Substances that mimic endogenous hormones may alter the cell signaling that govern prostate development and predispose it to developing lesions in adult and senile life. Bisphenol A is able to mimic estrogens, and studies have demonstrated that low levels of exposure to this compound have caused alterations during prostate development. The aim of this study was to describe the prostate development in both male and female neonatal gerbils in normal conditions and under exposure to BPA during intrauterine life, and also to analyze whether the effects of intrauterine exposure to BPA remain in adulthood. Morphological, stereological, three-dimensional reconstruction, and immunohistochemical methods were employed. The results demonstrated that in 1-day-old normal gerbils, the female paraurethral glands and the male ventral lobe are morphologically similar, although its tissue components-epithelial buds (EB), periurethral mesenchyme (PeM), paraurethral mesenchyme (PaM) or ventral mesenchymal pad (VMP), and smooth muscle (SM)-have presented different immunolabeling pattern for androgen receptor (AR), and for proliferating cell nuclear antigen (PCNA). Moreover, we observed a differential response of male and female prostate to intrauterine BPA exposure. In 1-day-old males, the intrauterine exposure to BPA caused a decrease of AR-positive cells in the PeM and SM, and a decrease of the proliferative status in the EB. In contrast, no morphological alterations were observed in ventral prostate of adult males. In 1-day-old females, BPA exposure promoted an increase of estrogen receptor alpha (ERα) positive cells in PeM and PaM, a decrease of AR-positive cells in EB and PeM, besides a reduction of cell proliferation in EB. Additionally, the adult female prostate of BPA-exposed animals presented an increase of AR- and PCNA-positive cells. These results suggest that the prostate of female gerbils were more susceptible to the intrauterine BPA effects, since they became more proliferative in adult life. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1740-1750, 2016.

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Prostate physiology is highly dependent on oestrogenic and androgenic homeostasis. Interferences in this equilibrium, especially in early periods of life, may disrupt the prostate and increase the susceptibility to the development of diseases with ageing. Taking this into account, and considering the increase of environmental chemicals with endocrine-disrupting potential such as bisphenol-A (BPA), this study aimed to evaluate the prostates of adult female gerbils exposed to BPA and BPA plus testosterone from pubertal to adult periods. Morphological, stereological and chemical analyses revealed that long-term BPA exposure, even in environmental dosages, increases the proliferative status of the prostate, increases the number of ERα-positive stromal cells and elicits the development of prostatic hyperplasia in adult female gerbils. Moreover, we also observed that the association with testosterone did not increase the proliferative status of the gland, which shows that low levels of BPA are enough to cause an oestrogenic disruption of the prostate in young adults. This evidence suggests that this oestrogenic endocrine disruptor may increase the susceptibility to prostatic disorders with ageing.

Chrysin is a plant-derived polyphenol that has the potential to increase endogenous testosterone levels both by inhibiting the aromatase enzyme and by stimulating testicular steroidogenesis. The effects of chrysin on the prostate are unknown, especially during its development and functional maturation. Thus, the aim of this study was to evaluate the effects of chrysin prepubertal exposure on the male and female prostates of both pubertal and adult gerbils. To evaluate the possible androgenic responses of chrysin, gerbils were also exposed to testosterone. Male and female gerbils were exposed to chrysin or to testosterone cypionate from postnatal day 15 to 42. Male and female gerbils were euthanized at either 43days or 90days age. The prostates were collected for biometrical, morphological and immunohistochemical analysis. The results showed that prepubertal exposure to chrysin had differential effects on the prostate of both pubertal and adult animals. The prostates of male and female pubertal gerbils showed no histological alterations, although there was increased frequency of androgen receptor (AR) in males and females, and estrogen receptor alpha (ERα) in females. Adult males and females presented developed prostate glands, with higher cell proliferative rate. In addition, AR and ERα frequency remained high in the prostate of adult animals. These results demonstrated that prepubertal exposure to chrysin disrupts steroid receptors regulation in the prostate, potentiating the response of this gland to the biological effects of endogenous steroids. In this context, excessive consumption of phytoestrogens during the critical stages of development should be considered with caution.