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Perinatal exposure to diesel exhaust affects gene expression in mouse cerebrum

  • Organ Toxicity and Mechanisms
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Abstract

Many environmental toxins alter reproductive function and affect the central nervous system (CNS). Gonadal steroid hormones cause differentiation of neurons and affect brain function and behavior during the perinatal period, and the CNS is thought to be particularly susceptible to toxic insult during this period. It was, therefore, hypothesized that inhalation of diesel exhaust (DE) during the fetal or suckling period would disrupt the sexual differentiation of brain function in mice, and the effects of exposure to DE during the perinatal period on sexual differentiation related gene expression of the brain were investigated. In the fetal period exposure group, pregnant ICR mice were exposed to DE from 1.5 days post-coitum (dpc) until 16 dpc. In the neonatal period exposure group, dams and their offspring were exposed to DE from the day of birth [postnatal day (PND)-0] until PND-16. Then, the cerebrums of males and females at PND-2, -5, and -16 from both groups were analyzed for expression level of mRNA encoding stress-related proteins [cytochrome P450 1A1 (CYP1A1), heme oxygenase-1 (HO-1)] and steroid hormone receptors [estrogen receptor alpha (ER alpha), estrogen receptor beta (ER beta), androgen receptor (AR)]. Expression levels of ER alpha and ER beta mRNA were increased in the cerebrum of newborns in the DE exposure groups as well as mRNA for CYP1A1 and HO-1. Results indicate that perinatal exposure to DE during the critical period of sexual differentiation of the brain may affect endocrine function.

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Acknowledgments

We thank the members in the Department of Hygiene Chemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science. This work was supported in part by a grant from CREST of JST and a Grant-in-Aid for Science Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Correspondence to Naomi Tsukue or Ken Takeda.

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Tsukue, N., Watanabe, M., Kumamoto, T. et al. Perinatal exposure to diesel exhaust affects gene expression in mouse cerebrum. Arch Toxicol 83, 985–1000 (2009). https://doi.org/10.1007/s00204-009-0459-2

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