Increased cellular distribution of vimentin and Ret in the cingulum induced by developmental hypothyroidism in rat offspring maternally exposed to anti-thyroid agents

To elucidate target molecules of white matter development responding to hypothyroidism, global gene expression profiling of cerebral white matter from male rat offspring was performed after maternal exposure to anti-thyroid agents, 6-propyl-2-thiouracil and methimazole, on postnatal day 20. Genes involved in central nervous system development commonly up- or down-regulated among groups treated with anti-thyroid agents. Immunohistochemical distributions of vimentin, Ret proto-oncogene (Ret), deleted in colorectal cancer protein (DCC), and Claudin11 (Cld11) were examined based on the gene expression profile. Immunoreactive cells for vimentin and Ret in the cingulum, and the immunoreactive intensity of Cld11 and DCC in whole white matter were increased by treatment with anti-thyroid agents. Immunoreactive cells for vimentin and Ret were immature astrocytes and oligodendrocytes, respectively. Thus, immunoreactive cells for vimentin and Ret may be quantitatively measurable targets of developmental hypothyroidism in white matter.

► Global gene expression of developmental hypothyroidism was analyzed in rats.
► White matter profile was obtained in offspring exposed to anti-thyroid agents.
► As candidate molecules, vimentin, Ret, DCC, and Cld11 were obtained.
► Immunoreactive cells of vimentin and Ret can be measured quantitatively.
► Vimentin-expression increased in immature astrocytes in response to hypothyroidism.
► Ret-expression increased in oligodendrocytes in response to hypothyroidism.