title: Bioinformatics approach reveals evidence for impaired endometrial maturation before and during early pregnancy in women who developed preeclampsia.
abstract: Impaired uterine invasion by extravillous trophoblast in early gestation is implicated in the genesis of preeclampsia, a potentially lethal malady of human pregnancy. However, reasons for extravillous trophoblast dysfunction remain unclear because of virtual inaccessibility of early placental and uterine tissues from women who develop preeclampsia, and the absence of animal models in which the disease spontaneously occurs. Consequently, the possibility that deficient or defective maturation of the endometrium (decidualization) may compromise extravillous trophoblast invasion in preeclampsia remains unexplored. Using a bioinformatics approach, we tested this hypothesis identifying 396 differentially expressed genes (DEG) in chorionic villous samples from women at ≈11.5 gestational weeks who developed severe preeclampsia symptoms 6 months later compared with chorionic villous samples from normal pregnancies. A large number, 154 or 40%, overlapped with DEG associated with various stages of normal endometrial maturation before and after implantation as identified by other microarray data sets (P=4.7×10(-14)). One-hundred and sixteen of the 154 DEG or 75% overlapped with DEG associated with normal decidualization in the absence of extravillous trophoblast, ie, late-secretory endometrium (LSE) and endometrium from tubal ectopic pregnancy (EP; P=4.2×10(-9)). Finally, 112 of these 154 DEG or 73% changed in the opposite direction in microarray data sets related to normal endometrial maturation (P=0.01), including 16 DEG upregulated in decidual (relative to peripheral blood) natural killer cells that were downregulated in chorionic villous samples from women who developed preeclampsia (P<0.0001). Taken together, these results suggest that insufficient or defective maturation of endometrium and decidual natural killer cells during the secretory phase and early pregnancy preceded the development of preeclampsia.
authors.affiliation: From the Department of Animal Reproduction, Universidad Nacional de Rio Cuarto, Rio Cuarto, Cordoba, Argentina (M.B.R.); Department of Obstetrics and Laboratory of Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, The Netherlands (E.D.P.U.); Department of Ob/Gyn, Magee Womens Hospital, Pittsburgh, PA (A.J., W.A.H.); and D.H. Barron Reproductive and Perinatal Biology Research Program, Departments of Physiology and Functional Genomics and of Ob/Gyn, University of Florida, Gainesville (E.D.P.U., K.P.C.). brabaglino@ufl.edu kpconrad@ufl.edu.
authors.forename: Maria B
authors.initials: MB
authors.lastname: Rabaglino
authors.affiliation: From the Department of Animal Reproduction, Universidad Nacional de Rio Cuarto, Rio Cuarto, Cordoba, Argentina (M.B.R.); Department of Obstetrics and Laboratory of Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, The Netherlands (E.D.P.U.); Department of Ob/Gyn, Magee Womens Hospital, Pittsburgh, PA (A.J., W.A.H.); and D.H. Barron Reproductive and Perinatal Biology Research Program, Departments of Physiology and Functional Genomics and of Ob/Gyn, University of Florida, Gainesville (E.D.P.U., K.P.C.).
authors.forename: Emiel D
authors.initials: ED
authors.lastname: Post Uiterweer
authors.affiliation: From the Department of Animal Reproduction, Universidad Nacional de Rio Cuarto, Rio Cuarto, Cordoba, Argentina (M.B.R.); Department of Obstetrics and Laboratory of Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, The Netherlands (E.D.P.U.); Department of Ob/Gyn, Magee Womens Hospital, Pittsburgh, PA (A.J., W.A.H.); and D.H. Barron Reproductive and Perinatal Biology Research Program, Departments of Physiology and Functional Genomics and of Ob/Gyn, University of Florida, Gainesville (E.D.P.U., K.P.C.).
authors.forename: Arun
authors.initials: A
authors.lastname: Jeyabalan
authors.affiliation: From the Department of Animal Reproduction, Universidad Nacional de Rio Cuarto, Rio Cuarto, Cordoba, Argentina (M.B.R.); Department of Obstetrics and Laboratory of Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, The Netherlands (E.D.P.U.); Department of Ob/Gyn, Magee Womens Hospital, Pittsburgh, PA (A.J., W.A.H.); and D.H. Barron Reproductive and Perinatal Biology Research Program, Departments of Physiology and Functional Genomics and of Ob/Gyn, University of Florida, Gainesville (E.D.P.U., K.P.C.).
authors.forename: William A
authors.initials: WA
authors.lastname: Hogge
authors.affiliation: From the Department of Animal Reproduction, Universidad Nacional de Rio Cuarto, Rio Cuarto, Cordoba, Argentina (M.B.R.); Department of Obstetrics and Laboratory of Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, The Netherlands (E.D.P.U.); Department of Ob/Gyn, Magee Womens Hospital, Pittsburgh, PA (A.J., W.A.H.); and D.H. Barron Reproductive and Perinatal Biology Research Program, Departments of Physiology and Functional Genomics and of Ob/Gyn, University of Florida, Gainesville (E.D.P.U., K.P.C.). brabaglino@ufl.edu kpconrad@ufl.edu.
authors.forename: Kirk P
authors.initials: KP
authors.lastname: Conrad
mesh_terms: D015193:Chorionic Villi Sampling; D003656:Decidua / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D010064:Embryo Implantation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D046228:Microarray Analysis; D011225:Pre-Eclampsia / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011271:Pregnancy, Ectopic / Q000276:immunology / Q000473:pathology; D013382:Subtraction Technique; D014327:Trophoblasts / Q000502:physiology
keywords: decidualization; endometrial cycle; natural killer cell; pregnancy; trophoblast