Abstract
Iron oxide nanoparticles (NPs) are commonly utilized for biomedical, industrial, and commercial applications due to their unique properties and potential biocompatibility. However, little is known about how exposure to iron oxide NPs may affect susceptible populations such as pregnant women and developing fetuses. To examine the influence of NP surface-charge and dose on the developmental toxicity of iron oxide NPs, Crl:CD1(ICR) (CD-1) mice were exposed to a single, low (10 mg/kg) or high (100 mg/kg) dose of positively-charged polyethyleneimine-Fe2O3-NPs (PEI-NPs), or negatively-charged poly(acrylic acid)-Fe2O3-NPs (PAA-NPs) during critical windows of organogenesis (gestation day (GD) 8, 9, or 10). A low dose of NPs, regardless of charge, did not induce toxicity. However, a high exposure led to charge-dependent fetal loss as well as morphological alterations of the uteri (both charges) and testes (positive only) of surviving offspring. Positively-charged PEI-NPs given later in organogenesis resulted in a combination of short-term fetal loss (42%) and long-term alterations in reproduction, including increased fetal loss for second generation matings (mice exposed in utero). Alternatively, negatively-charged PAA-NPs induced fetal loss (22%) earlier in organogenesis to a lesser degree than PEI-NPs with only mild alterations in offspring uterine histology observed in the long-term.
Highlights
Over the past few decades, interest, design, and implementation of engineered nanomaterials have grown exponentially, and the resulting influx of nanomaterial-containing products has greatly increased human exposure [1,2]
Maternal weight gain (MWG) during pregnancy was evaluated by subtracting the weight of the dam on gestation day (GD) 0 from the final weight of the dam minus the gravid uterus on GD 17
Several total litters were lost after treatment resulting in two complete early resorptions for PEI10+ and one for PAA10 ́. These results indicate a mechanism of toxicity for a high dose of positively-charged iron oxide NPs leading to fetal loss beginning on GD 10
Summary
Over the past few decades, interest, design, and implementation of engineered nanomaterials have grown exponentially, and the resulting influx of nanomaterial-containing products has greatly increased human exposure [1,2]. Nanomaterials, including nanoparticles (NPs), exhibit physical and chemical properties unique from larger materials with the same chemical composition, due primarily to their small size and high surface to volume ratios [3]. Due to these unique properties, NPs are routinely employed in many fields including industrial applications (e.g., pigments, catalysts, and solar cells), biomedical applications (e.g., drug delivery and diagnostics), and consumer products (e.g., sunscreens, paints, and food packaging) [4,5,6,7]. Greater evaluation and understanding of the mechanisms of iron oxide nanotoxicity are required for the future design and implementation of iron oxide NPs resulting in human exposures
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