Maternal titanium dioxide nanomaterial inhalation exposure compromises placental hemodynamics

The fetal consequences of gestational engineered nanomaterial (ENM) exposure are unclear. The placenta is a barrier protecting the fetus and allowing transfer of substances from the maternal circulation. The purpose of this study was to determine the effects of maternal pulmonary titanium dioxide nanoparticle (nano-TiO(2)) exposure on the placenta and umbilical vascular reactivity. We hypothesized that pulmonary nano-TiO(2) inhalation exposure increases placental vascular resistance and impairs umbilical vascular responsiveness. Pregnant Sprague-Dawley rats were exposed via whole-body inhalation to nano-TiO(2) with an aerodynamic diameter of 188 ± 0.36 nm. On gestational day (GD) 11, rats began inhalation exposures (6h/exposure). Daily lung deposition was 87.5 ± 2.7 μg. Animals were exposed for 6 days for a cumulative lung burden of 525 ± 16 μg. On GD 20, placentas, umbilical artery and vein were isolated, cannulated, and treated with acetylcholine (ACh), angiotensin II (ANGII), S-nitroso-N-acetyl-DL-penicillamine (SNAP), or calcium-free superfusate (Ca(2+)-free). Mean outflow pressure was measured in placental units. ACh increased outflow pressure to 53 ± 5 mm Hg in sham-controls but only to 35 ± 4 mm Hg in exposed subjects. ANGII decreased outflow pressure in placentas from exposed animals (17 ± 7 mm Hg) compared to sham-controls (31 ± 6 mm Hg). Ca(2+)-free superfusate yielded maximal outflow pressures in sham-control (63 ± 5 mm Hg) and exposed (30 ± 10 mm Hg) rats. Umbilical artery endothelium-dependent dilation was decreased in nano-TiO(2) exposed fetuses (30 ± 9%) compared to sham-controls (58 ± 6%), but ANGII sensitivity was increased (−79 ± 20% vs −36 ± 10%). These results indicate that maternal gestational pulmonary nano-TiO(2) exposure increases placental vascular resistance and impairs umbilical vascular reactivity.