- Title
- Low-dose tamoxifen treatment in juvenile males has long-term adverse effects on the reproductive system: implications for inducible transgenics
- Creator
- Patel, Saloni H.; O'Hara, Laura; Atanassova, Nina; Smith, Sarah E.; Curley, Michael K.; Rebourcet, Diane; Darbey, Annalucia L.; Gannon, Anne-Louise; Sharpe, Richard M.; Smith, Lee B.
- Relation
- Scientific Reports Vol. 7, Issue 21 August 2017, no. 8991
- Publisher Link
- http://dx.doi.org/10.1038/s41598-017-09016-4
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2017
- Description
- 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.
- Subject
- testes; reproductive system; tamoxifen
- Identifier
- http://hdl.handle.net/1959.13/1350463
- Identifier
- uon:30558
- Identifier
- ISSN:2045-2322
- Rights
- This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Language
- eng
- Full Text
- Reviewed
- Hits: 7350
- Visitors: 7667
- Downloads: 412
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT02 | Publisher version (open access) | 4 MB | Adobe Acrobat PDF | View Details Download |