Abstract
Extensive application of nanomaterials has dramatically increased the risk of silica nanoparticle (SiNP, SiO2) exposure, yet their biological effect on reproduction has not been fully elucidated. By tracking the uterine biodistribution of SiNP in pregnant mice, this study was conducted to evaluate the biological effect of SiNP on reproduction. First, SiNP was conjugated with FITC, and then the FITC-SiNP was administrated to trophoblast (100 µg/mL, 24 h) in vitro and pregnant mice (0.25 mg/mouse, 2–24 h) in vivo. It was found that the FITC-SiNP was internalized by trophoblast and deposited in the uterus. The internalization of SiNP caused trophoblast dysfunction and apoptosis, while SiNP accumulation in the uterus induced diffuse inflammatory infiltration. The genome-wide alteration of gene expression was studied by high throughput sequencing analysis, where 75 genes were found to be dysregulated after SiNP exposure, among which ACOT2, SCD1, and CPT1A were demonstrated to regulate the biosynthesis of unsaturated fatty acids. Moreover, the suppression of unsaturated fatty acids caused mitochondrial overload of long-chain fatty acyl-CoA (LACoA), which further induced both trophoblast apoptosis and endometrial inflammation. In conclusion, the successful conjugation of FITC onto SiNP facilitated the tracking of SiNP in vitro and in vivo, while exposure to FITC-SiNP induced uterine metabolic disorder, which was regulated by the ACOT/CPT1A/SCD1 axis through the biosynthesis of unsaturated fatty acids signaling pathway.
Highlights
With the rapid development of nanotechnology, a large number of nanomaterials are produced, which immensely increases the risk of nano-dust exposure through either manufacturing or daily life routes [1]
The dynamic light scattering (DLS) analysis was conducted to study the hydrodynamic radius of SiNP and fluorescein isothiocyanate (FITC)-SiNP (Fig. 1b), where the radius of SiNP slightly increased after FITC conjugation (35.71 ± 4.86 nm vs. 50.16 ± 5.55 nm)
For nanoparticles suspended in cell medium, the particle size of FITC-SiNP was increased, in combination with the corresponding Zeta potential and polydispersity index that were listed in Additional file 1: Table S1, all of which indicated an excellent monodispersity and stability of both nanoparticles in different solutions
Summary
With the rapid development of nanotechnology, a large number of nanomaterials are produced, which immensely increases the risk of nano-dust exposure through either manufacturing or daily life routes [1]. As one of the most widely used nanomaterials, SiNP is defined with a diameter between 5 and 100 nm and a surface area in the range of 25–50 m2/g [8]. The crucial role of the gastrointestinal tract in absorbing SiNP is attracting more and more attention as nanoparticles are increasingly applied in food [11], based on which it is estimated that the daily intake of SiNP ranges from 9.3 to 50.4 μg/mL [12]. SiNP has been becoming the dominant component of atmospheric particulates, and it increases in areas with severe air pollution. The concentration of atmospheric SiNP is closely associated with the prevalence of pulmonary diseases [13, 14]
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