Postnatal exposure to finasteride causes different effects on the prostate of male and female gerbils (original) (raw)
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Prenatal exposure to finasteride promotes sex-specific changes in gerbil prostate development
Reproduction, Fertility and Development, 2019
Finasteride is a drug that is widely used in the treatment of benign prostatic hyperplasia, hair loss and even as a chemotherapeutic agent in the treatment of prostatic adenocarcinoma. However, its use is known to cause several side effects in adults and it can also cause changes in the embryonic development of the male prostate, which is a cause for concern given the possibility of the accumulation of finasteride in the environment. Nevertheless, no studies have investigated the effects of finasteride on the development of the prostate in females, which occurs in several species of mammals. To evaluate the effects of intrauterine exposure to finasteride (500μgkg−1 day−1) on postnatal prostate development in the Mongolian gerbil in the present study, we used immunohistochemistry, immunofluorescence, serological analysis and three-dimensional reconstruction techniques. Differences were observed in the effects of finasteride on periductal smooth muscle and cell proliferation between t...
Reproduction, Fertility and Development, 2015
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 ...
Microscopy Research and Technique, 2012
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 lg/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.
International journal of experimental pathology, 2016
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. Immunohistoche...
International journal of experimental pathology, 2016
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 a...
International Journal of Experimental Pathology, 2009
As local steroid metabolism controls the bioavailability of active steroidal hormones in the prostate, the aim of this study, was to investigate the effects of absence of 5-alpha reductase (5a-r) and aromatase (Aro) enzymes on prostatic cellular and extracellular components after long-term inhibition. Young, adult and old male Mongolian gerbils were treated orally, once a day, for 30 consecutive days, with Finasteride (10.0 mg ⁄ kg) and Letrozole (1.0 mg ⁄ kg) (5a-r and Aro enzymes inhibitors respectively) simultaneously or separately. Animals were killed on 1, 7, 14 and 21 days post-treatment. Data obtained after double or single enzymatic inhibition with Finasteride and Letrozole demonstrated marked remodelling of epithelial and stromal compartments. During the post-treatment period, particularly on the first and the last analysed days, prostatic epithelial cells showed decreased cytoplasmic volume and secretory activity. In the stroma, collagen fibres had accumulated in the epithelial base and among smooth muscle cells, which showed reduced diameter and condensed cytoplasm, and some of them had a highly irregular external contour. Also in the sub-epithelial area, some fibroblasts acquired an activated phenotype besides increased deposits of amorphous granular material. In conclusion, the inhibition of 5a-r and Aro enzymes affected, in a persistent manner, the structural and ultrastructural morphology of the prostate, irrespective of the gerbil¢s age. Hence these enzymes appear to be crucial in the maintenance of this gland during postnatal development. Also, these data bring more light to the complex issue of the mechanisms of local steroid metabolism and prostatic histology. Thus, the blockade of the steroidmetabolizing enzymes provided an important novel tool to study the relationship between sex steroids and normal physiology and diseases of the prostate.
Biology of Reproduction, 2008
The present work aims to evaluate the response of the adult gerbil female prostate (paraurethral glands) and ovaries to shortterm exposure to antiestrogenic agents, consisting of daily oral doses of letrozole (1 mg kg À1 day À1) or intradermal doses of tamoxifen (1 mg/kg) every other day for 21 days. The serum levels of testosterone and estradiol were monitored, and the prostates and ovaries collected for structural, ultrastructural, and immunocytochemical analyses. The letrozole treatment resulted in increases of serum testosterone levels and secretory activity as well as in glandular hyperplasia and dysplastic growth, simulating the effects caused by the exogenous androgens. The effects caused by tamoxifen indicate that this endocrine agent acted as an estrogenic agonist on the prostate, causing glandular hypertrophy, secretory activity decrease, and the development of prostatic lesions. Therefore, it is possible to conclude that the letrozole and tamoxifen therapies result in a series of complex effects that endanger the physiology of hormone-dependent organs, including the female prostate and ovaries. The hormonal imbalance caused by administration of these drugs resulted in considerable changes in prostatic morphology, in a manner very similar to what occurs during the development of prostatic lesions in aged postmenopausal women. Thus, these therapies must be chosen carefully since long-term treatments can result in female prostate dysplasic lesions.
Reproductive Toxicology, 2017
We employed histological techniques to assess the effects of intrauterine exposure to different dosages of E2 on male and female Mongolian gerbils on the postnatal development of the prostate. E2 promotes alterations this gland branches in the female, but not in males, even at low dosage, at higher dosages, acini of altered aspect are verified in the male and female prostate, as well as a decrease in branching number, reduced cell proliferation and staining for FGF10, simultaneously to the increased labelling for TGF1, which may account for alterations on branching of the prostate. The sensitivity of the female prostate to intrauterine exposure to E2, which can reflect the E2 dependence of female prostate development. This becomes alarming in view of the occurrence of prostate in female of several mammals and including women, and the possibility that low E2 dosage exposures considered safe to males provoke developmental alterations in female prostate.