Unique features and emerging in vitro models of human placental development

Background: The placenta is an essential organ for the normal development of mammalian fetuses. Most of our knowledge on the molecular mechanisms of placental development has come from the analyses of mice, especially histopathological examination of knockout mice. Choriocarcinoma and immortalized cell lines have also been used for basic research on the human placenta. However, these cells are quite different from normal trophoblast cells. Methods: In this review, we first provide an overview of mouse and human placental development with particular focus on the differences in the anatomy, transcription factor networks, and epigenetic characteristics between these species. Next, we discuss pregnancy complications associated with abnormal placentation. Finally, we introduce emerging in vitro models to study the human placenta, including human trophoblast stem (TS) cells, trophoblast and endometrium organoids, and artificial embryos. Main findings: The placental structure and development differ greatly between humans and mice. The recent establishment of human TS cells and trophoblast and endometrial organoids enhances our understanding of the mechanisms underlying human placental development. Conclusion: These in vitro models will greatly advance our understanding of human placental development and potentially contribute to the elucidation of the causes of infertility and other pregnancy complications.