Low-dose tamoxifen treatment in juvenile males has long-term adverse effects on the reproductive system: implications for inducible transgenics

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/anta...

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Autores principales:	Saloni H. Patel, Laura O’Hara, Nina Atanassova, Sarah E. Smith, Michael K. Curley, Diane Rebourcet, Annalucia L. Darbey, Anne-Louise Gannon, Richard M. Sharpe, Lee B. Smith
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/01bc0ff80d6349639fcb5b2646820108
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spelling	oai:doaj.org-article:01bc0ff80d6349639fcb5b26468201082021-12-02T11:52:31ZLow-dose tamoxifen treatment in juvenile males has long-term adverse effects on the reproductive system: implications for inducible transgenics10.1038/s41598-017-09016-42045-2322https://doaj.org/article/01bc0ff80d6349639fcb5b26468201082017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09016-4https://doaj.org/toc/2045-2322Abstract 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.Saloni H. PatelLaura O’HaraNina AtanassovaSarah E. SmithMichael K. CurleyDiane RebourcetAnnalucia L. DarbeyAnne-Louise GannonRichard M. SharpeLee B. SmithNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Saloni H. Patel Laura O’Hara Nina Atanassova Sarah E. Smith Michael K. Curley Diane Rebourcet Annalucia L. Darbey Anne-Louise Gannon Richard M. Sharpe Lee B. Smith Low-dose tamoxifen treatment in juvenile males has long-term adverse effects on the reproductive system: implications for inducible transgenics
description	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.
format	article
author	Saloni H. Patel Laura O’Hara Nina Atanassova Sarah E. Smith Michael K. Curley Diane Rebourcet Annalucia L. Darbey Anne-Louise Gannon Richard M. Sharpe Lee B. Smith
author_facet	Saloni H. Patel Laura O’Hara Nina Atanassova Sarah E. Smith Michael K. Curley Diane Rebourcet Annalucia L. Darbey Anne-Louise Gannon Richard M. Sharpe Lee B. Smith
author_sort	Saloni H. Patel
title	Low-dose tamoxifen treatment in juvenile males has long-term adverse effects on the reproductive system: implications for inducible transgenics
title_short	Low-dose tamoxifen treatment in juvenile males has long-term adverse effects on the reproductive system: implications for inducible transgenics
title_full	Low-dose tamoxifen treatment in juvenile males has long-term adverse effects on the reproductive system: implications for inducible transgenics
title_fullStr	Low-dose tamoxifen treatment in juvenile males has long-term adverse effects on the reproductive system: implications for inducible transgenics
title_full_unstemmed	Low-dose tamoxifen treatment in juvenile males has long-term adverse effects on the reproductive system: implications for inducible transgenics
title_sort	low-dose tamoxifen treatment in juvenile males has long-term adverse effects on the reproductive system: implications for inducible transgenics
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/01bc0ff80d6349639fcb5b2646820108
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Low-dose tamoxifen treatment in juvenile males has long-term adverse effects on the reproductive system: implications for inducible transgenics

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