Molecular profiling of human blastocysts reveals primitive endoderm defects among embryos of decreased implantation potential

• Published in: Cell reports (Cambridge) 2024-02, Vol.43 (2), p.113701-113701, Article 113701
• Main Authors: Chousal, Jennifer N., Morey, Robert, Srinivasan, Srimeenakshi, Lee, Katherine, Zhang, Wei, Yeo, Ana Lisa, To, Cuong, Cho, Kyucheol, Garzo, V. Gabriel, Parast, Mana M., Laurent, Louise C., Cook-Andersen, Heidi
• Format: Article
• Language: English
• Subjects: bioinformatics; blastocyst; CP: Developmental biology; deconvolution; fertility; human; implantation; morphology; primitive endoderm; RNA sequencing; signaling
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2024.113701

Human embryo implantation is remarkably inefficient, and implantation failure remains among the greatest obstacles in treating infertility. Gene expression data from human embryos have accumulated rapidly in recent years; however, identification of the subset of genes that determine successful implantation remains a challenge. We leverage clinical morphologic grading—known for decades to correlate with implantation potential—and transcriptome analyses of matched embryonic and abembryonic samples to identify factors and pathways enriched and depleted in human blastocysts of good and poor morphology. Unexpectedly, we discovered that the greatest difference was in the state of extraembryonic primitive endoderm (PrE) development, with relative deficiencies in poor morphology blastocysts. Our results suggest that implantation success is most strongly influenced by the embryonic compartment and that deficient PrE development is common among embryos with decreased implantation potential. Our study provides a valuable resource for those investigating the markers and mechanisms of human embryo implantation. [Display omitted] •Transcriptome profiles of human blastocysts of high and low implantation potential•Identification of molecular factors associated with human embryo implantation•Identification of cell-cell signals associated with high implantation potential•Embryos of reduced potential demonstrate defects in primitive endoderm development Chousal et al. identify gene expression patterns and cell-cell signaling interactions specifically enriched and depleted in good-morphology human blastocysts of high implantation potential genome wide. In contrast, consistent primitive endoderm defects in poor-morphology blastocysts of reduced implantation potential demonstrate that primitive endoderm development is highly coupled with implantation success.