title: The apoptotic transcriptome of the human MII oocyte: characterization and age-related changes.
abstract: Fully competent oocytes represent the final outcome of a highly selective process. The decline of oocyte competence with ageing, coupled to quantitative decrease of ovarian follicles has been well established; on the contrary, its molecular bases are still poorly understood. Through quantitative high throughput PCR, we investigated the role of apoptotic machinery (AM) in this process. To this aim, we determined AM transcriptome in mature MII oocyte pools from women aged more than 38 years (cohort A), and compared to women aged up to 35 years (cohort B). Subsequently, 10 representative AM genes were selected and analyzed in 33 single oocytes (15 from cohort A and 18 from cohort B). These investigations led us to identify: (1) the significant upregulation of proapoptotic genes such us CD40, TNFRSF10A, TNFRSF21 and the downregulation of antiapoptotic genes such as BCL2 and CFLAR in cohort A respect to cohort B; (2) AM transcripts that have not previously been reported in human oocytes (BAG3, CD40, CFLAR, TNFRSF21, TRAF2, TRAF3). Our results demonstrated that during maturation the oocytes from older women selectively accumulate mRNAs that are able to trigger the extrinsic apoptotic pathway. These data contribute to clarify the molecular mechanisms of AM involvement in the natural selection strategy of removing low quality oocytes and preventing unfit or poorly fit embryos.
authors.affiliation: Dipartimento Gian Filippo Ingrassia, Sezione di Biologia, Genetica, Genomica Cellulare e Molecolare Giovanni Sichel, Università degli Studi di Catania, Catania, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Santonocito
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Guglielmino
authors.forename: Marilena
authors.initials: M
authors.lastname: Vento
authors.forename: Marco
authors.initials: M
authors.lastname: Ragusa
authors.forename: Davide
authors.initials: D
authors.lastname: Barbagallo
authors.forename: Placido
authors.initials: P
authors.lastname: Borzì
authors.forename: Ida
authors.initials: I
authors.lastname: Casciano
authors.forename: Paolo
authors.initials: P
authors.lastname: Scollo
authors.forename: Massimo
authors.initials: M
authors.lastname: Romani
authors.forename: Carla
authors.initials: C
authors.lastname: Tatone
authors.forename: Michele
authors.initials: M
authors.lastname: Purrello
authors.forename: Cinzia
authors.initials: C
authors.lastname: Di Pietro
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000375:Aging / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000235:genetics*; D019013:CD40 Antigens / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008423:Maternal Age; D009865:Oocytes / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D059467:Transcriptome; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C414431:BAG3 protein, human; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D019013:CD40 Antigens; C506386:CFLAR protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; C105190:TNFRSF10A protein, human; C114109:TNFRSF21 protein, human