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
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
2021
Embryology outcomes after oocyte vitrification with super-cooled slush nitrogen are similar to outcomes with conventional liquid nitrogen: a randomized controlled trial
Hanson BM, Kim JG, Suarez SI, Ackerman BK, Comito CE, Pangasnan R, Seli E, Hong KH, Scott RT. Embryology outcomes after oocyte vitrification with super-cooled slush nitrogen are similar to outcomes with conventional liquid nitrogen: a randomized controlled trial. Fertility And Sterility 2021, 117: 106-114. PMID: 34654569, DOI: 10.1016/j.fertnstert.2021.08.043.Peer-Reviewed Original ResearchConceptsMetaphase II oocytesEmbryology outcomesOocyte survivalII oocytesOocyte donor cyclesOocyte survival ratePreimplantation genetic testingBlastocyst formationWhole chromosome aneuploidyChromosome aneuploidySecondary outcomesPrimary outcomeDonor cyclesDonor oocytesRate of fertilizationMAIN OUTCOMESurvival rateOocyte vitrificationTrophectoderm biopsyGenetic testingDonor spermPrivate practiceNext-generation sequencingOutcomesDemonstrable improvementCumulus cells of euploid versus whole chromosome 21 aneuploid embryos reveal differentially expressed genes
Tiegs AW, Titus S, Mehta S, Garcia-Milian R, Seli E, Scott RT. Cumulus cells of euploid versus whole chromosome 21 aneuploid embryos reveal differentially expressed genes. Reproductive BioMedicine Online 2021, 43: 614-626. PMID: 34417138, DOI: 10.1016/j.rbmo.2021.06.015.Peer-Reviewed Original ResearchConceptsSerum response factorCumulus cellsDifferential gene expressionRNA sequencing analysisGene expression analysisIngenuity Pathway AnalysisCellular communication network factor 1Embryo developmental competenceExpression analysisPreimplantation embryo qualityGene expressionPathway analysisSegment polarity protein 2Sequencing analysisGenesProtein 2Response factorTrisomy 21Factor 1Developmental competenceAneuploid embryosReal-time polymerase chain reaction assaysDevelopment of biomarkersEmbryosCells
2020
The appraisal of body content (ABC) trial: obesity does not significantly impact gamete production in infertile men and women
Kim J, Juneau C, Patounakis G, Morin S, Neal S, Seli E, Scott R. The appraisal of body content (ABC) trial: obesity does not significantly impact gamete production in infertile men and women. Journal Of Assisted Reproduction And Genetics 2020, 37: 2733-2742. PMID: 32827101, PMCID: PMC7642175, DOI: 10.1007/s10815-020-01930-3.Peer-Reviewed Original ResearchConceptsBody mass indexLower serum AMHLower serum FSHOvarian reserve parametersPresence of PCOSControlled ovarian hyperstimulationNormal-weight counterpartsMature oocytesPercent body fatBF categoriesOvarian hyperstimulationSerum AMHOvarian reservePCOS diagnosisSerum FSHIVF outcomesLess muscle massOvarian responseMass indexFemale obesityInfertility treatmentReserve parametersBody fatInfertile menObesity
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 milieuProteinReticulumDeletionFusionPhenotypeApoptosisMaturationDiminished ovarian reserve versus ovarian aging: overlaps and differences.
Ata B, Seyhan A, Seli E. Diminished ovarian reserve versus ovarian aging: overlaps and differences. Current Opinion In Obstetrics & Gynecology 2019, 31: 139-147. PMID: 30870184, DOI: 10.1097/gco.0000000000000536.Peer-Reviewed Original ResearchConceptsNormal ovarian reserveOvarian reservePregnancy lossOocyte qualityReproductive technology cyclesAge-matched womenDiminished ovarian reserveLow ovarian reserveFetal chromosomal abnormalitiesQuantitative declineFecundity of womenOvarian stimulationNatural conceptionOvarian agingPoor responseART treatmentAged womenYoung womenChromosomal abnormalitiesAvailable evidenceDecreased numberQualitative declineOocyte poolWomenBlastocyst developmentTranslational 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 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 oocytesMetabolism of the oocyte and the preimplantation embryo
Scott R, Zhang M, Seli E. Metabolism of the oocyte and the preimplantation embryo. Current Opinion In Obstetrics & Gynecology 2018, 30: 163-170. PMID: 29708901, DOI: 10.1097/gco.0000000000000455.Peer-Reviewed Original ResearchMitochondrial 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 ResearchConceptsMetabolic 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
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 oocytesMitochondrial DNA as a biomarker for in-vitro fertilization outcome
Seli E. Mitochondrial DNA as a biomarker for in-vitro fertilization outcome. Current Opinion In Obstetrics & Gynecology 2016, 28: 158-163. PMID: 27077472, DOI: 10.1097/gco.0000000000000274.Peer-Reviewed Original Research