Intrauterine Exposure to Paracetamol and Aniline Impairs Female Reproductive Development by Reducing Follicle Reserves and Fertility.
Identifieur interne : 002121 ( PubMed/Curation ); précédent : 002120; suivant : 002122Intrauterine 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 :
- Toxicological sciences : an official journal of the Society of Toxicology [ 1096-0929 ] ; 2016.
Descripteurs français
- KwdFr :
- Acétaminophène (toxicité), Animaux, Dérivés de l'aniline (toxicité), Effets différés de l'exposition prénatale aux facteurs de risque (), Effets différés de l'exposition prénatale aux facteurs de risque (anatomopathologie), Effets différés de l'exposition prénatale aux facteurs de risque (physiopathologie), Femelle, Follicule ovarique (), Follicule ovarique (embryologie), Fécondité (), Grossesse, Mâle, Souris de lignée C57BL, Système génital de la femme (embryologie), Système génital de la femme (malformations), Âge gestationnel.
- MESH :
- anatomopathologie : Effets différés de l'exposition prénatale aux facteurs de risque.
- embryologie : Follicule ovarique, Système génital de la femme.
- malformations : Système génital de la femme.
- physiopathologie : Effets différés de l'exposition prénatale aux facteurs de risque.
- toxicité : Acétaminophène, Dérivés de l'aniline.
- Animaux, Effets différés de l'exposition prénatale aux facteurs de risque, Femelle, Follicule ovarique, Fécondité, Grossesse, Mâle, Souris de lignée C57BL, Âge gestationnel.
English descriptors
- KwdEn :
- Acetaminophen (toxicity), Aniline Compounds (toxicity), Animals, Female, Fertility (drug effects), Genitalia, Female (abnormalities), Genitalia, Female (embryology), Gestational Age, Male, Mice, Inbred C57BL, Ovarian Follicle (drug effects), Ovarian Follicle (embryology), Pregnancy, Prenatal Exposure Delayed Effects (chemically induced), Prenatal Exposure Delayed Effects (pathology), Prenatal Exposure Delayed Effects (physiopathology).
- MESH :
- chemical , toxicity : Acetaminophen, Aniline Compounds.
- abnormalities : Genitalia, Female.
- chemically induced : Prenatal Exposure Delayed Effects.
- drug effects : Fertility, Ovarian Follicle.
- embryology : Genitalia, Female, Ovarian Follicle.
- pathology : Prenatal Exposure Delayed Effects.
- physiopathology : Prenatal Exposure Delayed Effects.
- Animals, Female, Gestational Age, Male, Mice, Inbred C57BL, Pregnancy.
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
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Josephine Bowles<affiliation><nlm:affiliation>Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia; and.</nlm:affiliation><wicri:noCountry code="subField">Australia; and</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia; and.</nlm:affiliation><wicri:noCountry code="subField">Australia; and</wicri:noCountry></affiliation>Le document en format XML
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U1085-IRSET, Université de Rennes 1, Structure Fédérative Recherche Biosit, Rennes, France; EHESP-School of Public Health, Rennes</wicri:regionArea></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></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></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:26732887</idno><idno type="pmid">26732887</idno><idno type="doi">10.1093/toxsci/kfv332</idno><idno type="wicri:Area/PubMed/Corpus">002147</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" 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sort="Mazaud Guittot, Severine" uniqKey="Mazaud Guittot S" first="Severine" last="Mazaud-Guittot">Severine Mazaud-Guittot</name><affiliation wicri:level="1"><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale (Inserm) U1085-IRSET, Université de Rennes 1, Structure Fédérative Recherche Biosit, Rennes, France;</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale (Inserm) U1085-IRSET, Université de Rennes 1, Structure Fédérative Recherche Biosit, Rennes</wicri:regionArea></affiliation></author><author><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><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></affiliation></author><author><name sortKey="Chalmey, Clementine" sort="Chalmey, Clementine" uniqKey="Chalmey C" first="Clementine" last="Chalmey">Clementine Chalmey</name><affiliation wicri:level="1"><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale (Inserm) U1085-IRSET, Université de Rennes 1, Structure Fédérative Recherche Biosit, Rennes, France;</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale (Inserm) U1085-IRSET, Université de Rennes 1, Structure Fédérative Recherche Biosit, Rennes</wicri:regionArea></affiliation></author><author><name sortKey="Jensen, Benjamin" sort="Jensen, Benjamin" uniqKey="Jensen B" first="Benjamin" last="Jensen">Benjamin Jensen</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></affiliation></author><author><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><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></affiliation></author><author><name sortKey="Hansen, Cecilie Hurup" sort="Hansen, Cecilie Hurup" uniqKey="Hansen C" first="Cecilie Hurup" last="Hansen">Cecilie Hurup Hansen</name><affiliation wicri:level="1"><nlm:affiliation>Toxicology Laboratory, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark;</nlm:affiliation><country xml:lang="fr">Danemark</country><wicri:regionArea>Toxicology Laboratory, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen</wicri:regionArea></affiliation></author><author><name sortKey="Styrishave, Bjarne" sort="Styrishave, Bjarne" uniqKey="Styrishave B" first="Bjarne" last="Styrishave">Bjarne Styrishave</name><affiliation wicri:level="1"><nlm:affiliation>Toxicology Laboratory, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark;</nlm:affiliation><country xml:lang="fr">Danemark</country><wicri:regionArea>Toxicology Laboratory, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen</wicri:regionArea></affiliation></author><author><name sortKey="Svingen, Terje" sort="Svingen, Terje" uniqKey="Svingen T" first="Terje" last="Svingen">Terje Svingen</name><affiliation wicri:level="1"><nlm:affiliation>Division of Diet, Disease Prevention and Toxicology, National Food Institute, Technical University of Denmark, 2860 Søborg, Denmark;</nlm:affiliation><country xml:lang="fr">Danemark</country><wicri:regionArea>Division of Diet, Disease Prevention and Toxicology, National Food Institute, Technical University of Denmark, 2860 Søborg</wicri:regionArea></affiliation></author><author><name sortKey="Vinggaard, Anne Marie" sort="Vinggaard, Anne Marie" uniqKey="Vinggaard A" first="Anne Marie" last="Vinggaard">Anne Marie Vinggaard</name><affiliation wicri:level="1"><nlm:affiliation>Division of Diet, Disease Prevention and Toxicology, National Food Institute, Technical University of Denmark, 2860 Søborg, Denmark;</nlm:affiliation><country xml:lang="fr">Danemark</country><wicri:regionArea>Division of Diet, Disease Prevention and Toxicology, National Food Institute, Technical University of Denmark, 2860 Søborg</wicri:regionArea></affiliation></author><author><name sortKey="Koch, Holger Martin" sort="Koch, Holger Martin" uniqKey="Koch H" first="Holger Martin" last="Koch">Holger Martin Koch</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Prevention and Occupational Medicine of the German Social Accident Insurance Institute of the Ruhr-Universität Bochum (IPA), 44789 Bochum, Germany;</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Prevention and Occupational Medicine of the German Social Accident Insurance Institute of the Ruhr-Universität Bochum (IPA), 44789 Bochum</wicri:regionArea></affiliation></author><author><name sortKey="Bowles, Josephine" sort="Bowles, Josephine" uniqKey="Bowles J" first="Josephine" last="Bowles">Josephine Bowles</name><affiliation><nlm:affiliation>Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia; and.</nlm:affiliation><wicri:noCountry code="subField">Australia; and</wicri:noCountry></affiliation></author><author><name sortKey="Koopman, Peter" sort="Koopman, Peter" uniqKey="Koopman P" first="Peter" last="Koopman">Peter Koopman</name><affiliation><nlm:affiliation>Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia; and.</nlm:affiliation><wicri:noCountry code="subField">Australia; and</wicri:noCountry></affiliation></author><author><name sortKey="Jegou, Bernard" sort="Jegou, Bernard" uniqKey="Jegou B" first="Bernard" last="Jégou">Bernard Jégou</name><affiliation wicri:level="1"><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale (Inserm) U1085-IRSET, Université de Rennes 1, Structure Fédérative Recherche Biosit, Rennes, France; EHESP-School of Public Health, Rennes, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale (Inserm) U1085-IRSET, Université de Rennes 1, Structure Fédérative Recherche Biosit, Rennes, France; EHESP-School of Public Health, Rennes</wicri:regionArea></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></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></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><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">26732887</PMID><DateCreated><Year>2016</Year><Month>02</Month><Day>26</Day></DateCreated><DateCompleted><Year>2016</Year><Month>12</Month><Day>13</Day></DateCompleted><DateRevised><Year>2016</Year><Month>12</Month><Day>30</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1096-0929</ISSN><JournalIssue CitedMedium="Internet"><Volume>150</Volume><Issue>1</Issue><PubDate><Year>2016</Year><Month>Mar</Month></PubDate></JournalIssue><Title>Toxicological sciences : an official journal of the Society of Toxicology</Title><ISOAbbreviation>Toxicol. Sci.</ISOAbbreviation></Journal><ArticleTitle>Intrauterine Exposure to Paracetamol and Aniline Impairs Female Reproductive Development by Reducing Follicle Reserves and Fertility.</ArticleTitle><Pagination><MedlinePgn>178-89</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1093/toxsci/kfv332</ELocationID><Abstract><AbstractText>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.</AbstractText><CopyrightInformation>© The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Holm</LastName><ForeName>Jacob Bak</ForeName><Initials>JB</Initials><AffiliationInfo><Affiliation>*Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, 2100 Copenhagen, Denmark; david@moebjerg.com.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mazaud-Guittot</LastName><ForeName>Severine</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Institut National de la Santé et de la Recherche Médicale (Inserm) U1085-IRSET, Université de Rennes 1, Structure Fédérative Recherche Biosit, Rennes, France;</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Danneskiold-Samsøe</LastName><ForeName>Niels Banhos</ForeName><Initials>NB</Initials><AffiliationInfo><Affiliation>*Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, 2100 Copenhagen, Denmark;</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chalmey</LastName><ForeName>Clementine</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Institut National de la Santé et de la Recherche Médicale (Inserm) U1085-IRSET, Université de Rennes 1, Structure Fédérative Recherche Biosit, Rennes, France;</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jensen</LastName><ForeName>Benjamin</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>*Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, 2100 Copenhagen, Denmark;</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nørregård</LastName><ForeName>Mette Marie</ForeName><Initials>MM</Initials><AffiliationInfo><Affiliation>*Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, 2100 Copenhagen, Denmark;</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hansen</LastName><ForeName>Cecilie Hurup</ForeName><Initials>CH</Initials><AffiliationInfo><Affiliation>Toxicology Laboratory, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark;</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Styrishave</LastName><ForeName>Bjarne</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Toxicology Laboratory, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark;</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Svingen</LastName><ForeName>Terje</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Division of Diet, Disease Prevention and Toxicology, National Food Institute, Technical University of Denmark, 2860 Søborg, Denmark;</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vinggaard</LastName><ForeName>Anne Marie</ForeName><Initials>AM</Initials><AffiliationInfo><Affiliation>Division of Diet, Disease Prevention and Toxicology, National Food Institute, Technical University of Denmark, 2860 Søborg, Denmark;</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Koch</LastName><ForeName>Holger Martin</ForeName><Initials>HM</Initials><AffiliationInfo><Affiliation>Institute for Prevention and Occupational Medicine of the German Social Accident Insurance Institute of the Ruhr-Universität Bochum (IPA), 44789 Bochum, Germany;</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bowles</LastName><ForeName>Josephine</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia; and.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Koopman</LastName><ForeName>Peter</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia; and.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jégou</LastName><ForeName>Bernard</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Institut National de la Santé et de la Recherche Médicale (Inserm) U1085-IRSET, Université de Rennes 1, Structure Fédérative Recherche Biosit, Rennes, France; EHESP-School of Public Health, Rennes, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kristiansen</LastName><ForeName>Karsten</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>*Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, 2100 Copenhagen, Denmark;</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kristensen</LastName><ForeName>David Møbjerg</ForeName><Initials>DM</Initials><AffiliationInfo><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.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>01</Month><Day>05</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Toxicol Sci</MedlineTA><NlmUniqueID>9805461</NlmUniqueID><ISSNLinking>1096-0929</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000814">Aniline Compounds</NameOfSubstance></Chemical><Chemical><RegistryNumber>362O9ITL9D</RegistryNumber><NameOfSubstance UI="D000082">Acetaminophen</NameOfSubstance></Chemical><Chemical><RegistryNumber>SIR7XX2F1K</RegistryNumber><NameOfSubstance UI="C023650">aniline</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000082" MajorTopicYN="N">Acetaminophen</DescriptorName><QualifierName UI="Q000633" MajorTopicYN="Y">toxicity</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000814" MajorTopicYN="N">Aniline Compounds</DescriptorName><QualifierName UI="Q000633" MajorTopicYN="Y">toxicity</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005298" MajorTopicYN="N">Fertility</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005836" MajorTopicYN="N">Genitalia, Female</DescriptorName><QualifierName UI="Q000002" MajorTopicYN="Y">abnormalities</QualifierName><QualifierName UI="Q000196" MajorTopicYN="N">embryology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005865" MajorTopicYN="N">Gestational Age</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008810" MajorTopicYN="N">Mice, Inbred C57BL</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006080" MajorTopicYN="N">Ovarian Follicle</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000196" MajorTopicYN="N">embryology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011247" MajorTopicYN="N">Pregnancy</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011297" MajorTopicYN="N">Prenatal Exposure Delayed Effects</DescriptorName><QualifierName UI="Q000139" MajorTopicYN="Y">chemically induced</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">aniline</Keyword><Keyword MajorTopicYN="N">development</Keyword><Keyword MajorTopicYN="N">follicle reserves</Keyword><Keyword MajorTopicYN="N">intrauterine exposure</Keyword><Keyword MajorTopicYN="N">paracetamol/acetaminophen</Keyword><Keyword MajorTopicYN="N">reproduction</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2016</Year><Month>1</Month><Day>7</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2016</Year><Month>1</Month><Day>7</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2016</Year><Month>12</Month><Day>15</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">26732887</ArticleId><ArticleId IdType="pii">kfv332</ArticleId><ArticleId IdType="doi">10.1093/toxsci/kfv332</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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