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Although numerous reports exist on the potential beneficial role of nutritional phytoestrogens in human health, their molecular mechanism in target cells is still not completely understood. Phytoestrogens promote estrogen and antiestrogen effects by interacting with numerous molecules, carrier proteins, enzymes and membrane and nuclear receptors, directly or indirectly involved in the transfer of estrogen signals. The hypothesis that the ERβ subtype plays a key role in antiproliferative effect of phytoestrogens, especially in breast cancer, is examined here.This review focus on the effects of phytoestrogens in developmental processes such as those linked to reproductive function, tumorigenesis and angiogenesis. [Copyright &y& Elsevier]

Endocrine disruptors may play substantial roles in the high incidence of breast cancer. We previously described how early exposure to the mixture of phytoestrogen genistein (G) and the anti-androgen vinclozolin (V) affects peripubertal mammary development. This study evaluates the carcinogenic potential of exposure to V alone or associated with G from conception until weaning in Wistar rats. Dams were exposed to V, G or GV during pregnancy/lactation. At PND50 offspring were treated with DMBA[7,12-dimethylbenz(a)anthracene]. V or GV maternal exposure decreased number of DMBA-induced mammary tumors in the offspring, without significant modifications in tumor incidence, multiplicity and latency. G exposure decreased number of tumors, incidence and multiplicity. Unexpectedly, GV exposure increased tumor volume ( p = 0.04 vs controls) and epithelial proliferation ( p = 0.001 vs controls; p = 0.005 vs G,V only). All tumors were in situ carcinomas. Concluding, maternal gestation/lactation exposure to a vinclozolin and genistein mixture significantly increases offspring tumor growth without changes in carcinogenesis susceptibility. [ABSTRACT FROM AUTHOR]

Exposure to low doses of environmental estrogens such as bisphenol A and genistein (G) alters mammary gland development. The effects of environmental anti-androgens, such as the fungicide vinclozolin (V), on mammary gland morphogenesis are unknown. We previously reported that perinatal exposure to G, V, and the GV combination causes histological changes in the mammary gland during the peripubertal period, suggesting alterations to the peripubertal hormone response. We now investigate whether perinatal exposure to these compounds alters the gene expression profiles of the developing glands to identify the dysregulated signaling pathways and the underlying mechanisms. G, V, or GV (1 mg/kg body weight per day) was added to diet of Wistar rats, from conception to weaning; female offspringmammary glands were collected at postnatal days (PNDs) 35 and 50. Genes displaying differential expression and belonging to different functional categories were validated by quantitative PCR and immunocytochemistry. At PND35, G had little effect; the slight changes noted were in genes related to morphogenesis. The changes following exposure to V concerned the functional categories associated with development (Cldn1, Krt17, and Sprr1a), carbohydrate metabolism, and steroidogenesis. The GV mixture upregulated genes (Krt17, Pvalb, and Tnni2) involved in muscle development, indicating effects on myoepithelial cells duringmammary glandmorphogenesis. Importantly, at PND50, cycling females exposed to GV showed an increase in the expression of genes (Csn2, Wap, and Elf5) related to differentiation, consistent with the previously reported abnormal lobuloalveolar development previously described. Thus, perinatal exposure to GV alters the mammary gland hormone response differently at PND35 (puberty) and in animals with established cycles. [ABSTRACT FROM AUTHOR]

Abstract: 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 1mg/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 GV- as compared to V-exposed rats at PND35. Surprisingly, a significant number of GV- 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. [Copyright &y& Elsevier]

Presents information on a study which investigated whether estradiol induces the production of vascular endothelial growth factor messenger RNA and protein in the smooth muscle cell from human saphenous veins and aorta. Methodology of the study; Results and discussion on the study.