TY - JOUR
T1 - The apoptotic transcriptome of the human MII oocyte
T2 - Characterization and age-related changes
AU - Santonocito, Manuela
AU - Guglielmino, Maria Rosa
AU - Vento, Marilena
AU - Ragusa, Marco
AU - Barbagallo, Davide
AU - Borzì, Placido
AU - Casciano, Ida
AU - Scollo, Paolo
AU - Romani, Massimo
AU - Tatone, Carla
AU - Purrello, Michele
AU - Di Pietro, Cinzia
PY - 2013/2
Y1 - 2013/2
N2 - 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.
AB - 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.
KW - Apoptotic machinery genes
KW - Human oocyte
KW - Reproductive ageing
KW - Transcriptome
UR - http://www.scopus.com/inward/record.url?scp=84877108756&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84877108756&partnerID=8YFLogxK
U2 - 10.1007/s10495-012-0783-5
DO - 10.1007/s10495-012-0783-5
M3 - Article
C2 - 23179180
AN - SCOPUS:84877108756
VL - 18
SP - 201
EP - 211
JO - Apoptosis : an international journal on programmed cell death
JF - Apoptosis : an international journal on programmed cell death
SN - 1360-8185
IS - 2
ER -