Department of Human Genetics, University of Chicago, Chicago, United States; Department of Organismal Biology and Anatomy, University of Chicago, Chicago, United States
Department of Human Genetics, University of Chicago, Chicago, United States; Department of Organismal Biology and Anatomy, University of Chicago, Chicago, United States
Department of Molecular Biology and Genetics, Cornell University, Chicago, United States
Joanne Muter
Tommy’s National Centre for Miscarriage Research, University Hospitals Coventry & Warwickshire, Coventry, United Kingdom; Division of Biomedical Sciences, Clinical Sciences Research Laboratories, Warwic Medical School, University of Warwick, Buffalo, United States
Tommy’s National Centre for Miscarriage Research, University Hospitals Coventry & Warwickshire, Coventry, United Kingdom; Division of Biomedical Sciences, Clinical Sciences Research Laboratories, Warwic Medical School, University of Warwick, Buffalo, United States
Evolutionary changes in the anatomy and physiology of the female reproductive system underlie the origins and diversification of pregnancy in Eutherian (‘placental’) mammals. 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. 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. We found that hundreds of genes gained or lost endometrial expression in the human lineage. 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). These data suggest that explicit evolutionary studies of anatomical systems complement traditional methods for characterizing the genetic architecture of disease. 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. Furthermore, the gene expression changes we identified may contribute to the development of diagnostics and interventions for adverse pregnancy outcomes.
