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Int. J. Mol. Sci. 2015, 16(12), 30251-30268; doi:10.3390/ijms161226231

Short- and Long-Term Effects of Prenatal Exposure to Iron Oxide Nanoparticles: Influence of Surface Charge and Dose on Developmental and Reproductive Toxicity

1
Department of Biological Sciences, the University of Alabama, Tuscaloosa, AL 35487, USA
2
Department of Chemical and Biological Engineering, the University of Alabama, Tuscaloosa, AL 35487, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Anna Cristina S. Samia and Masato Matsuoka
Received: 31 July 2015 / Revised: 27 October 2015 / Accepted: 10 December 2015 / Published: 18 December 2015
(This article belongs to the Special Issue Developmental and Reproductive Toxicity of Iron Oxide Nanoparticles)
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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. View Full-Text
Keywords: iron oxide; nanoparticles; developmental toxicity; fetotoxicity; surface charge; nanotoxicity iron oxide; nanoparticles; developmental toxicity; fetotoxicity; surface charge; nanotoxicity
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MDPI and ACS Style

Di Bona, K.R.; Xu, Y.; Gray, M.; Fair, D.; Hayles, H.; Milad, L.; Montes, A.; Sherwood, J.; Bao, Y.; Rasco, J.F. Short- and Long-Term Effects of Prenatal Exposure to Iron Oxide Nanoparticles: Influence of Surface Charge and Dose on Developmental and Reproductive Toxicity. Int. J. Mol. Sci. 2015, 16, 30251-30268.

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