Department of Human Genetics, University of Chicago, Chicago, United States.
Department of Organismal Biology and Anatomy, University of Chicago, Chicago, United States.
Elife. 2021 Oct 8;10:e69584. doi: 10.7554/eLife.69584.
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 () and maternal-fetal immunotolerance () systems, as well as vascular remodeling and deep placental invasion (). 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.
女性生殖系统解剖结构和生理功能的进化变化是真兽类（“胎盘”）哺乳动物妊娠起源和多样化的基础。这种发育和进化史限制了正常的生理功能，并影响了功能障碍导致生殖特征疾病和不良妊娠结局的方式。在这里，我们表明，人类妊娠期间子宫内膜的基因表达变化与人类特有的特征和妊娠病理的进化有关。我们发现，数百个基因在人类谱系中获得或失去了子宫内膜的表达。其中包括可能有助于人类特有的母婴交流（）和母婴免疫耐受（）系统，以及血管重塑和深层胎盘浸润（）的基因。这些数据表明，对解剖系统的明确进化研究补充了传统的疾病遗传结构特征的方法。我们还预计，我们的研究结果将推进进化和医学（“进化医学”）的新兴综合，并为更复杂的母婴界面研究提供起点。此外，我们确定的基因表达变化可能有助于开发用于不良妊娠结局的诊断和干预措施。
