2021
Individual-oocyte transcriptomic analysis shows that genotoxic chemotherapy depletes human primordial follicle reserve in vivo by triggering proapoptotic pathways without growth activation
Titus S, Szymanska K, Musul B, Turan V, Taylan E, Garcia- Milian R, Mehta S, Oktay K. Individual-oocyte transcriptomic analysis shows that genotoxic chemotherapy depletes human primordial follicle reserve in vivo by triggering proapoptotic pathways without growth activation. Scientific Reports 2021, 11: 407. PMID: 33431979, PMCID: PMC7801500, DOI: 10.1038/s41598-020-79643-x.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisCyclophosphamideDNA DamageFemaleGene Expression ProfilingHeterograftsHumansMiceMice, Inbred NODMice, SCIDOocytesOogenesisOvarian FollicleOvarian ReserveOvarySignal TransductionSingle-Cell AnalysisTranscriptomeYoung AdultConceptsPrimordial follicle oocytesFollicle lossGrowth activationHuman ovarian xenograft modelPI3K/PTEN/AktFollicle oocytesDNA damagePI3K/PTEN/Akt pathwayOvarian reserve depletionPrimordial follicle reservePTEN/AKT pathwayIngenuity Pathway AnalysisOvarian xenograft modelPTEN/AKTSevere DNA damageExpression of AktGonadotoxic chemotherapyAnti-apoptotic Bcl2Early menopauseFollicle reserveTranscriptomic analysisCyclophosphamide injectionHuman ovaryPhosphorylation statusRNA sequencing
2020
Unraveling the mechanisms of chemotherapy-induced damage to human primordial follicle reserve: road to developing therapeutics for fertility preservation and reversing ovarian aging
Szymanska K, Tan X, Oktay K. Unraveling the mechanisms of chemotherapy-induced damage to human primordial follicle reserve: road to developing therapeutics for fertility preservation and reversing ovarian aging. Molecular Human Reproduction 2020, 26: 553-566. PMID: 32514568, PMCID: PMC7411370, DOI: 10.1093/molehr/gaaa043.Peer-Reviewed Original ResearchConceptsPrimordial follicle reserveChemotherapy-induced damageFollicle reserveOvarian reserveChemotherapy-induced lossOvarian reserve depletionApoptotic deathPrimordial follicle oocytesFertility preservationAcute reductionOvarian agingHuman ovaryFollicle activationPrimordial folliclesAcute exposureStromal damageTranslational evidenceChemotherapeutic agentsApoptotic lossFollicle oocytesDNA double-strand breaksDNA DSBsCurrent literatureDeathActivation