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.
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.
Research Unit n 01/UR/08-07, Tunis El Manar University, Faculty of Medicine, Tunis, Tunisia.
Wided
W
Kouidhi
Catherine
C
Desmetz
Afef
A
Nahdi
Raymond
R
Bergès
Jean-Pierre
JP
Cravedi
Jacques
J
Auger
Michèle
M
El May
Marie Chantal
MC
Canivenc-Lavier
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004032:Diet; D004338:Drug Combinations; D004435:Eating / Q000187:drug effects; D052244:Endocrine Disruptors / Q000633:toxicity; D004781:Environmental Exposure; D005260:Female; D019833:Genistein / Q000633:toxicity*; D007774:Lactation; D008297:Male; D018811:Maternal Exposure; D010080:Oxazoles / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D017978:Receptors, Growth Factor / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D011987:Receptors, Steroid / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D012469:Salivary Glands / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology
D004338:Drug Combinations; D052244:Endocrine Disruptors; D010080:Oxazoles; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D011987:Receptors, Steroid; D019833:Genistein; C025643:vinclozolin