title: Carbon black nanoparticle exposure during middle and late fetal development induces immune activation in male offspring mice.
abstract: Increasing exposure to nanoparticles (NPs) has raised concerns regarding their health and safety profiles in humans and animals, especially in developing organisms, which may display increased sensitivity to NP toxicity. The present study examined the effects of gestational exposure to carbon black NP (CB-NP) on the development of the offspring immune system. Pregnant mice were exposed to CB-NP (95μg/kg body weight) by intranasal instillation on gestational days 9 and 15. The thymus and spleen were collected from their offspring mice on postnatal day (PND) 1, 3 and 5. Thymocyte and splenocyte phenotypes were examined by determining the expression of cell-surface molecules using flow cytometry. Gene expression in the thymus and spleen was examined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Prenatal exposure to CB-NP increased total thymocytes and their immunophenotypes (CD4(-)CD8(-) and CD4(+)CD8(+) cells). It also induced an increase in total lymphocytes, and CD4(-)CD8(-), particularly CD3(-)B220(-)cells, at PND 5 in the spleen of newborn male offspring, reflecting the stimulation of immature splenocytes. Furthermore, mRNA expression of genes related to the induction of peripheral tolerance (i.e. thymic Traf6) was upregulated. These data suggest that respiratory exposure to CB-NP during middle and late gestation may have allergic or inflammatory effects in male offspring, and may provide initial information on the potential developmental immunotoxicity of nanoparticles.
authors.affiliation: The Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan; Department of Veterinary Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Egypt. Electronic address: yasser_tf@yahoo.com.
authors.forename: Yasser S
authors.initials: YS
authors.lastname: El-Sayed
authors.affiliation: Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: Ryuhei
authors.initials: R
authors.lastname: Shimizu
authors.affiliation: Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: Atsuto
authors.initials: A
authors.lastname: Onoda
authors.affiliation: The Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan; Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Takeda
authors.affiliation: The Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan; Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Umezawa
mesh_terms: D000818:Animals; D001835:Body Weight; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D007107:Immune System / Q000187:drug effects* / Q000276:immunology; D008297:Male; D018811:Maternal Exposure; D051379:Mice; D008813:Mice, Inbred ICR; D053758:Nanoparticles / Q000633:toxicity*; D011247:Pregnancy; D012744:Sex Ratio; D053260:Soot / Q000633:toxicity*
chemical_list: D053260:Soot
keywords: Carbon black; Flow cytometry; Gene expression; Immunotoxicity; Mice; Nanotoxicology