Table 1.

Summary of the different models to study toxic effects on the human placental barrier.

Models	Interests in Toxicology Studies	Advantages	Drawbacks
Animal models	• impact on pregnancy and outcomes • fetotoxicity studies	• in vivo • low cost • chronic exposure possible	• cautious extrapolation to animal model in view of the specificity of human placentation
Ex-vivo placental perfusion	• transplacental passage • placental kinetics and metabolism • placental accumulation of pollutants	• access to organized placental tissue (a whole cotyledon perfused)	• only possible in term placentas • do not allow chronic exposure • nonplacental pharmacokinetic factors
Chorionic villous explant cultures	• barrier permeability and tissular accumulation of pollutants • impact on cell viability • hormonal production	• physiological villi • near-physiological 3D microenvironment	• in vitro • fast ST necrosis • limited time exposures (less than 15 days)
Primary human trophoblast cultures	• impact on trophoblast viability • hormonal production • cellular internalization of pollutants	• recapitulate physiological differentiation to form the syncytium • isolation from term and first trimester placentas	• in vitro • limited period of culture due to cell necrosis • not adapted for chronic exposure
Cell line cultures	• impact on cell viability • cellular internalization of pollutants • cell signaling and hormonal production	• low cost • acquired resistance to apoptosis • possible adaptation to long term exposures	• in vitro • cancerous/immortalized cells’ properties distinct from physiological trophoblasts
2D co-cultures and placenta-on-a-chip	• barrier permeability and bypassing • impact on cells’ viability • cell signaling and hormonal production	• near-physiological 3D microenvironment	• in vitro • cancerous/immortalized cells’ properties distinct from physiological trophoblasts
3D models (organoids)	still under development	• recapitulate the human placenta villi • anatomically and functionally close to the villous placenta • long term culture possible (chronic exposure possible)	• in vitro • from first trimester placentas only • the polarity of the organoids (ST within the organoid cavity) needs to be reversed for toxicological studies.