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

Patel, Shweta, Jana, Sarmita, Chetty, Rajlakshmi, Thakore, Sonal, Singh, Man, Devkar, Ranjitsinh·2018·Scientific Reports
DOI 10.1038/s41598-018-23215-7PMC PMC5859020
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Abstract

Titanium dioxide nanoparticles (TiO 2 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 TiO 2 NPs with egg albumen reveals that lower doses of TiO 2 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 TiO 2 NPs. The morphometric data of chicken embryo recorded a reduction at all the doses of TiO 2 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 TiO 2 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 TiO 2 NPs treatment warrants detailed studies of NP toxicity at lower doses prior to their biomedical applications.

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Figure 1 Physicochemical analysis of titanium dioxide nanoparticles and their interaction with egg albumen. Density, Viscosity, Surface tension, Friccohesity, Activation energy and Molecular radii of TiO2 NPs in albumen (a–f) respectively.
Figure 1 Physicochemical analysis of titanium dioxide nanoparticles and their interaction with egg albumen. Density, Viscosity, Surface tension, Friccohesity, Activation energy and Molecular radii of TiO2 NPs in albumen (a–f) respectively.CC BY · PubMed Central
Figure 2 FTIR spectra of native egg albumen and TiO2 NPs + Albumen. (a) Entire spectral range from 400–4000 cm−1; (b–d) Gaussian curve fitting of secondary derivative of Native Albumen and TiO2 NPs + Albumen with Comparative Secondary structure elements from FTIR spectra.
Figure 2 FTIR spectra of native egg albumen and TiO2 NPs + Albumen. (a) Entire spectral range from 400–4000 cm−1; (b–d) Gaussian curve fitting of secondary derivative of Native Albumen and TiO2 NPs + Albumen with Comparative Secondary structure elements from FTIR spectra.CC BY · PubMed Central
Figure 3 TiO2 NPs induces developmental deformities in chicken embryo. (a) Percentages of living normal, dead and malformed embryos in 19-day-old chick embryos. (b) Mean body weight (g) and lengths (cm) of living 19-day-old chick embryos in control and treated groups. (c) Concentrations of Ti in embryos of control and TiO2 NPs-treated group (4 day old) by ICP-OES. (d) Chicken-embryo development after 19 days of incubation, control (i), 10–100 µg/ml TiO2 NPs-treated groups (ii,iii,iv), 10 µg/ml TiO2 Bulk (v) and 10 µg/ml cadmium chloride (vi), (Scale bar: 1 cm). Embryos treated with 10 µg/ml TiO2 NPs (ii) exhibits omphalocele (red arrow) & flexed limbs (white arrow). (e) Photographs showing endoskeleton (bone and cartilage) of 19-day-old chick embryos, control (i) and TiO2 NPs–treated (ii) stained with Alizarin red S and alcian blue staining. TiO2 NPs treated (10 µg/ml) embryos exhibits flexed digits (arrow). The data are expressed as Mean ± SD. Statistical analysis was done by one way ANOVA, *p ≤ 0.05, **p < 0.01, ***p < 0.001, ns- not significant, C- control, P-placebo, B- TiO2 Bulk (10 µg/ml), Cd- cadmium chloride (10 µg/ml).
Figure 3 TiO2 NPs induces developmental deformities in chicken embryo. (a) Percentages of living normal, dead and malformed embryos in 19-day-old chick embryos. (b) Mean body weight (g) and lengths (cm) of living 19-day-old chick embryos in control and treated groups. (c) Concentrations of Ti in embryos of control and TiO2 NPs-treated group (4 day old) by ICP-OES. (d) Chicken-embryo development after 19 days of incubation, control (i), 10–100 µg/ml TiO2 NPs-treated groups (ii,iii,iv), 10 µg/ml TiO2 Bulk (v) and 10 µg/ml cadmium chloride (vi), (Scale bar: 1 cm). Embryos treated with 10 µg/ml TiO2 NPs (ii) exhibits omphalocele (red arrow) & flexed limbs (white arrow). (e) Photographs showing endoskeleton (bone and cartilage) of 19-day-old chick embryos, control (i) and TiO2 NPs–treated (ii) stained with Alizarin red S and alcian blue staining. TiO2 NPs treated (10 µg/ml) embryos exhibits flexed digits (arrow). The data are expressed as Mean ± SD. Statistical analysis was done by one way ANOVA, *p ≤ 0.05, **p < 0.01, ***p < 0.001, ns- not significant, C- control, P-placebo, B- TiO2 Bulk (10 µg/ml), Cd- cadmium chloride (10 µg/ml).CC BY · PubMed Central
Figure 4 Expression of Wnt signaling pathway-related genes in TiO2 NPs-treated chicken embryos. The expression of Wnt signaling pathway-related genes (a–h) including CTNNB1, PITX2, LEF1, WNT11, PRKCA, CAMK2D, ROCK1 and ROCK2 and (i) limb development gene HOXD13 was analyzed using reverse transcription polymerase chain reaction (RT-PCR) in control and TiO2 NPs-treated embryos (n = 3), 4 h after treatment in shell-less culture at 60 h. All the Wnt signaling pathway related genes and limb development gene were downregulated in TiO2 NPs-treated embryos compared to those of control embryos. *p < 0.05, **p < 0.01, ***p < 0.001, ns = not significant. (j) Somite numbers in control and TiO2 NPs-treated embryos 24 h after treatment in shell-less culture (HH-23). There is a reduction in the number of somites in TiO2 NPs-treated embryos as compared to the control embryos. The data are expressed as Mean ± SD. Statistical analysis was done by one way ANOVA followed by Dunnett’s test. *p < 0.05, **p < 0.01, ***p < 0.001, ns = not significant.
Figure 4 Expression of Wnt signaling pathway-related genes in TiO2 NPs-treated chicken embryos. The expression of Wnt signaling pathway-related genes (a–h) including CTNNB1, PITX2, LEF1, WNT11, PRKCA, CAMK2D, ROCK1 and ROCK2 and (i) limb development gene HOXD13 was analyzed using reverse transcription polymerase chain reaction (RT-PCR) in control and TiO2 NPs-treated embryos (n = 3), 4 h after treatment in shell-less culture at 60 h. All the Wnt signaling pathway related genes and limb development gene were downregulated in TiO2 NPs-treated embryos compared to those of control embryos. *p < 0.05, **p < 0.01, ***p < 0.001, ns = not significant. (j) Somite numbers in control and TiO2 NPs-treated embryos 24 h after treatment in shell-less culture (HH-23). There is a reduction in the number of somites in TiO2 NPs-treated embryos as compared to the control embryos. The data are expressed as Mean ± SD. Statistical analysis was done by one way ANOVA followed by Dunnett’s test. *p < 0.05, **p < 0.01, ***p < 0.001, ns = not significant.CC BY · PubMed Central

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Metadata

Authors
Patel, S., Jana, S., Chetty, R., Thakore, S., Singh, M., & Devkar, R.
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2018-03-19
Volume
8
Issue
1
ISSN
2045-2322
DOI
10.1038/s41598-018-23215-7
PMC
PMC5859020
Cited by
23
References
1
Language
en
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Patel, S., Jana, S., Chetty, R., Thakore, S., Singh, M., & Devkar, R. (2018). TiO2 nanoparticles induce omphalocele in chicken embryo by disrupting Wnt signaling pathway. Scientific Reports. https://doi.org/10.1038/s41598-018-23215-7