Sub-NOAEL amounts of vinclozolin and xenoestrogens target rat chondrogenesis in vivo
2014
Auxiètre, Thuy-Anh | Dumontier, Marie-France | Balguy, Irene | Frapart, Yves | Canivenc-Lavier, Marie-Chantal | Berges, Raymond | Boudalia, Sofiane | Auger, Jacques | Corvol, Marie-Thérèse | Savouret, Jean-François | Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124) ; Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM) | Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601) ; Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS) | Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA) ; Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS) | Hôpital Cochin [AP-HP] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP) | INRA (CSGA-Dijon and Toxalim-Toulouse); INSERM, Universites Paris Descartes and Paris Diderot; Assistance Publique-Hopitaux de Paris (AP-HP); French National Program on Endocrine disruptors (PNRPE; Ministry of Ecology, durable development and Energy (MEDDE)
Several endocrine disrupting compounds (EDC) elicit skeletal dysgenesis at pharmacological doses. We have investigated the impact of doses below the "No Observed Adverse Effect" (NOAEL) for vinclozolin (V), an anti-androgenic fungicide, alone or associated with xenoestrogens (Genistein, G and bisphenol-A, BPA). V, G, BPA and their combinations were administered orally to female Wistar rats during gestation and lactation. F1 and F2 offspring were investigated for skeletal anomalies at post-natal days 30, 110 (d30, d110). Skeletal development was monitored by measuring caudal vertebrae and long bones dimensions by X-ray micro-CT-scan. A significant increase in Inter Transverse Apophysis (ITA) distance at the upper head of caudal vertebrae, associated with a reduction in vertebral body height was observed in treated F1 females, but not males. Histometrical analysis of vertebral body growth plate cartilage was performed on serial sections of caudal vertebrae. F1 females but not males showed a diminution in growth plate thickness, with greater impact on the hypertrophic zone. All effects were maximal at d30. Effects on ITA width persisted until d110 while effects on growth plate disappeared. These effects were essentially vinclozolin or BPA-dependent. F2 animals were not affected. Our data suggest that vinclozolin and xenoestrogens act as cartilage developmental disruptors. We suggest that present NOAEL values for these compounds, and EDC at large, might be reconsidered using gestational exposure models. Finally, micro CT-scan appears a valuable non-invasive technique to detect EDC effects on live fauna.
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