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These stages happen in all mammals, but the details are different in humans. It has three phases: the body recognizes the embryo, it maintains the pregnancy, and finally, it induces labor. Furthermore, the gene expression changes we identified may contribute to the development of diagnostics and interventions for adverse pregnancy outcomes. We also anticipate our results will advance the emerging synthesis of evolution and medicine (‘evolutionary medicine’) and be a starting point for more sophisticated studies of the maternal–fetal interface. These data suggest that explicit evolutionary studies of anatomical systems complement traditional methods for characterizing the genetic architecture of disease. Among these are genes that may contribute to human-specific maternal–fetal communication ( HTR2B) and maternal–fetal immunotolerance ( PDCD1LG2) systems, as well as vascular remodeling and deep placental invasion ( CORIN). We found that hundreds of genes gained or lost endometrial expression in the human lineage.

Here, we show that gene expression changes in the human endometrium during pregnancy are associated with the evolution of human-specific traits and pathologies of pregnancy.

This developmental and evolutionary history constrains normal physiological functions and biases the ways in which dysfunction contributes to reproductive trait diseases and adverse pregnancy outcomes. Evolutionary changes in the anatomy and physiology of the female reproductive system underlie the origins and diversification of pregnancy in Eutherian (‘placental’) mammals.

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