Single-cell atlas of the equine placenta reveals cellular heterogeneity and gestational-stage-associated programs.

INTRODUCTIONThe placenta mediates critical interactions between mother and offspring that guide development and impact long-term health. Despite its importance, the cellular organization of the equine (Equus caballus) placenta remains poorly defined. The equine epitheliochorial placenta, characterized by the absence of trophoblast invasion and prominent endocrine activity, provides a unique comparative model for studying placental cellular composition and development.

METHODSWe applied single-cell RNA sequencing to chorioallantois tissue collected from first-trimester (n = 1) and term (n = 2) equine placentas to generate a comprehensive cellular atlas across gestation.

RESULTSWe identified four major fetal cell lineages: trophoblast, stromal, endothelial, and Hofbauer-like cells. Subclustering revealed ten transcriptionally distinct cell populations, highlighting previously unrecognized heterogeneity within trophoblast, stromal, and Hofbauer-like cells. Comparative analyses between first-trimester and term placentas demonstrated marked gestational-stage-associated differences in cellular composition and gene expression programs. The early-stage placenta was dominated by shared transcriptional signatures associated with growth, extracellular matrix organization, and cell cycle activity, whereas term placentas exhibited increased immune-related and tissue remodeling pathways and greater cell type-specific specialization.

DISCUSSIONTogether, this study provides the first high-resolution single-cell transcriptomic atlas of the equine placenta, offering fundamental insights into placental cellular diversity and developmental dynamics. This resource establishes a foundation for comparative placental biology and for investigating equine gestational disorders.