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Article Addendum

Cell death in fetal oocytes: Many players for multiple pathways

Massimo De Felici, Anna Maria Lobascio and Francesca Gioia Klinger

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We devised a short-term culture system allowing us to define novel characteristics of programmed cell death (PCD) of fetal oocytes and to underscore new aspects of this process. Mouse fetal oocytes cultured in conditions allowing meiotic progression underwent apoptotic degeneration as revealed by TUNEL staining, DNA ladder, Annexin V binding, PARP cleavage and, usually, caspase activation. TEM observations show, however, recurrent atypical apoptotic morphologies characterized by the absence of chromatin margination and nuclear fragmentation; oocytes with autophagic and necrotic features are also observed. Moreover, under the fluorescence microscope a subpopulation of TUNEL⁺ oocytes appear morphologically healthy and do not show detectable caspase activity. Finally, caspase inhibitors are able to slow down, but not to abolish, oocyte cell death, whereas calpain inhibitor I significantly reduces the number of TUNEL⁺ oocytes after 4 days of culture, and rapamycin (mTOR inhibitor) increases such numbers both at day 3 and 4. These observations together with results showing expression in cultured oocytes undergoing cell death of apoptosis inducing factor and Beclin 1, two important players of caspase-independent and autophagic cell death, respectively, demonstrate that fetal oocytes posses and are able to activate several players of various forms of cell death. However, causal correlation among different cell death pathways in such oocytes remains to be determined and stimuli causing the activation of these pathways in vitro and in vivo also clarified.

Addendum to: Lobascio AM, Klinger FG, Scaldaferri ML, Farini D, De Felici M. Analysis of programmed cell death in mouse fetal oocytes. Reproduction 2007; 134:241-52.

Authors

Massimo De Felici

University of Tor Vergata

Anna Maria Lobascio

University of Tor Vergata

Francesca Gioia Klinger

University of Tor Vergata

Purchase article for $19

Subscribe to this journal for $99/year