Allelic transcriptomic profiling identifies the role of PRD-like homeobox genes in human embryonic-cleavage-stage arrest

Cleavage-stage arrest in human embryos substantially limits the success rate of infertility treatment, with maternal-to-zygotic transition (MZT) abnormalities being a potential contributor. However, the underlying mechanisms and regulators remain unclear. Here, by performing allelic transcriptome analysis on human preimplantation embryos, we accurately quantified MZT progression by allelic ratio and identified a fraction of 8-cell embryos, at the appropriate developmental time point and exhibiting normal morphology, were in transcriptionally arrested status. Furthermore, we identified PAIRED (PRD)-like homeobox transcription factors divergent paired-related homeobox (DPRX) and arginine-fifty homeobox (ARGFX) as factors involved in MZT, whose deficiency severely impairs MZT and lineage specification and leads to aberrant retention of histone acetylation. By reversing the acetylation retention caused by DPRX and ARGFX defects, embryonic arrest can be partially rescued. Our study identifies factors involved in human MZT and elucidates the etiology underlying human cleavage-stage arrest.