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

Accumulating evidence indicates that fragmentation of ovulated murine oocyt es, resulting spontaneously or following exposure to lethal stimuli such as anticancer drugs during in-vitro culture, occurs with several hallmark fea tures of apoptosis. However, recent work has failed to demonstrate a correl ation between DNA cleavage, as assessed by DNA 3'-end-labelling, or of phos phatidylserine exposure on the outer leaflet of the plasma membrane, as mea sured 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 su ch a mechanism is involved in the elimination or prevention of fertilizatio n of oocytes with cytoplasmic or chromosomal defects'. Here, we have re-ass essed DNA cleavage in normal and fragmented murine oocytes, have provided n ew evidence of an additional biochemical marker of apoptosis in fragmented oocytes (i.e. caspase activity), and have re-evaluated published reports re garding oocyte fragmentation, in an effort to clarify these discrepant find ings. The results and discussions presented herein fully support previous c onclusions reached by ourselves and others that fragmentation of ovulated o ocytes is in fact an unequivocal example of apoptotic cell death.