Developmental Neurotoxicity of Dioxin and Its Related Compounds.

Kakeyama, Masaki; Tohyama, Chiharu

doi:10.2486/indhealth.41.215

Cited by 70 publications

(38 citation statements)

References 125 publications

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“…The arylhydrocarbon receptor (AhR) is believed to mediate the effects of polycyclic aromatic hydrocarbons (PAHs), a family of toxic compounds including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polychlorinated biphenyls, polycyclic aromatic hydrocarbons, and others [9][10][11][12][13][14][15][16]. AhR is a member of the Per-AhR nuclear translocator (Arnt)-Sim/basic-helix-loop-helix superfamily of ligand-activated transcription factors that also includes transcription factors involved in hypoxic response, development of the central nervous system, and day-night adaptations [13].…”

Section: Days Postc O I T U M ( D P C ) U S I N G T H E R E a L -T I mentioning

confidence: 99%

Effects of In Utero Exposure to Bisphenol A on mRNA Expression of Arylhydrocarbon and Retinoid Receptors in Murine Embryos

et al. 2005

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Abstract.To evaluate the effects of bisphenol A (BPA), a candidate endocrine disruptor (ED), on embryonic development, we examined the mRNA expression levels of the arylhydrocarbon receptor (AhR), which binds with many EDs and plays crucial roles in xenobiotic metabolism, and of the retinoic acid receptor (RAR) α and retinoid X receptor (RXR) α, key factors in nuclear receptordependent retinoid signal transduction, in murine embryos exposed in utero to BPA (0.02, 2, 200, and 20,000 µg/kg/day) at 6.5-13.5 or 6.5-17.5 days post coitum (dpc), using the real-time reverse transcription-polymerase chain reaction (RT-PCR) method. Extremely low-dose BPA (0.02 µg/kg/ day; 1/100 the dose of environmental exposure) remarkably increased AhR mRNA expression in the cerebra, cerebella, and gonads (testes and ovaries) of male and female 14.5-and 18.5-dpc-embryos. In utero exposure to BPA at 2, 200, and 20,000 µg/kg/day also increased levels of AhR mRNA. In gonads of 14.5-dpc-embryos, AhR mRNA levels were elevated and showed diphasic (U) dose-response curves following exposure to BPA, but inverted U dose-response curves were obtained for 18.5-dpcembryos. Exposure to BPA increased expression levels of RARα and RXRα mRNAs in the cerebra, cerebella, and gonads of male and female 14.5-and 18.5-dpc-embryos. Extremely low-dose BPA (0.02 µg/kg/day) increased RARα mRNA expression in the cerebella of male and female 14.5-and 18.5-dpc-embryos and in the gonads of female 14.5-dpc-embryos, and significantly increased RXRα mRNA expression in the cerebra and cerebella of male and female 14.5-dpc-embryos. The present findings confirm that in utero exposure to an extremely low dose of BPA up-regulates the mRNA expression of AhR, RARα, and RXRα in murine embryos and disrupts the receptor-dependent signal transducing systems, and will contribute to the assessment of the toxic effects of BPA on xenobiotic metabolism and retinoid signals in embryogenesis. Key words: Arylhydrocarbon receptor (AhR), Bisphenol A, Murine embryo, Retinoic acid receptor (RAR) α, Retinoid X receptor (RXR) α (J. Reprod. Dev. 51: [315][316][317][318][319][320][321][322][323][324] 2005) isphenol A [BPA; 2,2-bis (4-hydroxyphenyl) p r o p a n e ] , a c o m m o n p l a s t i c i z e r a n d a candidate environmental endocrine disruptor (ED), has toxicological effects on the reproductive, immunological, and nervous systems of mammals [1][2][3][4]. BPA binds to estrogen receptor-α (ERα; NR3A1) and -β (ERβ; NR3A2), and induces

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Section: Days Postc O I T U M ( D P C ) U S I N G T H E R E a L -T I mentioning

confidence: 99%

Effects of In Utero Exposure to Bisphenol A on mRNA Expression of Arylhydrocarbon and Retinoid Receptors in Murine Embryos

et al. 2005

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“…Среди диоксинов наиболее токсичным является 2,3,7,8-тетра-хлор-бензо-р-диоксин. Его введение беременным крысам вызывало не только нарушение функционирования плаценты, молочных желез, но сопровождалось увеличением массы щито-видной железы, снижением секреции тироксина и повы-шением секреции тиреотропного гормона (ТТГ) [26,27]. Стойкое снижение концентрации тиреоидных гормонов и повышение ТТГ обнаружено у ветеранов вьетнамской войны, применявших большие количества диоксинсодер-жащих химикатов в качестве дефолиантов [28].…”

Section: биологическое действие эндокринных дизрапторов на живые оргаunclassified

Endocrine Disruptors Are a Novel Direction of Endocrinologic Scientific Investigation

Яглова

Яглов

2012

Annals RAMS

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“…To d e t e r m i n e t h e e f f e c t s o f B P A ( W a k o P u r e Chemicals, Osaka, Japan), pregnant mice were orally administered BPA (0.02, 2, 200, or 20,000 µg/ kg/day; dissolved in olive oil) and E2 (5 µg/kg/ day dissolved in olive oil; Wako). These doses were based on our previous studies [12,36,37]. The oral administration was performed in the afternoon (12:00 to 14:00) from 6.5 to 13.5, and 6.5 to 17.5 dpc (8 and 12 times, respectively).…”

Section: Preparation Of Embryonic Tissuementioning

confidence: 99%

“…The aryl hydrocarbon receptor (AhR) mediates the toxicological effects of polycyclic aromatic hydrocarbons (PAHs), a family of toxic compounds that includes 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polychlorinated biphenyls, and polycyclic aromatic hydrocarbons [11][12][13][14][15][16][17][18]. The major toxic effects of PAHs, mainly TCDD, are mediated by AhR, which has high binding affinity for PAHs.…”

mentioning

confidence: 99%

Effects of Exposure <i>In Utero</i> to Bisphenol A on the Expression of Aryl Hydrocarbon Receptor, Related Factors, and Xenobiotic Metabolizing Enzymes in Murine Embryos

Nishizawa

Imanishi

Manabe

2005

Journal of Reproduction and Development

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Abstract.To evaluate the effects of bisphenol A (BPA), a candidate endocrine disruptor (ED), on embryonic development, we examined the mRNA expression levels of the aryl hydrocarbon receptor (AhR; which binds with many EDs and plays crucial roles in their metabolism) and related factors [aryl hydrocarbon receptor repressor (AhRR) and AhR nuclear translocator (Arnt)], xenobiotic metabolizing enzymes [XMEs; cytochrome P450 1A1 (CYP1A1) and UDP-glucuronosyltransferase, and the glutathione S-transferase Ya subunit (GST)], in murine embryos exposed in utero to BPA (0.02, 2, 200, and 20,000 µg/kg/day) and 17β-estradiol (E2; 5 µg/kg/day, used as a positive control) at 6.5-13.5 or 6.5-17.5 days post coitum (dpc) using the quantitative real-time reverse transcriptionpolymerase chain reaction (RT-PCR) method. Protein levels of CYP1A1 and GST in embryonic livers were estimated by Western immunoblotting. Exposure in utero to BPA [0.02 (1/100 dose of environmental exposure), 2, 200, and 20,000 µg/kg/day] increased AhR mRNA expression in the cerebra, cerebella, and gonads (testes and ovaries) of male and female mid-and late-developmental stage (14.5-and 18.5-dpc, respectively) embryos. BPA dose-independently up-regulated the expression of AhRR and Arnt in mid-and late-stage embryos. BPA had no remarkable effect on the mRNA levels of XMEs in mid-stage embryos, but dose-dependently up-regulated the expression in late-stage embryos. Moreover, the protein levels of these enzymes in the livers of late-stage embryos were increased. The present findings revealed that exposure to BPA in utero disrupts the expression of AhR and related factors and of xenobiotic metabolizing enzymes, and that mid-stage embryos, in the organogenic stage, are sensitive to BPA. Key words: Aryl hydrocarbon receptor (AhR), AhR relating factor, Bisphenol A (BPA), Murine embryo, Xenobiotic metabolizing enzymes (XMEs) (J. Reprod. Dev. 51: [593][594][595][596][597][598][599][600][601][602][603][604][605] 2005) isphenol A [BPA; 2,2-bis (4-hydroxyphenyl) propane], which is composed of two benzene rings and in conformation resembles a synthetic estrogen, diethylstilbestrol (DES), is a common plasticizer for polycarbonate and epoxy resins and a candidate environmental endocrine disruptor (ED) [1,2]. BPA has toxicological effects on the reproductive, immunological, and nervous systems in mammals, binds with estrogen receptor-α (ERα; NR3A1) and ER-β (NR3A2), and induces estrogenic activity [3][4][5][6]. BPA affects the expression levels of ERs and ER-like nuclear receptor mRNAs in the rat uterus [6], but the mechanism of its actions has yet

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Developmental Neurotoxicity of Dioxin and Its Related Compounds.

Cited by 70 publications

References 125 publications

Effects of In Utero Exposure to Bisphenol A on mRNA Expression of Arylhydrocarbon and Retinoid Receptors in Murine Embryos

Effects of In Utero Exposure to Bisphenol A on mRNA Expression of Arylhydrocarbon and Retinoid Receptors in Murine Embryos

Endocrine Disruptors Are a Novel Direction of Endocrinologic Scientific Investigation

Effects of Exposure <i>In Utero</i> to Bisphenol A on the Expression of Aryl Hydrocarbon Receptor, Related Factors, and Xenobiotic Metabolizing Enzymes in Murine Embryos

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