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

Saloni H Patel, Laura O'Hara, Nina N Atanassova, Sarah E Smith, Michael K Curley, Diane Rebourcet, Annalucia Darbey, Anne-Louise Gannon, Richard M Sharpe, Lee B. Smith

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Article number8991
Number of pages12
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - 21 Aug 2017

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