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
2020
Impaired Mitochondrial Stress Response due to CLPP Deletion Is Associated with Altered Mitochondrial Dynamics and Increased Apoptosis in Cumulus Cells
Esencan E, Jiang Z, Wang T, Zhang M, Soylemez-Imamoglu G, Seli E. Impaired Mitochondrial Stress Response due to CLPP Deletion Is Associated with Altered Mitochondrial Dynamics and Increased Apoptosis in Cumulus Cells. Reproductive Sciences 2020, 27: 621-630. PMID: 31939198, DOI: 10.1007/s43032-019-00063-y.Peer-Reviewed Original ResearchConceptsCaseinolytic peptidase PCumulus cell functionClpP deletionMitochondrial unfolded protein responseMitochondrial stress responseCumulus cellsUnfolded protein responseRNA sequencing analysisAltered mitochondrial dynamicsCell functionProtein homeostasisMitochondrial dynamics genesCLPP resultsMitochondrial dynamicsDynamic genesPhagosome pathwayProtein responseCellular metabolismGene expressionWild typeStress responseCumulus oophorus complexesMitochondrial ultrastructureSequencing analysisApoptotic activityMitochondrial Dysfunction and Ovarian Aging
Kasapoğlu I, Seli E. Mitochondrial Dysfunction and Ovarian Aging. Endocrinology 2020, 161: bqaa001. PMID: 31927571, DOI: 10.1210/endocr/bqaa001.Peer-Reviewed Original Research
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 mechanismOocytesActivationMaturationTranscriptionMitochondrial unfolded protein response: a stress response with implications for fertility and reproductive aging
Seli E, Wang T, Horvath TL. Mitochondrial unfolded protein response: a stress response with implications for fertility and reproductive aging. Fertility And Sterility 2019, 111: 197-204. PMID: 30691623, DOI: 10.1016/j.fertnstert.2018.11.048.Peer-Reviewed Original ResearchConceptsMitochondrial unfolded protein responseTwo-cell embryo developmentUnfolded protein responseImpaired oocyte maturationMorphology of mitochondriaMitochondrial dysfunction resultsPremature reproductive agingNovel mechanistic insightsMitochondrial DNA contentReactive oxygen species productionPrevention of agingCLPP resultsProtein responseOxygen species productionReproductive agingPreimplantation embryosAge-related accumulationOxidative phosphorylationStress responseEmbryo developmentForm blastocystsMitochondrial functionMitochondriaMitochondrial dysfunctionEnergy metabolism
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
Mitochondrial dysfunction and ovarian aging
Wang T, Zhang M, Jiang Z, Seli E. Mitochondrial dysfunction and ovarian aging. American Journal Of Reproductive Immunology 2017, 77 PMID: 28194828, DOI: 10.1111/aji.12651.Peer-Reviewed Original ResearchEmbryonic 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
Ovarian Aging
Seli E. Ovarian Aging. Seminars In Reproductive Medicine 2015, 33: 375-376. PMID: 26565386, DOI: 10.1055/s-0035-1567817.Peer-Reviewed Original ResearchEmbryonic Poly(A)-Binding Protein (EPAB) Is Required for Granulosa Cell EGF Signaling and Cumulus Expansion in Female Mice
Yang CR, Lowther KM, Lalioti MD, Seli E. Embryonic Poly(A)-Binding Protein (EPAB) Is Required for Granulosa Cell EGF Signaling and Cumulus Expansion in Female Mice. Endocrinology 2015, 157: 405-416. PMID: 26492470, PMCID: PMC4701890, DOI: 10.1210/en.2015-1135.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Morphogenetic Protein 15Cell ProliferationCells, CulturedCoculture TechniquesCumulus CellsEpidermal Growth FactorErbB ReceptorsFemaleGranulosa CellsGrowth Differentiation Factor 9Luteinizing HormoneMAP Kinase Signaling SystemMice, KnockoutOocytesPhosphorylationPoly(A)-Binding ProteinsProtein Processing, Post-TranslationalReceptors, LHSignal TransductionConceptsEpidermal growth factorZygotic genome activationP90 ribosomal S6 kinaseBone morphogenetic protein 15Cumulus cellsRibosomal S6 kinaseImpaired oocyte maturationCumulus expansionGrowth differentiation factor 9Genome activationDifferentiation factor 9S6 kinaseEarly embryosTranslational activationEGF signalingEGF receptorFemale micePhosphorylated MEK1/2EGF treatmentBinding proteinFactor 9Cells exhibitOocyte maturationProteinProtein 15Oocyte 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
Prediction of pregnancy viability in bovine in vitro-produced embryos and recipient plasma with Fourier transform infrared spectroscopy
Muñoz M, Uyar A, Correia E, Díez C, Fernandez-Gonzalez A, Caamaño JN, Martínez-Bello D, Trigal B, Humblot P, Ponsart C, Guyader-Joly C, Carrocera S, Martin D, Le Guienne B, Seli E, Gomez E. Prediction of pregnancy viability in bovine in vitro-produced embryos and recipient plasma with Fourier transform infrared spectroscopy. Journal Of Dairy Science 2014, 97: 5497-5507. PMID: 24997663, PMCID: PMC4208725, DOI: 10.3168/jds.2014-8067.Peer-Reviewed Original ResearchThe 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 disorders