Apoptosis and gene expression in the developing mouse brain of fusarenon-X-treated pregnant mice

• Published in: Toxicology letters Vol. 229; no. 1; pp. 292 - 302
• Main Authors: Sutjarit, Samak, Nakayama, Shota M.M., Ikenaka, Yoshinori, Ishizuka, Mayumi, Banlunara, Wijit, Rerkamnuaychoke, Worawut, Kumagai, Susumu, Poapolathep, Amnart
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ireland Ltd 17.08.2014
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Apoptosis Regulatory Proteins - biosynthesis; Apoptosis Regulatory Proteins - genetics; Biocompatibility; Brain; Brain - drug effects; Brain - embryology; Brain - growth & development; Brain Chemistry - drug effects; DNA - biosynthesis; DNA - isolation & purification; DNA Fragmentation - drug effects; Electrophoresis, Agar Gel; Female; Fusarenon-X; Fusarium crookwellense; Gene expression; Gene Expression - drug effects; Gene expression profiling; Genetics; Hordeum vulgare; Immunohistochemistry; In Situ Hybridization; Mice; Mice, Inbred ICR; Microarray Analysis; Microscopy, Electron; Mouse fetal brain; Mycotoxins - toxicity; Polymerase Chain Reaction; Pregnancy; Proliferating Cell Nuclear Antigen - metabolism; RNA - biosynthesis; RNA - genetics; Toxicity; Toxicology; Transcriptome - drug effects; Trichothecenes - toxicity; Triticum aestivum; Mouse fetal brain; Fusarenon-X; Gene expression profiling; Apoptosis
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/j.toxlet.2014.06.843

•Fusarenon-X induced apoptosis in fetal mouse brain.•Intrinsic apoptosis pathway in fusarenon-X-induced apoptosis of fetal mouse brain. Fusarenon-X (FX), a type B trichothecene mycotoxin, is mainly produced by Fusarium crookwellense, which occurs naturally in agricultural commodities, such as wheat and barley. FX has been shown to exert a variety of toxic effects on multiple targets in vitro. However, the embryonic toxicity of FX in vivo remains unclear. In the present study, we investigated FX-induced apoptosis and the relationship between the genetic regulatory mechanisms and FX-induced apoptosis in the developing mouse brain of FX-treated pregnant mice. Pregnant mice were orally administered FX (3.5mg/kg b.w.) and were assessed at 0, 12, 24 and 48h after treatment (HAT). Apoptosis in the fetal brain was determined using hematoxylin and eosin staining, the TUNEL method, immunohistochemistry for PCNA and electron microscopy. Gene expressions were evaluated using microarray and real time-reverse transcription polymerase chain reaction (qRT-PCR). Histopathological changes showed that the number of apoptotic cells in the telencephalon of the mouse fetus peaked at 12 HAT and decreased at 24 and 48 HAT. FX induced the up-regulation of Bax, Trp53 and Casp9 and down-regulated Bcl2 but the expression levels of Fas and Casp8 mRNA remained unchanged. These data suggested that FX induces apoptosis in the developing mouse brain in FX-treated dams. Moreover, the genetic regulatory mechanisms of FX-induced apoptosis are regulated by Bax, Bcl2, Trp53 and Casp9 or can be defined via an intrinsic apoptotic pathway.