Abnormal peripubertal development of the rat mammary gland following exposure in utero and during lactation to a mixture of genistein and the food contaminant vinclozolin
2011
El Sheikh, Saad H. | Meduri, Geri | Phrakonkham, Pascal | Berges, Raymond | Vacher, S. | Djallali, M. | Auger, Jacques | Canivenc-Lavier, Marie-Chantal | Perrot-Applanat, M. | Carcinose Angiogenèse et Recherche Translationnelle ; Angiogenese et recherche translationnelle (CART U965) ; Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM) | Hôpital Lariboisière-Fernand-Widal [APHP] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP) | Université Paris Diderot - Paris 7 (UPD7) | U553 ; Institut National de la Santé et de la Recherche Médicale (INSERM) | Hopital Saint-Louis [AP-HP] (AP-HP) ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP) | IFR 105 | U 693 ; Institut National de la Santé et de la Recherche Médicale (INSERM) | Université Paris-Sud - Paris 11 (UP11) | 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 René Huguenin [Saint-Cloud] ; Institut Curie - Saint Cloud (ICSC) | Institut Curie [Paris] | Institut National de la Santé et de la Recherche Médicale (INSERM) | U 553 ; Hopital Saint-Louis [AP-HP] (AP-HP) ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP) | Hôpital Cochin [AP-HP] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
The impact of early exposure to endocrine disruptor mixtures on mammary gland development is poorly known. Here, we identify the effects of a conception to weaning exposure of rats to the phytoestrogen genistein (G) and/or the antiandrogen vinclozolin (V) at 1 mg/kg-d, alone or in association. Using several approaches, we found that G- and GV-exposed rats displayed significantly greater epithelial branching and proliferation, wider terminal end buds than controls at PND35, as well as ductal hyperplasia and periductal fibrosis. Focal branching defects were present in V-exposed rats. An increased ER and AR expression was observed in G- and CV- as compared to V-exposed rats at PND35. Surprisingly, a significant number of CV- and to a lesser extent. V-exposed animals displayed abnormal hyperplasic alveolar structures at PND50. Thus, gestational and lactational exposure to low doses of genistein plus vinclozolin may seriously affect peripubertal development of the rat mammary gland.
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