Gene Expression Profiling of Human Endometrial-Trophoblast Interaction in a Coculture Model

Investigating the interaction of human endometrium and trophoblast during implantation is difficult in vitro and impossible in vivo. This study was designed to analyze the effect of trophoblast on endometrial stromal cells during implantation by comprehensive gene profiling. An in vitro coculture sy...

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Bibliographic Details
Published in:Endocrinology (Philadelphia) 2006-12, Vol.147 (12), p.5662-5675
Main Authors: Popovici, Roxana M, Betzler, Nina K, Krause, Miriam S, Luo, Man, Jauckus, Julia, Germeyer, Ariane, Bloethner, Sandra, Schlotterer, Andreas, Kumar, Rajiv, Strowitzki, Thomas, von Wolff, Michael
Format: Article
Language:English
Subjects:
Adult
Biological and medical sciences
Cell Culture Techniques
Coculture Techniques - methods
Embryo Implantation
Endometrium - cytology
Endometrium - metabolism
Female
Fluorescent Antibody Technique - methods
Fundamental and applied biological sciences. Psychology
Gene Expression
Gene Expression Profiling - methods
Humans
Models, Biological
Pregnancy
Trophoblasts - cytology
Trophoblasts - metabolism
Vertebrates: endocrinology
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Summary:Investigating the interaction of human endometrium and trophoblast during implantation is difficult in vitro and impossible in vivo. This study was designed to analyze the effect of trophoblast on endometrial stromal cells during implantation by comprehensive gene profiling. An in vitro coculture system of endometrial stromal cells with first-trimester trophoblast explants was established. Trophoblast and endometrial stromal cells were separated after 24 h. Gene expression of endometrial stromal cells after coculture was compared with the gene expression of endometrial stromal cells cultured alone by microarray analysis. We confirmed the expression of distinct genes using real-time PCR. Genes up-regulated included those for inflammatory response, immune response, and chemotaxis (pentraxin-related gene 3, chemokine ligands, IL-8, IL-1 receptors, IL-18 receptor, IL-15, IL-15 receptor, TNF-α-induced protein 6, and IL-6 signal transducer), regulators of cell growth (IGF-binding proteins 1 and 2) and signal transduction. Also up-regulated were genes for growth and development, glucose metabolism, and lipid metabolism: DKK-1, WISP, IGF-II, hydroxysteroid 11β-dehydrogenase 1, hydroxyprostaglandin dehydrogenase 15, prostaglandin E synthase, prostaglandin F receptor, aldehyde dehydrogenase 1 family, member A3 and phosphatidic acid phosphatase type 2B. Other genes included genes for cell-cell signaling (pre-B-cell colony-enhancing factor 1), proteolysis, calcium ion binding, regulation of transcription, and others. Down-regulated genes included genes for proteolysis (MMP-11 and mitochondrial intermediate peptidase), genes for cell death (caspase 6, death-associated protein kinase 1, and histone deacetylase 5), transcription factors (sex determining region Y-box 4, dachshund homolog 1, ets variant gene 1, and zinc finger protein 84 and 435), and genes for humoral immune response (CD24 antigen). Trophoblast has a significant impact on endometrial stromal cell gene expression. Some of the genes regulated by trophoblast in endometrial stromal cells are already known to be regulated by progesterone and show the endocrine function of trophoblast during pregnancy. Others are genes so far unknown to play a role in endometrial-trophoblast interaction and open a wide field of investigation.
ISSN:0013-7227
1945-7170
DOI:10.1210/en.2006-0916