The unique applicability of the human placenta to the Adverse Outcome Pathway (AOP) concept: the placenta provides fundamental insights into human organ functions at multiple levels of biological organization.

Despite the short lifespan of the human placenta, the proper formation and function of the organ is of crucial importance for fetal development. Placental dysfunction increases the risk of complications for mother and child during pregnancy and childbirth and beyond as it predisposes to fetal programming. The placenta is an upstream organ of the fetus. It performs the functions of fetal lungs, liver, intestines, kidneys and glands as long as these organs are not fully functional. Furthermore, it is the only human organ that is non-invasively available either after elective abortion or after birth. This is a crucial point given that the conceptual framework of Adverse Outcome Pathway (AOP) requires data on organ function. In vitro and ex vivo placental studies, combined with epidemiological and clinical data on pregnant women, newborns, and infants can uniquely cover all levels of information needed to develop new AOPs and complement existing AOPs related to reproductive toxicity and beyond. To stimulate further research in this area and to support researchers in future studies dealing with the development of AOPs related to the placenta, this review first gives a brief description of placental structure, placental development and relevant pregnancy diseases. The state of knowledge about the available placental models, their particularities and limitations are briefly discussed. Finally, the use of placental research for the development of AOPs is presented with an illustrative example.