Exposure to Alumina Nanoparticles in Female Mice During Pregnancy Induces Neurodevelopmental Toxicity in the Offspring

Abstract

Alumina nanoparticles (AlNP) have been shown to accumulate in organs and penetrate biological barriers which lead to toxic effects in many organ systems. However, it is not known whether AlNP exposure to female mice during pregnancy can affect the development of the central nervous system or induce neurodevelopmental toxicity in the offspring. The present study aims to examine the effect of AlNP on neurodevelopment and associated underlying mechanism. ICR strain adult female mice were randomly divided into four groups, which were treated with normal saline (control), 10 μm particle size of alumina (bulk-Al), and 50 and 13 nm AlNP during entire pregnancy period. Aluminum contents in the hippocampus of newborns were measured and neurodevelopmental behaviors were tracked in the offspring from birth to 1 month of age. Furthermore, oxidative stress and neurotransmitter levels were measured in the cerebral cortex of the adolescents. Our results showed that aluminum contents in the hippocampus of newborns in AlNP-treated groups were significantly higher than those in bulk-Al and controls. Moreover, the offspring delivered by AlNP-treated female mice displayed stunted neurodevelopmental behaviors. Finally, the offspring of AlNP-treated mice demonstrated significantly increased anxiety-like behavior with impaired learning and memory performance at 1 month of age. The underlying mechanism could be related to increased oxidative stress and decreased neurotransmitter levels in the cerebral cortex. We therefore conclude that AlNP exposure of female mice during pregnancy can induce neurodevelopmental toxicity in offspring.

Effect of low-dose exposure of aluminium oxide nanoparticles in Swiss albino mice: Histopathological changes and oxidative damage

“…Significant changes in mouse sperm parameters due to exposure to iron oxide NPs were also reported (Varzeghani et al, 2018). Moreover, Al 2 O 3 NP has been reported to induce spermatotoxicity (Yousef et al, 2016) and neuro-developmental toxicity (Zhang et al, 2018) in mice. The effect of low doses of Al 2 O 3 NP on developmental toxicity and spermatogenesis are areas for further investigation.…”

Translocation of (ultra)fine particles and nanoparticles across the placenta; a systematic review on the evidence of in vitro, ex vivo, and in vivo studies

“…, poly(glycidyl methacrylate) (PGMA), and PS) (Table 3 ). Fetal/embryonic NP accumulation was observed in 32 of the included animal studies, more specifically NPs were detected in the fetal brain [ 27 , 44 , 48 , 52 , 60 , 73 , 78 , 80 , 81 , 91 ], fetal liver [ 27 , 48 , 50 , 52 , 60 , 69 , 73 , 83 , 84 , 86 ], fetal lung [ 27 , 48 , 52 , 75 ], fetal kidney [ 48 , 52 , 84 ], fetal gastrointestinal tract (GIT) [ 88 ], and fetal blood [ 92 ]. The preferred method for NP administration was intravenous (i.v.)…”

“…, single particle, sector field, and laser ablation ICP-MS), was the most frequently used quantitative technique ( N = 29) among the included studies. In addition, 6 of the included studies used atomic absorption spectrometry (AAS) as elemental analysis tool for detection of metallic NPs in maternal-fetal tissue [ 33 , 44 , 48 , 49 , 59 , 66 ].…”

“…This supports the finding that the placenta is not an impenetrable barrier, as already confirmed for other xenobiotics such as drugs and alcohol [ 131 ]. In animal models, transplacental passage has been reported for Ag NPs [ 47 – 54 ], Al 2 O 3 NPs [ 44 ], Au NPs [ 57 , 59 – 61 ], CeO 2 NPs [ 67 ], DEP [ 91 ], QDs [ 62 ], SiO 2 NPs [ 70 , 71 , 73 , 74 ], TiO 2 NPs [ 73 , 75 , 76 , 78 , 80 , 81 ], ZnO NPs [ 83 – 85 ], ZrO 2 NPs [ 86 ], Fe 2 O 3 NPs [ 69 ], C60 fullerenes [ 87 ], PGMA NPs [ 89 ], and PS NPs [ 27 ]. Among these particles, only Ag NPs [ 37 ], Au NPs [ 31 , 38 ], and PS NPs [ 40 – 43 ] showed transplacental transfer in an ex vivo perfusion model, whereas SiO 2 NPs [ 25 ] and TiO 2 NPs [ 34 ] were retained in the placental tissue.…”

Toxicological Evaluation of SiO2 Nanoparticles by Zebrafish Embryo Toxicity Test

“…In rodents, several kinds of metal-bearing NPs exhibit reproductive [ 29 ] and neurodevelopmental toxicities [ 30 ], probably due to oxidative stress, inflammation, or DNA damage [ 31 ]. Apoptosis induced by DNA damage and/or oxidative stress might be a mechanism underlying the developmental toxicity of SiO 2 NPs in zebrafish embryos, as shown in other studies on NP toxicity [ 32 , 33 , 34 ].…”