Ethinylestradiol and its effects on the macrophages in the prostate of adult and senile gerbils.

Prenatal and neonatal exposure to estrogenic compounds, such as ethinylestradiol (EE), promotes a variety of developmental disorders, including malformations and alterations in the morphology of glands, such as the prostate gland. Therefore, the aim of this study was to evaluate the morphological effects of neonatal exposure to EE on prostatic tissue and on the identification and quantification of gerbil gland macrophages in adult and senile Mongolian gerbils. The animals were exposed to EE (10 µg/kg/day) and to the vehicle, mineral oil (100 µL) (control group) during the first 10 days of postnatal life (lactation period). Adult gerbils were euthanized at 120 days and senile gerbils at 12 months of age. Our findings permitted verification of the presence of areas with proliferative foci in the prostate glandular portions in the adult and senile animals exposed to EE. There was also an increase in macrophages in the prostate tissue of adult and senile gerbils; these cell types alter the stromal microenvironment and possibly modify the interactions between the epithelium and stroma. Neonatal exposure to EE changes the pattern of prostatic development, leading to alterations in the arrangement of cells, including macrophages, and may be related to the onset of proliferative disorders in the prostate of adult gerbils and during aging.

Prepubertal chrysin exposure upregulates either AR in male ventral prostate or AR and ERα in Skene's paraurethral gland of pubertal and adult gerbils.

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.

Pubertal exposure to ethinylestradiol promotes different effects on the morphology of the prostate of the male and female gerbil during aging.

In rodents, the final growth and maturation of the prostate occur at puberty, a crucial period for prostate development. The present study is a serological, morphological, morphometric, and immunohistochemical analysis of the effects of exposure to ethinylestradiol (EE) (15 µg/kg/day) during puberty (EE/PUB group) on the male ventral and female prostate in senile gerbils. In the study, male and female gerbils (Meriones unguiculatus) (42 days) received by gavage 15 µg/kg/day of EE (a component of the contraceptive pill), diluted in 100 µL of Nujol® for 1 week (EE/PUB group). In the control group, males and females were not treated. Animals were killed (n = 5) after 12 months in the experimental groups. In the senile male in the EE/PUB group, we observed a reduction in testosterone levels and a decrease in the prostatic epithelial thickness, as well as in the thickness of the muscle layer. In addition, an increase in PIN multiplicity and prostatic inflammation was observed. In the senile female in the EE/PUB group, we observed increased testosterone and estradiol levels, an enhanced prostatic epithelial thickness and an increase in the thickness of the muscle layer. Immunohistochemical analysis revealed an increase in positive cells (%) for AR and PCNA in the male prostate and an increase in positive basal cells for p63 in the female prostate of the EE/PUB group. Exposure to EE during puberty resulted in an inhibitory action on the male ventral prostate and an anabolic effect on the female prostate in senile gerbils. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 477-489, 2017.

Neonatal exposure to ethinylestradiol increases ventral prostate growth and promotes epithelial hyperplasia and inflammation in adult male gerbils.

The aim of this study was to analyse morphologically the ventral prostate of adult Mongolian gerbils exposed to ethinylestradiol (EE) during the first week of postnatal development. Lactating females received daily, by gavage, doses of 10 µg/kg of EE diluted in 100 µl of mineral oil from the 1st to 10th postnatal day of the pups (EE group). In the control group (C), the lactating females received only the vehicle. Upon completing 120 days of age, the male offspring were euthanized and the prostates collected for analyses. We employed morphological, stereological-morphometrical, immunohistochemical and ultrastructural methods. The results showed that the postnatal exposure to EE doubled the prostatic complex weight, increasing the epithelial and stromal compartments, in addition to the secretory activity of the ventral lobe of the prostate. All glands exposed to EE showed strong stromal remodelling, and some foci of epithelial hyperplasia and inflammatory infiltrate in both luminal and epithelial or stromal compartments. Cells positive for anti-AR and anti-PCNA reactions increased into the epithelial and stromal tissues. ERα-positive cells, which are normally found in the stromal compartment of intact prostates, were frequently observed in the prostatic epithelium of treated animals. This study demonstrated that the exposure to EE during postnatal development causes histophysiological alterations in this gland, predisposing to the development of prostatic lesions during life. These results are important for public health, considering that women worldwide have commonly used EE. Moreover, the bioaccumulation of this chemical has increased in different ecosystems.

Prenatal exposure to ethinylestradiol alters the morphologic patterns and increases the predisposition for prostatic lesions in male and female gerbils during ageing.

Ethinylestradiol (EE) is an endocrine disruptor (ED) which acts as an oestrogen agonist; this compound is known as an oral contraceptive. Male and female rodents exposed to EE during critical time points of development, such as in the prenatal period, show alterations in their reproductive tract during adulthood. Few studies have placed an emphasis on the effects of EE during ageing. Thus, this study had as it's objective the analysis of the morphological and immunohistochemical effects of exposure to EE in the prenatal period on ventral male prostate and female prostate of gerbils (Meriones unguiculatus) during ageing. The animals were exposed to EE (15 µg/kg/day) during the 18-22th days of prenatal life (EE/PRE group), and the analyses were performed when the male and female reached 12 months of age. Our results showed an increase in the development of prostatic intraepithelial neoplasia (PIN), which was observed in the male and female prostate of EE/PRE groups. Immunohistochemistry showed a rise in prostatic epithelial and basal cells immunoreactivity, respectively, and to AR and p63 in the male EE/PRE. There were alterations in the morphological pattern of the prostatic glands and increase in predisposition to emergence of prostatic lesions of both sexes during ageing. Despite male and female having been exposed to the same doses of EE, the "exposure to EE promoted modifications" more accentuated in the male prostate. Thus the male gland is more sensitive to the action of this synthetic oestrogen than the female prostate.

Prenatal exposure to testosterone masculinises the female gerbil and promotes the development of lesions in the prostate (Skene's gland).

Androgenic imbalance may disrupt prostate development, leading to morphological alterations in adulthood and predisposing this gland to develop diseases during ageing. However, little is known about the endocrine disruption of the prostate that is caused by androgenic compounds, especially in female experimental models. Therefore, this study aimed to evaluate the prostates of aged female gerbils exposed to testosterone at certain periods in intrauterine and postnatal life, to determine whether exposure at a particular age increases susceptibility to prostatic lesions in these animals. To this end, morphological, stereological, immunohistochemical and immunofluorescence analyses were employed. It was found that females exposed to testosterone during intrauterine life were masculinised, showing increased anogenital distance, absence of the vaginal opening and ectopic development of prostatic tissue. Several areas of adenomatous hyperplasia, generally associated with inflammatory foci and mainly located in the ectopic prostatic tissue around the vaginal wall, were also observed. In conclusion, the results showed that abnormal prenatal exposure to testosterone severely affects the reproductive systems of female animals by disrupting normal prostate morphogenesis and increasing susceptibility to the development of prostatic diseases during ageing.

Microscopic comparative study of the exposure effects of testosterone cypionate and ethinylestradiol during prenatal life on the prostatic tissue of adult gerbils.

There is an increasing variety of endocrine disrupting chemicals (EDCs) either with (anti)estrogenic or (anti)androgenic potential widely present in the environment. These xenosteroids may mimic endogenous steroid hormones disrupting the homeostasis of physiological pathways and leading to several disturbances, especially in tissues highly dependent on steroid hormones such as the prostate. Taking this into account, this comparative study aimed to verify the potential of ethinylestradiol (EE) and testosterone acting as ECDs on the prostate of both male and female adult gerbils exposed to these agents during the embryonic phase. Consequently, pregnant gerbils were treated either with 10 µg/kg/day of EE or with a single dose of 1 mg of testosterone cypionate. The pups that were born 6-8 days after testosterone exposure and the pups that were born after 3 days of EE exposure were allowed to grow but were sacrificed within 4 months. Serological, morphological, stereological, and immunohistochemical analyses were used. Overall, the results showed that both sexes exposed to testosterone and EE during gestation had a prostatic gland with an increased stromal and epithelial and a reduced luminal compartment. Moreover, we observed that glands affected with prostatic intraepithelial neoplasia showed intense stromal reshuffling. In conclusion, although these alterations were observed in both sexes, more relevant to this study was the differential responsiveness of males and females exposed to these different drugs. Whereas the EE affected males more, the testosterone was more harmful to the females.

Hormonal oscillations during the estrous cycle influence the morphophysiology of the gerbil (Meriones unguiculatus) female prostate (skene paraurethral glands).

The hormonal oscillations that occur during the female reproductive cycle influence the morphophysiology of several organs of the reproductive system. The female prostate is a functional organ sensitive to the action of steroidal hormones, but it is not known whether the hormonal oscillations that occur during the reproductive cycle can alter the biology of this gland. Thus, the present work aims to evaluate the morphofunctional aspects of the female prostate during the gerbil estrous cycle. For this purpose, morphological, morphometric-stereological, serological, and immunocytochemical analyses were carried out. The results of the present study show that the hormonal oscillations that occurred during the estrous cycle altered both the structure and functionality of the gerbil female prostate. These alterations include increased prostatic growth and augmented secretory activity during the proestrus and estrus phases and a gradual decrease of the secretory activity and glandular development in the diestrus I and II phases. These cyclical oscillations appear to be determined by the hormonal peaks of estrogen in diestrus II and by the high levels of progesterone during estrus, since the androgen levels remained constant throughout the estrous cycle.