Employing human blastoids to discover the genetic and molecular determinants of blastocyst implantation in utero.

Early human pregnancy has long been difficult to study due to limited accessibility. We recently developed stem cell–derived blastocyst models, or blastoids (Nature 2018; Nature 2021; Cell 2023), that mimic natural blastocysts in morphology, lineage composition, and transcriptional profiles. By combining human blastoids with endometrial organoids and deep learning models of chromatin accessibility and gene regulation, we uncovered molecular and evolutionary determinants of human blastocyst competence for implantation in utero. Blastoids provide a powerful platform to dissect mechanisms of human reproduction and trace their evolutionary origins, informing strategies to improve reproductive health.