Transplacental Transfer and Biotransformation of Genistein in Human Placenta

Abstract Objective To study transplacental transfer and biotransformation of genistein in the human placenta. Study design and outcomes Human placentae obtained from healthy term singleton pregnancies were utilised in a dual re-circulating model of ex-vivo placental perfusion. Four placentae were pe...

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Veröffentlicht in:Placenta (Eastbourne) 2010-06, Vol.31 (6), p.506-511
Hauptverfasser: Balakrishnan, B, Thorstensen, E.B, Ponnampalam, A.P, Mitchell, M.D
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container_end_page 511
container_issue 6
container_start_page 506
container_title Placenta (Eastbourne)
container_volume 31
creator Balakrishnan, B
Thorstensen, E.B
Ponnampalam, A.P
Mitchell, M.D
description Abstract Objective To study transplacental transfer and biotransformation of genistein in the human placenta. Study design and outcomes Human placentae obtained from healthy term singleton pregnancies were utilised in a dual re-circulating model of ex-vivo placental perfusion. Four placentae were perfused for 180 min following addition of genistein (10 ng/mL) to the maternal perfusate. Antipyrine and FITC dextran were used as positive and negative controls respectively to validate integrity of the circuits. Concentrations of genistein and its conjugates were determined by liquid chromatography-mass spectrometry (LC–MS). Results The transfer percentage for antipyrine and genistein was 25.6 ± 1.40% and 22.1 ± 1.61% respectively and the transfer index for genistein was 0.90 ± 0.04 after 180 min of perfusion. 12.0 ± 2.40% of genistein in the fetal compartment and 7.36 ± 4.73% of genistein in the maternal compartment were in the conjugated form. Conclusions Genistein can transfer across the human placenta at environmentally relevant levels. Placental metabolizing enzymes conjugate a small fraction of genistein into the glucuronide/sulphate form, which is devoid of estrogenic action.
doi_str_mv 10.1016/j.placenta.2010.03.007
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Study design and outcomes Human placentae obtained from healthy term singleton pregnancies were utilised in a dual re-circulating model of ex-vivo placental perfusion. Four placentae were perfused for 180 min following addition of genistein (10 ng/mL) to the maternal perfusate. Antipyrine and FITC dextran were used as positive and negative controls respectively to validate integrity of the circuits. Concentrations of genistein and its conjugates were determined by liquid chromatography-mass spectrometry (LC–MS). Results The transfer percentage for antipyrine and genistein was 25.6 ± 1.40% and 22.1 ± 1.61% respectively and the transfer index for genistein was 0.90 ± 0.04 after 180 min of perfusion. 12.0 ± 2.40% of genistein in the fetal compartment and 7.36 ± 4.73% of genistein in the maternal compartment were in the conjugated form. Conclusions Genistein can transfer across the human placenta at environmentally relevant levels. Placental metabolizing enzymes conjugate a small fraction of genistein into the glucuronide/sulphate form, which is devoid of estrogenic action.</description><identifier>ISSN: 0143-4004</identifier><identifier>EISSN: 1532-3102</identifier><identifier>DOI: 10.1016/j.placenta.2010.03.007</identifier><identifier>PMID: 20413155</identifier><identifier>CODEN: PLACDF</identifier><language>eng</language><publisher>Kidlington: Elsevier Ltd</publisher><subject>Biological and medical sciences ; Biotransformation ; Chromatography, High Pressure Liquid ; Embryology: invertebrates and vertebrates. Teratology ; Endocrine disruptors ; Female ; Fundamental and applied biological sciences. Psychology ; Genistein ; Genistein - pharmacokinetics ; Genistein glucuronide ; Humans ; Internal Medicine ; Maternal-Fetal Exchange - drug effects ; Obstetrics and Gynecology ; Phytoestrogens ; Phytoestrogens - pharmacokinetics ; Placenta - drug effects ; Placental perfusion ; Placental transfer ; Pregnancy ; Tandem Mass Spectrometry</subject><ispartof>Placenta (Eastbourne), 2010-06, Vol.31 (6), p.506-511</ispartof><rights>Elsevier Ltd</rights><rights>2010 Elsevier Ltd</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c452t-a16819e511f6caee3ddb197fbc6f86683da6d9d81d46697f5b8a57121d438a713</citedby><cites>FETCH-LOGICAL-c452t-a16819e511f6caee3ddb197fbc6f86683da6d9d81d46697f5b8a57121d438a713</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.placenta.2010.03.007$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27922,27923,45993</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=22861939$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20413155$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Balakrishnan, B</creatorcontrib><creatorcontrib>Thorstensen, E.B</creatorcontrib><creatorcontrib>Ponnampalam, A.P</creatorcontrib><creatorcontrib>Mitchell, M.D</creatorcontrib><title>Transplacental Transfer and Biotransformation of Genistein in Human Placenta</title><title>Placenta (Eastbourne)</title><addtitle>Placenta</addtitle><description>Abstract Objective To study transplacental transfer and biotransformation of genistein in the human placenta. Study design and outcomes Human placentae obtained from healthy term singleton pregnancies were utilised in a dual re-circulating model of ex-vivo placental perfusion. Four placentae were perfused for 180 min following addition of genistein (10 ng/mL) to the maternal perfusate. Antipyrine and FITC dextran were used as positive and negative controls respectively to validate integrity of the circuits. Concentrations of genistein and its conjugates were determined by liquid chromatography-mass spectrometry (LC–MS). Results The transfer percentage for antipyrine and genistein was 25.6 ± 1.40% and 22.1 ± 1.61% respectively and the transfer index for genistein was 0.90 ± 0.04 after 180 min of perfusion. 12.0 ± 2.40% of genistein in the fetal compartment and 7.36 ± 4.73% of genistein in the maternal compartment were in the conjugated form. Conclusions Genistein can transfer across the human placenta at environmentally relevant levels. Placental metabolizing enzymes conjugate a small fraction of genistein into the glucuronide/sulphate form, which is devoid of estrogenic action.</description><subject>Biological and medical sciences</subject><subject>Biotransformation</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Embryology: invertebrates and vertebrates. Teratology</subject><subject>Endocrine disruptors</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genistein</subject><subject>Genistein - pharmacokinetics</subject><subject>Genistein glucuronide</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Maternal-Fetal Exchange - drug effects</subject><subject>Obstetrics and Gynecology</subject><subject>Phytoestrogens</subject><subject>Phytoestrogens - pharmacokinetics</subject><subject>Placenta - drug effects</subject><subject>Placental perfusion</subject><subject>Placental transfer</subject><subject>Pregnancy</subject><subject>Tandem Mass Spectrometry</subject><issn>0143-4004</issn><issn>1532-3102</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1r3DAQQEVpaLZp_0LwJfTk7Yxky_alJA35KCyk0PQstNIYtLWljWQH8u-rze620EtBIGZ4MyO9YewcYYmA8vNmuR20IT_pJYecBLEEaN6wBdaClwKBv2ULwEqUFUB1yt6ntAGArkL-jp1yqFBgXS_Y6jFqn469huI17CkW2tviqwvTaxziqCcXfBH64o68SxM5X-RzP4_aF98P5R_YSa-HRB8P9xn7eXvzeH1frh7uvl1frUpT1XwqNcoWO6oRe2k0kbB2jV3Tr43sWylbYbW0nW3RVlLmfL1udd0gz7FodYPijH3a993G8DRTmtTokqFh0J7CnFQjBAoJTZVJuSdNDClF6tU2ulHHF4WgdiLVRh0_r3YiFQiVRebC88OIeT2S_VN2NJeBiwOgk9FDnz0Zl_5yvJXYiS5zl3uOspBnR1El48gbsi6SmZQN7v9v-fJPCzM47_LUX_RCaRPm6LNuhSpxBerHbu27rWNeOGLTiN_IXaky</recordid><startdate>20100601</startdate><enddate>20100601</enddate><creator>Balakrishnan, B</creator><creator>Thorstensen, E.B</creator><creator>Ponnampalam, A.P</creator><creator>Mitchell, M.D</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>IQODW</scope><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>7X8</scope></search><sort><creationdate>20100601</creationdate><title>Transplacental Transfer and Biotransformation of Genistein in Human Placenta</title><author>Balakrishnan, B ; Thorstensen, E.B ; Ponnampalam, A.P ; Mitchell, M.D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c452t-a16819e511f6caee3ddb197fbc6f86683da6d9d81d46697f5b8a57121d438a713</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Biological and medical sciences</topic><topic>Biotransformation</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Embryology: invertebrates and vertebrates. Teratology</topic><topic>Endocrine disruptors</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genistein</topic><topic>Genistein - pharmacokinetics</topic><topic>Genistein glucuronide</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>Maternal-Fetal Exchange - drug effects</topic><topic>Obstetrics and Gynecology</topic><topic>Phytoestrogens</topic><topic>Phytoestrogens - pharmacokinetics</topic><topic>Placenta - drug effects</topic><topic>Placental perfusion</topic><topic>Placental transfer</topic><topic>Pregnancy</topic><topic>Tandem Mass Spectrometry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Balakrishnan, B</creatorcontrib><creatorcontrib>Thorstensen, E.B</creatorcontrib><creatorcontrib>Ponnampalam, A.P</creatorcontrib><creatorcontrib>Mitchell, M.D</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Placenta (Eastbourne)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Balakrishnan, B</au><au>Thorstensen, E.B</au><au>Ponnampalam, A.P</au><au>Mitchell, M.D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transplacental Transfer and Biotransformation of Genistein in Human Placenta</atitle><jtitle>Placenta (Eastbourne)</jtitle><addtitle>Placenta</addtitle><date>2010-06-01</date><risdate>2010</risdate><volume>31</volume><issue>6</issue><spage>506</spage><epage>511</epage><pages>506-511</pages><issn>0143-4004</issn><eissn>1532-3102</eissn><coden>PLACDF</coden><abstract>Abstract Objective To study transplacental transfer and biotransformation of genistein in the human placenta. Study design and outcomes Human placentae obtained from healthy term singleton pregnancies were utilised in a dual re-circulating model of ex-vivo placental perfusion. Four placentae were perfused for 180 min following addition of genistein (10 ng/mL) to the maternal perfusate. Antipyrine and FITC dextran were used as positive and negative controls respectively to validate integrity of the circuits. Concentrations of genistein and its conjugates were determined by liquid chromatography-mass spectrometry (LC–MS). Results The transfer percentage for antipyrine and genistein was 25.6 ± 1.40% and 22.1 ± 1.61% respectively and the transfer index for genistein was 0.90 ± 0.04 after 180 min of perfusion. 12.0 ± 2.40% of genistein in the fetal compartment and 7.36 ± 4.73% of genistein in the maternal compartment were in the conjugated form. Conclusions Genistein can transfer across the human placenta at environmentally relevant levels. Placental metabolizing enzymes conjugate a small fraction of genistein into the glucuronide/sulphate form, which is devoid of estrogenic action.</abstract><cop>Kidlington</cop><pub>Elsevier Ltd</pub><pmid>20413155</pmid><doi>10.1016/j.placenta.2010.03.007</doi><tpages>6</tpages></addata></record>
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subjects Biological and medical sciences
Biotransformation
Chromatography, High Pressure Liquid
Embryology: invertebrates and vertebrates. Teratology
Endocrine disruptors
Female
Fundamental and applied biological sciences. Psychology
Genistein
Genistein - pharmacokinetics
Genistein glucuronide
Humans
Internal Medicine
Maternal-Fetal Exchange - drug effects
Obstetrics and Gynecology
Phytoestrogens
Phytoestrogens - pharmacokinetics
Placenta - drug effects
Placental perfusion
Placental transfer
Pregnancy
Tandem Mass Spectrometry
title Transplacental Transfer and Biotransformation of Genistein in Human Placenta
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