The apoptotic transcriptome of the human MII oocyte: Characterization and age-related changes

Manuela Santonocito, Maria Rosa Guglielmino, Marilena Vento, Marco Ragusa, Davide Barbagallo, Placido Borzì, Ida Casciano, Paolo Scollo, Massimo Romani, Carla Tatone, Michele Purrello, Cinzia Di Pietro

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)201-211
Number of pages11
JournalApoptosis
Volume18
Issue number2
DOIs
Publication statusPublished - Feb 2013

Keywords

  • Apoptotic machinery genes
  • Human oocyte
  • Reproductive ageing
  • Transcriptome

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry
  • Biochemistry, medical
  • Cancer Research
  • Pharmaceutical Science
  • Pharmacology

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