Increased Incidence of Apoptosis in Transforming Growth Factor -Deficient Mouse Blastocysts¹

^a Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6018

We previously demonstrated that exogenous transforming growth factor alpha (TGF) 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, TGF may function as a cell survival factor in the preimplantation mouse embryo. To extend these studies, we have now examined the development of TGF-deficient preimplantation embryos in vitro and in vivo in TGF-deficient mothers. We found that in both instances the incidence of apoptosis is dramatically increased in the TGF-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 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 functions as a cell survival factor in the preimplantation mouse embryo.

¹ This research was supported by a grant from the NIH to R.M.S. (HD 22681). D.R.B. was supported by a training grant (T32 HD 07305) and fellowship from the NIH (F32 HD 07957). The Biomedical Image Analysis Facility used for laser-scanning confocal microscopy was supported by a grant from the NIH (RR-2483).

² Correspondence: Richard Schultz, Department of Biology, University of Pennsylvania, 415 South University Avenue, Philadelphia, PA 19104-6018. FAX: (215) 898-8780; rschultz{at}mail.sas.upenn.edu

³ Current address: Department of Reproductive Medicine, St. Mary's Hospital, Manchester M13 OJH, UK.

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