Effect of bredinin on early embryonic development in mice.

Bredinin, an immunosuppressive agent, had a teratogenic effect and a decreasing effect in litter size in mice and in rats. We investigated the direct effect of bredinin on the development of mouse preimplantation embryos in vitro. Bredinin strongly inhibited the first differentiation step from the morula to the blastocyst stage, whereas the steps from the two-cell embryo to the morula stage were not inhibited. At 10(-6) or 10(-5) M of bredinin, only one or none of the morula embryos developed to a blastocyst after a 48 h culture; while approximately 90% of the embryos developed to blastocysts in the absence of bredinin. To determine whether the bredinin inhibition was reversible, the morula embryos were cultured with 10(-5) M of bredinin for 48 h. The embryos were transferred to bredinin-free culture conditions, and their development was observed. The inhibitory effect of bredinin was reversible. The expansion of zona-free blastocyst was also inhibited by bredinin. When blastocyst embryos were cultured in the presence of bredinin (10(-6) M), the mean size of the embryos was reduced to half the initial size. In addition, the steps of hatching from the zona pellucida and attaching to the substratum were significantly inhibited by bredinin. Trophoblast outgrowth was completely inhibited by 10(-6) M bredinin; however, the area of trophoblast outgrowth was expanded to 18-fold the initial size after a 96 h culture in the absence of bredinin. Thus, the decrease in the number of offspring is due to the direct effect of bredinin on mice embryos.