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Concerns about the widespread use of rodent models for human risk assessments of endocrine disruptors

By René Habert, Vincent Muczynski, Tiphany Grisin, Delphine Moison, Sébastien Messiaen, René Frydman, Alexandra Benachi, Géraldine Delbes, Romain Lambrot, Abdelali Lehraiki, Thierry N'Tumba-Byn, Marie-Justine Guerquin, Christine Levacher, Virginie Rouiller-Fabre and Gabriel Livera

Abstract

International audienceFetal testis is a major target of endocrine disruptors (EDs). During the last 20 years, we have developed an organotypic culture system that maintains the function of the different fetal testis cell types and have used this approach as a toxicological test to evaluate the effects of various compounds on gametogenesis and steroidogenesis in rat, mouse and human testes. We named this test rat, mouse and human fetal testis assay. With this approach, we compared the effects of six potential EDs ((mono-(2-ethylhexyl) phthalate (MEHP), cadmium, depleted uranium, diethylstilboestrol (DES), bisphenol A (BPA) and metformin) and one signalling molecule (retinoic acid (RA)) on the function of rat, mouse and human fetal testis at a comparable developmental stage. We found that the response is similar in humans and rodents for only one third of our analyses. For instance, RA and MEHP have similar negative effects on gametogenesis in the three species. For another third of our analyses, the threshold efficient concentrations that disturb gametogenesis and/or steroidogenesis differ as a function of the species. For instance, BPA and metformin have similar negative effects on steroidogenesis in human and rodents, but at different threshold doses. For the last third of our analyses, the qualitative response is species specific. For instance, MEHP and DES affect steroidogenesis in rodents, but not in human fetal testis. These species differences raise concerns about the extrapolation of data obtained in rodents to human health risk assessment and highlight the need of rigorous comparisons of the effects in human and rodent models, when assessing ED risk

Topics: [ SDV.TOX ] Life Sciences [q-bio]/Toxicology, [ SDV.BDLR ] Life Sciences [q-bio]/Reproductive Biology, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Publisher: BioScientifica
Year: 2014
DOI identifier: 10.1530/REP-13-0497
OAI identifier: oai:HAL:hal-01178768v1
Provided by: Hal-Diderot

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