Low-dose tamoxifen treatment in juvenile males has long-term adverse effects on the reproductive system: implications for inducible transgenics
Identifieur interne : 000864 ( Main/Exploration ); précédent : 000863; suivant : 000865Low-dose tamoxifen treatment in juvenile males has long-term adverse effects on the reproductive system: implications for inducible transgenics
Auteurs : Saloni H. Patel ; Laura O Ara ; Nina Atanassova [Bulgarie] ; Sarah E. Smith ; Michael K. Curley ; Diane Rebourcet ; Annalucia L. Darbey ; Anne-Louise Gannon ; Richard M. Sharpe ; Lee B. SmithSource :
- Scientific Reports [ 2045-2322 ] ; 2017.
Abstract
The tamoxifen-inducible Cre system is a popular transgenic method for controlling the induction of recombination by Cre at a specific time and in a specific cell type. However, tamoxifen is not an inert inducer of recombination, but an established endocrine disruptor with mixed agonist/antagonist activity acting via endogenous estrogen receptors. Such potentially confounding effects should be controlled for, but >40% of publications that have used tamoxifen to generate conditional knockouts have not reported even the minimum appropriate controls. To highlight the importance of this issue, the present study investigated the long-term impacts of different doses of a single systemic tamoxifen injection on the testis and the wider endocrine system. We found that a single dose of tamoxifen less than 10% of the mean dose used for recombination induction, caused adverse effects to the testis and to the reproductive endocrine system that persisted long-term. These data raise significant concerns about the widespread use of tamoxifen induction of recombination, and highlight the importance of including appropriate controls in all pathophysiological studies using this means of induction.
Url:
DOI: 10.1038/s41598-017-09016-4
PubMed: 28827578
PubMed Central: 5566418
Affiliations:
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Smith</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 7988</institution-id><institution-id institution-id-type="GRID">grid.4305.2</institution-id><institution></institution><institution>MRC Centre for Reproductive Health, The Queen’s Medical Research Institute, 47 Little France Crescent,</institution></institution-wrap>Edinburgh, EH16 4TJ UK</nlm:aff><wicri:noCountry code="subfield">EH16 4TJ UK</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 8831 109X</institution-id><institution-id institution-id-type="GRID">grid.266842.c</institution-id><institution></institution><institution>School of Environmental and Life Sciences, University of Newcastle,</institution></institution-wrap>Callaghan, NSW 2308 Australia</nlm:aff><wicri:noCountry code="subfield">NSW 2308 Australia</wicri:noCountry></affiliation></author></analytic><series><title level="j">Scientific Reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">The tamoxifen-inducible Cre system is a popular transgenic method for controlling the induction of recombination by Cre at a specific time and in a specific cell type. However, tamoxifen is not an inert inducer of recombination, but an established endocrine disruptor with mixed agonist/antagonist activity acting via endogenous estrogen receptors. Such potentially confounding effects should be controlled for, but >40% of publications that have used tamoxifen to generate conditional knockouts have not reported even the minimum appropriate controls. To highlight the importance of this issue, the present study investigated the long-term impacts of different doses of a single systemic tamoxifen injection on the testis and the wider endocrine system. We found that a single dose of tamoxifen less than 10% of the mean dose used for recombination induction, caused adverse effects to the testis and to the reproductive endocrine system that persisted long-term. These data raise significant concerns about the widespread use of tamoxifen induction of recombination, and highlight the importance of including appropriate controls in all pathophysiological studies using this means of induction.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Danielian, Ps" uniqKey="Danielian P">PS Danielian</name></author><author><name sortKey="White, R" uniqKey="White R">R White</name></author><author><name sortKey="Hoare, Sa" uniqKey="Hoare S">SA Hoare</name></author><author><name sortKey="Fawell, Se" uniqKey="Fawell S">SE Fawell</name></author><author><name sortKey="Parker, Mg" uniqKey="Parker M">MG Parker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Feil, R" uniqKey="Feil R">R Feil</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Feil, R" uniqKey="Feil R">R Feil</name></author><author><name sortKey="Wagner, J" uniqKey="Wagner J">J 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Smith</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kilcoyne, Kr" uniqKey="Kilcoyne K">KR Kilcoyne</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Gendt, K" uniqKey="De Gendt K">K De Gendt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Welsh, M" uniqKey="Welsh M">M Welsh</name></author><author><name sortKey="Saunders, Pt" uniqKey="Saunders P">PT Saunders</name></author><author><name sortKey="Atanassova, N" uniqKey="Atanassova N">N Atanassova</name></author><author><name sortKey="Sharpe, Rm" uniqKey="Sharpe R">RM Sharpe</name></author><author><name sortKey="Smith, Lb" uniqKey="Smith L">LB Smith</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Baker, Pj" uniqKey="Baker P">PJ Baker</name></author><author><name sortKey="O Haughnessy, Pj" uniqKey="O Haughnessy P">PJ O’Shaughnessy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Livak, Kj" uniqKey="Livak K">KJ Livak</name></author><author><name sortKey="Schmittgen, Td" uniqKey="Schmittgen T">TD Schmittgen</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Bulgarie</li></country></list><tree><noCountry><name sortKey="Curley, Michael K" sort="Curley, Michael K" uniqKey="Curley M" first="Michael K." last="Curley">Michael K. Curley</name><name sortKey="Darbey, Annalucia L" sort="Darbey, Annalucia L" uniqKey="Darbey A" first="Annalucia L." last="Darbey">Annalucia L. Darbey</name><name sortKey="Gannon, Anne Louise" sort="Gannon, Anne Louise" uniqKey="Gannon A" first="Anne-Louise" last="Gannon">Anne-Louise Gannon</name><name sortKey="O Ara, Laura" sort="O Ara, Laura" uniqKey="O Ara L" first="Laura" last="O Ara">Laura O Ara</name><name sortKey="Patel, Saloni H" sort="Patel, Saloni H" uniqKey="Patel S" first="Saloni H." last="Patel">Saloni H. Patel</name><name sortKey="Rebourcet, Diane" sort="Rebourcet, Diane" uniqKey="Rebourcet D" first="Diane" last="Rebourcet">Diane Rebourcet</name><name sortKey="Sharpe, Richard M" sort="Sharpe, Richard M" uniqKey="Sharpe R" first="Richard M." last="Sharpe">Richard M. Sharpe</name><name sortKey="Smith, Lee B" sort="Smith, Lee B" uniqKey="Smith L" first="Lee B." last="Smith">Lee B. Smith</name><name sortKey="Smith, Sarah E" sort="Smith, Sarah E" uniqKey="Smith S" first="Sarah E." last="Smith">Sarah E. Smith</name></noCountry><country name="Bulgarie"><noRegion><name sortKey="Atanassova, Nina" sort="Atanassova, Nina" uniqKey="Atanassova N" first="Nina" last="Atanassova">Nina Atanassova</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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