Fragmentation and death (a.k.a. apoptosis) of ovulated oocytes

Accumulating evidence indicates that fragmentation of ovulated murine oocytes, resulting spontaneously or following exposure to lethal stimuli such as anticancer drugs during in-vitro culture, occurs with several hallmark features of apoptosis. However, recent work has failed to demonstrate a correlation between DNA cleavage, as assessed by DNA 3'-end-labelling, or of phosphatidylserine exposure on the outer leaflet of the plasma membrane, as measured by annexin V-staining, with fragmentation of ovulated mouse or human oocytes maintained in vitro. Consequently, these authors stated that it is 'premature to conclude that apoptosis occurs in ovulated oocytes or that such a mechanism is involved in the elimination or prevention of fertilization of oocytes with cytoplasmic or chromosomal defects'. Here, we have re-assessed DNA cleavage in normal and fragmented murine oocytes, have provided new evidence of an additional biochemical marker of apoptosis in fragmented oocytes (i.e. caspase activity), and have re-evaluated published reports regarding oocyte fragmentation, in an effort to clarify these discrepant findings. The results and discussions presented herein fully support previous conclusions reached by ourselves and others that fragmentation of ovulated oocytes is in fact an unequivocal example of apoptotic cell death.