Abstract
BackgroundThere is evidence that nanoparticles (NP) cross epithelial and endothelial body barriers. We hypothesized that gold (Au) NP, once in the blood circulation of pregnant rats, will cross the placental barrier during pregnancy size-dependently and accumulate in the fetal organism by 1. transcellular transport across the hemochorial placenta, 2. transcellular transport across amniotic membranes 3. transport through ~20 nm wide transtrophoblastic channels in a size dependent manner. The three AuNP sizes used to test this hypothesis are either well below, or of similar size or well above the diameters of the transtrophoblastic channels.MethodsWe intravenously injected monodisperse, negatively charged, radio-labelled 1.4 nm, 18 nm and 80 nm 198AuNP at a mass dose of 5, 3 and 27 ?g/rat, respectively, into pregnant rats on day 18 of gestation and in non-pregnant control rats and studied the biodistribution in a quantitative manner based on the radio-analysis of the stably labelled 198AuNP after 24 hours.ResultsWe observed significant biokinetic differences between pregnant and non-pregnant rats. AuNP fractions in the uterus of pregnant rats were at least one order of magnitude higher for each particle size roughly proportional to the enlarged size and weight of the pregnant uterus. All three sizes of 198AuNP were found in the placentas and amniotic fluids with 1.4 nm AuNP fractions being two orders of magnitude higher than those of the larger AuNP on a mass base. In the fetuses, only fractions of 0.0006 (30 ng) and 0.00004 (0.1 ng) of 1.4 nm and 18 nm AuNP, respectively, were detected, but no 80 nm AuNP (<0.000004 (<0.1 ng)). These data show that no AuNP entered the fetuses from amniotic fluids within 24 hours but indicate that AuNP translocation occurs across the placental tissues either through transtrophoblastic channels and/or via transcellular processes.ConclusionOur data suggest that the translocation of AuNP from maternal blood into the fetus is NP-size dependent which is due to mechanisms involving (1) transport through transtrophoblastic channels ¿ also present in the human placenta ¿ and/or (2) endocytotic and diffusive processes across the placental barrier.
Highlights
There is evidence that nanoparticles (NP) cross epithelial and endothelial body barriers
Lower lung retention and higher liver retention were significantly different (p < 0.0001) for pregnant rats when compared to non-pregnant rats, but there was no difference in spleen retention
In conclusion, our study design and results allowed to differentiate between two potential 198AuNP pathways from maternal blood to the fetus in a pregnant rat model at gestation day 18 – (1) via placenta by transtrophoblastic channels competing with transcellular endocytotic passage across multiple cell layers and (2) via transport across the amniotic membrane – both pathways are 198AuNP size dependent:
Summary
There is evidence that nanoparticles (NP) cross epithelial and endothelial body barriers. We hypothesized that gold (Au) NP, once in the blood circulation of pregnant rats, will cross the placental barrier during pregnancy size-dependently and accumulate in the fetal organism by 1. The multiple benefits associated with the increasing manufacturing of nanotechnology based products are met with increasing concerns about potential adverse health effects from exposure of consumers to engineered nanoparticles (NP) [1]. These concerns are based on findings from biokinetic studies in humans and experimental animals revealing that NP may enter the body via the respiratory tract or the gastro-intestinal-tract and thereby be distributed throughout the body [1,2,3,4,5,6].
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