Increased incidence of apoptosis in transforming growth factor α-deficient mouse blastocysts

We previously demonstrated that exogenous transforming growth factor alpha (TGF alpha) reduces the incidence of apoptosis in mouse blastocysts that develop in vitro but does not result in an increase ire cell number or the incidence of development to the blastocyst stage. Thus, TGF alpha may function as a cell survival factor in the preimplantation mouse embryo. To extend these studies, we have now examined the development of TGF alpha-deficient preimplantation embryos in vitro and in vivo in TGF alpha-deficient mothers. We found that in both instances the incidence of apoptosis is dramatically increased in the TGF alpha-deficient blastocysts and that this increase is essentially restricted to the cells of the inner cell mass when the embryos develop in vivo but extends to the trophectoderm cells for embryos that develop in vitro. The absence of endogenous TGF alpha has little effect on the incidence of development to the blastocyst stage and cell number, cell lineage allocation, blastocoel volume, and the timing and incidence of hatching in these blastocysts, when compared to wild-type embryos. These results buttress our previous suggestion that TGF alpha functions as a cell survival factor in the preimplantation mouse embryo.