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

We previously demonstrated that exogenous transforming growth factor alpha (TGFalpha) reduces the incidence of apoptosis in mouse blastocysts that develop in vitro but does not result in an increase in cell number or the incidence of development to the blastocyst stage. Thus, TGFalpha may function as a cell survival factor in the preimplantation mouse embryo. To extend these studies, we have now examined the development of TGFalpha-deficient preimplantation embryos in vitro and in vivo in TGFalpha-deficient mothers. We found that in both instances the incidence of apoptosis is dramatically increased in the TGFalpha-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 TGFalpha 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 TGFalpha functions as a cell survival factor in the preimplantation mouse embryo.