Demonstration of the Clathrin- and Caveolin-Mediated Endocytosis at the Maternal–Fetal Barrier in Mouse Placenta after Intravenous Administration of Gold Nanoparticles

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  • RATTANAPINYOPITUK Kasem
    Department of Veterinary Pathology, Tottori University, 4–101 Koyama Minami, Tottori 680–8553, Japan The United Graduate School of Veterinary Science, Yamaguchi University, 1667–1 Yoshida, Yamaguchi 753–8515, Japan
  • SHIMADA Akinori
    Laboratory of Pathology, School of Life and Environmental Science, Azabu University, 1–17–71 Fuchinobe, Sagamihara-shi, Kanagawa 252–5201, Japan
  • MORITA Takehito
    Department of Veterinary Pathology, Tottori University, 4–101 Koyama Minami, Tottori 680–8553, Japan The United Graduate School of Veterinary Science, Yamaguchi University, 1667–1 Yoshida, Yamaguchi 753–8515, Japan
  • SAKURAI Masashi
    Department of Veterinary Pathology, Tottori University, 4–101 Koyama Minami, Tottori 680–8553, Japan The United Graduate School of Veterinary Science, Yamaguchi University, 1667–1 Yoshida, Yamaguchi 753–8515, Japan
  • ASANO Atsushi
    Department of Veterinary Biochemistry, Tottori University, 4–101 Koyama Minami, Tottori 680–8553, Japan
  • HASEGAWA Tatsuya
    Department of Environmental Biochemistry, Yamanashi Institute of Environmental Sciences, 5597-1 Fujiyoshida, Yamanashi 403–0005, Japan
  • INOUE Kenichiro
    Basic Medical Research Center, International University of Health and Welfare, 2600–1 Kitakanamura, Ootawara-shi, Tochigi 324–8501, Japan
  • TAKANO Hirohisa
    Department of Environmental Engineering, Kyoto University Graduate School of Engineering, Kyoto Daigaku Katsura, Saikyo-ku, Kyoto 615–8530, Japan

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Exposure to nanoparticles during pregnancy is a public concern, because nanoparticles may pass from the mother to the fetus across the placenta. The purpose of this study was to determine the possible translocation pathway of gold nanoparticles across the maternal–fetal barrier as well as the toxicity of intravenously administered gold nanoparticles to the placenta and fetus. Pregnant ICR mice were intravenously injected with 0.01% of 20- and 50-nm gold nanoparticle solutions on the 16th and 17th days of gestation. There was no sign of toxic damage to the placentas as well as maternal and fetal organs of the mice treated with 20- and 50-nm gold nanoparticles. ICP-MS analysis demonstrated significant amounts of gold deposited in the maternal livers and placentas, but no detectable level of gold in the fetal organs. However, electron microscopy demonstrated an increase of endocytic vesicles in the cytoplasm of syncytiotrophoblasts and fetal endothelial cells in the maternal–fetal barrier of mice treated with gold nanoparticles. Clathrin immunohistochemistry and immunoblotting showed increased immunoreactivity of clathrin protein in the placental tissues of mice treated with 20- and 50-nm gold nanoparticles; clathrin immunopositivity was observed in syncytiotrophoblasts and fetal endothelial cells. In contrast, caveolin-1 immunopositivity was observed exclusively in the fetal endothelium. These findings suggested that intravenous administration of gold nanoparticles may upregulate clathrin- and caveolin-mediated endocytosis at the maternal–fetal barrier in mouse placenta.

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