title: Development of an in vitro test battery for the screening of the receptor-mediated mechanism and the spindle-poison mode of action of estrogenic compounds.
abstract: The implementation of the REACH regulation has imposed the urgent need of developing alternative testing methods to screen large number of compounds more quickly and at lower costs. In this study, a battery of tests, suitable for reproductive toxicology testing, was developed with the objective of detecting the mechanism of action of estrogenic and xenoestrogenic compounds. With this aim, two compounds known for their estrogenic activity, diethylstilbestrol and 17β-estradiol, were used to set up four different in vitro tests: 1) bovine oocyte in vitro maturation assay, 2) bovine preimplantation embryo in vitro culture assay and 3) MCF-7 and 4) BALB/3T3 cell lines proliferation and cytotoxicity assay, respectively. The results show that this battery of tests allows to identify and to distinguish between two major mechanisms of action of (xeno)estrogenic compounds: the receptor-mediated mechanism and the spindle-poison effect on microtubules polimerization.
authors.affiliation: Avantea, Laboratory of Reproductive Technologies, Via Porcellasco 7/f, Cremona, 26100, Italy; Dept. of Veterinary Medical Sciences, University of Bologna, Via Tolara di Sopra 50, 40064, Ozzano dell'Emilia (BO), Italy. Electronic address: corinnequadalti@avantea.it.
authors.forename: Corinne
authors.initials: C
authors.lastname: Quadalti
authors.affiliation: Avantea, Laboratory of Reproductive Technologies, Via Porcellasco 7/f, Cremona, 26100, Italy; Dept. of Veterinary Medical Sciences, University of Bologna, Via Tolara di Sopra 50, 40064, Ozzano dell'Emilia (BO), Italy; Fondazione Avantea, Cremona, Italy. Electronic address: cesaregalli@avantea.it.
authors.forename: Cesare
authors.initials: C
authors.lastname: Galli
authors.affiliation: Avantea, Laboratory of Reproductive Technologies, Via Porcellasco 7/f, Cremona, 26100, Italy; Fondazione Avantea, Cremona, Italy. Electronic address: giovannalazzari@avantea.it.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lazzari
mesh_terms: D000826:Animal Testing Alternatives / Q000379:methods*; D000818:Animals; D041702:BALB 3T3 Cells; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004054:Diethylstilbestrol / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D047108:Embryonic Development / Q000187:drug effects; D004958:Estradiol / Q000633:toxicity; D004967:Estrogens / Q000633:toxicity*; D004968:Estrogens, Non-Steroidal / Q000633:toxicity; D006801:Humans; D059471:In Vitro Oocyte Maturation Techniques; D061986:MCF-7 Cells; D008540:Meiosis / Q000187:drug effects; D051379:Mice; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D012098:Reproduction / Q000187:drug effects; D008941:Spindle Apparatus / Q000187:drug effects*; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D004967:Estrogens; D004968:Estrogens, Non-Steroidal; D011960:Receptors, Estrogen; D004958:Estradiol; D004054:Diethylstilbestrol
keywords: Blastocyst; Diethylstilbestrol; Estradiol; Estrogen receptor alpha; In vitro oocyte maturation techniques (MeSH); MCF-7cells