Barrier capacity of human placenta for nanosized materials

Abstract

Background: Humans have been exposed to fine and ultrafine particles throughout their history. Since the Industrial Revolution, sources, doses, and types of nanoparticles have changed dramatically. In the last decade, the rapidly developing field of nanotechnology has led to an increase of engineered nanoparticles with novel physical and chemical properties. Regardless of whether this exposure is unintended or not, a careful assessment of possible adverse effects is needed. A large number of projects have been carried out to assess the consequences of combustion-derived or engineered nanoparticle exposure on human health. In recent years there has been a growing concern about the possible health influence of exposure to air pollutants during pregnancy, hence an implicit concern about potential risk for nanoparticle exposure in utero. Previous work has not addressed the question of whether nanoparticles may cross the placenta.

Objective: In this study we investigated whether particles can cross the placental barrier and affect the fetus.

Methods: We used the ex vivo human placental perfusion model to investigate whether nanoparticles can cross this barrier and whether this process is size dependent. Fluorescently labeled polystyrene beads with diameters of 50, 80, 240, and 500 nm were chosen as model particles.

Results: We showed that fluorescent polystyrene particles with diameter up to 240 nm were taken up by the placenta and were able to cross the placental barrier without affecting the viability of the placental explant.

Conclusions: The findings suggest that nanomaterials have the potential for transplacental transfer and underscore the need for further nanotoxicologic studies on this important organ system.

Figures

Figure 1

SEM and size distribution of PS beads. (A–D) SEM micrographs depict the beads with diameters of 50 nm (A), 80 nm (B), 240 nm (C), and 500 nm (D). (E) The size distributions of all applied particles were measured in the perfusion medium, presented as a size–density plot.

Figure 2

Perfusion profiles of PS beads and 14C-antipyrine. After the prephase, PS beads of different sizes were added to the maternal circuit to a final concentration of 25 μg/mL and the amount of 14C-antipyrine and PS beads in both maternal circuits (M, solid symbols) and fetal circuits (F, open symbols) were measured after the indicated time points. (A) In the fetal circuit, significantly increased levels of 50-, 80-, and 240-nm PS beads were measured after only a few minutes of perfusion, whereas the 500-nm beads were retained in the placental tissue and maternal circuit. A second addition of particles after 180 min (arrow) did not further increase the amount of beads in the fetal circuit. (B) The perfusion profiles of 14C-antipyrine were not affected by the presence of beads and maintained equilibrium until the end of the perfusion assay. Data represent mean ± SE of at least four independent experiments.

Figure 3

Size-dependent barrier capacity of the placental tissue. The ratios between fetal (F) and maternal (M) concentrations of 14C-antipyrine (open bars) and PS beads (blue bars) were calculated after 180 min of perfusion. The 14C-antipyrine values remain unchanged, whereas the perfusion rate of the beads showed size dependence. Data represent mean ± SE of at least four independent experiments. *p < 0.05 compared with 240-nm ratio value; **p < 0.05 compared with 80-nm ratio value; #p < 0.05 compared with 50-nm ratio value.

Figure 4

Viability and functionality of the placenta were not affected after perfusion with PS beads. (A) Glucose consumption and lactate production in the perfused tissue. (B) Human choriongonadotropin and leptin hormone net production during perfusion [NP divided by initial tissue content (T0)]. Data represent mean ± SE of at least four independent experiments.