Maternal titanium dioxide nanomaterial inhalation exposure compromises placental hemodynamics

• Published in: Toxicology and applied pharmacology 2019-03, Vol.367, p.51-61
• Main Authors: Abukabda, Alaeddin B., Bowdridge, Elizabeth C., McBride, Carroll R., Batchelor, Thomas P., Goldsmith, William T., Garner, Krista L., Friend, Sherri, Nurkiewicz, Timothy R.
• Format: Article
• Language: English
• Subjects: Animals; Engineered nanomaterials; Female; Hemodynamics - drug effects; Inhalation Exposure; Maternal Exposure; Metal Nanoparticles - toxicity; Microcirculation; Placenta; Placenta - blood supply; Pregnancy; Rats, Sprague-Dawley; Titanium - toxicity; Titanium dioxide nanoparticles
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2019.01.024

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-TiO2) exposure on the placenta and umbilical vascular reactivity. We hypothesized that pulmonary nano-TiO2 inhalation exposure increases placental vascular resistance and impairs umbilical vascular responsiveness. Pregnant Sprague-Dawley rats were exposed via whole-body inhalation to nano-TiO2 with an aerodynamic diameter of 188 ± 0.36 nm. On gestational day (GD) 11, rats began inhalation exposures (6 h/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 (Ca2+-free). Mean outflow pressure was measured in placental units. ACh increased outflow pressure to 53 ± 5 mmHg in sham-controls but only to 35 ± 4 mmHg in exposed subjects. ANGII decreased outflow pressure in placentas from exposed animals (17 ± 7 mmHg) compared to sham-controls (31 ± 6 mmHg). Ca2+-free superfusate yielded maximal outflow pressures in sham-control (63 ± 5 mmHg) and exposed (30 ± 10 mmHg) rats. Umbilical artery endothelium-dependent dilation was decreased in nano-TiO2 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-TiO2 exposure increases placental vascular resistance and impairs umbilical vascular reactivity. •Maternal gestational nano-TiO2 exposure increases placental vascular resistance.•Maternal gestational nano-TiO2 exposure is associated with a decreased placental endothelium-dependent response.•Placental and umbilical artery sensitivity to angiotensin II is increased by maternal nano-TiO2 exposure.•Umbilical artery and vein endothelium-dependent dilation is blunted by maternal nano-TiO2 exposure.