Effects of perinatal exposure to nanoparticles on lung function - 08/04/25

Nanoparticles (NP) are organic, inorganic, or composite materials with 3 dimensions between 1 and 100nm. Due to their physico-chemical characteristics, which give them interesting properties, they can be found in many daily products. In particular, Titanium dioxide (TiO₂) NP are widely used in industry in many applications (food additives, cosmetics, pigments, drugs etc.) due to their large range of properties (ultraviolet absorption, antimicrobial effect, food brightening and whitening agent etc.). This raises questions about their potential effect on health, particularly in the perinatal period, when the developing organism is more vulnerable to environmental stressors. Indeed, in mice models, TiO₂NP administered to pregnant or lactating mice can reach the fetus, crossing the placental barrier via the bloodstream, or the offspring after translocation in the breastmilk. However, the long-term consequences of such exposure are still poorly studied. Our goal is to better understand the perinatal toxicity of TiO₂NP on lung development and function, by studying two distinct TiO₂NP with different sizes and crystalline phases.

Pregnant and/or lactating C57BL/6J mice were exposed to 10nm anatase (Ti10) and 21nm anatase/rutile (P25) NP by non-surgical intra-tracheal instillation (100μg of NP) once a week, during the 3 weeks of gestation and/or lactation. The pulmonary phenotype of the offspring was analyzed on juvenile mice (D₂₃, 23 days after birth) and on adult mice (D₆₀, 60 days after birth) with n=8-12 per group. Mice were weighed every week from D₉to D₆₀. The pulmonary function was measured by two different techniques: whole-body plethysmography (VivoFlow®), a non-invasive technique on awake mice that measures respiratory times and the FlexiVent® system, an invasive technique on anesthetized mice that evaluates lung mechanical properties.

Perinatal exposure to P25 induced a decrease in body weight for both males and females from D₁₆until D₆₀. Ti10 exposure induced a decrease in body weight for males from D₃₂and a transient increase in females body weight from D₁₆to D₃₇. In juvenile mice, perinatal exposure to P25 and Ti10 NP induced abnormalities in respiratory parameters with no change in mechanical properties of the lung. Indeed, P25 gestational exposure induced a decrease of tidal volume (0.1873±0.0178ml n=11 vs. 0.2120±0.0332 n=8) wheareas Ti10 gestational+postnatal exposure induced an increase of tidal volume (0.1472±0.0169ml n=11 vs. 0.1255±0.0082 n=11). At the adult age, no difference in the pulmonary function was found in the Ti10 groups nor in the respiratory parameters in the P25 groups. On the other hand, regarding the mechanical properties of the lung, P25 gestational+postnatal exposure provoked male specific modifications characterized by a decrease of inspiratory capacity (0.7046±0.0496ml n=5 vs. 0.8237±0.0441 n=4) and forced vital capacity (0.9850±0.0836ml n=5 vs. 1.106±0.0247 n=4).

TiO₂NP maternal exposure during the gestation and/or the lactation periods had an impact on the offspring, while this impact is different for the 2 NP tested with different sizes and crystalline phases. Ti10 exposure induced transient changes on the body weight and on the respiratory parameters that do not last until the adult age. On the other hand, P25 exposure provoked a permanent decrease in body weight, induced transient abnormalities of the respiratory parameters in juvenile mice and lung mechanical defects at the adult age. Further experiments will be needed to better characterize the defects observed and to explore the underlying mechanisms.