Journal
TOXICOLOGY AND APPLIED PHARMACOLOGY
Volume 367, Issue -, Pages 51-61Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2019.01.024
Keywords
Engineered nanomaterials; Titanium dioxide nanoparticles; Microcirculation; Placenta
Categories
Funding
- National Institutes of Health [R01-ES015022]
- National Science Foundation
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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 SpragueDawley 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 pg. Animals were exposed for 6 days for a cumulative lung burden of 525 +/- 16 pg. 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). Ca-2-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.
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