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Interference of gestational exposure to dibutyl phthalate and of excessive intake of saturated lipids on the gerbil prostate   : histopathological alterations and involved mechanisms

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Mariana Marcielo de Jesus
Total Authors: 1
Document type: Doctoral Thesis
Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
Defense date:
Examining board members:
Alceu Afonso Jordão Junior; Ana Paula da Silva Perez; Marciane Milanski; Mary Anne Heidi Dolder
Advisor: Rejane Maira Góes

A high-fat diet and exposure to endocrine-disrupting chemicals (EDC) are two environmental factors to which the world population is exposed and which negatively affect prostate development and maintenance. The consumption of a high-lipid content diet affects the homeostasis of sex steroid hormones, altering prostate histophysiology and increasing the risk of prostate adenocarcinoma. It is known that lipid action on the prostate is variable, depending on the quantity and also the type of lipid ingested, and is far from being well understood. Dibutyl phthalate is an EDC involved in the deregulation of the development of the male reproductive tract when administered during the fetal period, impairing the formation of androgen-dependent organs. Nevertheless, its impact on development and consequences for prostate histophysiology are still little known. In this context, the present study investigated whether the lipid components (corn oil) of the maternal diet may (1) lead to developmental programming of the Mongolian gerbil prostate and (2) interfere with the effects caused in this gland by gestational exposure to dibutyl phthalate, and also analyzed (3) the effects of high-saturated lipid intake (diet enriched with lard), from weaning to adulthood, on prostate histophysiology. For this investigation, we used ventral prostatic lobes from adult gerbils (16 weeks old) born from mothers control (C) or those exposed, from gestational day 8 to 23, to corn oil (CO) or dibutyl phthalate (DBP), as well as from gerbils fed a diet with a high-saturated fat content, from weaning to adulthood (D). Data obtained indicate that the maternal intake of corn oil during gestation did not alter the body weight and fat deposits of offspring in adulthood. However, it did increase the serum levels of non-HDL cholesterol and 17beta-estradiol. Histopathological analysis revealed the presence of reactive hyperplasia and PIN in the prostate of the CO animals, associated with enhanced proliferative activity, and AR and ER? expression, and with an activation of the AKT signaling pathway. Exposure to high doses of dibutyl phthalate did not change the metabolic parameters, histophysiology and cell signaling pathways in the prostate of the DBP animals. Nevertheless, such exposure promoted tumorigenesis. The intake of a diet rich in saturated lipids, from weaning to adulthood, induced obesity, caused hypercholesterolemia, altered AR, AKT and TNF-alpha signaling and induced proliferation of stromal cells in the prostate of D animals, favoring the development of inflammatory, premalignant and malignant disorders. In conclusion, maternal intake of corn oil leads to developmental programming of the gerbil prostate, inducing an enhancement of circulating 17beta-estradiol and inflammatory and proliferative lesions in adult life. Its use as a dilutor vehicle in reproductive toxicology research should therefore be avoided. This vegetable oil also masks the effects of gestational exposure to dibutyl phthalate, except in relation to the promotion of prostate adenocarcinoma. High-saturated lipid intake from weaning is harmful to prostate health, favoring the onset of proliferative lesions and carcinoma at the beginning of adult life (AU)