Cited2 is a key regulator of placental development and plasticity

The biology of trophoblast cell lineage development and placentation is characterized by the involvement of several known transcription factors. Central to the action of a subset of these transcriptional regulators is CBP-p300 interacting transactivator with Glu/Asp-rich carboxy-terminal domain 2 (CITED2). CITED2 acts as a coregulator modulating transcription factor activities and affecting placental development and adaptations to physiological stressors. These actions of CITED2 on the trophoblast cell lineage and placentation are conserved across the mouse, rat, and human. Thus, aspects of CITED2 biology in hemochorial placentation can be effectively modeled in the mouse and rat. In this review, we present information on the conserved role of CITED2 in the biology of placentation and discuss the use of CITED2 as a tool to discover new insights into regulatory mechanisms controlling placental development. Hemochorial placentation in the human and rat is characterized by deep intrauterine trophoblast cell invasion and extensive trophoblast cell-guided spiral artery remodeling, which facilitates nutrient delivery to the fetus. CITED2 is a coregulator modulating transcription factors central to hemochorial placentation, placental adaptations to environmental stressors, fetal development, and pregnancy outcome. image