luminal epithelium and subsequent invasion into the uterus. This uterine preparation for implantation is regulated by estradiol-17
(E2) and progesterone (P4), acting through their transcription factor receptors. Using ovariectomized mice treated with physiological regimens of these hormones, combined with methods to isolate RNA specifically from the uterine epithelium followed by transcriptome analysis on cDNA microarrays, 222 genes were identified whose transcript abundance was specifically increased by P4E2 treatment. Gene ontology analysis revealed an emphasis on genes involved with immune responses, extracellular matrix metabolism and cell-to-cell communication. In situ hybridization to uterine sections isolated through the first 6 days of pregnancy identified novel sets of genes such as Bach, Myd88, Cd14, Isg20 and Lrp2 whose expression was restricted to the uterine epithelium during the implantation window. Particularly notable was the expression of the mRNA for members of the signaling pathway from the Toll-like receptors to its downstream targets such as Irg-1. The identification of these genes showing a cell type, hormonally regulated pattern of expression in the uterus suggests novel functions for them during implantation.
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