title: Fetal exposure to diesel exhaust affects X-chromosome inactivation factor expression in mice.
abstract: Several studies have shown effects of diesel exhaust (DE) on the central nervous system, but the mechanism is unclear. Fetal mice were exposed to whole DE (contains gases and particles) in an inhalation chamber, and cerebrum gene expression changes were examined by gene assay (microarray and quantitative real-time PCR). By microarray, upregulation of Xist, B-raf and Drwms2 were detected. Especially, mRNA expression of Xist was increased in a concentration-dependent manner in male and female mice. Xist (X-inactive specific transcript) is a major effector of the X-inactivation process, and X-linked genes are highly expressed in brain tissue and consistent with a role in brain developments. By quantitative real-time PCR, Tsix (crucial noncoding antisense partner of Xist) and other X-linked genes (Mecp2, Hprt1, and Sts) were examined; Tsix was upregulated, and other X-linked genes were unaffected in the male and female mice. Our findings suggest that exposure to DE increases Xist and Tsix gene expression in utero without influencing X-linked gene expression. An examination of Xist gene expression changes may provide an important biomarker for DE-induced effects. The possibility of avoiding X-chromosome inactivation (XCI) mechanisms by minimizing exposure to DE is expected.
authors.affiliation: School of Pharmaceutical Science, Ohu University, Fukushima, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kumamoto
authors.forename: Naomi
authors.initials: N
authors.lastname: Tsukue
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Takano
authors.forename: Ken
authors.initials: K
authors.lastname: Takeda
authors.forename: Shigeru
authors.initials: S
authors.lastname: Oshio
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000196:embryology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D019570:Inhalation Exposure / Q000009:adverse effects*; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D008431:Maternal-Fetal Exchange / Q000187:drug effects*; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology*; D062085:RNA, Long Noncoding / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D046888:Tissue Array Analysis; D001335:Vehicle Emissions / Q000633:toxicity*; D049951:X Chromosome Inactivation / Q000187:drug effects* / Q000235:genetics*
chemical_list: D062085:RNA, Long Noncoding; D012333:RNA, Messenger; C465658:Tsix transcript, mouse; D001335:Vehicle Emissions; C077885:XIST non-coding RNA