Dataset Information

Uptake of Cerium Dioxide Nanoparticles and Impact on Viability, Differentiation and Functions of Primary Trophoblast Cells from Human Placenta.

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 ?g/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.

SUBMITTER: Nedder M

PROVIDER: S-EPMC7407216 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Uptake of Cerium Dioxide Nanoparticles and Impact on Viability, Differentiation and Functions of Primary Trophoblast Cells from Human Placenta.

Nedder Margaux M Boland Sonja S Devineau Stéphanie S Zerrad-Saadi Amal A Rogozarski Jasmina J Lai-Kuen René R Baya Ibtissem I Guibourdenche Jean J Vibert Francoise F Chissey Audrey A Gil Sophie S Coumoul Xavier X Fournier Thierry T Ferecatu Ioana I

Nanomaterials (Basel, Switzerland) 20200703 7

The human placenta is at the interface between maternal and fetal circulations, and is crucial for fetal development. The nanoparticles of cerium dioxide (CeO<sub>2</sub> NPs) from air pollution are an unevaluated risk during pregnancy. Assessing the consequences of placenta exposure to CeO<sub>2</sub> 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 hu ...[more]

PMID: 32635405

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Project description:Cerium dioxide (CeO2) and silicon dioxide (SiO2) nanoparticles are of widespread use in modern life. This means that human beings are markedly exposed to them in their everyday life. Once passing biological barriers, these nanoparticles are expected to interact with endothelial cells, leading to systemic alterations with distinct influences on human health. In the present study we observed the metabolic impact of differently sized CeO2 (8 nm; 35 nm) and SiO2 nanoparticles (117 nm; 315 nm) on immortalized human microvascular (HMEC-1) and primary macrovascular endothelial cells (HUVEC), with particular focus on the CeO2 nanoparticles. The characterization of the CeO2 nanoparticles in cell culture media with varying serum content indicated a steric stabilization of nanoparticles due to interaction with proteins. After cellular uptake, the CeO2 nanoparticles were localized around the nucleus in a ring-shaped manner. The nanoparticles revealed concentration and time, but no size-dependent effects on the cellular adenosine triphosphate levels. HUVEC reacted more sensitively to CeO2 nanoparticle exposure than HMEC-1. This effect was also observed in relation to cytokine release after nanoparticle treatment. The CeO2 nanoparticles exhibited a specific impact on the release of diverse proteins. Namely, a slight trend towards pro-inflammatory effects, a slight pro-thrombotic impact, and an increase of reactive oxygen species after nanoparticle exposure were observed with increasing incubation time. For SiO2 nanoparticles, concentration- and time-dependent effects on the metabolic activity as well as pro-inflammatory reactions were detectable. In general, the effects of the investigated nanoparticles on endothelial cells were rather insignificant, since the alterations on the metabolic cell activity became visible at a nanoparticle concentration that is by far higher than those expected to occur in the in vivo situation (CeO2 nanoparticles: 100 µg/mL; SiO2 nanoparticles: 10 µg/mL).

Project description:Rationale: The availability of therapeutics to treat pregnancy complications is severely lacking, mainly due to the risk of harm to the fetus. In placental malaria, Plasmodium falciparum-infected erythrocytes (IEs) accumulate in the placenta by adhering to chondroitin sulfate A (CSA) on the surfaces of trophoblasts. Based on this principle, we have developed a method for targeted delivery of payloads to the placenta using a synthetic placental CSA-binding peptide (plCSA-BP) derived from VAR2CSA, a CSA-binding protein expressed on IEs. Methods: A biotinylated plCSA-BP was used to examine the specificity of plCSA-BP binding to mouse and human placental tissue in tissue sections in vitro. Different nanoparticles, including plCSA-BP-conjugated nanoparticles loaded with indocyanine green (plCSA-INPs) or methotrexate (plCSA-MNPs), were administered intravenously to pregnant mice to test their efficiency at drug delivery to the placenta in vivo. The tissue distribution and localization of the plCSA-INPs were monitored in live animals using an IVIS imaging system. The effect of plCSA-MNPs on fetal and placental development and pregnancy outcome were examined using a small-animal high-frequency ultrasound (HFUS) imaging system, and the concentrations of methotrexate in fetal and placental tissues were measured using high-performance liquid chromatography (HPLC). Results: plCSA-BP binds specifically to trophoblasts and not to other cell types in the placenta or to CSA-expressing cells in other tissues. Moreover, we found that intravenously administered plCSA-INPs accumulate in the mouse placenta, and ex vivo analysis of the fetuses and placentas confirmed placenta-specific delivery of these nanoparticles. We also demonstrate successful delivery of methotrexate specifically to placental cells by plCSA-BP-conjugated nanoparticles, resulting in dramatic impairment of placental and fetal development. Importantly, plCSA-MNPs treatment had no apparent adverse effects on maternal tissues. Conclusion: These results demonstrate that plCSA-BP-guided nanoparticles could be used for the targeted delivery of payloads to the placenta and serve as a novel placenta-specific drug delivery option.

Dataset Information

Uptake of Cerium Dioxide Nanoparticles and Impact on Viability, Differentiation and Functions of Primary Trophoblast Cells from Human Placenta.

Publications

Uptake of Cerium Dioxide Nanoparticles and Impact on Viability, Differentiation and Functions of Primary Trophoblast Cells from Human Placenta.

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