A generalized caspase inhibitor disrupts early mammalian development.

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.