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Intrauterine Exposure to Paracetamol and Aniline Impairs Female Reproductive Development by Reducing Follicle Reserves and Fertility.

Identifieur interne : 001C33 ( Main/Exploration ); précédent : 001C32; suivant : 001C34

Intrauterine Exposure to Paracetamol and Aniline Impairs Female Reproductive Development by Reducing Follicle Reserves and Fertility.

Auteurs : Jacob Bak Holm [Oman] ; Severine Mazaud-Guittot [France] ; Niels Banhos Danneskiold-Sams E [Danemark] ; Clementine Chalmey [France] ; Benjamin Jensen [Danemark] ; Mette Marie N Rreg Rd [Danemark] ; Cecilie Hurup Hansen [Danemark] ; Bjarne Styrishave [Danemark] ; Terje Svingen [Danemark] ; Anne Marie Vinggaard [Danemark] ; Holger Martin Koch [Allemagne] ; Josephine Bowles ; Peter Koopman ; Bernard Jégou [France] ; Karsten Kristiansen [Danemark] ; David M Bjerg Kristensen [Oman]

Source :

RBID : pubmed:26732887

Descripteurs français

English descriptors

Abstract

Studies report that fetal exposure to paracetamol/acetaminophen by maternal consumption can interfere with male reproductive development. Moreover, recent biomonitoring data report widespread presence of paracetamol in German and Danish populations, suggesting exposure via secondary (nonpharmaceutical) sources, such as metabolic conversion from the ubiquitous industrial compound aniline. In this study, we investigated the extent to which paracetamol and aniline can interfere with female reproductive development. Intrauterine exposure to paracetamol by gavage of pregnant dams resulted in shortening of the anogenital distance in adult offspring, suggesting that fetal hormone signaling had been disturbed. Female offspring of paracetamol-exposed mothers had ovaries with diminished follicle reserve and reduced fertility. Fetal gonads of exposed animals had also reduced gonocyte numbers, suggesting that the reduced follicle count in adults could be due to early disruption of germ cell development. However, ex vivo cultures of ovaries from 12.5 days post coitum fetuses showed no decrease in proliferation or expression following exposure to paracetamol. This suggests that the effect of paracetamol occurs prior to this developmental stage. Accordingly, using embryonic stem cells as a proxy for primordial germ cells we show that paracetamol is an inhibitor of cellular proliferation, but without cytotoxic effects. Collectively, our data show that intrauterine exposure to paracetamol at levels commonly observed in pregnant women, as well as its precursor aniline, may block primordial germ cell proliferation, ultimately leading to reduced follicle reserves and compromised reproductive capacity later in life.

DOI: 10.1093/toxsci/kfv332
PubMed: 26732887


Affiliations:


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Le document en format XML

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<title xml:lang="en">Intrauterine Exposure to Paracetamol and Aniline Impairs Female Reproductive Development by Reducing Follicle Reserves and Fertility.</title>
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<name sortKey="Holm, Jacob Bak" sort="Holm, Jacob Bak" uniqKey="Holm J" first="Jacob Bak" last="Holm">Jacob Bak Holm</name>
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<name sortKey="Vinggaard, Anne Marie" sort="Vinggaard, Anne Marie" uniqKey="Vinggaard A" first="Anne Marie" last="Vinggaard">Anne Marie Vinggaard</name>
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<name sortKey="Koch, Holger Martin" sort="Koch, Holger Martin" uniqKey="Koch H" first="Holger Martin" last="Koch">Holger Martin Koch</name>
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<name sortKey="Bowles, Josephine" sort="Bowles, Josephine" uniqKey="Bowles J" first="Josephine" last="Bowles">Josephine Bowles</name>
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<name sortKey="Koopman, Peter" sort="Koopman, Peter" uniqKey="Koopman P" first="Peter" last="Koopman">Peter Koopman</name>
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<nlm:affiliation>Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia; and.</nlm:affiliation>
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</affiliation>
</author>
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<name sortKey="Jegou, Bernard" sort="Jegou, Bernard" uniqKey="Jegou B" first="Bernard" last="Jégou">Bernard Jégou</name>
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<region type="region">Région Bretagne</region>
<region type="old region">Région Bretagne</region>
<settlement type="city">Rennes</settlement>
<settlement type="city">Rennes</settlement>
</placeName>
<orgName type="university">Université de Rennes 1</orgName>
</affiliation>
</author>
<author>
<name sortKey="Kristiansen, Karsten" sort="Kristiansen, Karsten" uniqKey="Kristiansen K" first="Karsten" last="Kristiansen">Karsten Kristiansen</name>
<affiliation wicri:level="1">
<nlm:affiliation>*Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, 2100 Copenhagen, Denmark;</nlm:affiliation>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea>*Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, 2100 Copenhagen</wicri:regionArea>
<placeName>
<settlement type="city">Copenhague</settlement>
<region type="région" nuts="2">Hovedstaden</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Kristensen, David M Bjerg" sort="Kristensen, David M Bjerg" uniqKey="Kristensen D" first="David M Bjerg" last="Kristensen">David M Bjerg Kristensen</name>
<affiliation wicri:level="1">
<nlm:affiliation>*Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, 2100 Copenhagen, Denmark; Institut National de la Santé et de la Recherche Médicale (Inserm) U1085-IRSET, Université de Rennes 1, Structure Fédérative Recherche Biosit, Rennes, France; david@moebjerg.com.</nlm:affiliation>
<country wicri:rule="url">Oman</country>
<wicri:regionArea>*Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, 2100 Copenhagen, Denmark; Institut National de la Santé et de la Recherche Médicale (Inserm) U1085-IRSET, Université de Rennes 1, Structure Fédérative Recherche Biosit, Rennes</wicri:regionArea>
<wicri:noRegion>Rennes</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Toxicological sciences : an official journal of the Society of Toxicology</title>
<idno type="eISSN">1096-0929</idno>
<imprint>
<date when="2016" type="published">2016</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<term>Acetaminophen (toxicity)</term>
<term>Aniline Compounds (toxicity)</term>
<term>Animals</term>
<term>Female</term>
<term>Fertility (drug effects)</term>
<term>Genitalia, Female (abnormalities)</term>
<term>Genitalia, Female (embryology)</term>
<term>Gestational Age</term>
<term>Male</term>
<term>Mice, Inbred C57BL</term>
<term>Ovarian Follicle (drug effects)</term>
<term>Ovarian Follicle (embryology)</term>
<term>Pregnancy</term>
<term>Prenatal Exposure Delayed Effects (chemically induced)</term>
<term>Prenatal Exposure Delayed Effects (pathology)</term>
<term>Prenatal Exposure Delayed Effects (physiopathology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Acétaminophène (toxicité)</term>
<term>Animaux</term>
<term>Dérivés de l'aniline (toxicité)</term>
<term>Effets différés de l'exposition prénatale aux facteurs de risque ()</term>
<term>Effets différés de l'exposition prénatale aux facteurs de risque (anatomopathologie)</term>
<term>Effets différés de l'exposition prénatale aux facteurs de risque (physiopathologie)</term>
<term>Femelle</term>
<term>Follicule ovarique ()</term>
<term>Follicule ovarique (embryologie)</term>
<term>Fécondité ()</term>
<term>Grossesse</term>
<term>Mâle</term>
<term>Souris de lignée C57BL</term>
<term>Système génital de la femme (embryologie)</term>
<term>Système génital de la femme (malformations)</term>
<term>Âge gestationnel</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="toxicity" xml:lang="en">
<term>Acetaminophen</term>
<term>Aniline Compounds</term>
</keywords>
<keywords scheme="MESH" qualifier="abnormalities" xml:lang="en">
<term>Genitalia, Female</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr">
<term>Effets différés de l'exposition prénatale aux facteurs de risque</term>
</keywords>
<keywords scheme="MESH" qualifier="chemically induced" xml:lang="en">
<term>Prenatal Exposure Delayed Effects</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en">
<term>Fertility</term>
<term>Ovarian Follicle</term>
</keywords>
<keywords scheme="MESH" qualifier="embryologie" xml:lang="fr">
<term>Follicule ovarique</term>
<term>Système génital de la femme</term>
</keywords>
<keywords scheme="MESH" qualifier="embryology" xml:lang="en">
<term>Genitalia, Female</term>
<term>Ovarian Follicle</term>
</keywords>
<keywords scheme="MESH" qualifier="malformations" xml:lang="fr">
<term>Système génital de la femme</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en">
<term>Prenatal Exposure Delayed Effects</term>
</keywords>
<keywords scheme="MESH" qualifier="physiopathologie" xml:lang="fr">
<term>Effets différés de l'exposition prénatale aux facteurs de risque</term>
</keywords>
<keywords scheme="MESH" qualifier="physiopathology" xml:lang="en">
<term>Prenatal Exposure Delayed Effects</term>
</keywords>
<keywords scheme="MESH" qualifier="toxicité" xml:lang="fr">
<term>Acétaminophène</term>
<term>Dérivés de l'aniline</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Animals</term>
<term>Female</term>
<term>Gestational Age</term>
<term>Male</term>
<term>Mice, Inbred C57BL</term>
<term>Pregnancy</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Animaux</term>
<term>Effets différés de l'exposition prénatale aux facteurs de risque</term>
<term>Femelle</term>
<term>Follicule ovarique</term>
<term>Fécondité</term>
<term>Grossesse</term>
<term>Mâle</term>
<term>Souris de lignée C57BL</term>
<term>Âge gestationnel</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">Studies report that fetal exposure to paracetamol/acetaminophen by maternal consumption can interfere with male reproductive development. Moreover, recent biomonitoring data report widespread presence of paracetamol in German and Danish populations, suggesting exposure via secondary (nonpharmaceutical) sources, such as metabolic conversion from the ubiquitous industrial compound aniline. In this study, we investigated the extent to which paracetamol and aniline can interfere with female reproductive development. Intrauterine exposure to paracetamol by gavage of pregnant dams resulted in shortening of the anogenital distance in adult offspring, suggesting that fetal hormone signaling had been disturbed. Female offspring of paracetamol-exposed mothers had ovaries with diminished follicle reserve and reduced fertility. Fetal gonads of exposed animals had also reduced gonocyte numbers, suggesting that the reduced follicle count in adults could be due to early disruption of germ cell development. However, ex vivo cultures of ovaries from 12.5 days post coitum fetuses showed no decrease in proliferation or expression following exposure to paracetamol. This suggests that the effect of paracetamol occurs prior to this developmental stage. Accordingly, using embryonic stem cells as a proxy for primordial germ cells we show that paracetamol is an inhibitor of cellular proliferation, but without cytotoxic effects. Collectively, our data show that intrauterine exposure to paracetamol at levels commonly observed in pregnant women, as well as its precursor aniline, may block primordial germ cell proliferation, ultimately leading to reduced follicle reserves and compromised reproductive capacity later in life.</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>Allemagne</li>
<li>Danemark</li>
<li>France</li>
<li>Oman</li>
</country>
<region>
<li>Hovedstaden</li>
<li>Région Bretagne</li>
</region>
<settlement>
<li>Copenhague</li>
<li>Rennes</li>
</settlement>
<orgName>
<li>Université de Rennes 1</li>
</orgName>
</list>
<tree>
<noCountry>
<name sortKey="Bowles, Josephine" sort="Bowles, Josephine" uniqKey="Bowles J" first="Josephine" last="Bowles">Josephine Bowles</name>
<name sortKey="Koopman, Peter" sort="Koopman, Peter" uniqKey="Koopman P" first="Peter" last="Koopman">Peter Koopman</name>
</noCountry>
<country name="Oman">
<noRegion>
<name sortKey="Holm, Jacob Bak" sort="Holm, Jacob Bak" uniqKey="Holm J" first="Jacob Bak" last="Holm">Jacob Bak Holm</name>
</noRegion>
<name sortKey="Kristensen, David M Bjerg" sort="Kristensen, David M Bjerg" uniqKey="Kristensen D" first="David M Bjerg" last="Kristensen">David M Bjerg Kristensen</name>
</country>
<country name="France">
<region name="Région Bretagne">
<name sortKey="Mazaud Guittot, Severine" sort="Mazaud Guittot, Severine" uniqKey="Mazaud Guittot S" first="Severine" last="Mazaud-Guittot">Severine Mazaud-Guittot</name>
</region>
<name sortKey="Chalmey, Clementine" sort="Chalmey, Clementine" uniqKey="Chalmey C" first="Clementine" last="Chalmey">Clementine Chalmey</name>
<name sortKey="Jegou, Bernard" sort="Jegou, Bernard" uniqKey="Jegou B" first="Bernard" last="Jégou">Bernard Jégou</name>
</country>
<country name="Danemark">
<region name="Hovedstaden">
<name sortKey="Danneskiold Sams E, Niels Banhos" sort="Danneskiold Sams E, Niels Banhos" uniqKey="Danneskiold Sams E N" first="Niels Banhos" last="Danneskiold-Sams E">Niels Banhos Danneskiold-Sams E</name>
</region>
<name sortKey="Hansen, Cecilie Hurup" sort="Hansen, Cecilie Hurup" uniqKey="Hansen C" first="Cecilie Hurup" last="Hansen">Cecilie Hurup Hansen</name>
<name sortKey="Jensen, Benjamin" sort="Jensen, Benjamin" uniqKey="Jensen B" first="Benjamin" last="Jensen">Benjamin Jensen</name>
<name sortKey="Kristiansen, Karsten" sort="Kristiansen, Karsten" uniqKey="Kristiansen K" first="Karsten" last="Kristiansen">Karsten Kristiansen</name>
<name sortKey="N Rreg Rd, Mette Marie" sort="N Rreg Rd, Mette Marie" uniqKey="N Rreg Rd M" first="Mette Marie" last="N Rreg Rd">Mette Marie N Rreg Rd</name>
<name sortKey="Styrishave, Bjarne" sort="Styrishave, Bjarne" uniqKey="Styrishave B" first="Bjarne" last="Styrishave">Bjarne Styrishave</name>
<name sortKey="Svingen, Terje" sort="Svingen, Terje" uniqKey="Svingen T" first="Terje" last="Svingen">Terje Svingen</name>
<name sortKey="Vinggaard, Anne Marie" sort="Vinggaard, Anne Marie" uniqKey="Vinggaard A" first="Anne Marie" last="Vinggaard">Anne Marie Vinggaard</name>
</country>
<country name="Allemagne">
<noRegion>
<name sortKey="Koch, Holger Martin" sort="Koch, Holger Martin" uniqKey="Koch H" first="Holger Martin" last="Koch">Holger Martin Koch</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>

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