2 | HOW MIGHT NANOPARTICLES INTERACT WITH PLACENTAL TISSUES?
NP in uterine or placental tissue compartments may cause adverse effects during pregnancy. Direct access of blood to the placental surface is limited during the first trimester, but early pregnancy effects on uterine function such as decidualisation are pertinent. From second trimester, particles might access the surface of chorionic villi, accumulate in the intervillous space, become incorporated into villous tissue or even cross the placenta to gain access to fetal blood and tissues. Human placental barrier thickness diminishes progressively over the course of pregnancy and in the third trimester may be only 3-4µm, overlying fetal capillaries to form so-called vasculo-syncytial membranes. Ingestion of NP into syncytiotrophoblast may be via fluid phase pinocytosis, phagocytosis or endocytosis or via clathrin-coated vesicles for receptor-mediated uptake (Figure 1). Where the syncytial epithelium suffers local damage, as always occurs even in normal pregnancy, a paracellular route into the placental villous mesenchyme and potentially fetal circulation is available across the fibrinoid matrix but this is limited to substances of relatively low molecular mass and unlikely to be utilised by NPs. Intact syncytium has been reported to contain nanopores that connect the maternal blood space with the area between the syncytial basal surface and the basement membrane; in principle these might offer a direct route of access for NPs (<10nm) to the stroma.
Uptake of microparticles by the placenta and evidence for translocation to the fetus in both human and various animals have been reviewed.1-3 In studies of other species, different barrier anatomy must be taken into account; the haemochorial placenta (seen in human, other primates, mouse, rat and rabbit) is unique in allowing direct access of blood-borne particles to trophoblast at the outer surface, though the number of tissue layers may vary. Accurate reporting of basic placental anatomy in the context of the particles detected is critical in assessing the barrier roles of different tissue layers and locations, optimising sampling protocols and evaluating the likelihood that NP might gain access to fetal tissues.4-7