Exposure to manufactured nanoparticles during gestation: Impact on the respiratory tract of the offspring in a mouse model - 04/04/15

Due to several commercial applications of manufactured nanoparticles (NPs), such as silver (Ag NPs), titanium dioxide (TiO₂ NPs) and cerium dioxide (CeO₂ NPs), knowledge of the toxicity of those NPs is of great importance. Many studies have linked exposure to fine and ultrafine particles (from air pollution) to an increase of morbidity or mortality due to various respiratory or cardiovascular diseases. Several works have focused on the effects of pulmonary exposure to manufactured NPs. It has been shown that exposure to NPs may lead to an inflammatory response, pulmonary fibrosis and emphysema. However, less is known on the effect of exposure to NPs on the offspring. It has been reported that exposure during pregnancy to TiO₂ NPs and SiO₂ NPs is associated with fetal hypertrophy, neurotoxicity, and exposure to carbon black NPs induced renal disease in the offspring. NPs may interfere with normal fetal lung development. In addition, a recent study reported that pulmonary exposure of newborn mice to TiO₂ NPs was associated with pulmonary inflammation and impaired lung development.

Therefore, the aim of this study is to assess the impact of exposure by the respiratory route to various NP during pregnancy on lung development of the offspring in a mouse model, and to determine the key parameters involved in lung alterations.

For this study, we used three metal NPs: TiO₂, Ag, and CeO₂ with the same size and shape, to assess the impact of NPs physico-chemical properties in the potential effects on lung development. C57Bl6/J pregnant mice were exposed weekly to 100μg NPs by nonsurgical intratracheal instillation. Analysis (biological, histological and functional) of the lungs of the offspring were made at different time of lung development: one day before delivery (18GD for gestational day), 14days after birth (pulmonary alveolization) and 21days after birth (lung maturity).

Preliminary results show that the exposure to TiO2 NPs during pregnancy did not affect the number of fetuses per litter, or the weight of uterus and placenta. However, the weight of fetuses whose mothers were exposed to TiO₂ NPs is significantly decreased. A decrease of VEGF-A gene expression, involved in lung development, was also observed at 18GD.

These preliminary results suggest that exposure to TiO₂ NPs during pregnancy could affect the development of the offspring. For the remainder of this work, pregnant mice will be exposed to other NPs (Ag and CeO₂) in order to see if this effect depends on the type of NP. Moreover additional analyzes will be performed to confirm whether lung alterations are observed at later times after birth, and to understand the key parameters and mechanism associated with these changes.