These results suggest that activin A does not generally support cell proliferation throughout the early development of bovine embryos but rather stimulates it for a limited period or at a limited developmental stage. Activin A may act on bovine embryos until the third cell cycle and may enhance subsequent development of embryos. The activation of embryonic transcription, which follows the transition from maternal to embryonic control of development, is known as zygotic gene activation (ZGA). In bovine embryos, this transition occurs at the 8-cell stage or earlier. The absence of appropriate ZGA leads to the failure of further embryo development beyond the early cleavage divisions. Therefore, the development-enhancing effect of activin A may be associated with ZGA. In addition, bovine embryos normally develop to the 8- to 16-cell stage and are transported from the oviduct into uterus at 3-4 days after ovulation. The developmental period during which addition of activin A to medium affected bovine embryo development in vitro in the present study (prior to the 9- to 16-cell stage at 90 h postinsemination) seems to coincide with the period during which bovine embryos are present in the oviduct in vivo. Since activin A is produced by oviduct epithelial cells in mice and cows, addition of activin A to embryo culture in vitro may reproduce the environment of the cleavage-stage embryos in the oviduct in vivo. proventil inhaler
In conclusion, our results suggest that activin A and fol-listatin may play important roles in the regulation of the developmental competence of bovine embryos. Both acti-vin A and follistatin are present in mammalian oviducts and may physiologically regulate the development of early preimplantation embryos. Since addition of activin A to culture medium up to the third cell cycle of embryos is effective, identification of the mechanism by which activin A promotes embryo development may provide insights into the processes by which regulatory molecules control the specific developmental processes in a temporal manner.