Accurate Control of 17β-Estradiol Long-Term Release Increases Reliability and Reproducibility of Preclinical Animal StudiesReport as inadecuate




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Journal of Mammary Gland Biology and Neoplasia

, Volume 22, Issue 1, pp 1–11

First Online: 26 November 2016Received: 28 April 2016Accepted: 21 November 2016DOI: 10.1007-s10911-016-9368-1

Cite this article as: Gérard, C., Gallez, A., Dubois, C. et al. J Mammary Gland Biol Neoplasia 2017 22: 1. doi:10.1007-s10911-016-9368-1

Abstract

Estrogens are the subject of intensive researches aiming to elucidate their mechanism of action on the various tissues they target and especially on mammary gland and breast cancer. The use of ready-to-use slow releasing devices to administer steroids, especially estrogens, to small experimental animals remains the method of choice in terms of animal well-being and of safety for both the researcher and the animal. In this study, we evaluated and compared, in vitro and in vivo, the release kinetic of estradiol E2 over sixty days from two different slow-releasing systems: the matrix pellet MP and the reservoir implant RI. We compared the impact of these systems in three E2-sensitive mouse models : mammary gland development, human MCF7 adenocarcinoma xenograft and mouse melanoma progression. The real amount of E2 that is released from both types of devices could differ from manufacturer specifications due to inadequate release for MP and initial burst effect for RI. Compared to MP, the interindividual variability was reduced with RI thanks to a superior control of the E2 release. Depending on the dose-dependent sensitivity of the physiological or pathological readout studied, this could lead to an improvement of the statistical power of in vivo experiments and thus to a reduction of the required animal number. Altogether, our data draw attention on the importance to adequately select the slow-releasing device that is the most appropriated to a specific experiment to better fulfill the 3Rs rule Replacement, Reduction, Refinement related to animal welfare and protection.

KeywordsEstrogen Estradiol Hormone administration Matrix Pellet Reservoir Implant Pharmacokinetics Mouse Rat Slow-release Animal welfare  Download fulltext PDF



Author: Céline Gérard - Anne Gallez - Charline Dubois - Pierre Drion - Philippe Delahaut - Etienne Quertemont - Agnès Noël - Ch

Source: https://link.springer.com/



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