title: Ectopic pregnancy as a model to identify endometrial genes and signaling pathways important in decidualization and regulated by local trophoblast.
abstract: The endometrium in early pregnancy undergoes decidualization and functional changes induced by local trophoblast, which are not fully understood. We hypothesized that endometrium from tubal ectopic pregnancy (EP) could be interrogated to identify novel genes and pathways involved in these processes. Gestation-matched endometrium was collected from women with EP (n = 11) and intrauterine pregnancies (IUP) (n = 13). RNA was extracted from the tissue. In addition, tissues were prepared for histological analysis for degree of decidualization. We compared a) the samples from EP that were decidualized (n = 6) with non-decidualized samples (n = 5), and b) the decidualized EP (n = 6) with decidualization-matched IUP (n = 6) samples using an Affymetrix gene array platform, with Ingenuity Pathway Analysis, combined with quantitative RT-PCR. Expression of PRL and IGFBP1 was used to confirm the degree of decidualization in each group. There were no differences in PRL or IGFBP1 expression in the decidualization-matched samples but a marked reduction (P<0.001) in the non-decidualized samples. Decidualization was associated with increased expression of 428 genes including SCARA5 (181-fold), DKK1 (71-fold) and PROK1 (32-fold), and decreased expression of 230 genes including MMP-7 (35-fold) and SFRP4 (21-fold). The top canonical pathways associated with these differentially expressed genes were Natural Killer Cell and Wnt/b-Catenin signaling. Local trophoblast was associated with much less alteration of endometrial gene expression with an increase in 56 genes, including CSH1 (8-fold), and a reduction in 29 genes including CRISP3 (8-fold). The top associated canonical pathway was Antigen Presentation. The study of endometrium from tubal EP may promote novel insights into genes involved in decidualization and those influenced by factors from neighboring trophoblast. This has afforded unique information not highlighted by previous studies and adds to our understanding of the endometrium in early pregnancy.
authors.affiliation: MRC Centre for Reproductive Health, The University of Edinburgh, Edinburgh, Midlothian, United Kingdom.
authors.forename: W Colin
authors.initials: WC
authors.lastname: Duncan
authors.forename: Julie L V
authors.initials: JL
authors.lastname: Shaw
authors.forename: Stewart
authors.initials: S
authors.lastname: Burgess
authors.forename: Sarah E
authors.initials: SE
authors.lastname: McDonald
authors.forename: Hilary O D
authors.initials: HO
authors.lastname: Critchley
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Horne
mesh_terms: D002460:Cell Line; D003656:Decidua / Q000378:metabolism*; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D005768:Gastrointestinal Hormones / Q000235:genetics; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D020783:Matrix Metalloproteinase 7 / Q000235:genetics; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D011271:Pregnancy, Ectopic / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051117:Scavenger Receptors, Class A / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*; D014327:Trophoblasts / Q000378:metabolism*; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived / Q000235:genetics; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D005768:Gastrointestinal Hormones; D036341:Intercellular Signaling Peptides and Proteins; D020783:Matrix Metalloproteinase 7; D011518:Proto-Oncogene Proteins; D051117:Scavenger Receptors, Class A; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived; C501126:DKK1 protein, human; C467610:PROK1 protein, human; C569833:SCARA5 protein, human; C118723:SFRP4 protein, human; D000094742:Secreted Frizzled-Related Proteins; C060932:MMP7 protein, human