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

Manuela Santonocito1, Maria Rosa Guglielmino, Marilena Vento

  • 1Dipartimento Gian Filippo Ingrassia, Sezione di Biologia, Genetica, Genomica Cellulare e Molecolare Giovanni Sichel, Università degli Studi di Catania, Catania, Italy.

Apoptosis : an International Journal on Programmed Cell Death
|November 27, 2012
PubMed

Insights

Oocyte competence declines with age due to molecular changes in the apoptotic machinery (AM). Older women

Area of Science:

  • Reproductive biology
  • Molecular genetics
  • Cellular apoptosis

Background:

  • Oocyte competence naturally declines with advanced maternal age.
  • The molecular mechanisms underlying age-related oocyte quality decline are poorly understood.
  • The apoptotic machinery (AM) plays a role in selecting competent oocytes.

Purpose of the Study:

  • To investigate the role of the apoptotic machinery (AM) in age-related oocyte competence decline.
  • To compare the AM transcriptome in oocytes from younger and older women.

Main Methods:

  • Quantitative high-throughput PCR was used to analyze the AM transcriptome in oocyte pools.
  • Gene expression of 10 representative AM genes was analyzed in single oocytes from two age cohorts (≤35 years and >38 years).
  • Comparison of gene expression profiles between the two cohorts.

Main Results:

  • Significant upregulation of pro-apoptotic genes (e.g., CD40, TNFRSF10A, TNFRSF21) and downregulation of anti-apoptotic genes (e.g., BCL2, CFLAR) were observed in oocytes from older women (cohort A).
  • Novel AM transcripts (BAG3, CD40, CFLAR, TNFRSF21, TRAF2, TRAF3) were identified in human oocytes.
  • Oocytes from older women selectively accumulate mRNAs that activate the extrinsic apoptotic pathway.

Conclusions:

  • Age-related oocyte quality decline is associated with altered expression of apoptotic machinery genes.
  • The extrinsic apoptotic pathway appears to be activated in oocytes from older women.
  • These findings elucidate the molecular basis of AM's role in oocyte quality selection and preventing the development of compromised embryos.

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