Discordant Growth of Monozygotic Twins Starts at the Blastocyst Stage: A Case Study

•Two ICMs within the same blastocyst were at different stages of development•IGF1-mediated signaling is likely to be the major driver behind these differences•The expression pattern of YAP1 is different in human embryos from in the mouse

SummaryDiscordant growth is a common complication of monochorionic/diamniotic pregnancies; in approximately 50% of cases, the cause is unknown. The case presented here suggests that discordant growth of monozygotic twins could start during preimplantation development. Two inner cell masses (ICMs) within the same blastocyst may originate in uneven splitting of a single “parental” ICM, or the two ICMs may be formed independently de novo. We studied the transcriptomes of two morphologically distinct ICMs within a single blastocyst using high-resolution RNA sequencing. The data indicated that the two ICM were at different stages of development; one was in the earliest stages of lineage commitment, while the other had already differentiated into epiblast and primitive endoderm. IGF1-mediated signaling is likely to play a key role in ICM growth and to be the major driver behind these differences.