title: Accurate Control of 17β-Estradiol Long-Term Release Increases Reliability and Reproducibility of Preclinical Animal Studies.
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.
authors.affiliation: Laboratory of Tumor and Development Biology, GIGA-Cancer, University of Liege, CHU-B23, Hippocrate avenue 13, B-4000, Liège, Belgium.
authors.forename: Céline
authors.initials: C
authors.lastname: Gérard
authors.affiliation: Laboratory of Tumor and Development Biology, GIGA-Cancer, University of Liege, CHU-B23, Hippocrate avenue 13, B-4000, Liège, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: Gallez
authors.affiliation: Laboratory of Tumor and Development Biology, GIGA-Cancer, University of Liege, CHU-B23, Hippocrate avenue 13, B-4000, Liège, Belgium.
authors.forename: Charline
authors.initials: C
authors.lastname: Dubois
authors.affiliation: Experimental Surgery unit, GIGA & Credec, University of Liege, 4000, Liège, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Drion
authors.affiliation: CER Groupe, Health Department, 6900, Marloie, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Delahaut
authors.affiliation: Department of Psychology, Cognition and Behavior, University of Liege, 4000, Liège, Belgium.
authors.forename: Etienne
authors.initials: E
authors.lastname: Quertemont
authors.affiliation: Laboratory of Tumor and Development Biology, GIGA-Cancer, University of Liege, CHU-B23, Hippocrate avenue 13, B-4000, Liège, Belgium.
authors.forename: Agnès
authors.initials: A
authors.lastname: Noël
authors.affiliation: Laboratory of Tumor and Development Biology, GIGA-Cancer, University of Liege, CHU-B23, Hippocrate avenue 13, B-4000, Liège, Belgium. C.Pequeux@ulg.ac.be.
authors.forename: Christel
authors.initials: C
authors.lastname: Pequeux
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D004958:Estradiol / Q000008:administration & dosage*; D004967:Estrogens / Q000008:administration & dosage; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results
chemical_list: D004967:Estrogens; D004958:Estradiol
keywords: Animal welfare; Estradiol; Estrogen; Hormone administration; Implant; Matrix; Mouse; Pellet; Pharmacokinetics; Rat; Reservoir; Slow-release