Effects of neonatal exposure to bisphenol A and 17-β estradiol on the mammary gland of adult female Mongolian gerbil

Author(s)

Ellen Cristina Rivas Leonel

• Document type: Doctoral Thesis
• Press: São José do Rio Preto. 2019-03-29.
• Institution: Universidade Estadual Paulista (Unesp). Instituto de Biociências Letras e Ciências Exatas. São José do Rio Preto
• Defense date: 2019-03-15
• Advisor: Sebastião Roberto Taboga; Silvana Gisele Pegorin de Campos

Abstract

The incidence of breast cancer has increased considerably over the years. Facing this high epidemiological rate, attention to the causes of this disease has been significant among research groups. Genetic factors and some risk situations, such as exposure to chemical endocrine disrupting components may stimulate its development. Bisphenol A (BPA), a compound used in the manufacture of plastics and resins, can be released from these components and exert estrogenic effects, causing disturbances of endocrine function and increasing the predisposition to carcinogenesis. Some studies have demonstrated the long-term effects of BPA, in a way that exposure during embryonic development (perinatal phase) may predispose the mammary gland (MG) to development of cancer in adults. Its mechanism of action, as that of endogenous estradiol, is mainly based on cellular hormonal receptors binding, which can stimulate the proliferation, promoting an imbalance of breast cell cycles and renewal. For these carcinogenesis studies, the Mongolian gerbil (Meriones unguiculatus) is an interesting experimental model, since it has the ability to develop spontaneous tumors in hormone-responsive organs, naturally mimicking the environment of an individual predisposed to tumorigenesis. Thus, the aims of this study were to (1) characterize morphologically the mammary gland of Mongolian gerbil females at different stages of functionality, (2) describe morphological changes found in the MG of adult females exposed to BPA or 17-β estradiol during the perinatal development evaluating the presence of histopathological lesions, cell proliferation index and expression of the epigenetic alteration marker, EZH2, as well as (3) to describe the variations in hormone receptors expression taking into account hormonal serum levels, with the purpose of clarifying the possible effects of BPA administered during embryonic development in adult MG. Our results demonstrated that at 6 months age there was a significant increase in proliferative index, incidence of hyperplasia and considerable alteration in the deposition of collagen fibers in the stromal compartment of the gland. There was an increase in EZH2 expression in the mammary epithelial cells of animals treated with corn oil (vehicle), revealing an unexpected action of it in MG. Hormone receptor analsis showed that significant differences in expression rates occurred in the mammary glands of the groups treated with both, BPA and 17β-estradiol compared to the intact control group. Thus, we observed that neonatal exposure to BPA causes morphological and molecular changes in the MG of Mongolian gerbils reflected after 6 months age, which may indicate signs of pre-malignancy, confirming the carcinogenic effect of this compound. (AU)

• FAPESP's process: 15/01548-5 - Evaluation of the Bisphenol-A carcinogenic effect in the mammary gland of Mongolian Gerbil (Merionis unguiculatus)
• Grantee: Ellen Cristina Rivas Leonel
• Support Opportunities: Scholarships in Brazil - Doctorate