In utero exposure to low doses of environmental pollutants disrupts fetal ovarian development in sheep
Identifieur interne : 000378 ( Ncbi/Merge ); précédent : 000377; suivant : 000379In utero exposure to low doses of environmental pollutants disrupts fetal ovarian development in sheep
Auteurs : Paul A. Fowler [Royaume-Uni] ; Natalie J. Dorà [Royaume-Uni] ; Helen Mcferran [Royaume-Uni] ; Maria R. Amezaga [Royaume-Uni] ; David W. Miller [Australie] ; Richard G. Lea [Royaume-Uni] ; Phillip Cash [Royaume-Uni] ; Alan S. Mcneilly [Royaume-Uni] ; Neil P. Evans [Royaume-Uni] ; Corinne Cotinot [France] ; Richard M. Sharpe [Royaume-Uni] ; Stewart M. Rhind [Royaume-Uni]Source :
- Molecular Human Reproduction [ 1360-9947 ] ; 2008.
Abstract
Epidemiological studies of the impact of environmental chemicals on reproductive health demonstrate consequences of exposure but establishing causative links requires animal models using ‘real life’
Url:
DOI: 10.1093/molehr/gan020
PubMed: 18436539
PubMed Central: 2408934
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Dorà</name><affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>Department of Obstetrics and Gynaecology</addr-line>,<institution>Institute of Medical Sciences, CLSM, University of Aberdeen</institution>,<addr-line>Foresterhill, Aberdeen AB25 2ZD</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Mcferran, Helen" sort="Mcferran, Helen" uniqKey="Mcferran H" first="Helen" last="Mcferran">Helen Mcferran</name><affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>Department of Obstetrics and Gynaecology</addr-line>,<institution>Institute of Medical Sciences, CLSM, University of Aberdeen</institution>,<addr-line>Foresterhill, Aberdeen AB25 2ZD</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Amezaga, Maria R" sort="Amezaga, Maria R" uniqKey="Amezaga M" first="Maria R." last="Amezaga">Maria R. Amezaga</name><affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>Department of Obstetrics and Gynaecology</addr-line>,<institution>Institute of Medical Sciences, CLSM, University of Aberdeen</institution>,<addr-line>Foresterhill, Aberdeen AB25 2ZD</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Miller, David W" sort="Miller, David W" uniqKey="Miller D" first="David W." last="Miller">David W. Miller</name><affiliation wicri:level="1"><nlm:aff id="af3"><addr-line>School of Veterinary and Biomedical Sciences</addr-line>,<institution>Murdoch University</institution>,<addr-line>Murdoch, WA 6150</addr-line>,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lea, Richard G" sort="Lea, Richard G" uniqKey="Lea R" first="Richard G." last="Lea">Richard G. Lea</name><affiliation wicri:level="1"><nlm:aff id="af4"><addr-line>School of Veterinary Medicine and Science</addr-line>,<institution>University of Nottingham</institution>,<addr-line>Sutton Bonington, Leicestershire LE12 5RD</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Cash, Phillip" sort="Cash, Phillip" uniqKey="Cash P" first="Phillip" last="Cash">Phillip Cash</name><affiliation wicri:level="1"><nlm:aff id="af5"><addr-line>Department of Medical Microbiology</addr-line>,<institution>Institute of Medical Sciences, University of Aberdeen</institution>,<addr-line>Foresterhill, Aberdeen AB25 2ZD</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Mcneilly, Alan S" sort="Mcneilly, Alan S" uniqKey="Mcneilly A" first="Alan S." last="Mcneilly">Alan S. Mcneilly</name><affiliation wicri:level="1"><nlm:aff id="af2"><addr-line>MRC Human Reproductive Sciences Unit</addr-line>,<institution>Queen’s Medical Research Institute, University of Edinburgh</institution>,<addr-line>47 Little France Crescent, Edinburgh EH16 4TJ</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Evans, Neil P" sort="Evans, Neil P" uniqKey="Evans N" first="Neil P." last="Evans">Neil P. Evans</name><affiliation wicri:level="1"><nlm:aff id="af6"><addr-line>Division of Cell Sciences</addr-line>,<institution>Institute of Comparative Medicine, University of Glasgow Veterinary School</institution>,<addr-line>Glasgow G61 1QH</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Cotinot, Corinne" sort="Cotinot, Corinne" uniqKey="Cotinot C" first="Corinne" last="Cotinot">Corinne Cotinot</name><affiliation wicri:level="1"><nlm:aff id="af7"><addr-line>INRA, UMR 1198, Biologie du Développement et de la Reproduction, 78350, Jouy-en-Josas</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></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 wicri:level="1"><nlm:aff id="af2"><addr-line>MRC Human Reproductive Sciences Unit</addr-line>,<institution>Queen’s Medical Research Institute, University of Edinburgh</institution>,<addr-line>47 Little France Crescent, Edinburgh EH16 4TJ</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Rhind, Stewart M" sort="Rhind, Stewart M" uniqKey="Rhind S" first="Stewart M." last="Rhind">Stewart M. Rhind</name><affiliation wicri:level="1"><nlm:aff id="af8"><institution>Macaulay Institute, Craigiebuckler</institution>,<addr-line>Aberdeen AB15 8QH</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">18436539</idno><idno type="pmc">2408934</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2408934</idno><idno type="RBID">PMC:2408934</idno><idno type="doi">10.1093/molehr/gan020</idno><date when="2008">2008</date><idno type="wicri:Area/Pmc/Corpus">001511</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001511</idno><idno type="wicri:Area/Pmc/Curation">001371</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001371</idno><idno type="wicri:Area/Pmc/Checkpoint">002A67</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">002A67</idno><idno type="wicri:Area/Ncbi/Merge">000378</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main"><italic>In utero</italic> exposure to low doses of environmental pollutants disrupts fetal ovarian development in sheep</title><author><name sortKey="Fowler, Paul A" sort="Fowler, Paul A" uniqKey="Fowler P" first="Paul A." last="Fowler">Paul A. Fowler</name><affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>Department of Obstetrics and Gynaecology</addr-line>,<institution>Institute of Medical Sciences, CLSM, University of Aberdeen</institution>,<addr-line>Foresterhill, Aberdeen AB25 2ZD</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Dora, Natalie J" sort="Dora, Natalie J" uniqKey="Dora N" first="Natalie J." last="Dorà">Natalie J. Dorà</name><affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>Department of Obstetrics and Gynaecology</addr-line>,<institution>Institute of Medical Sciences, CLSM, University of Aberdeen</institution>,<addr-line>Foresterhill, Aberdeen AB25 2ZD</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Mcferran, Helen" sort="Mcferran, Helen" uniqKey="Mcferran H" first="Helen" last="Mcferran">Helen Mcferran</name><affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>Department of Obstetrics and Gynaecology</addr-line>,<institution>Institute of Medical Sciences, CLSM, University of Aberdeen</institution>,<addr-line>Foresterhill, Aberdeen AB25 2ZD</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Amezaga, Maria R" sort="Amezaga, Maria R" uniqKey="Amezaga M" first="Maria R." last="Amezaga">Maria R. Amezaga</name><affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>Department of Obstetrics and Gynaecology</addr-line>,<institution>Institute of Medical Sciences, CLSM, University of Aberdeen</institution>,<addr-line>Foresterhill, Aberdeen AB25 2ZD</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Miller, David W" sort="Miller, David W" uniqKey="Miller D" first="David W." last="Miller">David W. Miller</name><affiliation wicri:level="1"><nlm:aff id="af3"><addr-line>School of Veterinary and Biomedical Sciences</addr-line>,<institution>Murdoch University</institution>,<addr-line>Murdoch, WA 6150</addr-line>,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lea, Richard G" sort="Lea, Richard G" uniqKey="Lea R" first="Richard G." last="Lea">Richard G. Lea</name><affiliation wicri:level="1"><nlm:aff id="af4"><addr-line>School of Veterinary Medicine and Science</addr-line>,<institution>University of Nottingham</institution>,<addr-line>Sutton Bonington, Leicestershire LE12 5RD</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Cash, Phillip" sort="Cash, Phillip" uniqKey="Cash P" first="Phillip" last="Cash">Phillip Cash</name><affiliation wicri:level="1"><nlm:aff id="af5"><addr-line>Department of Medical Microbiology</addr-line>,<institution>Institute of Medical Sciences, University of Aberdeen</institution>,<addr-line>Foresterhill, Aberdeen AB25 2ZD</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Mcneilly, Alan S" sort="Mcneilly, Alan S" uniqKey="Mcneilly A" first="Alan S." last="Mcneilly">Alan S. Mcneilly</name><affiliation wicri:level="1"><nlm:aff id="af2"><addr-line>MRC Human Reproductive Sciences Unit</addr-line>,<institution>Queen’s Medical Research Institute, University of Edinburgh</institution>,<addr-line>47 Little France Crescent, Edinburgh EH16 4TJ</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Evans, Neil P" sort="Evans, Neil P" uniqKey="Evans N" first="Neil P." last="Evans">Neil P. Evans</name><affiliation wicri:level="1"><nlm:aff id="af6"><addr-line>Division of Cell Sciences</addr-line>,<institution>Institute of Comparative Medicine, University of Glasgow Veterinary School</institution>,<addr-line>Glasgow G61 1QH</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Cotinot, Corinne" sort="Cotinot, Corinne" uniqKey="Cotinot C" first="Corinne" last="Cotinot">Corinne Cotinot</name><affiliation wicri:level="1"><nlm:aff id="af7"><addr-line>INRA, UMR 1198, Biologie du Développement et de la Reproduction, 78350, Jouy-en-Josas</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></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 wicri:level="1"><nlm:aff id="af2"><addr-line>MRC Human Reproductive Sciences Unit</addr-line>,<institution>Queen’s Medical Research Institute, University of Edinburgh</institution>,<addr-line>47 Little France Crescent, Edinburgh EH16 4TJ</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Rhind, Stewart M" sort="Rhind, Stewart M" uniqKey="Rhind S" first="Stewart M." last="Rhind">Stewart M. Rhind</name><affiliation wicri:level="1"><nlm:aff id="af8"><institution>Macaulay Institute, Craigiebuckler</institution>,<addr-line>Aberdeen AB15 8QH</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Molecular Human Reproduction</title><idno type="ISSN">1360-9947</idno><idno type="eISSN">1460-2407</idno><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Epidemiological studies of the impact of environmental chemicals on reproductive health demonstrate consequences of exposure but establishing causative links requires animal models using ‘real life’ <italic>in utero</italic> exposures. We aimed to determine whether prolonged, low-dose, exposure of pregnant sheep to a mixture of environmental chemicals affects fetal ovarian development. Exposure of treated ewes (<italic>n</italic> = 7) to pollutants was maximized by surface application of processed sewage sludge to pasture. Control ewes (<italic>n</italic> = 10) were reared on pasture treated with inorganic fertilizer. Ovaries and blood were collected from fetuses (<italic>n</italic> = 15 control and <italic>n</italic> = 8 treated) on Day 110 of gestation for investigation of fetal endocrinology, ovarian follicle/oocyte numbers and ovarian proteome. Treated fetuses were 14% lighter than controls but fetal ovary weights were unchanged. Prolactin (48% lower) was the only measured hormone significantly affected by treatment. Treatment reduced numbers of growth differentiation factor (GDF9) and induced myeloid leukaemia cell differentiation protein (MCL1) positive oocytes by 25–26% and increased pro-apoptotic BAX by 65% and 42% of protein spots in the treated ovarian proteome were differently expressed compared with controls. Nineteen spots were identified and included proteins involved in gene expression/transcription, protein synthesis, phosphorylation and receptor activity. Fetal exposure to environmental chemicals, via the mother, significantly perturbs fetal ovarian development. If such effects are replicated in humans, premature menopause could be an outcome.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article" xml:lang="EN"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Mol Hum Reprod</journal-id><journal-id journal-id-type="publisher-id">molehr</journal-id><journal-id journal-id-type="hwp">molehr</journal-id><journal-title>Molecular Human Reproduction</journal-title><issn pub-type="ppub">1360-9947</issn><issn pub-type="epub">1460-2407</issn><publisher><publisher-name>Oxford University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">18436539</article-id><article-id pub-id-type="pmc">2408934</article-id><article-id pub-id-type="doi">10.1093/molehr/gan020</article-id><article-id pub-id-type="publisher-id">gan020</article-id><article-categories><subj-group subj-group-type="heading"><subject>Articles</subject></subj-group></article-categories><title-group><article-title><italic>In utero</italic> exposure to low doses of environmental pollutants disrupts fetal ovarian development in sheep</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Fowler</surname><given-names>Paul A.</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="corresp" rid="cor1">9</xref></contrib><contrib contrib-type="author"><name><surname>Dorà</surname><given-names>Natalie J.</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>McFerran</surname><given-names>Helen</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Amezaga</surname><given-names>Maria R.</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Miller</surname><given-names>David W.</given-names></name><xref ref-type="aff" rid="af3">3</xref></contrib><contrib contrib-type="author"><name><surname>Lea</surname><given-names>Richard G.</given-names></name><xref ref-type="aff" rid="af4">4</xref></contrib><contrib contrib-type="author"><name><surname>Cash</surname><given-names>Phillip</given-names></name><xref ref-type="aff" rid="af5">5</xref></contrib><contrib contrib-type="author"><name><surname>McNeilly</surname><given-names>Alan S.</given-names></name><xref ref-type="aff" rid="af2">2</xref></contrib><contrib contrib-type="author"><name><surname>Evans</surname><given-names>Neil P.</given-names></name><xref ref-type="aff" rid="af6">6</xref></contrib><contrib contrib-type="author"><name><surname>Cotinot</surname><given-names>Corinne</given-names></name><xref ref-type="aff" rid="af7">7</xref></contrib><contrib contrib-type="author"><name><surname>Sharpe</surname><given-names>Richard M.</given-names></name><xref ref-type="aff" rid="af2">2</xref></contrib><contrib contrib-type="author"><name><surname>Rhind</surname><given-names>Stewart M.</given-names></name><xref ref-type="aff" rid="af8">8</xref></contrib></contrib-group><aff id="af1"><label>1</label><addr-line>Department of Obstetrics and Gynaecology</addr-line>,<institution>Institute of Medical Sciences, CLSM, University of Aberdeen</institution>,<addr-line>Foresterhill, Aberdeen AB25 2ZD</addr-line>,<country>UK</country></aff><aff id="af2"><label>2</label><addr-line>MRC Human Reproductive Sciences Unit</addr-line>,<institution>Queen’s Medical Research Institute, University of Edinburgh</institution>,<addr-line>47 Little France Crescent, Edinburgh EH16 4TJ</addr-line>,<country>UK</country></aff><aff id="af3"><label>3</label><addr-line>School of Veterinary and Biomedical Sciences</addr-line>,<institution>Murdoch University</institution>,<addr-line>Murdoch, WA 6150</addr-line>,<country>Australia</country></aff><aff id="af4"><label>4</label><addr-line>School of Veterinary Medicine and Science</addr-line>,<institution>University of Nottingham</institution>,<addr-line>Sutton Bonington, Leicestershire LE12 5RD</addr-line>,<country>UK</country></aff><aff id="af5"><label>5</label><addr-line>Department of Medical Microbiology</addr-line>,<institution>Institute of Medical Sciences, University of Aberdeen</institution>,<addr-line>Foresterhill, Aberdeen AB25 2ZD</addr-line>,<country>UK</country></aff><aff id="af6"><label>6</label><addr-line>Division of Cell Sciences</addr-line>,<institution>Institute of Comparative Medicine, University of Glasgow Veterinary School</institution>,<addr-line>Glasgow G61 1QH</addr-line>,<country>UK</country></aff><aff id="af7"><label>7</label><addr-line>INRA, UMR 1198, Biologie du Développement et de la Reproduction, 78350, Jouy-en-Josas</addr-line>,<country>France</country></aff><aff id="af8"><label>8</label><institution>Macaulay Institute, Craigiebuckler</institution>,<addr-line>Aberdeen AB15 8QH</addr-line>,<country>UK</country></aff><author-notes><corresp id="cor1"><label>9</label>Correspondence address. Tel: <phone>+44-1224-552633</phone>; Fax: <fax>+44-1224-555844</fax>; E-mail: <email>p.a.fowler@abdn.ac.uk</email></corresp></author-notes><pub-date pub-type="ppub"><month>5</month><year>2008</year></pub-date><pub-date pub-type="epub"><day>23</day><month>4</month><year>2008</year></pub-date><pub-date pub-type="pmc-release"><day>23</day><month>4</month><year>2008</year></pub-date><volume>14</volume><issue>5</issue><fpage>269</fpage><lpage>280</lpage><history><date date-type="received"><day>26</day><month>2</month><year>2008</year></date><date date-type="rev-recd"><day>28</day><month>3</month><year>2008</year></date><date date-type="accepted"><day>15</day><month>4</month><year>2008</year></date></history><copyright-statement>© The Author 2008. 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>2008</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 work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org</p></license><abstract><p>Epidemiological studies of the impact of environmental chemicals on reproductive health demonstrate consequences of exposure but establishing causative links requires animal models using ‘real life’ <italic>in utero</italic> exposures. We aimed to determine whether prolonged, low-dose, exposure of pregnant sheep to a mixture of environmental chemicals affects fetal ovarian development. Exposure of treated ewes (<italic>n</italic> = 7) to pollutants was maximized by surface application of processed sewage sludge to pasture. Control ewes (<italic>n</italic> = 10) were reared on pasture treated with inorganic fertilizer. Ovaries and blood were collected from fetuses (<italic>n</italic> = 15 control and <italic>n</italic> = 8 treated) on Day 110 of gestation for investigation of fetal endocrinology, ovarian follicle/oocyte numbers and ovarian proteome. Treated fetuses were 14% lighter than controls but fetal ovary weights were unchanged. Prolactin (48% lower) was the only measured hormone significantly affected by treatment. Treatment reduced numbers of growth differentiation factor (GDF9) and induced myeloid leukaemia cell differentiation protein (MCL1) positive oocytes by 25–26% and increased pro-apoptotic BAX by 65% and 42% of protein spots in the treated ovarian proteome were differently expressed compared with controls. Nineteen spots were identified and included proteins involved in gene expression/transcription, protein synthesis, phosphorylation and receptor activity. Fetal exposure to environmental chemicals, via the mother, significantly perturbs fetal ovarian development. If such effects are replicated in humans, premature menopause could be an outcome.</p></abstract><kwd-group><title>Keywords</title><kwd>environmental chemicals</kwd><kwd>fetal development</kwd><kwd>oocyte</kwd><kwd>granulosa cell</kwd><kwd>sewage sludge</kwd></kwd-group></article-meta></front></pmc><affiliations><list><country><li>Australie</li><li>France</li><li>Royaume-Uni</li></country></list><tree><country name="Royaume-Uni"><noRegion><name sortKey="Fowler, Paul A" sort="Fowler, Paul A" uniqKey="Fowler P" first="Paul A." last="Fowler">Paul A. Fowler</name></noRegion><name sortKey="Amezaga, Maria R" sort="Amezaga, Maria R" uniqKey="Amezaga M" first="Maria R." last="Amezaga">Maria R. Amezaga</name><name sortKey="Cash, Phillip" sort="Cash, Phillip" uniqKey="Cash P" first="Phillip" last="Cash">Phillip Cash</name><name sortKey="Dora, Natalie J" sort="Dora, Natalie J" uniqKey="Dora N" first="Natalie J." last="Dorà">Natalie J. Dorà</name><name sortKey="Evans, Neil P" sort="Evans, Neil P" uniqKey="Evans N" first="Neil P." last="Evans">Neil P. Evans</name><name sortKey="Lea, Richard G" sort="Lea, Richard G" uniqKey="Lea R" first="Richard G." last="Lea">Richard G. Lea</name><name sortKey="Mcferran, Helen" sort="Mcferran, Helen" uniqKey="Mcferran H" first="Helen" last="Mcferran">Helen Mcferran</name><name sortKey="Mcneilly, Alan S" sort="Mcneilly, Alan S" uniqKey="Mcneilly A" first="Alan S." last="Mcneilly">Alan S. Mcneilly</name><name sortKey="Rhind, Stewart M" sort="Rhind, Stewart M" uniqKey="Rhind S" first="Stewart M." last="Rhind">Stewart M. Rhind</name><name sortKey="Sharpe, Richard M" sort="Sharpe, Richard M" uniqKey="Sharpe R" first="Richard M." last="Sharpe">Richard M. Sharpe</name></country><country name="Australie"><noRegion><name sortKey="Miller, David W" sort="Miller, David W" uniqKey="Miller D" first="David W." last="Miller">David W. Miller</name></noRegion></country><country name="France"><noRegion><name sortKey="Cotinot, Corinne" sort="Cotinot, Corinne" uniqKey="Cotinot C" first="Corinne" last="Cotinot">Corinne Cotinot</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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