title: Global decrease in the expression of signalling pathways' genes in murine uterus during preimplantation pregnancy.
abstract: Early preimplantation embryo-maternal communication is crucial for the establishment and development of pregnancy. Though the involvement of several candidate genes and proteins in this complex event has been described, the hierarchy of molecular networks governing this communication remains unknown. The primary objective of this study was to determine whether the presence of embryos in the uterine lumen stimulated or inhibited gene expression in the uterine tissue on day 3.5 post coitum. To answer this question, we investigated the gene expression of dedicated signal transduction pathways in the uterus of CD-1 mice during the preimplantation stage of pregnancy and compared this expression to mice with induced pseudopregnancy. The expression levels of 84 genes assigned to nine intracellular signalling pathways were investigated by real-time PCR. The results demonstrated down-regulation of the uterine gene expression in the majority of pathways. Among target genes, 27 were significantly (p<0.05) down-regulated, and only three were significantly up-regulated. A majority of the down-regulated genes were found to be regulated by the TGFB and NFKB pathways, which suggests that the presence of the embryo selectively regulates signalling within signal transduction pathways. One of the up-regulated genes crucial for early pregnancy was Ptgs2 (p<0.05). The increased amount of both Ptgs2 gene and protein products indicates that Ptgs2 expression may be the earliest positive embryo signal for implantation and pregnancy recognition in mice. In conclusion, our results not only underline which signalling pathways are regulated in embryo-maternal communication before implantation but also support "the quiet state hypothesis" of silencing gene expression.
authors.affiliation: Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Buska
authors.affiliation: Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: Anna Ewa
authors.initials: AE
authors.lastname: Kedzierska
authors.affiliation: Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Slawek
authors.affiliation: Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland; Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland. Electronic address: soyta@iitd.pan.wroc.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Chelmonska-Soyta
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains; D001755:Blastocyst / Q000502:physiology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D010064:Embryo Implantation; D004790:Enzyme Induction; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D011247:Pregnancy / Q000378:metabolism*; D011555:Pseudopregnancy / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013047:Specific Pathogen-Free Organisms; D014599:Uterus / Q000201:enzymology / Q000378:metabolism*
chemical_list: C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2
keywords: Gene expression; Implantation; PTGS2; Signal transduction; Uterus