Abstract
Nanoparticles are widely used in commodities, and pregnant women are inevitably exposed to these particles. The placenta protects the growing fetus from foreign or toxic materials, and provides energy and oxygen. Here we report that autophagy, a cellular mechanism to maintain homeostasis, engulfs platinum nanoparticles (nPt) to reduce their cytotoxicity in trophoblasts. Autophagy was activated by nPt in extravillous trophoblast (EVT) cell lines, and EVT functions, such as invasion and vascular remodeling, and proliferation were inhibited by nPt. These inhibitory effects by nPt were augmented in autophagy-deficient cells. Regarding the dynamic state of nPt, analysis using ICP-MS demonstrated a higher accumulation of nPt in the autophagosome-rich than the cytoplasmic fraction in autophagy-normal cells. Meanwhile, there were more nPt in the nuclei of autophagy-deficient cells, resulting in greater DNA damage at a lower concentration of nPt. Thus, we found a new protective mechanism against the cytotoxicity of nPt in human trophoblasts.
Highlights
Pregnant women and developing fetuses are very susceptible to foreign toxins, including air pollutants, microbes, and nanoparticles[1,2,3]
We report that platinum nanoparticles, which are one nanometer in size, activated autophagy in two extravillous trophoblast (EVT) cell lines. nPt impaired the functions, such as invasion and vascular remodeling, and proliferation of EVT cell lines, and this impairment was reduced in autophagy-deficient cells
We first evaluated the effects of nPt on autophagy in EVT cells. nPt promoted the conversion of MAP1LC3B-I to MAP1LC3B-II, and decreased SQSTM1/p62 levels, a substrate of the autophagosome, in HchEpC1b cells, an EVT cell line (Fig. 1a)
Summary
Pregnant women and developing fetuses are very susceptible to foreign toxins, including air pollutants, microbes, and nanoparticles[1,2,3]. Placental insufficiency or poor placentation, which is related to insufficient invasion of EVT cells into the maternal side[19], causes severe pregnancy complications such as preeclampsia, fetal growth restriction, or placental abruption[20,21]. Among these small potentially hazardous particles, differently sized and typed nanoparticles that cross the placenta can reach the fetal brain, resulting in neurodevelopmental. From the viewpoint of autophagic functions for nanoparticles, autophagy protects cells from internalized nanoparticles, which exert toxicity through oxidative stress[32], mitochondrial damage[33], lysosomal dysfunction[34], or direct inhibition of the AKT-TSC-mTOR pathway[35]. Autophagy protected against the cytotoxicity of nPt in the EVT cell lines
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