title: Short- and Long-Term Effects of Prenatal Exposure to Iron Oxide Nanoparticles: Influence of Surface Charge and Dose on Developmental and Reproductive Toxicity.
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.
authors.affiliation: Department of Biological Sciences, the University of Alabama, Tuscaloosa, AL 35487, USA. roger064@crimson.ua.edu.
authors.forename: Kristin R
authors.initials: KR
authors.lastname: Di Bona
authors.affiliation: Department of Chemical and Biological Engineering, the University of Alabama, Tuscaloosa, AL 35487, USA. yxu22@crimson.ua.edu.
authors.forename: Yaolin
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Biological Sciences, the University of Alabama, Tuscaloosa, AL 35487, USA. msgray1@crimson.ua.edu.
authors.forename: Marquita
authors.initials: M
authors.lastname: Gray
authors.affiliation: Department of Biological Sciences, the University of Alabama, Tuscaloosa, AL 35487, USA. dcfair@crimson.ua.edu.
authors.forename: Douglas
authors.initials: D
authors.lastname: Fair
authors.affiliation: Department of Biological Sciences, the University of Alabama, Tuscaloosa, AL 35487, USA. hshayles@uab.edu.
authors.forename: Hunter
authors.initials: H
authors.lastname: Hayles
authors.affiliation: Department of Biological Sciences, the University of Alabama, Tuscaloosa, AL 35487, USA. lemilad@crimson.ua.edu.
authors.forename: Luckie
authors.initials: L
authors.lastname: Milad
authors.affiliation: Department of Biological Sciences, the University of Alabama, Tuscaloosa, AL 35487, USA. amontes2784@gmail.com.
authors.forename: Alex
authors.initials: A
authors.lastname: Montes
authors.affiliation: Department of Chemical and Biological Engineering, the University of Alabama, Tuscaloosa, AL 35487, USA. jasherwood@crimson.ua.edu.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Sherwood
authors.affiliation: Department of Chemical and Biological Engineering, the University of Alabama, Tuscaloosa, AL 35487, USA. ybao@eng.ua.edu.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Department of Biological Sciences, the University of Alabama, Tuscaloosa, AL 35487, USA. jrasco@ua.edu.
authors.forename: Jane F
authors.initials: JF
authors.lastname: Rasco
mesh_terms: D000818:Animals; D002585:Cesarean Section; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D005290:Ferric Compounds / Q000633:toxicity*; D005298:Fertility / Q000187:drug effects; D005333:Fetus / Q000187:drug effects; D008098:Litter Size; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000473:pathology*; D012098:Reproduction / Q000187:drug effects*; D013499:Surface Properties; D013737:Testis / Q000187:drug effects / Q000473:pathology; D013997:Time Factors; D014599:Uterus / Q000187:drug effects / Q000473:pathology
chemical_list: D005290:Ferric Compounds; C000499:ferric oxide
keywords: developmental toxicity; fetotoxicity; iron oxide; nanoparticles; nanotoxicity; surface charge