2024
Mitochondrial 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 ResearchMeSH KeywordsAnimalsEndopeptidase ClpFemaleFertilityInfertility, FemaleMiceMitochondriaOocytesUnfolded Protein ResponseConceptsCaseinolytic 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
Targeted Deletion of Mitofusin 1 and Mitofusin 2 Causes Female Infertility and Loss of Follicular Reserve
Cozzolino M, Ergun Y, Seli E. Targeted Deletion of Mitofusin 1 and Mitofusin 2 Causes Female Infertility and Loss of Follicular Reserve. Reproductive Sciences 2022, 30: 560-568. PMID: 35739352, DOI: 10.1007/s43032-022-01014-w.Peer-Reviewed Original ResearchConceptsMitofusin 1Mitofusin 2Double deletionFemale reproductive competencePotential functional redundancyDynamic organellesCellular homeostasisFunctional redundancyMitochondrial dynamicsEnvironmental stressMitochondrial functionMitochondrial dysfunctionMfn1Reproductive competenceTargeted deletionMfn2Oocyte maturationDeletionCritical roleReproductive agingFemale infertilityOocytesOocyte qualityFusion mechanismMitofusinsMitochondrial 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
Mitochondrial function in women with polycystic ovary syndrome.
Cozzolino M, Seli E. Mitochondrial function in women with polycystic ovary syndrome. Current Opinion In Obstetrics & Gynecology 2020, 32: 205-212. PMID: 32068544, DOI: 10.1097/gco.0000000000000619.Peer-Reviewed Original ResearchConceptsPolycystic ovary syndromeLower mtDNA copy numberOvary syndromePathogenesis of PCOSMitochondrial dysfunctionMtDNA copy numberPotential protective rolePCOS phenotypeInsulin resistancePathophysiological mechanismsCommon findingDiagnostic modalitiesMetabolic milieuFunctional alterationsMitochondrial functional alterationsProtective roleCommon diseaseOxidative stressWomenMitochondrial functionDysfunctionSyndromeCopy numberProtein responseReactive oxygenMitochondrial DNA content is not predictive of reproductive competence in euploid blastocysts
Scott RT, Sun L, Zhan Y, Marin D, Tao X, Seli E. Mitochondrial DNA content is not predictive of reproductive competence in euploid blastocysts. Reproductive BioMedicine Online 2020, 41: 183-190. PMID: 32600944, DOI: 10.1016/j.rbmo.2020.04.011.Peer-Reviewed Original ResearchConceptsRelative mtDNA copy numberSingle embryo transferMitochondrial DNA copy numberMtDNA copy numberEmbryo transferSuccessful single embryo transferDNA copy numberRelative mtDNA levelsHuman blastocystsReal-time polymerase chain reactionQuantitative real-time polymerase chain reactionReproductive competenceIVF outcomesMaternal ageOngoing implantationPolymerase chain reactionEuploid blastocystsMitochondrial DNA contentReproductive outcomesSame patientClinical decisionTrophectoderm biopsySame cohortAmount of mtDNACopy numberImpaired 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 reserveOrganellesMitochondria as a Biomarker for IVF Outcome
Kim J, Seli E. Mitochondria as a Biomarker for IVF Outcome. Reproduction 2019, -1: r235-r242. PMID: 30844752, DOI: 10.1530/rep-18-0580.Peer-Reviewed Original ResearchConceptsKey cellular functionsAcid metabolismAmino acid metabolismCellular functionsMitochondrial DNASignal transductionFatty acid metabolismApoptotic regulationIon homeostasisEmbryo developmentMitochondrial contentInfertility treatment outcomesEmbryo metabolismAdvanced maternal ageMitochondriaEssential roleEmbryo viabilityIVF outcomesImplantation failureMaternal ageEuploid blastocystsTreatment outcomesAdditional biomarkersImplantation successMetabolismMitochondrial 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 metabolismMetabolic imaging via fluorescence lifetime imaging microscopy for egg and embryo assessment
Sanchez T, Zhang M, Needleman D, Seli E. Metabolic imaging via fluorescence lifetime imaging microscopy for egg and embryo assessment. Fertility And Sterility 2019, 111: 212-218. PMID: 30691624, DOI: 10.1016/j.fertnstert.2018.12.014.Peer-Reviewed Original ResearchConceptsMetabolic imagingInvasive diagnostic interventionsEmbryo assessmentPreimplantation genetic testingUseful diagnostic methodAssisted reproductive technology (ART) laboratoryClinical benefitSingle ETDiagnostic interventionsOxidative phosphorylationGenetic testingReproductive technology laboratoriesExperimental modelCopy number assessmentMetabolic functionsMorphologic parametersFluorescence lifetimeEmbryosClinical applicationMetabolic stateDiagnostic methodsEmbryo viabilityElectron transporterCentral roleCurrent strategies
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-S6The role of mitochondrial activity in female fertility and assisted reproductive technologies: overview and current insights
Cecchino GN, Seli E, Alves da Motta E, García-Velasco J. The role of mitochondrial activity in female fertility and assisted reproductive technologies: overview and current insights. Reproductive BioMedicine Online 2018, 36: 686-697. PMID: 29598846, DOI: 10.1016/j.rbmo.2018.02.007.Peer-Reviewed Original ResearchMeSH KeywordsDNA, MitochondrialFemaleFertilityHumansMitochondriaOocytesReproductive Techniques, AssistedConceptsMetabolic stress modelsMitochondrial functionFemale fertilityFemale reproductive processesPoor outcomeReplacement therapyOvarian agingMitochondrial DNA contentInfertility treatmentTherapeutic attemptsOocyte qualityClinical implicationsEmbryo potentialOocyte maturationReproductive processesPrecursor cellsEarly embryo developmentReproductive technologiesDisease-causing mutationsMitochondrial capacityRole of mitochondriaMitochondrial impactCurrent insightsTrophectoderm cellsWomen
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 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 oocytes
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