Kawai Y, Yoshida A, Nakagawa S, Hama T, Mayumi T
Faculty of Pharmaceutical Sciences, Kobe-Gakuin University, Japan.
Biol Pharm Bull. 1993 Feb;16(2):133-6. doi: 10.1248/bpb.16.133.
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.
布累迪宁是一种免疫抑制剂，对小鼠和大鼠有致畸作用，并能减少其窝产仔数。我们研究了布累迪宁对体外培养的小鼠植入前胚胎发育的直接影响。布累迪宁强烈抑制从桑椹胚到囊胚阶段的第一步分化，而从二细胞胚胎到桑椹胚阶段的步骤未受抑制。在10^(-6)或10^(-5)M的布累迪宁浓度下，48小时培养后只有一个或没有桑椹胚发育成囊胚；而在没有布累迪宁的情况下，约90%的胚胎发育成囊胚。为了确定布累迪宁的抑制作用是否可逆，将桑椹胚用10^(-5)M的布累迪宁培养48小时。然后将胚胎转移到不含布累迪宁的培养条件下，观察其发育情况。布累迪宁的抑制作用是可逆的。无透明带囊胚的扩张也受到布累迪宁的抑制。当囊胚胚胎在布累迪宁（10^(-6)M）存在的情况下培养时，胚胎的平均大小减小到初始大小的一半。此外，从透明带孵化并附着于基质的步骤受到布累迪宁的显著抑制。10^(-6)M的布累迪宁完全抑制滋养层细胞生长；然而，在没有布累迪宁的情况下培养96小时后，滋养层细胞生长面积扩大到初始大小的18倍。因此，后代数量的减少是由于布累迪宁对小鼠胚胎的直接作用。
