Role of the blastocoele microenvironment in early mouse embryo differentiation

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Abstract
During preimplantation development, the mouse embryo differentiates into an outer layer of cells, the trophectoderm, and an inner group, the inner cell mass. Tarkowski and Wróblewska1 proposed that this differentiation depends on the position of blastomeres in the morula, with outside cells giving rise to trophectoderm and inside cells producing the inner cell mass. This epigenetic hypothesis has been confirmed by other studies in which blastomere position was altered at the 4-cell or 8-cell stage, thus demonstrating the totipotency of the blastomeres at these stages2–4. It was recently found that the inner cell mass of the early blastocyst is also totipotent and can form trophectoderm when isolated by immunosurgery5–8. Because inner cells apparently become committed during the time that they are exposed to the distinct microenvironment of the blastocyst9–11, we postulated that diffusible components or other factors in the blastocoele may have a role in the commitment of cells in the inner cell mass. We report here results, obtained by injecting donor cells into host blastocysts, showing that totipotent cells exposed only to blastocoele fluid differentiate into morphologically normal blastocysts, whereas those in contact with the blastocyst's inner surface do not.