Abstract
The human placenta is at the interface between maternal and fetal circulations, and is crucial for fetal development. The nanoparticles of cerium dioxide (CeO2 NPs) from air pollution are an unevaluated risk during pregnancy. Assessing the consequences of placenta exposure to CeO2 NPs could contribute to a better understanding of NPs’ effect on the development and functions of the placenta and pregnancy outcome. We used primary villous cytotrophoblasts purified from term human placenta, with a wide range of CeO2 NPs concentrations (0.1–101 μg/cm2) and exposure time (24–72 h), to assess trophoblast uptake, toxicity and impact on trophoblast differentiation and endocrine function. We have shown the capacity of both cytotrophoblasts and syncytiotrophoblasts to internalize CeO2 NPs. CeO2 NPs affected trophoblast metabolic activity in a dose and time dependency, induced caspase activation and a LDH release in the absence of oxidative stress. CeO2 NPs decreased the fusion capacity of cytotrophoblasts to form a syncytiotrophoblast and disturbed secretion of the pregnancy hormones hCG, hPL, PlGF, P4 and E2, in accordance with NPs concentration. This is the first study on the impact of CeO2 NPs using human primary trophoblasts that decrypts their toxicity and impact on placental formation and functions.
Highlights
Over the past decades, the development and utilization of engineered nanomaterials have grown exponentially and various nanoparticles (NPs) are used in an increasing number of consumer products [1,2,3,4,5]
We focused our study on the uptake of CeO2 NPs by human primary trophoblast cells, their potential cytotoxicity and mechanisms of action as regard to the induction of oxidative stress, anti-oxidant enzymes and caspase activation
This study is the first to address the toxicity of CeO2 NPs on human primary trophoblasts, the mechanisms of their toxicity (p53 and caspase activation), their effect on oxidative stress
Summary
The development and utilization of engineered nanomaterials have grown exponentially and various nanoparticles (NPs) are used in an increasing number of consumer products [1,2,3,4,5] Due to their size being less than 100 nm (ISO/TS 80004:2015), NPs have a large surface-to-volume ratio and confer upon the materials they compose unique physicochemical characteristics, including higher surface reactivity, increased catalytic efficiency, and higher resistance when compared to their bulk material counterparts. Novel NPs of cerium dioxide (CeO2 NPs or nanoceria) have attracted the attention of the scientific community because they have been used in a range of industrial, commercial and biomedical applications [6] These include applications as fuel additive-combustion catalyst in gasoline, as additives in cigarettes, in self-cleaning ovens, as polishing agents and in UV protection [7]. The concentration of cerium is around 9 μg/L in fuel (18 mg/L Ce in fuel-additive) [12]
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