title: Sub-NOAEL amounts of vinclozolin and xenoestrogens target rat chondrogenesis in vivo.
abstract: 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.
authors: INSERM UMRS747, Universite Paris Descartes, UFR Biomedicale, 45 rue des Saints Peres, Paris F-75006, France.
authors: Thuy-Anh
authors: TA
authors: Auxietre
authors: INSERM UMRS747, Universite Paris Descartes, UFR Biomedicale, 45 rue des Saints Peres, Paris F-75006, France.
authors: Marie-France
authors: MF
authors: Dumontier
authors: INSERM UMRS747, Universite Paris Descartes, UFR Biomedicale, 45 rue des Saints Peres, Paris F-75006, France.
authors: Irene
authors: I
authors: Balguy
authors: CNRS UMR 8601, Universite Paris Descartes, UFR Biomedicale, 45 rue des Saints Peres, Paris F-75006, France.
authors: Yves
authors: Y
authors: Frapart
authors: Centre des Sciences du Gout et de l'Alimentation, UMR 1324 CSGA, INRA, 17 rue Sully, BP 86510, Dijon F-21065, France.
authors: Marie-Chantal
authors: MC
authors: Canivenc-Lavier
authors: Centre des Sciences du Gout et de l'Alimentation, UMR 1324 CSGA, INRA, 17 rue Sully, BP 86510, Dijon F-21065, France.
authors: Raymond
authors: R
authors: Berges
authors: Centre des Sciences du Gout et de l'Alimentation, UMR 1324 CSGA, INRA, 17 rue Sully, BP 86510, Dijon F-21065, France.
authors: Sofiane
authors: S
authors: Boudalia
authors: Histologie-Embryologie, Biologie de la Reproduction, CECOS, Cochin/Broca/Hôtel Dieu, Hopitaux Universitaires Paris Centre, 53, avenue de l'Observatoire, Paris F-75014, France.
authors: Jacques
authors: J
authors: Auger
authors: INSERM UMRS747, Universite Paris Descartes, UFR Biomedicale, 45 rue des Saints Peres, Paris F-75006, France.
authors: Marie-Therese
authors: MT
authors: Corvol
authors: INSERM UMRS747, Universite Paris Descartes, UFR Biomedicale, 45 rue des Saints Peres, Paris F-75006, France. Electronic address: jfsavouret@gmail.com.
authors: Jean-François
authors: JF
authors: Savouret
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity; D001848:Bone Diseases, Developmental / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000473:pathology; D002356:Cartilage / Q000002:abnormalities / Q000000981:diagnostic imaging / Q000187:drug effects; D020219:Chondrogenesis / Q000187:drug effects*; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D005659:Fungicides, Industrial / Q000633:toxicity*; D019833:Genistein / Q000633:toxicity; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D010080:Oxazoles / Q000633:toxicity*; D010636:Phenols / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013131:Spine / Q000002:abnormalities / Q000000981:diagnostic imaging / Q000187:drug effects; D055114:X-Ray Microtomography; D015262:Xenobiotics / Q000633:toxicity; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D005659:Fungicides, Industrial; D019833:Genistein; D010080:Oxazoles; D010636:Phenols; D015262:Xenobiotics; C025643:vinclozolin; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Cartilage; Growth plate; NOAEL vinclozolin; Xenoestrogens