In utero exposure to low doses of environmental pollutants disrupts fetal ovarian development in sheep
Identifieur interne : 000378 ( Ncbi/Curation ); 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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PMC:2408934Le document en format XML
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exposure to low doses of environmental pollutants disrupts fetal ovarian development in sheep</title>
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exposure to low doses of environmental pollutants disrupts fetal ovarian development in sheep</title>
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<author><name sortKey="Dora, Natalie J" sort="Dora, Natalie J" uniqKey="Dora N" first="Natalie J." last="Dorà">Natalie J. Dorà</name>
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,<addr-line>Murdoch, WA 6150</addr-line>
,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
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<author><name sortKey="Lea, Richard G" sort="Lea, Richard G" uniqKey="Lea R" first="Richard G." last="Lea">Richard G. Lea</name>
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,<institution>University of Nottingham</institution>
,<addr-line>Sutton Bonington, Leicestershire LE12 5RD</addr-line>
,<country>UK</country>
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<country xml:lang="fr">Royaume-Uni</country>
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<author><name sortKey="Cash, Phillip" sort="Cash, Phillip" uniqKey="Cash P" first="Phillip" last="Cash">Phillip Cash</name>
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<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>
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<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<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>
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<author><name sortKey="Cotinot, Corinne" sort="Cotinot, Corinne" uniqKey="Cotinot C" first="Corinne" last="Cotinot">Corinne Cotinot</name>
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</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<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>
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<author><name sortKey="Rhind, Stewart M" sort="Rhind, Stewart M" uniqKey="Rhind S" first="Stewart M." last="Rhind">Stewart M. Rhind</name>
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,<country>UK</country>
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<country xml:lang="fr">Royaume-Uni</country>
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<series><title level="j">Molecular Human Reproduction</title>
<idno type="ISSN">1360-9947</idno>
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<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>
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