Effects of In Utero Exposure to Bisphenol A on mRNA Expression of Arylhydrocarbon and Retinoid Receptors in Murine Embryos
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 (R...
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| Veröffentlicht in: | Journal of Reproduction and Development 2005, Vol.51(3), pp.315-324 |
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| creator | NISHIZAWA, Hanako MORITA, Maki SUGIMOTO, Miki IMANISHI, Satoshi MANABE, Noboru |
| description | 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 receptor-dependent 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-dpc-embryos. 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. |
| doi_str_mv | 10.1262/jrd.16008 |
| format | Article |
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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-dpc-embryos. 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.</description><identifier>ISSN: 0916-8818</identifier><identifier>EISSN: 1348-4400</identifier><identifier>DOI: 10.1262/jrd.16008</identifier><identifier>PMID: 15738621</identifier><language>eng</language><publisher>Japan: THE SOCIETY FOR REPRODUCTION AND DEVELOPMENT</publisher><subject>Animals ; Arylhydrocarbon receptor (AhR) ; Benzhydryl Compounds ; Bisphenol A ; Brain - drug effects ; Brain - embryology ; Brain - metabolism ; Dose-Response Relationship, Drug ; Embryo, Mammalian - drug effects ; Embryo, Mammalian - metabolism ; Estrogens, Non-Steroidal - administration & dosage ; Estrogens, Non-Steroidal - toxicity ; Female ; Gene Expression Regulation - drug effects ; Male ; Mice ; Mice, Inbred ICR ; Murine embryo ; Ovary - drug effects ; Ovary - embryology ; Ovary - metabolism ; Phenols - administration & dosage ; Phenols - toxicity ; Plasticizers - administration & dosage ; Plasticizers - toxicity ; Pregnancy ; Receptors, Aryl Hydrocarbon - genetics ; Receptors, Aryl Hydrocarbon - metabolism ; Receptors, Retinoic Acid - genetics ; Receptors, Retinoic Acid - metabolism ; Retinoic acid receptor (RAR) α ; Retinoic Acid Receptor alpha ; Retinoid X receptor (RXR) α ; Retinoid X Receptor alpha - genetics ; Retinoid X Receptor alpha - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - analysis ; RNA, Messenger - biosynthesis ; Testis - drug effects ; Testis - embryology ; Testis - metabolism</subject><ispartof>Journal of Reproduction and Development, 2005, Vol.51(3), pp.315-324</ispartof><rights>2005 Society for Reproduction and Development</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c540t-ea41c5c956c870567d5ff664b3eac8fb0ef5b7f6fadb809e0068c6556cd889f23</citedby><cites>FETCH-LOGICAL-c540t-ea41c5c956c870567d5ff664b3eac8fb0ef5b7f6fadb809e0068c6556cd889f23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,860,1877,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15738621$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>NISHIZAWA, Hanako</creatorcontrib><creatorcontrib>MORITA, Maki</creatorcontrib><creatorcontrib>SUGIMOTO, Miki</creatorcontrib><creatorcontrib>IMANISHI, Satoshi</creatorcontrib><creatorcontrib>MANABE, Noboru</creatorcontrib><title>Effects of In Utero Exposure to Bisphenol A on mRNA Expression of Arylhydrocarbon and Retinoid Receptors in Murine Embryos</title><title>Journal of Reproduction and Development</title><addtitle>J. Reprod. Dev.</addtitle><description>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 receptor-dependent 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-dpc-embryos. 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.</description><subject>Animals</subject><subject>Arylhydrocarbon receptor (AhR)</subject><subject>Benzhydryl Compounds</subject><subject>Bisphenol A</subject><subject>Brain - drug effects</subject><subject>Brain - embryology</subject><subject>Brain - metabolism</subject><subject>Dose-Response Relationship, Drug</subject><subject>Embryo, Mammalian - drug effects</subject><subject>Embryo, Mammalian - metabolism</subject><subject>Estrogens, Non-Steroidal - administration & dosage</subject><subject>Estrogens, Non-Steroidal - toxicity</subject><subject>Female</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred ICR</subject><subject>Murine embryo</subject><subject>Ovary - drug effects</subject><subject>Ovary - embryology</subject><subject>Ovary - metabolism</subject><subject>Phenols - administration & dosage</subject><subject>Phenols - toxicity</subject><subject>Plasticizers - administration & dosage</subject><subject>Plasticizers - toxicity</subject><subject>Pregnancy</subject><subject>Receptors, Aryl Hydrocarbon - genetics</subject><subject>Receptors, Aryl Hydrocarbon - metabolism</subject><subject>Receptors, Retinoic Acid - genetics</subject><subject>Receptors, Retinoic Acid - metabolism</subject><subject>Retinoic acid receptor (RAR) α</subject><subject>Retinoic Acid Receptor alpha</subject><subject>Retinoid X receptor (RXR) α</subject><subject>Retinoid X Receptor alpha - genetics</subject><subject>Retinoid X Receptor alpha - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - analysis</subject><subject>RNA, Messenger - biosynthesis</subject><subject>Testis - drug effects</subject><subject>Testis - embryology</subject><subject>Testis - metabolism</subject><issn>0916-8818</issn><issn>1348-4400</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkM1u1DAUha0KRIfCoi9QeYXURcp1EnucFZqOBqhUQKro2nKc645HiR1sR-rw9GQ6o7K5f-e7Z3EIuWRww0pRft7F7oYJAHlGFqyqZVHXAG_IAhomCimZPCfvU9oBVCUX9TtyzviykqJkC_J3Yy2anGiw9M7Tx4wx0M3zGNIUkeZAb10at-hDT1c0eDo8_Fwd9IgpuXmf31Zx32_3XQxGx3Y-ad_RB8zOB3cYDI45xESdpz-m6DzSzdDGfUgfyFur-4QfT_2CPH7d_F5_L-5_fbtbr-4Lw2vIBeqaGW4aLoxcAhfLjlsrRN1WqI20LaDl7dIKq7tWQoMAQhrBZ7yTsrFldUE-HX3HGP5MmLIaXDLY99pjmJIqgUvgvJnB6yNoYkgpolVjdIOOe8VAHYJWc9DqJeiZvTqZTu2A3X_ylOwMfDkCu5T1E74COmZnenyx4kxVx1Ix_qqYrY4KffUP1lKRSA</recordid><startdate>20050601</startdate><enddate>20050601</enddate><creator>NISHIZAWA, Hanako</creator><creator>MORITA, Maki</creator><creator>SUGIMOTO, Miki</creator><creator>IMANISHI, Satoshi</creator><creator>MANABE, Noboru</creator><general>THE SOCIETY FOR REPRODUCTION AND DEVELOPMENT</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>20050601</creationdate><title>Effects of In Utero Exposure to Bisphenol A on mRNA Expression of Arylhydrocarbon and Retinoid Receptors in Murine Embryos</title><author>NISHIZAWA, Hanako ; MORITA, Maki ; SUGIMOTO, Miki ; IMANISHI, Satoshi ; MANABE, Noboru</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c540t-ea41c5c956c870567d5ff664b3eac8fb0ef5b7f6fadb809e0068c6556cd889f23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>Arylhydrocarbon receptor (AhR)</topic><topic>Benzhydryl Compounds</topic><topic>Bisphenol A</topic><topic>Brain - drug effects</topic><topic>Brain - embryology</topic><topic>Brain - metabolism</topic><topic>Dose-Response Relationship, Drug</topic><topic>Embryo, Mammalian - drug effects</topic><topic>Embryo, Mammalian - metabolism</topic><topic>Estrogens, Non-Steroidal - administration & dosage</topic><topic>Estrogens, Non-Steroidal - toxicity</topic><topic>Female</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred ICR</topic><topic>Murine embryo</topic><topic>Ovary - drug effects</topic><topic>Ovary - embryology</topic><topic>Ovary - metabolism</topic><topic>Phenols - administration & dosage</topic><topic>Phenols - toxicity</topic><topic>Plasticizers - administration & dosage</topic><topic>Plasticizers - toxicity</topic><topic>Pregnancy</topic><topic>Receptors, Aryl Hydrocarbon - genetics</topic><topic>Receptors, Aryl Hydrocarbon - metabolism</topic><topic>Receptors, Retinoic Acid - genetics</topic><topic>Receptors, Retinoic Acid - metabolism</topic><topic>Retinoic acid receptor (RAR) α</topic><topic>Retinoic Acid Receptor alpha</topic><topic>Retinoid X receptor (RXR) α</topic><topic>Retinoid X Receptor alpha - genetics</topic><topic>Retinoid X Receptor alpha - metabolism</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - analysis</topic><topic>RNA, Messenger - biosynthesis</topic><topic>Testis - drug effects</topic><topic>Testis - embryology</topic><topic>Testis - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>NISHIZAWA, Hanako</creatorcontrib><creatorcontrib>MORITA, Maki</creatorcontrib><creatorcontrib>SUGIMOTO, Miki</creatorcontrib><creatorcontrib>IMANISHI, Satoshi</creatorcontrib><creatorcontrib>MANABE, Noboru</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Journal of Reproduction and Development</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>NISHIZAWA, Hanako</au><au>MORITA, Maki</au><au>SUGIMOTO, Miki</au><au>IMANISHI, Satoshi</au><au>MANABE, Noboru</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of In Utero Exposure to Bisphenol A on mRNA Expression of Arylhydrocarbon and Retinoid Receptors in Murine Embryos</atitle><jtitle>Journal of Reproduction and Development</jtitle><addtitle>J. Reprod. Dev.</addtitle><date>2005-06-01</date><risdate>2005</risdate><volume>51</volume><issue>3</issue><spage>315</spage><epage>324</epage><pages>315-324</pages><issn>0916-8818</issn><eissn>1348-4400</eissn><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 receptor-dependent 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-dpc-embryos. 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.</abstract><cop>Japan</cop><pub>THE SOCIETY FOR REPRODUCTION AND DEVELOPMENT</pub><pmid>15738621</pmid><doi>10.1262/jrd.16008</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Arylhydrocarbon receptor (AhR) Benzhydryl Compounds Bisphenol A Brain - drug effects Brain - embryology Brain - metabolism Dose-Response Relationship, Drug Embryo, Mammalian - drug effects Embryo, Mammalian - metabolism Estrogens, Non-Steroidal - administration & dosage Estrogens, Non-Steroidal - toxicity Female Gene Expression Regulation - drug effects Male Mice Mice, Inbred ICR Murine embryo Ovary - drug effects Ovary - embryology Ovary - metabolism Phenols - administration & dosage Phenols - toxicity Plasticizers - administration & dosage Plasticizers - toxicity Pregnancy Receptors, Aryl Hydrocarbon - genetics Receptors, Aryl Hydrocarbon - metabolism Receptors, Retinoic Acid - genetics Receptors, Retinoic Acid - metabolism Retinoic acid receptor (RAR) α Retinoic Acid Receptor alpha Retinoid X receptor (RXR) α Retinoid X Receptor alpha - genetics Retinoid X Receptor alpha - metabolism Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - analysis RNA, Messenger - biosynthesis Testis - drug effects Testis - embryology Testis - metabolism |
| title | Effects of In Utero Exposure to Bisphenol A on mRNA Expression of Arylhydrocarbon and Retinoid Receptors in Murine Embryos |
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