TiO2 nanoparticles induce omphalocele in chicken embryo by disrupting Wnt signaling pathway

Abstract

Titanium dioxide nanoparticles (TiO2 NPs) are among abundantly used metal oxide NPs but their interactions with biomolecules and subsequent embryonic toxicity in higher vertebrates is not extensively reported. Physicochemical interactions of TiO2 NPs with egg albumen reveals that lower doses of TiO2 NPs (10 and 25 µg/ml) accounted for higher friccohesity and activation energy but an increment in molecular radii was recorded at higher doses (50 and 100 µg/ml). FTIR analysis revealed conformational changes in secondary structure of egg albumen as a result of electrostratic interactions between egg albumen and TiO2 NPs. The morphometric data of chicken embryo recorded a reduction at all the doses of TiO2 NPs, but toxicity and developmental deformity (omphalocele and flexed limbs) were recorded at lower doses only. Inductively coupled plasma optical emission spectrometry (ICP-OES) confirmed presence of Ti in chicken embryos. mRNA levels of genes involved in canonical and non-canonical Wnt signaling were lowered following TiO2 NPs treatment resulting in free radical mediated disruption of lateral plate mesoderm and somite myogenesis. Conformational changes in egg albumen and subsequent developmental deformity in chicken embryo following TiO2 NPs treatment warrants detailed studies of NP toxicity at lower doses prior to their biomedical applications.

Maternal exposure to iron oxide nanoparticles is associated with ferroptosis in the brain: A chicken embryo model analysis

“…of IONPs. Supporting previous reports (Patel et al, 2018;Xie et al, 2016) The cell death induced by IONPs is iron dependent. Iron chelators can inhibit cell death and block ferroptosis in poly(ethylene glycol)-coated silica NPs-treated melanoma cells (Kim et al, 2016).…”

“…Interaction with proteins strongly affects the IONPs fate and biodistribution in the biological systems (Liu et al, 2013). The inverse relationship between dose and toxicity for chicken embryos may be attributed to the possibility that the lower doses of NPs are less likely to interact with the egg albumen, leading to their more effective biodistribution (Patel et al, 2018).…”

“…Understanding the mechanisms of NPs toxicity is crucial for the assessment of their risk. We used chicken embryo, as a sensitive and widely employed model for assessing the developmental toxicity of NPs (El-Deep et al, 2020;Patel et al, 2018), to investigate whether ferroptosis implicates the potential effects of the maternal exposure to two different forms of IONPs on the developing brain.…”

Particle toxicology and health - where are we?

“…This model has also allowed comparative analysis of the developmental toxicity of NPs with different properties, such as size [180, 181], chemical composition [182, 183], and surface modification [184]. On the other hand, the chicken embryo model has an advantage that the direct effect of NPs on the embryonic development can be evaluated by removing the indirect effect mediated by maternal factors easily, as reported for the results of developmental toxicity of TiO 2 -NP [185] and carbon NPs [186–188]. In addition, the use of Drosophila, which has a short life span and 77% of the human disease genes [189], has just started in terms of developing cost-effective high-throughput screening methods for assessment of the developmental toxicity of NPs [190].…”

Results of operative treatment of omphalocele with an additional lobe of the liver, and pyloric stenosis

“…По данным последних исследований выявлены генетические локусы, ответственные за иннервацию гладкомышечной мускулатуры пилорического отдела желудка [24]. Генетическая предрасположенность возникновения омфалоцеле также описывается в нескольких работах [25,26]. В изученной нами литературе сочетание омфалоцеле с врожденным гипертрофическим пилоростенозом не описано, также в литературе не описано генетической сочетаемости этих пороков развития.…”