The study of developmental effect of xenobiotics in humans is limited and often relies on epidemiological data. Whether and to which extent potentially toxic compounds may cross the placental barrier, and whether adverse effects on embryo development are the consequence of direct or indirect placental-mediated action is debated. The availability of in vitro models simulating the feto-maternal interface could contribute to elucidate this issue. Here, we report the development of a novel in vitro model using murine blastocyst derived trophoblast stem cells (TSC) to mimic the placental barrier and mouse embryoid bodies (EBs) to represent the embryonic tissues. We demonstrate that this model can be used for translocation studies, as well as embryotoxicity assessment of titanium dioxide nanoparticles (TiO(2)NPs). By evaluating trans-epithelial electrical resistance, translocation of fluorescein isothiocyanate-dextran beads and expression of junctional complex proteins, we show that TSCs cultured on transwell inserts under differentiating condition form syncytia. We also show that TiO(2)NPs administered in the upper transwell compartment are able to reach the lower compartment and interfere with EB differentiation when no TSC are cultured on the insert. On the contrary, when TSC are present, NPs translocate to a lesser extent and do not affect EB development. These results indicate that the proposed in vitro model is suitable to study the correlation between translocation and toxicity of TiO(2)NPs and suggest a direct effect of the particles on EB development. We propose that this model could be exploited to study developmental effect of other xenobiotics.

Lacconi, V., Massimiani, M., Paglione, L., Messina, A., Battistini, B., De Filippis, P., et al. (2022). An improved in vitro model simulating the feto-maternal interface to study developmental effects of potentially toxic compounds: The example of titanium dioxide nanoparticles. TOXICOLOGY AND APPLIED PHARMACOLOGY, 446, 116056 [10.1016/j.taap.2022.116056].

An improved in vitro model simulating the feto-maternal interface to study developmental effects of potentially toxic compounds: The example of titanium dioxide nanoparticles

Massimiani, Micol;Messina, Alessandra;De Filippis, Patrizia;Magrini, Andrea;Pietroiusti, Antonio;Campagnolo, Luisa
2022-07-01

Abstract

The study of developmental effect of xenobiotics in humans is limited and often relies on epidemiological data. Whether and to which extent potentially toxic compounds may cross the placental barrier, and whether adverse effects on embryo development are the consequence of direct or indirect placental-mediated action is debated. The availability of in vitro models simulating the feto-maternal interface could contribute to elucidate this issue. Here, we report the development of a novel in vitro model using murine blastocyst derived trophoblast stem cells (TSC) to mimic the placental barrier and mouse embryoid bodies (EBs) to represent the embryonic tissues. We demonstrate that this model can be used for translocation studies, as well as embryotoxicity assessment of titanium dioxide nanoparticles (TiO(2)NPs). By evaluating trans-epithelial electrical resistance, translocation of fluorescein isothiocyanate-dextran beads and expression of junctional complex proteins, we show that TSCs cultured on transwell inserts under differentiating condition form syncytia. We also show that TiO(2)NPs administered in the upper transwell compartment are able to reach the lower compartment and interfere with EB differentiation when no TSC are cultured on the insert. On the contrary, when TSC are present, NPs translocate to a lesser extent and do not affect EB development. These results indicate that the proposed in vitro model is suitable to study the correlation between translocation and toxicity of TiO(2)NPs and suggest a direct effect of the particles on EB development. We propose that this model could be exploited to study developmental effect of other xenobiotics.
1-lug-2022
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/44 - MEDICINA DEL LAVORO
English
Titanium-Dioxide Nanoparticles
Embryoid Bodies
Embryotoxicity
In Vitro Translocation Study
Placenta
Syncytiotrophoblast
Lacconi, V., Massimiani, M., Paglione, L., Messina, A., Battistini, B., De Filippis, P., et al. (2022). An improved in vitro model simulating the feto-maternal interface to study developmental effects of potentially toxic compounds: The example of titanium dioxide nanoparticles. TOXICOLOGY AND APPLIED PHARMACOLOGY, 446, 116056 [10.1016/j.taap.2022.116056].
Lacconi, V; Massimiani, M; Paglione, L; Messina, A; Battistini, B; De Filippis, P; Magrini, A; Pietroiusti, A; Campagnolo, L
Articolo su rivista
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/314970
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