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Basal Ti level in the human placenta and meconium and evidence of a materno-foetal transfer of food-grade TiO2 nanoparticles in an ex vivo placental perfusion model

ABSTRACT: Background Titanium dioxide (TiO2) is broadly used in common consumer goods, including as a food additive (E171 in Europe) for colouring and opacifying properties. The E171 additive contains TiO2 nanoparticles (NPs), part of them being absorbed in the intestine and accumulated in several systemic organs. Exposure to TiO2-NPs in rodents during pregnancy resulted in alteration of placental functions and a materno-foetal transfer of NPs, both with toxic effects on the foetus. However, no human data are available for pregnant women exposed to food-grade TiO2-NPs and their potential transfer to the foetus. In this study, human placentae collected at term from normal pregnancies and meconium (the first stool of newborns) from unpaired mothers/children were analysed using inductively coupled plasma mass spectrometry (ICP-MS) and scanning transmission electron microscopy (STEM) coupled to energy-dispersive X-ray (EDX) spectroscopy for their titanium (Ti) contents and for analysis of TiO2 particle deposition, respectively. Using an ex vivo placenta perfusion model, we also assessed the transplacental passage of food-grade TiO2 particles. Results By ICP-MS analysis, we evidenced the presence of Ti in all placentae (basal level ranging from 0.01 to 0.48?mg/kg of tissue) and in 50% of the meconium samples (0.02–1.50?mg/kg), suggesting a materno-foetal passage of Ti. STEM-EDX observation of the placental tissues confirmed the presence of TiO2-NPs in addition to iron (Fe), tin (Sn), aluminium (Al) and silicon (Si) as mixed or isolated particle deposits. TiO2 particles, as well as Si, Al, Fe and zinc (Zn) particles were also recovered in the meconium. In placenta perfusion experiments, confocal imaging and SEM-EDX analysis of foetal exudate confirmed a low transfer of food-grade TiO2 particles to the foetal side, which was barely quantifiable by ICP-MS. Diameter measurements showed that 70 to 100% of the TiO2 particles recovered in the foetal exudate were nanosized. Conclusions Altogether, these results show a materno-foetal transfer of TiO2 particles during pregnancy, with food-grade TiO2 as a potential source for foetal exposure to NPs. These data emphasize the need for risk assessment of chronic exposure to TiO2-NPs during pregnancy.

SUBMITTER: Guillard A

PROVIDER: S-EPMC7541303 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Exposure to maternal stress during pregnancy can have adverse effects on the fetus, which has potential long-term effects on offspring´s development and health. We investigated the kinetics and metabolism of the hormones and amino acids: cortisol, cortisone, tryptophan and serotonin in the term placenta in an ex vivo human placental perfusion model. The placentas used in the experiments were donated from families participating in the Maternal Stress and Placental Function project with a known maternal stress background. METHOD:Cortisol, cortisone, tryptophan and serotonin were added simultaneously to the maternal side in the 6 hour ex vivo term human recirculating placental perfusion model, in four experimental set-ups: without inhibitors, with carbenoxolone -that inhibits cortisol metabolism into cortisone, with fluoxetine that inhibits the serotonin transporter, and with PCPA that inhibits metabolism of tryptophan into serotonin. The concentration of cortisol and cortisone, and tryptophan and serotonin were quantified using UPLC and HPLC-MS respectively. RESULTS:Cortisol was rapidly metabolized into cortisone in the placenta, to a somewhat lesser degree when adding the inhibitor carbenoxolone, resulting in higher fetal exposure to cortisol. Serotonin was also rapidly metabolized in the placenta. When adding fluoxetine a peak of fetal serotonin levels was seen in the first hour of the perfusion. No effect was seen of the maternal stress levels on placental transport kinetics in this study. CONCLUSION:Inhibiting the metabolism of cortisol in the placenta increased fetal exposure to cortisol as expected. Unexpectedly we saw an increased fetal exposure to serotonin when inhibiting the serotonin transporter, which may be related to the increased serotonin concentration on the maternal side of the placenta. No effect on placental kinetics were evident on maternal stress levels during the pregnancy as the majority of participating mothers had normal stress levels.

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Basal Ti level in the human placenta and meconium and evidence of a materno-foetal transfer of food-grade TiO2 nanoparticles in an ex vivo placental perfusion model

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