Featured Publications
Trophoblast inclusions in the human placenta: Identification, characterization, quantification, and interrelations of subtypes
Kliman HJ, Firestein MR, Hofmann KM, Milano KM, Holzer PH, Brink LT, Odendaal HJ, Fifer WP. Trophoblast inclusions in the human placenta: Identification, characterization, quantification, and interrelations of subtypes. Placenta 2020, 103: 172-176. PMID: 33152642, PMCID: PMC8448462, DOI: 10.1016/j.placenta.2020.10.014.Peer-Reviewed Original ResearchPlacental Pathology Findings in Unexplained Pregnancy Losses
Thompson B, Holzer P, Kliman H. Placental Pathology Findings in Unexplained Pregnancy Losses. Reproductive Sciences 2023, 31: 488-504. PMID: 37725247, PMCID: PMC10827979, DOI: 10.1007/s43032-023-01344-3.Peer-Reviewed Original ResearchWeeks of gestationCommon pathologic featureSmall placentaPathologic featuresPregnancy lossChorionic villiPlacental pathology findingsUnexplained lossUnexplained pregnancy lossAntepartum stillbirthPlacental examinationUnexplained stillbirthPathology findingsUnexplained miscarriagePrevalent abnormalityPathologic diagnosisClinical databaseStillbirthMiscarriagePathology slidesDiagnostic categoriesGenetic abnormalitiesClassification systemPlacentaPotential mechanisms
2024
Pilot PET study of vaginally administered bioadhesive nanoparticles in cynomolgus monkeys: Kinetics and safety evaluation
Grun M, Honhar P, Wang Y, Rossano S, Khang M, Suh H, Fowles K, Kliman H, Cavaliere A, Carson R, Marquez‐Nostra B, Saltzman W. Pilot PET study of vaginally administered bioadhesive nanoparticles in cynomolgus monkeys: Kinetics and safety evaluation. Bioengineering & Translational Medicine 2024, 9 PMCID: PMC11561825, DOI: 10.1002/btm2.10661.Peer-Reviewed Original ResearchVaginal dosage formsBioadhesive nanoparticlesCynomolgus monkeysAnalysis of inflammatory biomarkersVaginal microbicidesVaginal canalMultiple dosesInflammatory biomarkersTherapeutic efficacyVaginal fluidSystemic circulationLong-term deliveryNoninvasive imagingClinical translationDosage formsNon-human primatesDelivery vehiclesMonkeysDeliveryVaginitisUterusMicrobicidesSafety evaluationBiodistributionDose
2023
Progress on the Endometrium
Frankfurter D, Kliman H. Progress on the Endometrium. Obstetrics And Gynecology Clinics Of North America 2023, 50: 677-694. PMID: 37914487, DOI: 10.1016/j.ogc.2023.09.002.Peer-Reviewed Original ResearchConceptsAbsence of pregnancyEvidence-based approachEndometrial assessmentStromal maturationEndometrial proliferationEndometrial pathologyInflammatory mediatorsOvarian steroidsImplantation failureBlastocyst implantationEndometrial sloughingDiagnostic measuresEndometriumOffer hopeDynamic tissueDevelopmental markersSingle testTissueInternal reproductionMaturationEndometriosisPregnancyDecidualizationInfertilityUterus
2022
Sex differences in early and term placenta are conserved in adult tissues
Olney K, Plaisier S, Phung T, Silasi M, Perley L, O’Bryan J, Ramirez L, Kliman H, Wilson M. Sex differences in early and term placenta are conserved in adult tissues. Biology Of Sex Differences 2022, 13: 74. PMID: 36550527, PMCID: PMC9773522, DOI: 10.1186/s13293-022-00470-y.Peer-Reviewed Original ResearchConceptsFirst trimester placentaLate first trimesterTerm placentaTrimester placentaFirst trimesterAdult tissuesGene expressionSex differencesLifelong health outcomesSex-differential gene expressionGenetic sexInnate immune responseFull-term placentaSex-linked genesInnate immune genesImmune responsePlacenta samplesHealth outcomesBrain tissuePlacentaGametologous genesDifferent timepointsSex chromosomesImmune genesSexX chromosome inactivation in the human placenta is patchy and distinct from adult tissues
Phung TN, Olney KC, Pinto BJ, Silasi M, Perley L, O'Bryan J, Kliman HJ, Wilson MA. X chromosome inactivation in the human placenta is patchy and distinct from adult tissues. Human Genetics And Genomics Advances 2022, 3: 100142. PMID: 36187227, PMCID: PMC9519611, DOI: 10.1016/j.xhgg.2022.100142.Peer-Reviewed Original ResearchInsulin increases placental triglyceride as a potential mechanism for fetal adiposity in maternal obesity
Anam AK, Cooke KM, Dratver MB, O'Bryan JV, Perley LE, Guller SM, Hwang JJ, Taylor HS, Goedeke L, Kliman HJ, Vatner DF, Flannery CA. Insulin increases placental triglyceride as a potential mechanism for fetal adiposity in maternal obesity. Molecular Metabolism 2022, 64: 101574. PMID: 35970449, PMCID: PMC9440306, DOI: 10.1016/j.molmet.2022.101574.Peer-Reviewed Original ResearchConceptsDe novo lipogenesisFetal adiposityFatty acid uptakeMaternal obesityObese womenNormal weightExcess adiposityVillous explantsInsulin receptorNewborns of mothersNormal-weight womenAcid uptakePlacental villous explantsTranscription factor SREBP-1Insulin-like growth factor 2Effect of insulinFatty acid oxidationPlacental triglyceridesPlacental responsesElevated triglyceridesMaternal hyperglycemiaWeight womenGrowth factor 2Diabetes riskPlacental metabolismPathologic Assessment of the Placenta: Evidence Compared With Tradition
Pinar H, Gordijn SJ, Grynspan D, Kingdom J, Roberts DJ, Kerzner L, Bates SV, Carreon CK, Leeman KT, Salafia C, Cohen M, Castro E, Ravishankar S, Kliman HJ, Dahlstrom J, Silver B, Heazell A. Pathologic Assessment of the Placenta: Evidence Compared With Tradition. Obstetrics And Gynecology 2022, 140: 341-342. PMID: 35852288, DOI: 10.1097/aog.0000000000004883.Peer-Reviewed Original ResearchX chromosome inactivation in the human placenta is patchy and distinct from adult tissues
Phung TN, Olney KC, Pinto BJ, Silasi M, Perley L, O’Bryan J, Kliman HJ, Wilson MA. X chromosome inactivation in the human placenta is patchy and distinct from adult tissues. Human Genetics And Genomics Advances 2022, 3: 100121. PMID: 35712697, PMCID: PMC9194956, DOI: 10.1016/j.xhgg.2022.100121.Peer-Reviewed Original ResearchX-chromosome inactivationAdult tissuesChromosome inactivationX chromosomeX chromosome expressionTissue-specific mapsPaternal X chromosomeHuman adult tissuesChromosome expressionX inactivationAllele-specific approachesGenetic femalesLarge patchesChromosomesHuman placentaInactivationTissueGenesRNADNAObserved sex differencesExpressionPlacentaTrophoblast inclusions and adverse birth outcomes
Firestein MR, Kliman HJ, Sania A, Brink LT, Holzer PH, Hofmann KM, Milano KM, Pini N, Shuffrey LC, Odendaal HJ, Fifer WP. Trophoblast inclusions and adverse birth outcomes. PLOS ONE 2022, 17: e0264733. PMID: 35231069, PMCID: PMC8887719, DOI: 10.1371/journal.pone.0264733.Peer-Reviewed Original ResearchConceptsBirth outcomesGestational ageLiveborn deliveryLive birthsFull-term live birthsChorionic villiPreterm live birthsSpecific placental pathologyFull-term birthInduction of laborAdverse birth outcomesGestational age birthweightSafe Passage StudyTrophoblast inclusionsGreater odds ratioWarrants further investigationPlacental infarctionPlacenta accretaPreterm birthPlacental pathologyVillous edemaPatient populationAlcohol exposureOdds ratioChorionic plate
2021
Bone Marrow-Derived Progenitor Cells Contribute to Remodeling of the Postpartum Uterus
Tal R, Kisa J, Abuwala N, Kliman HJ, Shaikh S, Chen AY, Lyu F, Taylor HS. Bone Marrow-Derived Progenitor Cells Contribute to Remodeling of the Postpartum Uterus. Stem Cells 2021, 39: 1489-1505. PMID: 34224633, PMCID: PMC9313624, DOI: 10.1002/stem.3431.Peer-Reviewed Original ResearchConceptsPostpartum uterusEndometrial stem/progenitor cellsBone marrow-derived progenitor cellsMarrow-derived progenitor cellsF4/80 macrophage markerUterine tissue regenerationProgenitor cellsC57BL/6J female micePostpartum day 1Cytokeratin-positive epithelial cellsBlood vessel endotheliumStem/progenitor cellsPrepregnancy levelsBM transplantsEndometrial regenerationEndometrial cellsFemale miceMacrophage markersPan-leukocytesLuminal epitheliumBone marrowDay 1BMDCsUterine cellsVessel endotheliumYAP1 nuclear efflux and transcriptional reprograming follow membrane diminution upon VSV-G-induced cell fusion
Feliciano D, Ott CM, Espinosa-Medina I, Weigel AV, Benedetti L, Milano KM, Tang Z, Lee T, Kliman HJ, Guller SM, Lippincott-Schwartz J. YAP1 nuclear efflux and transcriptional reprograming follow membrane diminution upon VSV-G-induced cell fusion. Nature Communications 2021, 12: 4502. PMID: 34301937, PMCID: PMC8302681, DOI: 10.1038/s41467-021-24708-2.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAMP-Activated Protein KinasesAnimalsBiological TransportCell FusionCell LineCell Line, TumorCell MembraneCell NucleusCells, CulturedGiant CellsHEK293 CellsHumansMembrane GlycoproteinsMiceRNA-SeqSignal TransductionTranscription FactorsTranscription, GeneticViral Envelope ProteinsYAP-Signaling ProteinsConceptsCell cycle arrestCell fusionNew cellular statesPlasma membrane surface areaRNA-seq analysisCell fusion systemTranscriptional programsNutrient stressCellular statesTranscriptional changesNuclear effluxCytoplasmic glucoseExtrinsic cuesUndifferentiated cellsGlucose transporterFused cellsMechanistic insightsMembrane surface areaNew functionsEndocytosisYAP1 inhibitionEnergetic stateSyncytiaCellsVSVLoss of Cxcr4 in Endometriosis Reduces Proliferation and Lesion Number while Increasing Intraepithelial Lymphocyte Infiltration
Tal A, Tal R, Kliman HJ, Taylor HS. Loss of Cxcr4 in Endometriosis Reduces Proliferation and Lesion Number while Increasing Intraepithelial Lymphocyte Infiltration. American Journal Of Pathology 2021, 191: 1292-1302. PMID: 33964217, PMCID: PMC8261475, DOI: 10.1016/j.ajpath.2021.04.011.Peer-Reviewed Original ResearchConceptsEndometriosis lesionsEpithelial compartmentLesion numberDisruption of CXCR4Intraepithelial lymphocyte infiltrationAdult female miceLoss of CXCR4CXCL12-CXCR4 axisTotal lesion areaProgesterone receptor promoterEndometriosis inductionLymphocyte infiltrationCXCR4 expressionFemale miceHost miceControl lesionsProestrus stageEpithelial proliferationImmune evasionCXCR4LesionsTherapeutic potentialLesion areaReduces ProliferationEpithelial cellsMaternal respiratory SARS-CoV-2 infection in pregnancy is associated with a robust inflammatory response at the maternal-fetal interface
Lu-Culligan A, Chavan AR, Vijayakumar P, Irshaid L, Courchaine EM, Milano KM, Tang Z, Pope SD, Song E, Vogels CBF, Lu-Culligan WJ, Campbell KH, Casanovas-Massana A, Bermejo S, Toothaker JM, Lee HJ, Liu F, Schulz W, Fournier J, Muenker MC, Moore AJ, Team Y, Konnikova L, Neugebauer KM, Ring A, Grubaugh ND, Ko AI, Morotti R, Guller S, Kliman HJ, Iwasaki A, Farhadian SF. Maternal respiratory SARS-CoV-2 infection in pregnancy is associated with a robust inflammatory response at the maternal-fetal interface. Med 2021, 2: 591-610.e10. PMID: 33969332, PMCID: PMC8084634, DOI: 10.1016/j.medj.2021.04.016.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionMaternal-fetal interfaceACE2 expressionNatural killerPregnant womenPlacental cellsAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSARS-CoV-2-infected womenTerm placentaSyndrome coronavirus 2 infectionCoronavirus 2 infectionPotential immune mechanismsRobust inflammatory responseRobust immune responseCoronavirus disease 2019Detectable viral RNAInterferon-related genesLower ACE2 expressionMajority of placentasPregnancy complicationsPlacental histologyHofbauer cellsEarly pregnancyImmune activationGenetics, not the uterine environment, drive the formation of trophoblast inclusions: Insights from a twin study
Katz J, Holzer PH, Kliman HJ. Genetics, not the uterine environment, drive the formation of trophoblast inclusions: Insights from a twin study. Placenta 2021, 114: 133-138. PMID: 33941390, DOI: 10.1016/j.placenta.2021.04.010.Peer-Reviewed Original ResearchConceptsMean differenceUterine environmentTwin pairsTrophoblast inclusionsRetrospective case seriesCase seriesPregnancy lossIntrauterine environmentFetal geneticsMZ twinsDZ twinsDizygotic twin pairsMZ twin pairsGenetic abnormalitiesPlacentaZygosity groupsTwin individualsAverage numberMonozygoticTwin studiesMean absolute differenceAbsolute differenceDifferencesGroupFetusesPlacenta
Kliman H. Placenta. 2021, 3499-3506. DOI: 10.1007/978-3-319-91280-6_1553.Peer-Reviewed Original Research
2020
Noyes, Hertig, and Rock revisited
Kliman HJ. Noyes, Hertig, and Rock revisited. F&S Reports 2020, 1: 2-4. PMID: 34223203, PMCID: PMC8244307, DOI: 10.1016/j.xfre.2020.04.004.Peer-Reviewed Original ResearchEfficacy of telotristat ethyl: A peripheral tryptophan hydroxylase inhibitor that blocks serotonin biosynthesis against cultured liposarcoma, colon cancer, and cholangiocarcinoma cell lines.
Kliman H, Ling I, Milano K. Efficacy of telotristat ethyl: A peripheral tryptophan hydroxylase inhibitor that blocks serotonin biosynthesis against cultured liposarcoma, colon cancer, and cholangiocarcinoma cell lines. Journal Of Clinical Oncology 2020, 38: e15602-e15602. DOI: 10.1200/jco.2020.38.15_suppl.e15602.Peer-Reviewed Original ResearchTelotristat ethylTryptophan hydroxylase inhibitorCholangiocarcinoma cell linesCancer cell linesHydroxylase inhibitorColon cancerCell linesTE groupPR-positive breast cancerPositive breast cancerBlood-brain barrierCentral nervous systemLiposarcoma cell lineColon cancer cell linesLow power microscopic examinationPeripheral cancersCell line growthPositive cancersBrain barrierHT-29 cellsBreast cancerTPH inhibitorsCell confluenceNervous systemTumor cell line growth
2019
An experimental test of the ovulatory homolog model of female orgasm
Pavlicev M, Zupan AM, Barry A, Walters S, Milano KM, Kliman HJ, Wagner GP. An experimental test of the ovulatory homolog model of female orgasm. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 20267-20273. PMID: 31570579, PMCID: PMC6789565, DOI: 10.1073/pnas.1910295116.Peer-Reviewed Original ResearchConceptsCopulation-induced ovulationOvulation rateEffects of fluoxetineHuman chorionic gonadotropinNeuro-endocrine mechanismsFluoxetine treatmentDaily dosesSerotonin functionChorionic gonadotropinSingle injectionPharmacological agentsFluoxetineFemale orgasmOvulationOrgasmRabbitsAnimalsGonadotropinDosesAdult bone marrow progenitors become decidual cells and contribute to embryo implantation and pregnancy
Tal R, Shaikh S, Pallavi P, Tal A, López-Giráldez F, Lyu F, Fang YY, Chinchanikar S, Liu Y, Kliman HJ, Alderman M, Pluchino N, Kayani J, Mamillapalli R, Krause DS, Taylor HS. Adult bone marrow progenitors become decidual cells and contribute to embryo implantation and pregnancy. PLOS Biology 2019, 17: e3000421. PMID: 31513564, PMCID: PMC6742226, DOI: 10.1371/journal.pbio.3000421.Peer-Reviewed Original ResearchConceptsBM transplantsDecidual cellsPregnancy lossMesenchymal stem cellsAdult bone marrow progenitorsDecidualization-related genesBone marrow progenitorsAdult bone marrowWT donorsPhysiologic contributionSuccessful pregnancyBMDC recruitmentStromal expansionImmune cellsEndometrial cellsDeficient miceUterine expressionUterine tissueDecidual stromaPregnancyBone marrowNonhematopoietic cellsBMDCsHemochorial placentaMarrow progenitors