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. 2021 Apr-Jun;13(2):74-80.
doi: 10.18502/ajmb.v13i2.5524.

Developmental Toxicity of the Neural Tube Induced by Titanium Dioxide Nanoparticles in Mouse Embryos

Nahid Mohamadzadeh  1 , Masoumeh Zirak Javanmard  1 , Mojtaba Karimipour  1 , Gholamhosain Farjah  1
Affiliations

Developmental Toxicity of the Neural Tube Induced by Titanium Dioxide Nanoparticles in Mouse Embryos

Nahid Mohamadzadeh et al. Avicenna J Med Biotechnol. 2021 Apr-Jun.

Abstract

Background: This study investigated the potential effects of Titanium dioxide nanoparticles (Tio2NPs) followed by maternal gavage on fetal development and neural tube formation during pregnancy in mice.

Methods: Thirty pregnant mice were randomly divided into five main study groups including the untreated control and 4 experimental groups (n=6 per group). The control group was treated with normal saline and the experimental groups were orally treated with doses of 30, 150, 300, and 500 mg/kg Body Weight (BW) of Tio2NPs during pregnancy. On gestational day 16 and 19 (n=3 per group), pregnant mice were euthanized and then examined for neural tube defects and compared with control. Serial transverse sections were prepared in both cranial region and in lumbar region of spinal cord.

Results: Treatment with Tio2NPs resulted in low fetal weight and short length, dilation of lateral ventricle, thinning of cerebral cortex and spinal cord, spina bifida occulta and an increase in the number of apoptotic neurons in exposed embryos at doses of 300 and 500 mg/kg (p<0.05).

Conclusion: It seems that exposure to nanoparticles of Tio2 during pregnancy induces growth retardation and for the first time, teratogenicity of this nanomaterial in neural tube development and induction of defects such as spinal bifida, reduction in cortical thickness and dilatation of lateral ventricles were verified which can be related to incidence of apoptosis in central nervous system.

Keywords: Fetal development; Mice; Neural tube defects; Titanium dioxide.

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Conflict of interest statement

Conflict of Interest The authors notify that they have no conflicts of interest.

Figures

Figure 1
Figure 1
Macroscopic examination of fetuses on E16 (Upper row) and E19 (Lower row) revealed stunted growth including body weight loss and decrease of length in Tio2 NPs exposed groups. Size reduction was significant at doses of 300 and 500 mg/kg of Tio2 NPs compared with the control group, p<0.05. # comparison with control on E16 and * E19.
Figure 2
Figure 2
Reduction in cortical thickness and dilatation of lateral ventricles in the control and Tio2-NPs exposed embryos on E16 (A1-E1) and E19 (A2-E2). Heads of control and exposure groups were transversely sectioned and stained with H&E. Decreased cortical thickness and lateral ventricular dilatation after nanoparticle exposure increased significantly (p<0.05) at higher doses (300 and 500 mg/kg) compared with control. Data are presented as mean±SD. # comparison with control on E16 and * E19.
Figure 3
Figure 3
Transverse section of spinal cord and formation of vertebra in the control and Tio2-NPs exposed embryos on E16 (A1-E1) and E19 (A2-E2). Microscopic sections showing complete formation of vertebra in control group, fusion of Right Lamina (RL) and Left Lamina (LL) and formation of Spinous Process (SP). The red curve represents the distance between the laminas. Data are presented as mean±SD. # Comparison with control on E16 and * E19.
Figure 4
Figure 4
Photomicrographs of TUNEL-stained sections of fetuses in cortex (A1-E1) and spinal cord (A2-E2) on E19. The apoptotic cells were predominant in Tio2 NPs groups compared to the control group. The number of TUNEL-positive cells (Red arrow) was significantly higher in the 300 and 500 mg/kg groups than in the control group, # comparison with control on E16 and * E19.
See this image and copyright information in PMC

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