Transcriptomic profiling of day 3 human embryos of poor quality reveals molecular links to divergent developmental...

Poor-quality (PQ) embryos are commonly formed in assisted reproduction and often discarded, but emerging evidence suggests that some can develop into healthy children. Here, we performed single-embryo transcriptome profiling of day 3 human embryos of both good quality (GQ) and PQ. Our analyses revealed that day 3 PQ embryos can be categorized into two distinct subgroups: genuine PQ (gPQ) and morphological PQ (mPQ) embryos. This was further supported by additional transcriptomic data of GQ and PQ embryos donated by the same individuals. gPQ embryos showed greater impairments in both RNA decay and zygotic genome activation (ZGA) compared to mPQ embryos. Blastocysts that emerged from PQ embryos, more likely from mPQ embryos, demonstrated transcriptomic similarity to normal blastocysts. We also identified genes highly upregulated in day 3 gPQ embryos. These molecular insights may improve embryo selection and offer valuable clues for enhancing embryo quality in the future.