Convergent gene expression in epithelial cells illuminates the evolution of uterine receptivity

The independent evolution of convergent embryo implantation mechanisms in humans and mice, differing from the ancestral mammalian phenotype, is poorly understood. Endometrial epithelial cells are the first maternal interface encountered by the embryo. We combined organoid models and single-cell transcriptomics to investigate how gene expression has evolved in endometrial epithelial cells between human, non-human primates, and mouse at key points in the hormonal cycle. We discovered that many maternal genes involved in uterine receptivity and embryo implantation exhibit more similar expression patterns between human and mouse compared to macaque and marmoset. In particular, we show that the endometrial expression of LIF , a crucial actor of endometrial receptivity in both human and mouse, is likely an evolutionary convergence rather than a conserved feature as previously hypothesised.