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

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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.

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Acknowledgments

This project was financed with funds from Ministero dell’Università e della Ricerca Scientifica e Tecnologica to CDP (in particular, PRA 2007: Marcatori molecolari correlati alla qualità follicolare ed ovocitaria. PRA 2008: Stemness genes negli ovociti umani). We acknowledge the assignment to Dr D. Barbagallo of a fellowship by the Facoltà di Medicina e Chirurgia, Università di Catania to work on this project (Title: Marcatori molecolari correlati alla qualità follicolare ed ovocitaria ed ai meccanismi di impianto).

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Authors and Affiliations

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

    Manuela Santonocito, Maria Rosa Guglielmino, Marco Ragusa, Davide Barbagallo, Michele Purrello & Cinzia Di Pietro

  2. Servizio di PMA/Azienda Ospedaliera Cannizzaro, Catania, Italy

    Marilena Vento, Placido Borzì & Paolo Scollo

  3. Tumor Genetics and Epigenetics, IRCCS San Martino—IST Genova, Genova, Italy

    Ida Casciano & Massimo Romani

  4. Department of Life, Health and Environmental Sciences, University of L’Aquila, L’Aquila, Italy

    Carla Tatone

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  1. Manuela Santonocito
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  2. Maria Rosa Guglielmino
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  3. Marilena Vento
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  4. Marco Ragusa
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  5. Davide Barbagallo
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  11. Michele Purrello
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  12. Cinzia Di Pietro
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Correspondence to Cinzia Di Pietro.

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Santonocito, M., Guglielmino, M.R., Vento, M. et al. The apoptotic transcriptome of the human MII oocyte: characterization and age-related changes. Apoptosis 18, 201–211 (2013). https://doi.org/10.1007/s10495-012-0783-5

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