Combined effects of exposure to di-n-butyl phtalate and obesogenic environment on the prostatic response of adult gerbils

Abstract

The prostate is an accessory gland of the male genital tract responsible for the secretion of substances involved in the survival, viability and motility of spermatozoa. Because androgen dependence, this gland is subject to various pathological changes during aging and can be considered an important indicator of reproductive toxicity. Phthalates are used in the manufacture of various products such as cosmetics, food packaging, toys and construction materials. Experimental studies indicate that they act as endocrine disruptors, especially when exposed at high doses and during pregnancy because of altered androgen signaling and impairment of androgen dependent organs. Obesity also affects the steroid hormone milieu, influencing its synthesis and bioavailability, and may thus result in serious fertility problems and increase the incidence of prostate cancer. The aim of this study is to evaluate the combined effects of exposure to the obesogenic environment and low doses of endocrine disruptor di-n-butyl phthalate, from pregnancy to sexual maturity on the tissue response of ventral prostate in adult male gerbils. The obesogenic environment will be induced to the mothers and offspring by consumption of diet containing 20% saturated lipids di-n-butyl phthalate (DBP) will be administered in the drinking water (dose 5 mg/kg body weight/day). The gerbilos adults (14 weeks of age) will be grouped into: Control group (C) - children of mothers treated with balanced diet for rodents and fed the same diet until sexual maturity; Group treated with di-n-butyl phthalate (F) - gerbils subjected to normal diet, according to the group C, but exposed to DBP during gestation, lactation to adulthood; Group subject to the obesogenic environment during pregnancy, lactation until sexual maturity (Ob) - children of mothers treated with high-fat diet and fed the same diet from the weaning until sexual maturity; and Group subject to the obesogenic environment during pregnancy, lactation sexual maturity and concomitant exposure to DBP (ObF) - gerbils fed with high-fat diet, according to the group Ob, and exposed to the DBP during pregnancy, lactation until sexual maturity. The prostatic response will be evaluated on the basis of the histological and stereological analisys and in the incidence and multiplicity of malignant and premalignant lesions. By means of immunocytochemistry will be estimated cell proliferation and death activities and the signaling steroid hormones in the gland will be evaluated on the basis of the expression of the androgen and estrogen type B receptors. We consider that this study will bring new insights for understanding the relationship between obesogenic environment and exposure to endocrine disruptors on the male prostate morphophysiology.