REMOVAL OF CYTOPLASM FROM ONE-CELLED MOUSE EMBRYOS INDUCES EARLY BLASTOCYST FORMATION

It has been recognized for several decades that the number of cleavage divisions which precede blastocyst formation in the mammalian embryo is rigorously fixed, such that removal of cells from the embryo, or au gmentation of cell number by embryo aggregation, does not affect the t iming of blastulation. Instead, embryos manipulated so as to reduce ce ll number form small blastocysts with fewer numbers of cells, while ag gregate embryos form giant blastocysts. This tight control of the numb er of cleavage divisions ensures that the timing of blastocyst formati on corresponds to the period of uterine receptivity for implantation. As yet, no experimental manipulation has succeeded in altering control of the number of cleavage divisions prior to blastulation, and as a c onsequence, the biological basis for the control mechanism is entirely obscure. We report here that removal of cytoplasm from one-celled mou se embryos does not alter the rate of cleavage, but does induce precoc ious formation of small blastocysts. These findings suggest that the e arly embryo ''counts'' cleavage divisions by measuring the size of its blastomeres, and that experimental reduction of cell size disturbs th e counting mechanism and leads to abnormally early blastulation. (C) 1 997 Wiley-Liss, Inc.