Figure 3.

(A; main figure) Schematic representation of branching process model of cell division and cell death in an embryo, and approximate correspondence between generations, developmental stages and chronological time, with day of oocyte retrieval being day 0. The equivalence between generations 0 to 4 and the 1- to 16- cell stages is straightforward, but that for subsequent generations is more imprecise. Confocal analysis of preimplantation human embryos indicates that compaction does not occur before the 16- to 32-cell stages (i.e., generations 4 and 5) (14). Newly expanded blastocysts of good morphology on day 5 were found to have, on average, 58 cells (8), which means that they were at about generation 6. Day 6 and 7 blastocysts had a mean of 84 and 126 cells, respectively. Thus we can assign generations 4 and 5 to the morula stage, and 6 to 8 to the blastocyst stage. To relate the model to the data in Fig. 2A, we make the simplest possible choice that each fragmented nucleus in Fig. 2A is equivalent to one cell dying during the last generation simulated by the model. This assumption was tested and found to be reasonable by extending the model to allow for different rates of dead cell clearance (see supplemental Appendix, www.pnas.org). (B Inset) Choice of actions and associated probabilities at each branch.