Effect of fetal or neonatal exposure to monobutyl phthalate (MBP) on testicular development and function in the marmoset
Identifieur interne : 000E75 ( Istex/Corpus ); précédent : 000E74; suivant : 000E76Effect of fetal or neonatal exposure to monobutyl phthalate (MBP) on testicular development and function in the marmoset
Auteurs : Chris Mckinnell ; Rod T. Mitchell ; Marion Walker ; Keith Morris ; Chris J. H. Kelnar ; W. Hamish Wallace ; Richard M. SharpeSource :
- Human Reproduction [ 0268-1161 ] ; 2009-09.
Abstract
BACKGROUND Fetal exposure of male rats to some phthalates induces reproductive abnormalities, raising concerns for similar effects in humans. In order to address this in a more appropriate animal model, the aim of the present studies was to investigate the effect of fetal/neonatal exposure to monobutyl phthalate (MBP) in a non-human primate, the marmoset. In particular, to determine if exposure resulted in effects at birth, or in adulthood, similar to those in male rats, and whether there was evidence for induction of carcinoma-in-situ (CIS) or testicular germ cell tumours (TGCT). METHODS Pregnant female marmosets were dosed from 715 weeks gestation with 500 mg/kg/day MBP and male offspring studied at birth (15 days; n 6) or in adulthood (n 5). In another study, newborn males (n 5 co-twins) were dosed with 500 mg/kg/day MBP for 14 days, commencing at 4 days of age. RESULTS Fetal exposure of marmosets to MBP did not affect gross testicular morphology, reproductive tract development or testosterone levels at birth, nor were germ cell number and proliferation, Sertoli cell number or germ:Sertoli cell ratio affected. In two of six MBP-exposed animals, unusual clusters of undifferentiated germ cells were found, but their significance is unclear. Neonatal MBP treatment did not affect germ cell numbers or differentiation. Fetal exposure to MBP did not affect testis size/morphology, germ cell numbers or fertility in adulthood. There was no evidence for CIS or TGCT. CONCLUSIONS Fetal exposure of marmosets to MBP does not measurably affect testis development/function or cause testicular dysgenesis, and no effects emerge by adulthood. Some effects on germ cell development were found, but these were inconsistent and of uncertain significance.
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DOI: 10.1093/humrep/dep200
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Mitchell</name><affiliation><mods:affiliation>MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK</mods:affiliation></affiliation></author><author><name sortKey="Walker, Marion" sort="Walker, Marion" uniqKey="Walker M" first="Marion" last="Walker">Marion Walker</name><affiliation><mods:affiliation>MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK</mods:affiliation></affiliation></author><author><name sortKey="Morris, Keith" sort="Morris, Keith" uniqKey="Morris K" first="Keith" last="Morris">Keith Morris</name><affiliation><mods:affiliation>MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK</mods:affiliation></affiliation></author><author><name sortKey="Kelnar, Chris J H" sort="Kelnar, Chris J H" uniqKey="Kelnar C" first="Chris J. H." last="Kelnar">Chris J. H. Kelnar</name><affiliation><mods:affiliation>Edinburgh Royal Hospital for Sick Children, 9 Sciennes Road, Edinburgh EH9 1LF, UK</mods:affiliation></affiliation></author><author><name sortKey="Wallace, W Hamish" sort="Wallace, W Hamish" uniqKey="Wallace W" first="W. Hamish" last="Wallace">W. Hamish Wallace</name><affiliation><mods:affiliation>Edinburgh Royal Hospital for Sick Children, 9 Sciennes Road, Edinburgh EH9 1LF, UK</mods:affiliation></affiliation></author><author><name sortKey="Sharpe, Richard M" sort="Sharpe, Richard M" uniqKey="Sharpe R" first="Richard M." last="Sharpe">Richard M. Sharpe</name><affiliation><mods:affiliation>MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Human Reproduction</title><idno type="ISSN">0268-1161</idno><idno type="eISSN">1460-2350</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2009-09">2009-09</date><biblScope unit="volume">24</biblScope><biblScope unit="issue">9</biblScope><biblScope unit="page" from="2244">2244</biblScope><biblScope unit="page" to="2254">2254</biblScope></imprint><idno type="ISSN">0268-1161</idno></series><idno type="istex">B2D49AEC8D1DDF0C767AB30494A189211B225D32</idno><idno type="DOI">10.1093/humrep/dep200</idno><idno type="ArticleID">dep200</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0268-1161</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">BACKGROUND Fetal exposure of male rats to some phthalates induces reproductive abnormalities, raising concerns for similar effects in humans. In order to address this in a more appropriate animal model, the aim of the present studies was to investigate the effect of fetal/neonatal exposure to monobutyl phthalate (MBP) in a non-human primate, the marmoset. In particular, to determine if exposure resulted in effects at birth, or in adulthood, similar to those in male rats, and whether there was evidence for induction of carcinoma-in-situ (CIS) or testicular germ cell tumours (TGCT). METHODS Pregnant female marmosets were dosed from 715 weeks gestation with 500 mg/kg/day MBP and male offspring studied at birth (15 days; n 6) or in adulthood (n 5). In another study, newborn males (n 5 co-twins) were dosed with 500 mg/kg/day MBP for 14 days, commencing at 4 days of age. RESULTS Fetal exposure of marmosets to MBP did not affect gross testicular morphology, reproductive tract development or testosterone levels at birth, nor were germ cell number and proliferation, Sertoli cell number or germ:Sertoli cell ratio affected. In two of six MBP-exposed animals, unusual clusters of undifferentiated germ cells were found, but their significance is unclear. Neonatal MBP treatment did not affect germ cell numbers or differentiation. Fetal exposure to MBP did not affect testis size/morphology, germ cell numbers or fertility in adulthood. There was no evidence for CIS or TGCT. CONCLUSIONS Fetal exposure of marmosets to MBP does not measurably affect testis development/function or cause testicular dysgenesis, and no effects emerge by adulthood. Some effects on germ cell development were found, but these were inconsistent and of uncertain significance.</div></front></TEI><istex><corpusName>oup</corpusName><author><json:item><name>Chris McKinnell</name><affiliations><json:string>MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK</json:string><json:string>E-mail: c.mckinnell@hrsu.mrc.ac.uk</json:string></affiliations></json:item><json:item><name>Rod T. Mitchell</name><affiliations><json:string>MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK</json:string></affiliations></json:item><json:item><name>Marion Walker</name><affiliations><json:string>MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK</json:string></affiliations></json:item><json:item><name>Keith Morris</name><affiliations><json:string>MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK</json:string></affiliations></json:item><json:item><name>Chris J.H. Kelnar</name><affiliations><json:string>Edinburgh Royal Hospital for Sick Children, 9 Sciennes Road, Edinburgh EH9 1LF, UK</json:string></affiliations></json:item><json:item><name>W. Hamish Wallace</name><affiliations><json:string>Edinburgh Royal Hospital for Sick Children, 9 Sciennes Road, Edinburgh EH9 1LF, UK</json:string></affiliations></json:item><json:item><name>Richard M. Sharpe</name><affiliations><json:string>MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>fetal</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>germ cells</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>monobutyl phthalate</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>neonatal</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>testis</value></json:item></subject><articleId><json:string>dep200</json:string></articleId><language><json:string>eng</json:string></language><originalGenre><json:string>research-article</json:string></originalGenre><abstract>BACKGROUND Fetal exposure of male rats to some phthalates induces reproductive abnormalities, raising concerns for similar effects in humans. In order to address this in a more appropriate animal model, the aim of the present studies was to investigate the effect of fetal/neonatal exposure to monobutyl phthalate (MBP) in a non-human primate, the marmoset. In particular, to determine if exposure resulted in effects at birth, or in adulthood, similar to those in male rats, and whether there was evidence for induction of carcinoma-in-situ (CIS) or testicular germ cell tumours (TGCT). METHODS Pregnant female marmosets were dosed from 715 weeks gestation with 500 mg/kg/day MBP and male offspring studied at birth (15 days; n 6) or in adulthood (n 5). In another study, newborn males (n 5 co-twins) were dosed with 500 mg/kg/day MBP for 14 days, commencing at 4 days of age. RESULTS Fetal exposure of marmosets to MBP did not affect gross testicular morphology, reproductive tract development or testosterone levels at birth, nor were germ cell number and proliferation, Sertoli cell number or germ:Sertoli cell ratio affected. In two of six MBP-exposed animals, unusual clusters of undifferentiated germ cells were found, but their significance is unclear. Neonatal MBP treatment did not affect germ cell numbers or differentiation. Fetal exposure to MBP did not affect testis size/morphology, germ cell numbers or fertility in adulthood. There was no evidence for CIS or TGCT. CONCLUSIONS Fetal exposure of marmosets to MBP does not measurably affect testis development/function or cause testicular dysgenesis, and no effects emerge by adulthood. Some effects on germ cell development were found, but these were inconsistent and of uncertain significance.</abstract><qualityIndicators><score>9</score><pdfVersion>1.5</pdfVersion><pdfPageSize>612.283 x 790.866 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>5</keywordCount><abstractCharCount>1760</abstractCharCount><pdfWordCount>7281</pdfWordCount><pdfCharCount>45017</pdfCharCount><pdfPageCount>11</pdfPageCount><abstractWordCount>271</abstractWordCount></qualityIndicators><title>Effect of fetal or neonatal exposure to monobutyl phthalate (MBP) on testicular development and function in the marmoset</title><genre><json:string>research-article</json:string></genre><host><volume>24</volume><publisherId><json:string>humrep</json:string></publisherId><pages><last>2254</last><first>2244</first></pages><issn><json:string>0268-1161</json:string></issn><issue>9</issue><genre><json:string>journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1460-2350</json:string></eissn><title>Human Reproduction</title></host><categories><wos><json:string>OBSTETRICS & GYNECOLOGY</json:string><json:string>REPRODUCTIVE BIOLOGY</json:string></wos></categories><publicationDate>2009</publicationDate><copyrightDate>2009</copyrightDate><doi><json:string>10.1093/humrep/dep200</json:string></doi><id>B2D49AEC8D1DDF0C767AB30494A189211B225D32</id><score>0.2491413</score><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/B2D49AEC8D1DDF0C767AB30494A189211B225D32/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/B2D49AEC8D1DDF0C767AB30494A189211B225D32/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/B2D49AEC8D1DDF0C767AB30494A189211B225D32/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a">Effect of fetal or neonatal exposure to monobutyl phthalate (MBP) on testicular development and function in the marmoset</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Oxford University Press</publisher><availability><p>The Author 2009. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissionsoxfordjournals.org</p></availability><date>2009-06-02</date></publicationStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a">Effect of fetal or neonatal exposure to monobutyl phthalate (MBP) on testicular development and function in the marmoset</title><author xml:id="author-1"><persName><forename type="first">Chris</forename><surname>McKinnell</surname></persName><email>c.mckinnell@hrsu.mrc.ac.uk</email><affiliation>MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK</affiliation></author><author xml:id="author-2"><persName><forename type="first">Rod T.</forename><surname>Mitchell</surname></persName><affiliation>MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK</affiliation></author><author xml:id="author-3"><persName><forename type="first">Marion</forename><surname>Walker</surname></persName><affiliation>MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK</affiliation></author><author xml:id="author-4"><persName><forename type="first">Keith</forename><surname>Morris</surname></persName><affiliation>MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK</affiliation></author><author xml:id="author-5"><persName><forename type="first">Chris J.H.</forename><surname>Kelnar</surname></persName><affiliation>Edinburgh Royal Hospital for Sick Children, 9 Sciennes Road, Edinburgh EH9 1LF, UK</affiliation></author><author xml:id="author-6"><persName><forename type="first">W. Hamish</forename><surname>Wallace</surname></persName><affiliation>Edinburgh Royal Hospital for Sick Children, 9 Sciennes Road, Edinburgh EH9 1LF, UK</affiliation></author><author xml:id="author-7"><persName><forename type="first">Richard M.</forename><surname>Sharpe</surname></persName><affiliation>MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK</affiliation></author></analytic><monogr><title level="j">Human Reproduction</title><idno type="pISSN">0268-1161</idno><idno type="eISSN">1460-2350</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2009-09"></date><biblScope unit="volume">24</biblScope><biblScope unit="issue">9</biblScope><biblScope unit="page" from="2244">2244</biblScope><biblScope unit="page" to="2254">2254</biblScope></imprint></monogr><idno type="istex">B2D49AEC8D1DDF0C767AB30494A189211B225D32</idno><idno type="DOI">10.1093/humrep/dep200</idno><idno type="ArticleID">dep200</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2009-06-02</date></creation><langUsage><language ident="en">en</language></langUsage><abstract><p>BACKGROUND Fetal exposure of male rats to some phthalates induces reproductive abnormalities, raising concerns for similar effects in humans. In order to address this in a more appropriate animal model, the aim of the present studies was to investigate the effect of fetal/neonatal exposure to monobutyl phthalate (MBP) in a non-human primate, the marmoset. In particular, to determine if exposure resulted in effects at birth, or in adulthood, similar to those in male rats, and whether there was evidence for induction of carcinoma-in-situ (CIS) or testicular germ cell tumours (TGCT). METHODS Pregnant female marmosets were dosed from 715 weeks gestation with 500 mg/kg/day MBP and male offspring studied at birth (15 days; n 6) or in adulthood (n 5). In another study, newborn males (n 5 co-twins) were dosed with 500 mg/kg/day MBP for 14 days, commencing at 4 days of age. RESULTS Fetal exposure of marmosets to MBP did not affect gross testicular morphology, reproductive tract development or testosterone levels at birth, nor were germ cell number and proliferation, Sertoli cell number or germ:Sertoli cell ratio affected. In two of six MBP-exposed animals, unusual clusters of undifferentiated germ cells were found, but their significance is unclear. Neonatal MBP treatment did not affect germ cell numbers or differentiation. Fetal exposure to MBP did not affect testis size/morphology, germ cell numbers or fertility in adulthood. There was no evidence for CIS or TGCT. CONCLUSIONS Fetal exposure of marmosets to MBP does not measurably affect testis development/function or cause testicular dysgenesis, and no effects emerge by adulthood. Some effects on germ cell development were found, but these were inconsistent and of uncertain significance.</p></abstract><textClass><keywords scheme="keyword"><list><head>keywords</head><item><term>fetal</term></item><item><term>germ cells</term></item><item><term>monobutyl phthalate</term></item><item><term>neonatal</term></item><item><term>testis</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2009-06-02">Created</change><change when="2009-09">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/B2D49AEC8D1DDF0C767AB30494A189211B225D32/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus oup" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//NLM//DTD Journal Publishing DTD v2.3 20070202//EN" URI="journalpublishing.dtd" name="istex:docType"></istex:docType><istex:document><article article-type="research-article"><front><journal-meta><journal-id journal-id-type="publisher-id">humrep</journal-id><journal-id journal-id-type="hwp">humrep</journal-id><journal-title>Human Reproduction</journal-title><issn pub-type="ppub">0268-1161</issn><issn pub-type="epub">1460-2350</issn><publisher><publisher-name>Oxford University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.1093/humrep/dep200</article-id><article-id pub-id-type="publisher-id">dep200</article-id><article-categories><subj-group subj-group-type="heading"><subject>ORIGINAL ARTICLES</subject><subj-group subj-group-type="heading"><subject>Reproductive biology</subject></subj-group></subj-group></article-categories><title-group><article-title>Effect of fetal or neonatal exposure to monobutyl phthalate (MBP) on testicular development and function in the marmoset</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>McKinnell</surname><given-names>Chris</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="corresp" rid="cor1">3</xref></contrib><contrib contrib-type="author"><name><surname>Mitchell</surname><given-names>Rod T.</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Walker</surname><given-names>Marion</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Morris</surname><given-names>Keith</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Kelnar</surname><given-names>Chris J.H.</given-names></name><xref ref-type="aff" rid="af2">2</xref></contrib><contrib contrib-type="author"><name><surname>Wallace</surname><given-names>W. Hamish</given-names></name><xref ref-type="aff" rid="af2">2</xref></contrib><contrib contrib-type="author"><name><surname>Sharpe</surname><given-names>Richard M.</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib></contrib-group><aff id="af1"><label>1</label><addr-line>MRC Human Reproductive Sciences Unit</addr-line>, <institution>Centre for Reproductive Biology, The Queen's Medical Research Institute</institution>, <addr-line>47 Little France Crescent, Edinburgh EH16 4TJ</addr-line>, <country>UK</country></aff><aff id="af2"><label>2</label><institution>Edinburgh Royal Hospital for Sick Children</institution>, <addr-line>9 Sciennes Road, Edinburgh EH9 1LF</addr-line>, <country>UK</country></aff><author-notes><corresp id="cor1"><label>3</label>Correspondence address. Tel: <phone>+44-131-242-9113</phone>; Fax: <fax>+44-131-242-6231</fax>; E-mail: <email>c.mckinnell@hrsu.mrc.ac.uk</email></corresp></author-notes><pub-date pub-type="ppub"><month>9</month><year>2009</year></pub-date><pub-date pub-type="epub"><day>2</day><month>6</month><year>2009</year></pub-date><volume>24</volume><issue>9</issue><fpage>2244</fpage><lpage>2254</lpage><history><date date-type="received"><day>5</day><month>3</month><year>2009</year></date><date date-type="rev-recd"><day>27</day><month>4</month><year>2009</year></date><date date-type="accepted"><day>6</day><month>5</month><year>2009</year></date></history><copyright-statement>© The Author 2009. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org</copyright-statement><copyright-year>2009</copyright-year><license license-type="creative-commons" xlink:href="http://creativecommons.org/licenses/by-nc/2.0/uk/"><p>The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed: the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given: if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative word this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org</p></license><abstract><sec><title>BACKGROUND</title><p>Fetal exposure of male rats to some phthalates induces reproductive abnormalities, raising concerns for similar effects in humans. In order to address this in a more appropriate animal model, the aim of the present studies was to investigate the effect of fetal/neonatal exposure to monobutyl phthalate (MBP) in a non-human primate, the marmoset. In particular, to determine if exposure resulted in effects at birth, or in adulthood, similar to those in male rats, and whether there was evidence for induction of carcinoma-in-situ (<italic>CIS</italic>) or testicular germ cell tumours (TGCT).</p></sec><sec><title>METHODS</title><p>Pregnant female marmosets were dosed from ∼7–15 weeks gestation with 500 mg/kg/day MBP and male offspring studied at birth (1–5 days; <italic>n</italic> = 6) or in adulthood (<italic>n</italic> = 5). In another study, newborn males (<italic>n</italic> = 5 co-twins) were dosed with 500 mg/kg/day MBP for 14 days, commencing at ∼4 days of age.</p></sec><sec><title>RESULTS</title><p>Fetal exposure of marmosets to MBP did not affect gross testicular morphology, reproductive tract development or testosterone levels at birth, nor were germ cell number and proliferation, Sertoli cell number or germ:Sertoli cell ratio affected. In two of six MBP-exposed animals, unusual clusters of undifferentiated germ cells were found, but their significance is unclear. Neonatal MBP treatment did not affect germ cell numbers or differentiation. Fetal exposure to MBP did not affect testis size/morphology, germ cell numbers or fertility in adulthood. There was no evidence for <italic>CIS</italic> or TGCT.</p></sec><sec><title>CONCLUSIONS</title><p>Fetal exposure of marmosets to MBP does not measurably affect testis development/function or cause testicular dysgenesis, and no effects emerge by adulthood. Some effects on germ cell development were found, but these were inconsistent and of uncertain significance.</p></sec></abstract><kwd-group><kwd>fetal</kwd><kwd>germ cells</kwd><kwd>monobutyl phthalate</kwd><kwd>neonatal</kwd><kwd>testis</kwd></kwd-group></article-meta></front></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Effect of fetal or neonatal exposure to monobutyl phthalate (MBP) on testicular development and function in the marmoset</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Effect of fetal or neonatal exposure to monobutyl phthalate (MBP) on testicular development and function in the marmoset</title></titleInfo><name type="personal"><namePart type="given">Chris</namePart><namePart type="family">McKinnell</namePart><affiliation>MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK</affiliation><affiliation>E-mail: c.mckinnell@hrsu.mrc.ac.uk</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Rod T.</namePart><namePart type="family">Mitchell</namePart><affiliation>MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Marion</namePart><namePart type="family">Walker</namePart><affiliation>MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Keith</namePart><namePart type="family">Morris</namePart><affiliation>MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Chris J.H.</namePart><namePart type="family">Kelnar</namePart><affiliation>Edinburgh Royal Hospital for Sick Children, 9 Sciennes Road, Edinburgh EH9 1LF, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">W. Hamish</namePart><namePart type="family">Wallace</namePart><affiliation>Edinburgh Royal Hospital for Sick Children, 9 Sciennes Road, Edinburgh EH9 1LF, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Richard M.</namePart><namePart type="family">Sharpe</namePart><affiliation>MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="research-article"></genre><originInfo><publisher>Oxford University Press</publisher><dateIssued encoding="w3cdtf">2009-09</dateIssued><dateCreated encoding="w3cdtf">2009-06-02</dateCreated><copyrightDate encoding="w3cdtf">2009</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract>BACKGROUND Fetal exposure of male rats to some phthalates induces reproductive abnormalities, raising concerns for similar effects in humans. In order to address this in a more appropriate animal model, the aim of the present studies was to investigate the effect of fetal/neonatal exposure to monobutyl phthalate (MBP) in a non-human primate, the marmoset. In particular, to determine if exposure resulted in effects at birth, or in adulthood, similar to those in male rats, and whether there was evidence for induction of carcinoma-in-situ (CIS) or testicular germ cell tumours (TGCT). METHODS Pregnant female marmosets were dosed from 715 weeks gestation with 500 mg/kg/day MBP and male offspring studied at birth (15 days; n 6) or in adulthood (n 5). In another study, newborn males (n 5 co-twins) were dosed with 500 mg/kg/day MBP for 14 days, commencing at 4 days of age. RESULTS Fetal exposure of marmosets to MBP did not affect gross testicular morphology, reproductive tract development or testosterone levels at birth, nor were germ cell number and proliferation, Sertoli cell number or germ:Sertoli cell ratio affected. In two of six MBP-exposed animals, unusual clusters of undifferentiated germ cells were found, but their significance is unclear. Neonatal MBP treatment did not affect germ cell numbers or differentiation. Fetal exposure to MBP did not affect testis size/morphology, germ cell numbers or fertility in adulthood. There was no evidence for CIS or TGCT. CONCLUSIONS Fetal exposure of marmosets to MBP does not measurably affect testis development/function or cause testicular dysgenesis, and no effects emerge by adulthood. Some effects on germ cell development were found, but these were inconsistent and of uncertain significance.</abstract><subject><genre>keywords</genre><topic>fetal</topic><topic>germ cells</topic><topic>monobutyl phthalate</topic><topic>neonatal</topic><topic>testis</topic></subject><relatedItem type="host"><titleInfo><title>Human Reproduction</title></titleInfo><genre type="journal">journal</genre><identifier type="ISSN">0268-1161</identifier><identifier type="eISSN">1460-2350</identifier><identifier type="PublisherID">humrep</identifier><identifier type="PublisherID-hwp">humrep</identifier><part><date>2009</date><detail type="volume"><caption>vol.</caption><number>24</number></detail><detail type="issue"><caption>no.</caption><number>9</number></detail><extent unit="pages"><start>2244</start><end>2254</end></extent></part></relatedItem><identifier type="istex">B2D49AEC8D1DDF0C767AB30494A189211B225D32</identifier><identifier type="DOI">10.1093/humrep/dep200</identifier><identifier type="ArticleID">dep200</identifier><accessCondition type="use and reproduction" contentType="copyright">The Author 2009. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. 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