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Fragmentation and death (a.k.a. apoptosis) of ovulated oocytes
G I Perez1, X J Tao, J L Tilly
1Department of Obstetrics and Gynecology, Massachusetts General Hospital/Harvard Medical School, Boston 02114, USA.
Abstract:
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.
Insights
Oocyte fragmentation, a process observed in mouse oocytes, is confirmed as apoptosis. This study provides new evidence, including caspase activity, to support this conclusion, clarifying previous research discrepancies.
Area of Science:
- Reproductive Biology
- Cell Biology
- Apoptosis Research
Background:
- Oocyte fragmentation, observed spontaneously or after exposure to stimuli like anticancer drugs, shares features with apoptosis.
- Previous studies yielded conflicting results regarding the correlation between DNA cleavage, phosphatidylserine exposure, and oocyte fragmentation.
- This led to debate about whether apoptosis is involved in the elimination of defective oocytes.
Purpose of the Study:
- To re-assess DNA cleavage in normal and fragmented murine oocytes.
- To investigate caspase activity as a biochemical marker of apoptosis in fragmented oocytes.
- To clarify discrepant findings regarding apoptosis in ovulated oocytes.
Main Methods:
- Re-assessment of DNA cleavage in murine oocytes using DNA 3'-end-labelling.
- Measurement of caspase activity in fragmented oocytes.
- Re-evaluation of published literature on oocyte fragmentation and apoptosis.
Main Results:
- New evidence confirms caspase activity as a marker in fragmented oocytes.
- The study supports previous findings that oocyte fragmentation is a form of apoptotic cell death.
- Discrepant findings in prior research are addressed and clarified.
Conclusions:
- Fragmentation of ovulated oocytes is unequivocally an example of apoptotic cell death.
- Caspase activity serves as an additional biochemical marker supporting apoptosis in fragmented oocytes.
- This research resolves previous debates and confirms the role of apoptosis in oocyte quality control.