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Updated: Aug 19, 2026

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
Published on: March 5, 2018
A generalized caspase inhibitor disrupts early mammalian development
Zahra Zakeri1, Richard A Lockshin, Luis-Miguel Criado-Rodríguez
1Department of Biology, Queens College and Graduate Center of the City University of New York, New York, USA. zahra_zakeri@qc.edu
Abstract:
The role and mechanism of cell death in early mammalian embryos is not well understood. In mouse embryos collected after fertilization and maintained in vitro until blastula formation, two instances of cell death are observed: the polar bodies and one or two cells near the equator, at the junction of the inner cell mass to the prototrophoblast. Inhibitors of caspases do not block the death of the polar bodies. Inhibitors of caspases 3, 7 and 8 do not affect post-cavitation death, but the pan-caspase inhibitor zVAD-FMK, when applied at the 1-2 cell stage, causes an expansion of post-cavitation death and ultimately malformation or death of the embryo. Our results indicate that the early deaths are not caspase-dependent and that there is a role for caspase activity in early embryos, which is not related to cell death.
Insights
Early mammalian embryo cell death is not caspase-dependent. Caspase activity plays a role in early embryos, but not in cell death, suggesting novel functions beyond apoptosis.
Area of Science:
- Developmental Biology
- Cell Biology
- Mammalian Embryogenesis
Background:
- The mechanisms of cell death in early mammalian embryos remain largely uncharacterized.
- Understanding these processes is crucial for developmental biology and reproductive health.
Purpose of the Study:
- To investigate the role and mechanisms of cell death in early mouse embryos.
- To determine the involvement of caspases in embryonic cell death.
Main Methods:
- Culturing mouse embryos in vitro from fertilization to blastula stage.
- Utilizing caspase inhibitors, including specific inhibitors for caspases 3, 7, and 8, and a pan-caspase inhibitor (zVAD-FMK).
- Observing and quantifying cell death events and embryonic development.
Main Results:
- Polar body death was not inhibited by caspase inhibitors.
- Post-cavitation cell death was unaffected by specific caspase inhibitors (3, 7, 8).
- Pan-caspase inhibition from the 1-2 cell stage led to expanded post-cavitation death and embryo malformation/death.
Conclusions:
- Early embryonic cell deaths in mice are not mediated by caspases.
- Caspase activity is present and plays a role in early mammalian embryos, independent of cell death.
- These findings suggest non-apoptotic functions for caspases during early embryogenesis.
Related Concept Videos
Caspases
In-vitro Mutagenesis
Cellular Injury V: Apoptosis and Autophagy
The Intrinsic Apoptotic Pathway

