1. In utero and lactational exposure to low-dose genistein-vinclozolin mixture affects the development and growth factor mRNA expression of the submandibular salivary gland in immature female rats
- Author
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Jean-Pierre Cravedi, Michèle El May, Jacques Auger, Wided Kouidhi, Afef Nahdi, Raymond Berges, Catherine Desmetz, Marie-Chantal Canivenc-Lavier, Centre des Sciences du Goût et de l'Alimentation (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Agroécologie [Dijon], Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université de Tunis El Manar (UTM), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées
- Subjects
Male ,Receptors, Steroid ,medicine.medical_treatment ,Genistein ,Apoptosis ,Endocrine Disruptors ,Toxicology ,Salivary Glands ,Eating ,chemistry.chemical_compound ,0302 clinical medicine ,Pregnancy ,Epidermal growth factor ,Vinclozolin ,Oxazoles ,0303 health sciences ,3. Good health ,Drug Combinations ,Endocrine disruptor ,Maternal Exposure ,Prenatal Exposure Delayed Effects ,Female ,medicine.medical_specialty ,Gland morphogenesis ,Biology ,Pathology and Forensic Medicine ,03 medical and health sciences ,Internal medicine ,medicine ,Animals ,Lactation ,Endocrine system ,Receptors, Growth Factor ,RNA, Messenger ,Rats, Wistar ,Molecular Biology ,Cell Proliferation ,030304 developmental biology ,Growth factor ,Environmental Exposure ,030206 dentistry ,Cell Biology ,Diet ,Rats ,Endocrinology ,Animals, Newborn ,chemistry ,[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition ,Transforming growth factor - Abstract
International audience; It has been suggested that hormonally controlled submandibular salivary gland (SSG) development and secretions may be affected by endocrine disruptor compounds. We investigated the effects of oral gestation-lactation exposure to 1 mg/kg body weight daily dose of the estrogenic soy-isoflavone genistein and/or the anti-androgenic food contaminant vinclozolin in female rats. The SSGs of female offspring were collected at postnatal day 35 to study gland morphogenesis and mRNA expression of sex-hormone receptors and endocrine growth factors as sex-dependent biomarkers. Because of high expression in neonatal SSG, mRNA expression of transforming growth factor α was also studied. Exposure to genistein, vinclozolin, or a genistein+vinclozolin mixture resulted in significantly lower numbers of striated ducts linked to an increase in their area and lower acinar proliferation (Ki-67–positive nuclei). Exposure to the mixture had the highest significant effects, which were particularly associated with repression of epidermal growth factor, nerve growth factor, and transforming growth factor α expression. In conclusion, early exposure to low doses of genistein and vinclozolin can affect glandular structure and endocrine gene mRNA expression in prepubertal SSG in female rats, and the effects are potentialized by the genistein+vinclozolin mixture. Our study provides the first evidence that SSG are targeted by both estrogenic and anti-androgenic disrupting compounds and are more sensitive to mixtures.
- Published
- 2012
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