Placental transfer of pesticides studied in human placental perfusion.

To investigate the transplacental transport of pesticides, the pyrethroid cypermethrin and the fungicide azoles, propiconazole and bitertanol were tested in the placental perfusion model. Cypermethrin, propiconazole and bitertanol were also tested in the BeWo cell transfer model. The pesticides were chosen with the selection criteria: use in Denmark, significant treated areas and knowledge on hormone-disrupting effects. Propiconazole and bitertanol showed rapid transfer and adsorbance to the system in both placental perfusion and BeWo cell system, whereas cypermethrin had a slower transport across the placental cell layers in the two models. There was no difference between data of the single pesticides and their mixture in either placental perfusion or BeWo cell transfer model. Both the placental perfusion model and the BeWo cell model metabolized the pesticides and released metabolites into both foetal and maternal circulation. Using human exposure models, this study shows the potential exposure of the human foetus to pesticides cypermethrin, propiconazole and bitertanol and their metabolites.

Airway exposure to TiO2 nanoparticles and quartz and effects on sperm counts and testosterone levels in male mice.

Several types of engineered nanoparticles (ENP) have been shown to adversely affect male reproduction in rodent studies, but the airway route of exposure has been little investigated. This precludes adequate risk assessment of ENP exposure in occupational settings. Titanium dioxide nanoparticles (TiO2 NP) have been shown to affect total sperm count in adult male mice after intravenous and oral administration. This study aimed to investigate whether also airway exposure would affect sperm counts in male mice. Mature C57BL/6J mice were intratracheally instilled with 63 µg of rutile nanosized TiO2, once weekly for seven weeks. Respirable α-quartz (SRM1878a) was included at a similar dose level as a positive control for pulmonary inflammation. BALF cell composition showed neutrophil granulocyte influx as indication of pulmonary inflammation in animals exposed to TiO2 NP and α-quartz, but none of the particle exposures affected weight of testes or the epididymis, sperm counts or plasma testosterone when assessed at termination of the study.

Kinetics of silica nanoparticles in the human placenta.

The potential medical applications of nanoparticles (NPs) warrant their investigation in terms of biodistribution and safety during pregnancy. The transport of silica NPs across the placenta was investigated using two models of maternal-foetal transfer in human placenta, namely, the BeWo b30 choriocarcinoma cell line and the ex vivo perfused human placenta. Nanotoxicity in BeWo cells was examined by the MTT assay which demonstrated decreased cell viability at concentrations >100 µg/mL. In the placental perfusion experiments, antipyrine crossed the placenta rapidly, with a foetal:maternal ratio of 0.97 ± 0.10 after 2 h. In contrast, the percentage of silica NPs reaching the foetal perfusate after 6 h was limited to 4.2 ± 4.9% and 4.6 ± 2.4% for 25 and 50 nm NPs, respectively. The transport of silica NPs across the BeWo cells was also limited, with an apparent permeability of only 1.54 × 10(-6) ± 1.56 × 10(-6) cm/s. Using confocal microscopy, there was visual confirmation of particle accumulation in both BeWo cells and in perfused placental tissue. Despite the low transfer of silica NPs to the foetal compartment, questions regarding biocompatibility could limit the application of unmodified silica NPs in biomedical imaging or therapy.

In vitro placental model optimization for nanoparticle transport studies.

BACKGROUND: Advances in biomedical nanotechnology raise hopes in patient populations but may also raise questions regarding biodistribution and biocompatibility, especially during pregnancy. Special consideration must be given to the placenta as a biological barrier because a pregnant woman's exposure to nanoparticles could have significant effects on the fetus developing in the womb. Therefore, the purpose of this study is to optimize an in vitro model for characterizing the transport of nanoparticles across human placental trophoblast cells. METHODS: The growth of BeWo (clone b30) human placental choriocarcinoma cells for nanoparticle transport studies was characterized in terms of optimized Transwell(®) insert type and pore size, the investigation of barrier properties by transmission electron microscopy, tight junction staining, transepithelial electrical resistance, and fluorescein sodium transport. Following the determination of nontoxic concentrations of fluorescent polystyrene nanoparticles, the cellular uptake and transport of 50 nm and 100 nm diameter particles was measured using the in vitro BeWo cell model. RESULTS: Particle size measurements, fluorescence readings, and confocal microscopy indicated both cellular uptake of the fluorescent polystyrene nanoparticles and the transcellular transport of these particles from the apical (maternal) to the basolateral (fetal) compartment. Over the course of 24 hours, the apparent permeability across BeWo cells grown on polycarbonate membranes (3.0 µm pore size) was four times higher for the 50 nm particles compared with the 100 nm particles. CONCLUSION: The BeWo cell line has been optimized and shown to be a valid in vitro model for studying the transplacental transport of nanoparticles. Fluorescent polystyrene nanoparticle transport was size-dependent, as smaller particles reached the basal (fetal) compartment at a higher rate.

Modeling placental transport: correlation of in vitro BeWo cell permeability and ex vivo human placental perfusion.

The placental passage of three compounds with different physicochemical properties was recently investigated in ex vivo human placental perfusion experiments (caffeine, benzoic acid, and glyphosate) [Mose, T., Kjaerstad, M.B., Mathiesen, L., Nielsen, J.B., Edelfors, S., Knudsen, L.E., 2008. Placental passage of benzoic acid, caffeine, and glyphosate in an ex vivo human perfusion system. J. Toxicol. Environ. Health, Part A 71, 984-991]. In this work, the transport of these same three compounds, plus the reference compound antipyrine, was investigated using BeWo (b30) cell monolayers. Transport across the BeWo cells was observed in the rank order of caffeine>antipyrine>benzoic acid>glyphosate in terms of both the apparent permeability coefficient and the initial slope, defined as the linear rate of substance transferred to the fetal compartment as percent per time, a parameter used to compare the two experimental models. The results from the in vitro studies were in excellent agreement with the ex vivo results (caffeine approximately antipyrine>benzoic acid>glyphosate). However the transfer rate was much slower in the BeWo cells compared to the perfusion system. The advantages and limitations of each model are discussed in order to assist in the preparation, prediction, and performance of future studies of maternal-fetal transfer.