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