2020
Acetaminophen Attenuates invasion and alters the expression of extracellular matrix enzymes and vascular factors in human first trimester trophoblast cells
Burman A, Garcia-Milian R, Wood M, DeWitt NA, Vasiliou V, Guller S, Abrahams VM, Whirledge S. Acetaminophen Attenuates invasion and alters the expression of extracellular matrix enzymes and vascular factors in human first trimester trophoblast cells. Placenta 2020, 104: 146-160. PMID: 33348283, DOI: 10.1016/j.placenta.2020.12.002.Peer-Reviewed Original ResearchConceptsFirst trimester trophoblast cellsHuman first trimester trophoblast cellsPrenatal acetaminophen useTrophoblast cellsAcetaminophen useTrophoblast functionsAcetaminophen exposureFetal developmentHTR-8/SVneo cellsPrenatal acetaminophen exposureAnti-inflammatory drug aspirinRecent epidemiological studiesPlacental cell typesMatrix metalloproteinases 2Expression of angiogenesisExtracellular matrix enzymesPrenatal acetaminophenCommon medicationsVascular factorsMaternal healthPlacental functionEpidemiological associationLong-term effectsCyclooxygenase-1Epidemiological studiesZika Virus-Infected Decidual Cells Elicit a Gestational Age-Dependent Innate Immune Response and Exaggerate Trophoblast Zika Permissiveness: Implication for Vertical Transmission.
Guzeloglu-Kayisli O, Guo X, Tang Z, Semerci N, Ozmen A, Larsen K, Mutluay D, Guller S, Schatz F, Kayisli UA, Lockwood CJ. Zika Virus-Infected Decidual Cells Elicit a Gestational Age-Dependent Innate Immune Response and Exaggerate Trophoblast Zika Permissiveness: Implication for Vertical Transmission. The Journal Of Immunology 2020, 205: 3083-3094. PMID: 33139490, DOI: 10.4049/jimmunol.2000713.Peer-Reviewed Original ResearchConceptsHuman decidual cellsDecidual cellsZika virusViral attachment factorsTerm decidual stromal cellsVertical transmissionDecidual cell supernatantsTerm decidual cellsInnate immune response genesInnate immune responsivenessExact pathogenic mechanismDecidual stromal cellsHuman first trimesterInnate immune responseSevere fetal defectsImmune response genesFetal sequelaeGestational ageFirst trimesterPlacental transmissionZIKV infectionCytotrophoblast culturesImmune responsivenessZika infectionLate pregnancyTrophoblast-secreted soluble-PD-L1 modulates macrophage polarization and function
Zhang Y, Aldo P, You Y, Ding J, Kaislasuo J, Petersen JF, Lokkegaard E, Peng G, Paidas MJ, Simpson S, Pal L, Guller S, Liu H, Liao AH, Mor G. Trophoblast-secreted soluble-PD-L1 modulates macrophage polarization and function. Journal Of Leukocyte Biology 2020, 108: 983-998. PMID: 32386458, PMCID: PMC8190653, DOI: 10.1002/jlb.1a0420-012rr.Peer-Reviewed Original ResearchConceptsSoluble PD-L1Macrophage polarizationTrophoblast cellsCell death ligand 1PD-L1/PDPD-1 blockageDeath ligand 1Macrophage differentiationModulates macrophage polarizationExpression/secretionDecidual macrophagesHealthy pregnancyPD-L1Pregnant womenTLR4 ligationM2 phenotypeExpression of typeFetal developmentLPS activationMacrophagesIFNPlacenta developmentLigand 1Constitutive productionGestation
2019
In Vitro Assays to Evaluate the Migration, Invasion, and Proliferation of Immortalized Human First-trimester Trophoblast Cell Lines.
Kisanga EP, Tang Z, Guller S, Whirledge S. In Vitro Assays to Evaluate the Migration, Invasion, and Proliferation of Immortalized Human First-trimester Trophoblast Cell Lines. Journal Of Visualized Experiments 2019 PMID: 30907868, DOI: 10.3791/58942.Peer-Reviewed Original ResearchConceptsCell movementCell migrationHuman first trimester trophoblast cell lineFirst trimester trophoblast cell lineIntrauterine growth restrictionCell linesTrophoblast cell linePregnancy disordersEarly pregnancyGrowth restrictionMaternal vasculatureTrophoblast migrationMigratory capacityPlacental developmentPotential mechanismsCellular changesVitro assaysInvasionTrophoblastProliferationThorough examinationMigrationAssaysIndividual factorsPregnancy
2018
Excess glucose induce trophoblast inflammation and limit cell migration through HMGB1 activation of Toll‐Like receptor 4
Heim KR, Mulla MJ, Potter JA, Han CS, Guller S, Abrahams VM. Excess glucose induce trophoblast inflammation and limit cell migration through HMGB1 activation of Toll‐Like receptor 4. American Journal Of Reproductive Immunology 2018, 80: e13044. PMID: 30175447, DOI: 10.1111/aji.13044.Peer-Reviewed Original ResearchConceptsToll-like receptor 4High mobility group box 1Damage-associated molecular patternsHMGB1 activationIL-1βIL-8Trophoblast responsesReceptor 4Human first trimester trophoblast cell lineFirst trimester trophoblast cell lineInflammatory IL-8Risk of preeclampsiaGroup box 1Uric acidIL-1β responseExcess glucoseTrophoblast cell lineCell migrationTrophoblast inflammationPregnancy outcomesTLR4 antagonistLPS-RSIL-6SFlt-1HMGB1 inhibitorGlucocorticoid signaling regulates cell invasion and migration in the human first‐trimester trophoblast cell line Sw.71
Kisanga EP, Tang Z, Guller S, Whirledge S. Glucocorticoid signaling regulates cell invasion and migration in the human first‐trimester trophoblast cell line Sw.71. American Journal Of Reproductive Immunology 2018, 80: e12974. PMID: 29774963, DOI: 10.1111/aji.12974.Peer-Reviewed Original ResearchConceptsGene expression profilesSERPINE1 promoterPolymerase IITranscriptional regulationGlucocorticoid receptorCell movementTranscriptional profilesGlucocorticoid treatmentExpression profilesMicroarray analysisStress responseCell invasionPrimary mediatorPathogenesis of preeclampsiaCell proliferationEffects of glucocorticoidsExtravillous trophoblast functionsGlucocorticoid signalingSynthetic glucocorticoid dexamethasoneGenesTrophoblast functionsAdrenal axisInvasionTrophoblast tissueGlucocorticoid dexamethasone
2017
Low molecular weight heparin and aspirin exacerbate human endometrial endothelial cell responses to antiphospholipid antibodies
Quao ZC, Tong M, Bryce E, Guller S, Chamley LW, Abrahams VM. Low molecular weight heparin and aspirin exacerbate human endometrial endothelial cell responses to antiphospholipid antibodies. American Journal Of Reproductive Immunology 2017, 79 PMID: 29135051, PMCID: PMC5728699, DOI: 10.1111/aji.12785.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, AntiphospholipidAntiphospholipid SyndromeAspirinBeta 2-Glycoprotein ICells, CulturedChemokinesDisease ProgressionDrug Therapy, CombinationEndometriumEndothelial CellsFemaleHeparin, Low-Molecular-WeightHumansMembrane ProteinsNeovascularization, PhysiologicPregnancyPregnancy ComplicationsTrophoblastsVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-1ConceptsLow molecular weight heparinHuman endometrial endothelial cellsMolecular weight heparinUterine endotheliumAntiphospholipid antibodiesWeight heparinInfluence of LMWHLow dose low molecular weight heparinAnti-angiogenic sFlt-1Chemokine MCP-1Endometrial endothelial cellsEffects of aPLSFlt-1 releaseAngiogenic factor secretionObstetric APSPregnancy complicationsControl IgGChemokine profilesEndothelium dysfunctionChemokine secretionPro-angiogenic VEGFCombination therapySFlt-1Impaired placentationMCP-1Dynamics of Base Excision Repair at the Maternal–Fetal Interface in Pregnancies Complicated by Preeclampsia
Tadesse S, Norwitz NG, Guller S, Arcuri F, Toti P, Norwitz ER, Kidane D. Dynamics of Base Excision Repair at the Maternal–Fetal Interface in Pregnancies Complicated by Preeclampsia. Reproductive Sciences 2017, 24: 856-864. PMID: 27707956, DOI: 10.1177/1933719116670519.Peer-Reviewed Original ResearchConceptsMaternal-fetal interfaceOxidative stressNormotensive controlsPlacental tissueHypoxia/reperfusion (H/R) modelPlacental endothelial dysfunctionPlacentas of womenHealthy control subjectsApyrimidinic endonuclease 1PE placental tissuesPregnancy ComplicatedEndothelial dysfunctionPreeclamptic womenPerinatal mortalityReperfusion modelControl subjectsDecidual cellsPathological basisVivo comparative studyPreeclampsiaMaternal cellsFetal cellsAPE1 expressionSignificant increaseWomen
2016
H19 long noncoding RNA alters trophoblast cell migration and invasion by regulating TβR3 in placentae with fetal growth restriction
Zuckerwise L, Li J, Lu L, Men Y, Geng T, Buhimschi CS, Buhimschi IA, Bukowski R, Guller S, Paidas M, Huang Y. H19 long noncoding RNA alters trophoblast cell migration and invasion by regulating TβR3 in placentae with fetal growth restriction. Oncotarget 2016, 7: 38398-38407. PMID: 27223264, PMCID: PMC5122399, DOI: 10.18632/oncotarget.9534.Peer-Reviewed Original ResearchConceptsFetal growth restrictionGrowth restrictionExtravillous trophoblastsDownregulation of H19Type III TGF-β receptorCell migrationEVT cell migrationNon-canonical TGFTGF-β receptorFGR placentasNeurodevelopmental impairmentPerinatal mortalityRisk factorsTherapeutic modalitiesEVT cellsH19 knockdownOnset disordersPlacentaInvasionMolecular mechanismsH19Let-7Novel regulatory targetMorbidityRegulatory pathways
2014
Trophoblast Induces Monocyte Differentiation Into CD14+/CD16+ Macrophages
Aldo PB, Racicot K, Craviero V, Guller S, Romero R, Mor G. Trophoblast Induces Monocyte Differentiation Into CD14+/CD16+ Macrophages. American Journal Of Reproductive Immunology 2014, 72: 270-284. PMID: 24995492, PMCID: PMC4230492, DOI: 10.1111/aji.12288.Peer-Reviewed Original ResearchConceptsUnique macrophage phenotypeMacrophage phenotypeMonocyte differentiationFirst trimester trophoblast cellsPeripheral blood monocytesPhenotype of macrophagesCD14 surface expressionNormal deciduaHealthy pregnancyIL-10Chemokine productionEarly pregnancyIP-10Monocyte exposureIL-1BBlood monocytesDecidual phenotypePhagocytic capacityTrophoblast cellsFlow cytometryMorphologic changesMacrophagesMonocytesSurface expressionPlacenta developmentSyncytiotrophoblast Vesicles Show Altered micro-RNA and Haemoglobin Content after Ex-vivo Perfusion of Placentas with Haemoglobin to Mimic Preeclampsia
Cronqvist T, Saljé K, Familari M, Guller S, Schneider H, Gardiner C, Sargent IL, Redman CW, Mörgelin M, Åkerström B, Gram M, Hansson SR. Syncytiotrophoblast Vesicles Show Altered micro-RNA and Haemoglobin Content after Ex-vivo Perfusion of Placentas with Haemoglobin to Mimic Preeclampsia. PLOS ONE 2014, 9: e90020. PMID: 24587192, PMCID: PMC3937405, DOI: 10.1371/journal.pone.0090020.Peer-Reviewed Original ResearchConceptsPathology of preeclampsiaCell-free HbMiR-517bMiR-517aSyncytiotrophoblast vesiclesExtracellular free hemoglobinPerfusion of placentaEx vivo perfusion systemMicro-RNAsMaternal circulationMimic preeclampsiaMaternal sidePerfusion mediumFree hemoglobinHuman placentaPerfusion phaseSurface markersPlacentaMiR-141Hemoglobin contentPerfusionPerfusion systemPreeclampsiaHemoglobinQuantitative PCRIn Vivo and In Vitro Evidence for Placental DNA Damage in Preeclampsia
Tadesse S, Kidane D, Guller S, Luo T, Norwitz NG, Arcuri F, Toti P, Norwitz ER. In Vivo and In Vitro Evidence for Placental DNA Damage in Preeclampsia. PLOS ONE 2014, 9: e86791. PMID: 24466242, PMCID: PMC3899334, DOI: 10.1371/journal.pone.0086791.Peer-Reviewed Original ResearchConceptsDecidual stromal cellsCytotrophoblast cellsMaternal decidual stromal cellsReactive oxygen speciesPlacental oxidative stressFetal-maternal interfaceDNA damagePE placental tissuesAnti-oxidant defensesMultisystem diseasePregnant womenPE placentasFetal sideMaternal deciduaOxidative DNA damagePreeclampsiaPlacental tissueNormal placentaStromal cellsPlacentaOxidative stressVitro EvidenceRepair responseDNA damage/repair responseΓH2AX foci
2012
Cutting‐Edge Report: TLR10 Plays a Role in Mediating Bacterial Peptidoglycan‐Induced Trophoblast Apoptosis
Mulla MJ, Myrtolli K, Tadesse S, Stanwood NL, Gariepy A, Guller S, Norwitz ER, Abrahams VM. Cutting‐Edge Report: TLR10 Plays a Role in Mediating Bacterial Peptidoglycan‐Induced Trophoblast Apoptosis. American Journal Of Reproductive Immunology 2012, 69: 449-453. PMID: 23279063, PMCID: PMC3620725, DOI: 10.1111/aji.12065.Peer-Reviewed Original ResearchConceptsIL-6 secretionTrophoblast apoptosisTLR2 coreceptorsHuman trophoblast cell lineIntrauterine bacterial infectionFirst-trimester human trophoblast cell lineThird-trimester human placental tissueHuman placental tissueTrophoblast cell linePositive bacterial componentsTLR10 expressionPreterm laborThird trimesterCaspase-3 activityIL-6TLR2 activationPlacental tissuePlacental apoptosisBacterial infectionsTLR10Bacterial componentsBacterial peptidoglycanTrophoblastCell linesApoptosisToll‐Like Receptor 4 Expression in Decidual Cells and Interstitial Trophoblasts Across Human Pregnancy
Schatz F, Kayisli UA, Vatandaslar E, Ocak N, Guller S, Abrahams VM, Krikun G, Lockwood CJ. Toll‐Like Receptor 4 Expression in Decidual Cells and Interstitial Trophoblasts Across Human Pregnancy. American Journal Of Reproductive Immunology 2012, 68: 146-153. PMID: 22564191, PMCID: PMC3395732, DOI: 10.1111/j.1600-0897.2012.01148.x.Peer-Reviewed Original ResearchConceptsToll-like receptor 4Interstitial trophoblastDecidual cellsDanger signalsToll-like receptor 4 expressionFirst trimester decidual cellsReceptor 4 expressionHuman pregnancyElective terminationNormal deliveryDecidua parietalisReceptor 4Luteal phaseStromal cellsGram-negative bacteriaSerial sectionsTrophoblastPrimary targetCellsClose contactEndometriumPregnancyHScoreGestationCytokeratin
2011
Hydroxychloroquine reduces binding of antiphospholipid antibodies to syncytiotrophoblasts and restores annexin A5 expression
Wu XX, Guller S, Rand JH. Hydroxychloroquine reduces binding of antiphospholipid antibodies to syncytiotrophoblasts and restores annexin A5 expression. American Journal Of Obstetrics And Gynecology 2011, 205: 576.e7-576.e14. PMID: 21871597, PMCID: PMC3224185, DOI: 10.1016/j.ajog.2011.06.064.Peer-Reviewed Original ResearchConceptsAntiphospholipid antibodiesHuman placental syncytiotrophoblastPlacental syncytiotrophoblastAnnexin A5 anticoagulant shieldA5 expressionEffect of hydroxychloroquineAnnexin A5 expressionFirst morphologic evidenceAntibody-mediated disruptionAntiphospholipid syndromeComputer-based morphometric analysisThrombogenic mechanismsBeWo trophoblastsImmune complexesNovel treatmentsHydroxychloroquineAntimalarial drugsImmunoglobulin G (IgG) bindingMorphologic evidenceSyncytiotrophoblastImmunoglobulin GsPrimary culturesAntibodiesAnnexin A5Laser confocal microscopyIsolation of Hofbauer Cells from Human Term Placentas with High Yield and Purity
Tang Z, Tadesse S, Norwitz E, Mor G, Abrahams VM, Guller S. Isolation of Hofbauer Cells from Human Term Placentas with High Yield and Purity. American Journal Of Reproductive Immunology 2011, 66: 336-348. PMID: 21545365, PMCID: PMC3154981, DOI: 10.1111/j.1600-0897.2011.01006.x.Peer-Reviewed Original ResearchConceptsHofbauer cellsHuman term placentaTerm placentaComplications of pregnancyCell typesMacrophage functionPhagocytotic activityFlow cytometryVillus functionConsensus methodologyVacuolated appearancePhagocytosis assaysPlacentaPercoll gradientCTFuture studiesFibroblastsHBCCellsDaysHigh levelsComplicationsCulture mediumPregnancyMacrophages
2010
Role of GnRH–GnRH receptor signaling at the maternal-fetal interface
Lee HJ, Snegovskikh VV, Park JS, Foyouzi N, Han KT, Hodgson EJ, Guller S, Norwitz ER. Role of GnRH–GnRH receptor signaling at the maternal-fetal interface. Fertility And Sterility 2010, 94: 2680-2687. PMID: 20400076, DOI: 10.1016/j.fertnstert.2010.03.016.Peer-Reviewed Original ResearchConceptsGnRHR-I mRNAMaternal-fetal interfaceDecidual stromal cellsHCG productionGnRH-IISelect cytokinesTrophoblast cellsCell linesEffects of GnRHUniversity Teaching HospitalExpression of GnRHFunction of GnRHReverse transcription-polymerase chain reactionDose-dependent fashionHuman trophoblast cellsTerm deliveryPolymerase chain reactionTeaching hospitalGnRH receptorMAIN OUTCOMEGnRHHuman trophoblastsStromal cellsWestern blotImmortalized cell lines
2009
The Isolation and Characterization of a Novel Telomerase Immortalized First Trimester Trophoblast Cell Line, Swan 71
Straszewski-Chavez SL, Abrahams VM, Alvero AB, Aldo PB, Ma Y, Guller S, Romero R, Mor G. The Isolation and Characterization of a Novel Telomerase Immortalized First Trimester Trophoblast Cell Line, Swan 71. Placenta 2009, 30: 939-948. PMID: 19766308, PMCID: PMC2784169, DOI: 10.1016/j.placenta.2009.08.007.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, CDAntigens, Differentiation, MyelomonocyticApoptosisCell LineChorionic GonadotropinCytokinesFemaleFibronectinsHistocompatibility Antigens Class IHLA AntigensHLA-G AntigensHumansIntercellular Signaling Peptides and ProteinsKeratin-7Leukocyte Common AntigensPregnancyPregnancy Trimester, FirstTelomeraseThy-1 AntigensTrophoblastsVimentinConceptsFirst trimester trophoblast cell lineSwan 71 cellsTrophoblast cell lineFirst trimester trophoblast cellsFibroblast-specific antigenHuman chorionic gonadotrophinPrimary trophoblast cellsTrophoblast cellsHuman telomerase reverse transcriptaseFetal fibronectinCell linesCD90/ThySwan 71Growth factor profileTNF-alpha-induced apoptosisChorionic gonadotrophinCytokeratin 7Specific antigenTelomerase reverse transcriptaseNormal placentaFactor profileKaryotypic abnormalitiesPatient samplesPrimary human cellsAdequate cell numbersORIGINAL ARTICLE: Regulation of Nod1 and Nod2 in First Trimester Trophoblast Cells
Mulla MJ, Yu AG, Cardenas I, Guller S, Panda B, Abrahams VM. ORIGINAL ARTICLE: Regulation of Nod1 and Nod2 in First Trimester Trophoblast Cells. American Journal Of Reproductive Immunology 2009, 61: 294-302. PMID: 19260860, DOI: 10.1111/j.1600-0897.2009.00694.x.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisBenzamidesCells, CulturedCytokinesDiaminopimelic AcidFemaleGene Expression Regulation, DevelopmentalHumansLipopolysaccharidesNF-kappa BNod1 Signaling Adaptor ProteinNod2 Signaling Adaptor ProteinPregnancyPregnancy Trimester, FirstSequence DeletionSignal TransductionThiazolesToll-Like Receptor 4TransgenesTrophoblastsConceptsFirst trimester trophoblast cellsTrophoblast cellsExpression of NOD1Cytoplasmic pattern recognition receptorsProduction of cytokinesNOD2 mRNA expressionPattern recognition receptorsNOD2 expressionCytokine responsesInflammatory responseNOD2 activationNOD1 activationNFkappaB inhibitorRecognition receptorsNOD1Nod1 stimulationNOD2Bacterial lipopolysaccharideMRNA expressionTLR4LipopolysaccharideNFkappaB pathwayRT-PCRBacterial peptidesTrophoblast
2008
Placental expression of ceruloplasmin in pregnancies complicated by severe preeclampsia
Guller S, Buhimschi CS, Y Y, Huang T, Yang L, Kuczynski E, Zambrano E, Lockwood CJ, Buhimschi IA. Placental expression of ceruloplasmin in pregnancies complicated by severe preeclampsia. Laboratory Investigation 2008, 88: 1057-1067. PMID: 18679377, PMCID: PMC2682720, DOI: 10.1038/labinvest.2008.74.Peer-Reviewed Original ResearchConceptsPlasminogen activator inhibitor-1Severe preeclampsiaReperfusion injurySFlt-1Soluble fms-like tyrosine kinase-1Fms-like tyrosine kinase-1Ischemia/reperfusion injuryLife-threatening syndromeSubsequent reperfusion injuryTerm control groupPathophysiology of preeclampsiaTyrosine kinase-1Activator inhibitor-1Release of factorsSignificant increasePresence of mRNAUpregulation of mRNACeruloplasmin mRNAPlacental damagePlacental factorsMicroarray gene profilingEndothelium dysfunctionPE placentasQuantitative real-time PCRIntervillous space