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.

Urinary Xist is a potential biomarker for membranous nephropathy

“…A few recent studies have documented distinct changes in Xist expression in response to different stimuli. For example, increased Xist levels in the brain were observed when fetal mice were exposed to diesel exhaust [28]. Similar increases in Xist expression were also found in response to HDAC inhibitor treatment for breast cancer, or chemotherapy for ovarian cancer [29,30].…”

Social Isolation-Induced Territorial Aggression in Male Offspring Is Enhanced by Exposure to Diesel Exhaust during Pregnancy

“…Previous studies have shown that in utero exposure to higher concentrations of DE significantly reduces locomotion of male offspring [ 14 , 50 ]. Recently, the effects of in utero DE inhalation on the central nervous system of offspring have also been reported [ 14 , 15 , 50 – 52 ]. However, the majority of these studies used substantially higher exposure levels than that encountered in the natural environment.…”

8th World Congress on Developmental Origins of Health and Disease

“…For females, most of expressions of X-linked genes are regulated by Xchromosome inactivation (XCI), which occurs during fetal period, and this mechanism is regulated by Xist and its antisense, Tsix. We have already reported that expressions of these genes are changed in fetal exposure to diesel exhaust in a concentration dependent manner in cerebrums (Kumamoto et al, 2013). To clarify the mechanisms of neurodevelopmental disorders by BPA, we exposed BPA to pregnant mice 8th World Congress on Developmental Origins of Health and Disease S333 and examined mRNA expression of X-chromosome inactivation factor, X-linked neurodevelopment related genes and epigenetical changes of these genes.…”