INCREASED INCIDENCE OF APOPTOSIS IN TRANSFORMING-GROWTH-FACTOR ALPHA-DEFICIENT MOUSE BLASTOCYSTS

We previously demonstrated that exogenous transforming growth factor a lpha (TGF alpha) reduces the incidence of apoptosis in mouse blastocys ts that develop in vitro but does not result in an increase ire cell n umber or the incidence of development to the blastocyst stage. Thus, T GF alpha may function as a cell survival factor in the preimplantation mouse embryo. To extend these studies, we have now examined the devel opment of TGF alpha-deficient preimplantation embryos in vitro and in vivo in TGF alpha-deficient mothers. We found that in both instances t he incidence of apoptosis is dramatically increased in the TGF alpha-d eficient blastocysts and that this increase is essentially restricted to the cells of the inner cell mass when the embryos develop in vivo b ut extends to the trophectoderm cells for embryos that develop in vitr o. The absence of endogenous TGF alpha has little effect on the incide nce of development to the blastocyst stage and cell number, cell linea ge allocation, blastocoel volume, and the timing and incidence of hatc hing in these blastocysts, when compared to wild-type embryos. These r esults buttress our previous suggestion that TGF alpha functions as a cell survival factor in the preimplantation mouse embryo.