2024
Disruption of mitochondrial unfolded protein response results in telomere shortening in mouse oocytes and somatic cells
Cozzolino M, Ergun Y, Ristori E, Garg A, Imamoglu G, Seli E. Disruption of mitochondrial unfolded protein response results in telomere shortening in mouse oocytes and somatic cells. Aging 2024, 16: 2047-2060. PMID: 38349865, PMCID: PMC10911389, DOI: 10.18632/aging.205543.Peer-Reviewed Original ResearchConceptsCaseinolytic peptidase PMitochondrial unfolded protein responseUnfolded protein responseTelomere integrityProtein responseGermline deletionSomatic cellsSomatic agingSomatic cell divisionDouble-stranded DNA breaksAged miceTelomere shorteningAssociated with cellular senescenceTelomeric regionsProtein homeostasisAccelerated follicular depletionChromosome stabilityCell divisionMtUPRDNA breaksTelomereAging phenotypesCellular senescenceFollicular depletionMouse oocytesMitochondrial Unfolded Protein Response Gene Clpp Is Required for Oocyte Function and Female Fertility
Ergun Y, Imamoglu A, Cozzolino M, Demirkiran C, Basar M, Garg A, Yildirim R, Seli E. Mitochondrial Unfolded Protein Response Gene Clpp Is Required for Oocyte Function and Female Fertility. International Journal Of Molecular Sciences 2024, 25: 1866. PMID: 38339144, PMCID: PMC10855406, DOI: 10.3390/ijms25031866.Peer-Reviewed Original ResearchConceptsCaseinolytic peptidase PMouse modelProtein homeostasisStress responseUnfolded protein stress responseProtein stress responseCumulus/granulosa cellsOocyte competenceOocyte functionGlobal deletionFunctional abnormalitiesGenes clpPMetabolic stress responseFemale subfertilityFemale infertilityOocyte-specificOocytesReproductive functionMtUPRMiceProtein degradationReproductive competenceFemale fertilityDeletionHomeostasis
2022
Mitochondrial dysfunction caused by targeted deletion of Mfn1 does not result in telomere shortening in oocytes.
Cozzolino M, Seli E. Mitochondrial dysfunction caused by targeted deletion of Mfn1 does not result in telomere shortening in oocytes. Zygote 2022, 30: 735-737. PMID: 35730364, DOI: 10.1017/s0967199422000089.Peer-Reviewed Original ResearchConceptsMitochondrial dysfunctionMaintenance of telomeresTargeted deletionEnd-protection functionTTAGGG repeatsMitochondrial fusionTelomeric repeatsSomatic cellsMitofusin 1Reactive oxygen speciesEnzyme complexWild-type miceOocyte growthDNA damageMouse oocytesTelomerase activityOocyte maturationDeletionFollicular depletionOxygen speciesTelomere lengthTelomeresFollicular developmentOocytesRepeats
2019
Mitofusin 1 is required for female fertility and to maintain ovarian follicular reserve
Zhang M, Bener MB, Jiang Z, Wang T, Esencan E, Scott III R, Horvath T, Seli E. Mitofusin 1 is required for female fertility and to maintain ovarian follicular reserve. Cell Death & Disease 2019, 10: 560. PMID: 31332167, PMCID: PMC6646343, DOI: 10.1038/s41419-019-1799-3.Peer-Reviewed Original ResearchConceptsOocyte-granulosa cell communicationDynamic organellesAccumulation of ceramideFemale reproductive agingMitofusin 1Secondary follicle stageMitochondrial dynamicsCell communicationReproductive phenotypesCeramide synthesis inhibitor myriocinDevelopmental arrestApoptotic cell lossMitochondrial dysfunctionTargeted deletionOvarian follicular reserveOocyte maturationFemale fertilityFollicle stageDeletionPhenotypeReproductive agingOocytesCadherinFollicular reserveOrganellesMitofusin 2 plays a role in oocyte and follicle development, and is required to maintain ovarian follicular reserve during reproductive aging
Zhang M, Bener MB, Jiang Z, Wang T, Esencan E, Scott R, Horvath T, Seli E. Mitofusin 2 plays a role in oocyte and follicle development, and is required to maintain ovarian follicular reserve during reproductive aging. Aging 2019, 11: 3919-3938. PMID: 31204316, PMCID: PMC6628992, DOI: 10.18632/aging.102024.Peer-Reviewed Original ResearchConceptsMitofusin 2Key regulatory proteinsImpaired oocyte maturationFollicle developmentMitochondrial fusionRegulatory proteinsEndoplasmic reticulumMitochondrial dysfunctionTargeted deletionOocyte maturationOocytesReproductive agingFemale subfertilityOocyte qualityOvarian follicular reserveTelomeresMitochondriaMetabolic milieuProteinReticulumDeletionFusionPhenotypeApoptosisMaturationTranslational activation of maternally derived mRNAs in oocytes and early embryos and the role of embryonic poly(A) binding protein (EPAB)
Esencan E, Kallen A, Zhang M, Seli E. Translational activation of maternally derived mRNAs in oocytes and early embryos and the role of embryonic poly(A) binding protein (EPAB). Biology Of Reproduction 2019, 100: 1147-1157. PMID: 30806655, PMCID: PMC8127035, DOI: 10.1093/biolre/ioz034.Peer-Reviewed Original ResearchConceptsTranslational activationBinding proteinSpecific protein complexesTranslation of mRNAsOocyte maturationCis-acting sequencesEarly embryo developmentProtein complexesXenopus modelEarly embryosKey regulatorGene expressionMolecular mechanismsEmbryo developmentTargeted disruptionMechanistic detailsProteinEarly developmentMRNAMice resultsKey mechanismOocytesActivationMaturationTranscription
2018
Metabolic imaging with the use of fluorescence lifetime imaging microscopy (FLIM) accurately detects mitochondrial dysfunction in mouse oocytes
Sanchez T, Wang T, Pedro MV, Zhang M, Esencan E, Sakkas D, Needleman D, Seli E. Metabolic imaging with the use of fluorescence lifetime imaging microscopy (FLIM) accurately detects mitochondrial dysfunction in mouse oocytes. Fertility And Sterility 2018, 110: 1387-1397. PMID: 30446247, PMCID: PMC6289735, DOI: 10.1016/j.fertnstert.2018.07.022.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedComputer SystemsEmbryo Culture TechniquesEmbryo, MammalianEmbryonic DevelopmentEndopeptidase ClpFemaleFlavin-Adenine DinucleotideFluorescenceMaleMaternal AgeMiceMice, Inbred C57BLMice, KnockoutMicroscopy, FluorescenceMitochondriaMolecular ImagingNADOocytesReactive Oxygen SpeciesConceptsBlastocyst development rateOocyte dysfunctionReactive oxygen species levelsFlavin adenine dinucleotide (FAD) autofluorescenceMetabolic dysfunctionOxygen species levelsYoung miceMetabolic parametersOld miceMAIN OUTCOMEGlobal knockoutDysfunctionNoninvasive toolNormal oocytesMetabolic imagingMitochondrial dysfunctionMiceOld oocytesFLIM parametersROS levelsMetabolic differencesMitochondrial functionNicotinamide adenine dinucleotide dehydrogenaseIndividual oocytesWild-type oocytesMitochondrial unfolded protein response gene Clpp is required to maintain ovarian follicular reserve during aging, for oocyte competence, and development of pre‐implantation embryos
Wang T, Babayev E, Jiang Z, Li G, Zhang M, Esencan E, Horvath T, Seli E. Mitochondrial unfolded protein response gene Clpp is required to maintain ovarian follicular reserve during aging, for oocyte competence, and development of pre‐implantation embryos. Aging Cell 2018, 17: e12784. PMID: 29851234, PMCID: PMC6052477, DOI: 10.1111/acel.12784.Peer-Reviewed Original ResearchConceptsMitochondrial unfolded protein responseUnfolded mitochondrial proteinsCaseinolytic peptidase PAbsence of ClpPUnfolded protein responsePre-implantation embryosExpression of genesOocyte mitochondrial functionTwo-cell embryosProtein homeostasisMTOR inhibitor rapamycinMitochondrial proteinsOocyte competenceClpPProtein responseInhibitor rapamycinMitochondrial functionP-Akt473P-S6KOvarian follicular reserveSmall mitochondriaMTOR pathway activationPathway activationEmbryosP-S6
2017
Embryonic poly(A)-binding protein is required at the preantral stage of mouse folliculogenesis for oocyte–somatic communication†
Lowther KM, Favero F, Yang CR, Taylor HS, Seli E. Embryonic poly(A)-binding protein is required at the preantral stage of mouse folliculogenesis for oocyte–somatic communication†. Biology Of Reproduction 2017, 96: 341-351. PMID: 28203794, DOI: 10.1095/biolreprod.116.141234.Peer-Reviewed Original Research
2016
Reproductive aging is associated with changes in oocyte mitochondrial dynamics, function, and mtDNA quantity
Babayev E, Wang T, Szigeti-Buck K, Lowther K, Taylor HS, Horvath T, Seli E. Reproductive aging is associated with changes in oocyte mitochondrial dynamics, function, and mtDNA quantity. Maturitas 2016, 93: 121-130. PMID: 27523387, PMCID: PMC5064871, DOI: 10.1016/j.maturitas.2016.06.015.Peer-Reviewed Original ResearchConceptsReactive oxygen speciesUnfolded protein response genesProtein response genesMitochondrial DNAMitochondrial dynamicsMitochondrial stressResponse genesMammalian reproductionMitochondria morphologyStressful conditionsMitochondrial changesMitochondriaROS levelsMtDNA levelsElevated expressionMtDNA quantityOxygen speciesOocytesGenesMature oocytesNumerous aspectsExpressionReproductive agingMII oocytesFollicle-enclosed oocytesCross-Talk Between FSH and Endoplasmic Reticulum Stress: A Mutually Suppressive Relationship
Babayev E, Lalioti MD, Favero F, Seli E. Cross-Talk Between FSH and Endoplasmic Reticulum Stress: A Mutually Suppressive Relationship. Reproductive Sciences 2016, 23: 352-364. PMID: 26342052, PMCID: PMC5933091, DOI: 10.1177/1933719115602770.Peer-Reviewed Original ResearchConceptsFollicle stimulating hormonePregnant mare serum gonadotropinMouse granulosa cellsGranulosa cellsFSH responseSerum gonadotropinFSH stimulationER stressStress-induced cellsPrimary mouse granulosa cellsUntreated granulosa cellsMessenger RNA levelsCalcium adenosine triphosphataseEndoplasmic reticulum stressEstradiol levelsMice 24Estradiol productionIntraperitoneal injectionStimulating hormoneAromatase expressionTP treatmentReticulum stressRNA levelsER stress-associated genesProtein levels
2015
Oocyte mitochondrial function and reproduction
Babayev E, Seli E. Oocyte mitochondrial function and reproduction. Current Opinion In Obstetrics & Gynecology 2015, 27: 175-181. PMID: 25719756, PMCID: PMC4590773, DOI: 10.1097/gco.0000000000000164.Peer-Reviewed Original ResearchConceptsOocyte mitochondrial functionMitochondrial functionEmbryonic developmentMitochondrial nutrientsMitochondrial replacementRole of mitochondriaOogonial stem cellsCellular organellesMammalian reproductionMitochondrial performanceMitochondrial diseaseEmbryo developmentMitochondrial activityMitochondrial dysfunctionOocyte developmentMitochondriaReproductive consequencesStem cellsOocyte maturationMitochondrial abnormalitiesPolar bodyReproductionEnergy productionIntake of compoundsNegative long-term health effects
2014
The impact of assisted reproductive technologies on genomic imprinting and imprinting disorders
Uyar A, Seli E. The impact of assisted reproductive technologies on genomic imprinting and imprinting disorders. Current Opinion In Obstetrics & Gynecology 2014, 26: 210-221. PMID: 24752003, PMCID: PMC4123998, DOI: 10.1097/gco.0000000000000071.Peer-Reviewed Original ResearchConceptsRelevant clinical dataReproductive technology proceduresConclusive clinical trialsBeckwith-Wiedemann syndromeCase seriesLarge registriesClinical trialsART proceduresClinical dataHigh prevalenceGeneral populationLow prevalenceART usePotential associationGenomic imprintingGene expressionDisordersEarly embryo developmentReproductive technologiesAllele-specific gene expressionFurther studiesTechnology proceduresPrevalenceImprinted gene expressionImprinting disordersEpab is dispensable for mouse spermatogenesis and male fertility
Ozturk S, Guzeloglu-Kayisli O, Lowther KM, Lalioti MD, Sakkas D, Seli E. Epab is dispensable for mouse spermatogenesis and male fertility. Molecular Reproduction And Development 2014, 81: 390-390. PMID: 24599567, PMCID: PMC4079073, DOI: 10.1002/mrd.22319.Peer-Reviewed Original Research
2013
Natural birth-induced UCP2 in brain development
Seli E, Horvath TL. Natural birth-induced UCP2 in brain development. Reviews In Endocrine And Metabolic Disorders 2013, 14: 347-350. PMID: 23979530, DOI: 10.1007/s11154-013-9262-8.Peer-Reviewed Original ResearchConceptsVaginal birthPost-operative surgical careLong-term outcomesEarly postnatal periodWild-type littermatesAdult brain structureUCP2 mRNA expressionTerm outcomesSurgical techniqueSurgical carePostnatal periodSurgical meansHippocampal formationMore deliveriesSynapse formationAxonal outgrowthC-sectionKnockout animalsMRNA expressionUCP2 expressionBrain developmentBrain structuresNeuronal differentiationBirthHippocampusCharacterization of the Gonadotropin Releasing Hormone Receptor (GnRHR) Expression and Activity in the Female Mouse Ovary
Torrealday S, Lalioti MD, Guzeloglu-Kayisli O, Seli E. Characterization of the Gonadotropin Releasing Hormone Receptor (GnRHR) Expression and Activity in the Female Mouse Ovary. Endocrinology 2013, 154: 3877-3887. PMID: 23913446, PMCID: PMC3776864, DOI: 10.1210/en.2013-1341.Peer-Reviewed Original ResearchConceptsGranulosa/cumulus cellsGranulosa cellsMouse ovariesReceptor expressionPrimary mouse granulosa cellsCumulus cellsPregnant mare serum gonadotropinIntracellular cAMPHormone receptor expressionGnRH receptor expressionCultured granulosa cellsOvarian granulosa cellsMouse granulosa cellsMechanism of actionGonadotoxic chemotherapyQuantitative RT-PCRGnRH agonistGnRHR mRNAFertility preservationMouse pituitary cellsLuciferase reporter plasmidSerum gonadotropinPituitary cell linePituitary cellsPituitary tissuemRNA-Binding Protein ZFP36 Is Expressed in Atherosclerotic Lesions and Reduces Inflammation in Aortic Endothelial Cells
Zhang H, Taylor WR, Joseph G, Caracciolo V, Gonzales DM, Sidell N, Seli E, Blackshear PJ, Kallen CB. mRNA-Binding Protein ZFP36 Is Expressed in Atherosclerotic Lesions and Reduces Inflammation in Aortic Endothelial Cells. Arteriosclerosis Thrombosis And Vascular Biology 2013, 33: 1212-1220. PMID: 23559629, PMCID: PMC3844532, DOI: 10.1161/atvbaha.113.301496.Peer-Reviewed Original ResearchConceptsVascular endothelial cellsEndothelial cellsAortic endothelial cellsAtherosclerotic lesionsFoam cellsAnti-inflammatory effectsHuman aortic endothelial cellsNuclear factor-κB transcriptional activationLow-density lipoproteinMacrophage foam cellsZinc finger protein 36Vascular inflammationAngiotensin IIInflammatory cytokinesCytokine mRNAZFP36 expressionBacterial lipopolysaccharideHealthy aortaInflammationTarget cellsLesionsZFP36Protein 36CellsMRNA transcripts
2012
Epab and Pabpc1 Are Differentially Expressed During Male Germ Cell Development
Ozturk S, Guzeloglu-Kayisli O, Demir N, Sozen B, Ilbay O, Lalioti MD, Seli E. Epab and Pabpc1 Are Differentially Expressed During Male Germ Cell Development. Reproductive Sciences 2012, 19: 911-922. PMID: 22814100, PMCID: PMC4046314, DOI: 10.1177/1933719112446086.Peer-Reviewed Original ResearchConceptsRound spermatidsGene expressionMale germ cell developmentGerm cell developmentPABPC1 expressionTranslational regulationCytoplasmic polyadenylationPosttranscriptional mechanismsPABPC1Key proteinsCell developmentEPABSpatial expressionMature testesMouse testisMessenger RNASpermatogenic cellsTail lengthProteinSpermatocytesExpressionSpermatogoniaTestisEarly postnatal lifePolyadenylationEmbryonic poly(A)-binding protein (EPAB) is required for oocyte maturation and female fertility in mice
Guzeloglu-Kayisli O, Lalioti MD, Aydiner F, Sasson I, Ilbay O, Sakkas D, Lowther KM, Mehlmann LM, Seli E. Embryonic poly(A)-binding protein (EPAB) is required for oocyte maturation and female fertility in mice. Biochemical Journal 2012, 446: 47-58. PMID: 22621333, PMCID: PMC3955213, DOI: 10.1042/bj20120467.Peer-Reviewed Original ResearchConceptsTranslational activationOocyte maturationZygotic genome activationFemale fertilityGenome activationGerminal vesicle stage oocytesDazl mRNAEarly embryogenesisMaternal mRNAsDownstream regulatorsMammalian reproductionGene expressionEPABStage oocytesXenopus oocytesEpidermal growthLate antral folliclesOogenesisMRNAOocytesMaturationProteinFemale miceCumulus expansionAntral folliclesThe mRNA‐Binding Protein Zfp36 Is Upregulated by β‐Adrenergic Stimulation and Represses IL‐6 Production in 3T3‐L1 Adipocytes
Brahma PK, Zhang H, Murray BS, Shu F, Sidell N, Seli E, Kallen CB. The mRNA‐Binding Protein Zfp36 Is Upregulated by β‐Adrenergic Stimulation and Represses IL‐6 Production in 3T3‐L1 Adipocytes. Obesity 2012, 20: 40-47. PMID: 21818148, PMCID: PMC4127993, DOI: 10.1038/oby.2011.259.Peer-Reviewed Original ResearchConceptsAU-rich elementsZFP36 expressionCell type-specific modulatorsPost-transcriptional levelMRNA-binding proteinRetinoic acidZinc finger protein 36Novel mechanistic approachTarget mRNAsMRNA targetsSuch proteinsPotent repressorAdipocyte-derived IL-6Protein 36Chronic inflammatory stateSystemic immune responsesDevelopment of diabetesDependent pathwayDiverse inflammatory disordersZFP36IL-6 productionAdrenergic receptor agonist isoproterenolCyclic adenosine monophosphateInterleukin-6 expressionΒ-Adrenergic Stimulation