RESUMO
The female prostate, also known as Skene's gland, is present in both humans and rodents. Prenatal exposure to ethinylestradiol (EE2), a synthetic estrogen found in oral contraceptives, induces pormotes neoplasic prostate lesions in gerbils (Meriones unguiculatus). Conversely, pequi oil (Pe), extracted from the Brazilian Cerrado fruit, has antioxidant, anti-inflammatory, and anticancer properties, mitigates risks associated with chronic diseases related to lifestyle and aging. This study evaluates the impact of prenatal exposure to Pe (300 mg/kg) on senile gerbil offspring's male and female prostates under normal conditions and EE2 exposure (15 µg/kg/day). Histological and morphometric analyses revealed that Pe reduced male body weight and prostate epithelial height, along with a thinner muscle layer. In females, EE2 exposure reduced prostatic weight, while Pe exposure lowered epithelial height and the relative stromal compartment volume, increasing the muscle layer. Pequi oil holds potential in mitigating alterations induced by exposure to the endocrine disruptor EE2.
Assuntos
Etinilestradiol , Gerbillinae , Efeitos Tardios da Exposição Pré-Natal , Próstata , Animais , Masculino , Feminino , Próstata/efeitos dos fármacos , Próstata/patologia , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Etinilestradiol/toxicidade , Gravidez , Óleos de Plantas , Envelhecimento/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , EricalesRESUMO
Several pollutants can alter neonatal prostatic development predisposing this gland to diseases. The toxicity and endocrine disrupting potential of aluminum has been reported in many organs, but little is known about its effects on the prostate. This study aimed to evaluate the effects that aluminum neonatal exposure can cause in the male ventral prostate and in the female prostate of adult and senile gerbils. Male and female pups were treated orally with aluminum chloride (10 mg/kg) from the 1st to the 14th day life. After treatment, the animals were aged until they reached 90 days or 1 year of life. The prostate glands were dissected out and submitted to morphological, immunohistochemical and ultrastructural analyses. Ventral prostates of adult males showed moderate hyperplasia and increased epithelial proliferation not associated with androgen receptor (AR) deregulation. On the other hand, senile males showed intense prostatic hyperplasia, and increased cell proliferation and epithelial AR regulation. Additionally, at both ages, there was a reduction in the prostate secretory function. The morphological changes observed in the female prostate were like those found in males. However, in adult females, prostatic hyperplasia was accompanied by a lower regulation of AR and estrogen receptor alpha, while in senile females, intense hyperplastic growth was associated with an increase in estrogen receptor alpha and a reduction in stromal AR. These results demonstrate that aluminum chloride neonatal exposure alters the hormonal regulation of the male and female prostate, inducing tissue damage that occurs in adulthood and intensifies during aging.
Assuntos
Hiperplasia Prostática , Animais , Humanos , Masculino , Feminino , Cloreto de Alumínio/toxicidade , Receptor alfa de Estrogênio , Gerbillinae , Alumínio , Envelhecimento , Receptores AndrogênicosRESUMO
The mammary gland (MG) and female prostate are plastic reproductive organs which are highly responsive to hormones. Thus, endocrine disruptors, such as bisphenol A (BPA) and exogenous estrogens, negatively affect glandular homeostasis. In addition to previously described alterations, changes in inflammatory markers expression also trigger the development of a microenvironment that contributes to tumor progression. The current work aimed to evaluate the inflammatory responses of the MG and prostate gland to BPA (50 µg/kg) and 17-ß estradiol (35 µg/kg) exposure during the perinatal window of susceptibility. The results showed that at 6 months of age there was an increase in the number of phospho-STAT3 (P-STAT3) positive cells in the female prostate from animals perinatally exposed to 50 µg/kg BPA daily. In addition, the number of macrophages increased in these animals in comparison with nonexposed animals, as shown by the F4/80 marker. Despite an increase in the incidence of lobuloalveolar and intraductal hyperplasia, the MG did not show any difference in the expression of the four inflammatory markers evaluated: tumor necrosis factor-α, COX-2, P-STAT3, and F4/80. Analysis of both glands from the same animal led to the conclusion that exposure to endocrine disruptors during the perinatal window of susceptibility leads to different inflammatory responses in different reproductive organs. As the prostate is more susceptible to these inflammatory mechanisms, it is reasonable to affirm that possible neoplastic alterations in this organ are related to changes in the inflammatory pattern of the stroma, a characteristic that is not evident in the MG.
Assuntos
Disruptores Endócrinos/farmacologia , Glândulas Endócrinas/efeitos dos fármacos , Glândulas Mamárias Animais/metabolismo , Animais , Animais Recém-Nascidos/metabolismo , Compostos Benzidrílicos/farmacologia , Disruptores Endócrinos/metabolismo , Glândulas Endócrinas/metabolismo , Estradiol/farmacologia , Feminino , Genitália Feminina/efeitos dos fármacos , Genitália Feminina/metabolismo , Gerbillinae , Humanos , Inflamação/metabolismo , Glândulas Mamárias Animais/efeitos dos fármacos , Fenóis/farmacologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Fator de Transcrição STAT3/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Esteroides/farmacologiaRESUMO
BACKGROUND: The male and female prostates are controlled by steroid hormones, suffering important morphological and physiological changes after castration. Prolactin is involved in the regulation of the male prostate, having already been identified in the tissue, acting through its receptor PRLR. In the Mongolian gerbil, in addition to the male prostate, the female prostate is also well developed and active in its secretion processes. The aim of the present study was to evaluate the effects of exposure to exogenous prolactin in the prostate of both intact and castrated male and female gerbils in order to establish if prolactin administration can sustain prostate cell activity in conditions of sexual hormone deprivation. METHODS: The morphological analyses were performed by biometric analysis, lesion histological analysis and morphometric-stereological aspects. In addition, immune-cytochemical tests were performed for prolactin and its receptor, as well as for the receptors of androgen and oestrogen and serum prolactin dosage. All data were submitted to ANOVA or Kruskal-Wallis tests for comparison between groups. P < 0.05 was considered to be statistically significant. RESULTS: The results showed a strong influence of prolactin on the morphology of the prostate, with the development of important epithelial alterations, after only 3 days of administration, and an expressive epithelial cell discard process after 30 days of administration. Prolactin acts in synergy with testosterone in males and mainly with oestrogens in females, establishing different steroid hormonal receptor immunoreactivity according to sex. It was also demonstrated that prolactin can assist in the recovery from some atrophic effects caused in the gland after castration, without causing additional tissue damage. CONCLUSIONS: The prolactin and its receptor are involved in the maintenance of the homeostasis of male and female gerbils, and also cause distinct histological alterations after exogenous exposure for 3 and 30 days. The effects of prolactin are related to its joint action on androgens and oestrogens and it can also assist in the recovery from the atrophic effects of castration.
Assuntos
Orquiectomia/efeitos adversos , Ovariectomia/efeitos adversos , Prolactina/administração & dosagem , Próstata/efeitos dos fármacos , Próstata/patologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Animais , Atrofia , Feminino , Gerbillinae , Masculino , Orquiectomia/tendências , Ovariectomia/tendências , Prolactina/metabolismo , Próstata/metabolismo , Receptores da Prolactina/agonistas , Receptores da Prolactina/metabolismo , Recuperação de Função Fisiológica/fisiologiaRESUMO
Morphophysiological changes of the female prostate during pregnancy are still little known. Considering that this gland is highly influenced by steroid hormones, the aim of this study was to evaluate the impact of the pregnancy on female prostate morphophysiology in gerbils. Pregnant females were timed, and the prostates were analyzed at pregnancy days 6 (P6), 12 (P12), 18 (P18), and 24 (P24). Virgin females were used as the control group (C). We observed a profound change in the hormonal profile during gestation, which was marked by a high oscillation of the progesterone (P4) hormone. P4 serum levels increased, peaking at the middle of gestation, and decreased to the end of the pregnancy. The morphology of the gland in pregnant females also changed, being marked by an increase of acini lumen, and a decrease in stroma. Indeed, the acinar changes during pregnancy were followed by a significant reduction of the epithelial height, besides a change of the smooth muscle cells' morphology that became more relaxed. The number of progesterone receptor (PR) and androgen receptor (AR)-positives cells decreased with the increase of progesterone serum levels, showing an inverse relationship. Finally, we observed a reduction of epithelial proliferation and a significant increase of gland PAS-positive secretion at the end of pregnancy. Altogether, these results showed, for the first time, that the female prostate morphophysioloy is profoundly influenced by the gestational period, suggesting that the fluctuation of the P4 serum levels is the main factor influencing the gland during this period.
Assuntos
Células Epiteliais/fisiologia , Glândulas Exócrinas/fisiologia , Próstata/fisiologia , Animais , Biomarcadores/sangue , Proliferação de Células , Células Epiteliais/metabolismo , Glândulas Exócrinas/citologia , Glândulas Exócrinas/metabolismo , Feminino , Gerbillinae , Masculino , Gravidez , Progesterona/sangue , Antígeno Nuclear de Célula em Proliferação/metabolismo , Próstata/citologia , Próstata/metabolismo , Antígeno Prostático Específico/metabolismo , Receptores Androgênicos/metabolismo , Receptores de Progesterona/metabolismo , Células Estromais/metabolismo , Células Estromais/fisiologia , Fatores de TempoRESUMO
Female ejaculation is a contentious topic. From a review of the literature, history indicates that it is not a modern concept; some females were aware of it in times past without understanding the role of the fluid or composition of the ejaculate. Over time, scholars experimented, mainly with anatomical studies, in an attempt to identify the source of the ejaculate and explore its physiological and anatomical benefits for the female sexual experience. Despite these studies, views about female ejaculation remain controversial and inconsistent, with no clear conclusion as to its function. This review discusses the history of studies of female ejaculation and presents various hypotheses from an anatomical and physiological perspective. After reviewing 44 publications from 1889 to 2019, it became apparent that clinical and anatomical studies conducted during recent decades provide substantial evidence in support of the female ejaculatory phenomenon. Anatomical studies have shown that the ejaculate originates in the paraurethral (Skene's) glands, but its composition has been debated. Female ejaculate differs from urine in its creatinine and urea concentrations. The fluid also contains prostate specific antigen (PSA) and could have antibacterial properties that serve to protect the urethra. While the specific function of female ejaculation remains a topic of debate, there is sufficient evidence to support the existence of the phenomenon.
Assuntos
Ejaculação/fisiologia , Orgasmo/fisiologia , Comportamento Sexual/história , Comportamento Sexual/fisiologia , Feminino , Genitália Feminina/anatomia & histologia , Genitália Feminina/fisiologia , História do Século XIX , História do Século XX , História do Século XXI , HumanosRESUMO
Since the industrial revolution, all living beings have become susceptible to numerous sources of aluminum (Al) exposure. In addition to causing proven toxicity in many organs and systems, Al can also have estrogenic activity when absorbed by the body. The reproductive organs are commonly affected by environmental pollutants with estrogenic activity, but little is known about the effects of Al on the prostate and gonads. Therefore, the aim of this study was to evaluate the effects of subchronic Al exposure on the prostate and gonads of male and female adult gerbils. After 30 days of oral exposure to aluminum chloride (10 mg/kg/day), the animals were euthanized and the organs processed for cytochemical, ultrastructural, and biochemical assays. Ventral male prostates exposed to Al became hyperplastic and showed signs of cell aging. In addition, the male prostate showed decreased catalase (CAT) and superoxide dismutase (SOD) activity. The female prostate was structurally more affected than the ventral male prostate, since it presented hyperplasia and punctual foci of inflammation and prostatic intraepithelial neoplasia. However, CAT and SOD activities did not change in this gland. In the testis, Al promoted immature germ cell detachment and degeneration, as well as reduced CAT activity. In the ovaries, Al caused reduction in folliculogenesis and decreased SOD activity. Together, these results indicate that Al is toxic to the prostate and gonads of adult gerbils and that continuous exposure to this metal can impair the fertility of individuals of both sexes.
Assuntos
Alumínio/toxicidade , Senescência Celular/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Neoplasia Prostática Intraepitelial/metabolismo , Cloreto de Alumínio/farmacologia , Cloreto de Alumínio/toxicidade , Animais , Catalase/metabolismo , Senescência Celular/genética , Feminino , Gerbillinae/metabolismo , Gônadas/efeitos dos fármacos , Gônadas/metabolismo , Gônadas/patologia , Masculino , Próstata/efeitos dos fármacos , Próstata/metabolismo , Próstata/patologia , Neoplasia Prostática Intraepitelial/induzido quimicamente , Neoplasia Prostática Intraepitelial/patologia , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Testosterona/metabolismoRESUMO
The development and maintenance of prostate function depend on a fine balance between oestrogen and androgen levels. Finasteride inhibits 5α-reductase, which is responsible for the conversion of testosterone into its most active form, dihydrotestosterone. Enzymes that metabolize these hormones have a highly relevant role in both the normal prostate metabolism and in the occurrence of pathological conditions. There are few studies on the impact of finasteride on male prostate development and fewer studies on the female prostate and possible intersexual differences. Therefore, we treated male and female gerbils from 7 to 14 days in postnatal life with a high dose of finasteride (500 µg/kg/day); the prostate complexes were then removed and submitted to immunohistochemistry, immunofluorescence and three-dimensional reconstruction. In addition, hormonal serum dosages were administered. Treatment with finasteride resulted in an increased thickness of the periductal smooth musculature in the prostate of both male and female gerbils, such as well as a reduction in the thickness of developing prostate alveoli in both sexes. In addition, intersexual differences were observed as increased epithelial proliferation and decreases in the number of developing alveoli in females. Together, the data indicate that postnatal exposure to finasteride causes greater changes in the female gerbil prostate than in the male.
Assuntos
Finasterida/toxicidade , Gerbillinae/crescimento & desenvolvimento , Próstata , Animais , Feminino , Masculino , Próstata/efeitos dos fármacos , Próstata/crescimento & desenvolvimento , Receptores Androgênicos/metabolismo , Testosterona/sangueRESUMO
The prostate is an accessory reproductive gland that is sensitive to the action of exogenous compounds known as endocrine disrupters that alter normal hormonal function. Finasteride is a widely used chemical that acts to inhibit the conversion of testosterone in its most active form, dihydrotestosterone. It is known that intrauterine exposure to finasteride causes changes in the male prostate even at low dosages; however, it is not known whether these dosages are capable of causing changes in the female prostate, which is present in a large number of mammalian species, including humans. In the present study, histochemistry, immunohistochemistry, immunofluorescence, serological dosages, and three-dimensional reconstruction techniques were employed to evaluate the effects of intrauterine exposure to a low dose of finasteride (100 µg.BW/d) on postnatal prostate development in male and female Mongolian gerbils. The results indicate that the gerbil female prostate also undergoes alterations following intrauterine exposure to finasteride, exhibiting a thickening of periductal smooth muscle and increased stromal proliferation. There are also intersex differences in the impact of exposure on the expression of the androgen receptor, which was increased in males, and of the estrogen-α receptor, which was decreased in the male prostate but unchanged in females. Altogether, this study indicates there are sex differences in the effects of finasteride exposure even at low dosages.
Assuntos
Desenvolvimento Embrionário/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Finasterida/toxicidade , Genitália Feminina/efeitos dos fármacos , Gerbillinae/embriologia , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Próstata/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Feminino , Genitália Feminina/embriologia , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Próstata/embriologia , Receptores Androgênicos/metabolismo , Reprodução/efeitos dos fármacos , Testosterona/metabolismoRESUMO
The prostate is a gland that is not exclusively present in males, being also found in females of several mammalian species, including humans. There is evidence that the prostate in both sexes is affected by the same pathologies such as prostatitis, benign alterations and even cancer. In view of the difficulties of manipulating the prostate gland, the Mongolian gerbil (Meriones unguiculatus), a rodent species with high incidence of functional prostates in females, is widely used in studies of the female prostate. However, despite knowing much about the similarities between the female and male prostate, little emphasis has been placed on the differences between them. This review investigates the intersex differences in prostate development, physiology and pathogenesis. The female prostate develops earlier than in males and studies indicate that it is more sensitive to oestrogens than the male prostate, as well as being more sensitive to exposure to xenoestrogens, such as Bisphenol A and methylparaben, with a higher susceptibility to benign lesions in the adult and senile prostate than in males. In addition, the female prostate is impacted by pregnancy and the oestrous cycle, and is also dependent on progesterone. The peculiarities of the female prostate raise concerns about the risk of it undergoing neglected changes as a result of environmental chemicals, since safe dosages are established exclusively for the male prostate.
RESUMO
Normal prostate development is highly dependent of an equilibrated hormonal regulation, so that sensible interferences during this period may predispose the gland to lesions during aging. Industrial activities have increased the exposure of this gland to active elements found in environment, such as aluminum (Al). Al presents toxic effect for living beings, having the potential to disrupt the development and growth of several organs and systems. Therefore, the aim of this study was to evaluate whether the prenatal exposure to Al may alter the development and morphophysiology of the gerbil prostate (Meriones unguiculatus). Pregnant females were orally exposed to aluminum chloride (100â¯mg/kg/day) from 17th to 21th gestational day. Following the birth, the male and female pups were euthanized with 1 (PN1) and 90-days-old (PN90). The prostates were collected for biometrical, three-dimensional reconstruction, morphometrical, stereological, and immunohistochemical analysis. Results indicated that Al decreases the body weight of PN1 males and females, and also reduce the anogenital distance of PN1 females. Moreover, Al changed the prostate developmental patterns of PN1 animals, causing an increase in proliferative status and decreasing androgen receptor immunostaining. The results suggest that Al-promoted changes were permanent, since low androgen receptor frequency, increased serum testosterone levels and high proliferation index were observed in adult gerbils. This study demonstrated that body and prostatic changes were more pronounced in females than in males, and that Al performed as an endocrine-disrupting chemical in gerbils.
Assuntos
Cloreto de Alumínio/toxicidade , Disruptores Endócrinos/toxicidade , Efeitos Tardios da Exposição Pré-Natal/patologia , Próstata/efeitos dos fármacos , Animais , Feminino , Gerbillinae , Masculino , GravidezRESUMO
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.
Assuntos
Receptor alfa de Estrogênio/metabolismo , Flavonoides/farmacologia , Próstata/efeitos dos fármacos , Receptores Androgênicos/metabolismo , Animais , Feminino , Gerbillinae , Masculino , Próstata/metabolismo , Maturidade Sexual , Testosterona/análogos & derivados , Testosterona/farmacologia , Regulação para Cima/efeitos dos fármacosRESUMO
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 TGFß1, 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.
Assuntos
Estradiol/toxicidade , Estrogênios/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Próstata/efeitos dos fármacos , Animais , Antígenos CD34/metabolismo , Estradiol/sangue , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Estrogênios/sangue , Feminino , Fator 10 de Crescimento de Fibroblastos/metabolismo , Gerbillinae , Masculino , Troca Materno-Fetal , Gravidez , Próstata/metabolismo , Próstata/patologia , Receptores Androgênicos/metabolismo , Fator de Crescimento Transformador beta1/metabolismoRESUMO
The effects of intrauterine exposure to 17ß-oestradiol (E2) are well studied for the male prostate and there are accumulating evidences that the exposure to high dosages leads to a hypomorphic development. However, there is a lack of information about the effects of intrauterine exposure to E2 in the prostate of rodent females, and such research becomes relevant in view of the presence of functional prostate in a proportion of women, and the morphophysiological similarities between the prostate of female rodents and the prostate of women. This study uses histochemical, immunohistochemical, immunofluorescence and three-dimensional (3D) reconstruction techniques to evaluate the effects of intrauterine exposure to E2 (500 BW/d) on neonatal prostate development in both male and female gerbils. It was verified that intrauterine exposure to E2 promotes epithelial proliferation and growth of prostatic budding in females, whereas in males the prostatic budding shows hypomorphic growth in the VMP (Ventral Mesenchymal Pad) as well as reduced epithelial proliferation. Together, the data demonstrate that intrauterine exposure to E2 causes different effects on male and female prostates of the gerbil even at the early postnatal development of the gland.
Assuntos
Estradiol/metabolismo , Estradiol/farmacologia , Próstata/efeitos dos fármacos , Animais , Animais Recém-Nascidos/embriologia , Animais Recém-Nascidos/metabolismo , Disruptores Endócrinos/metabolismo , Disruptores Endócrinos/farmacologia , Feminino , Gerbillinae/embriologia , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Próstata/embriologia , Receptores Androgênicos/efeitos dos fármacos , Receptores de Estrogênio/efeitos dos fármacos , Fatores SexuaisRESUMO
The female prostate was first described by Reijnier de Graaf in 1672, and even after several years this gland is still a matter of controversy. Part of this is because the biological function of this female gland is unclear. Moreover, when compared with the male prostate, the existence of this organ in females does not make sense, mainly when we consider that the major function of this gland is to produce a secretion that is responsible for guarantee the sperm survival and assure the reproductive success. However, even under a controversy field, we now have a lot of scientific information which enhances our knowledge of several important biological aspects of this gland. It is clear that this gland is found in some female mammals including humans, rodents, rabbits, bats, and dogs. Several studies with rodents showed that the female prostate is homolog of the male prostate, showing strong macroscopic and microscopic similarities with the ventral lobe of males. Besides these aspects, there are several studies reporting that diseases such as cysts, hyperplasia, and carcinoma may affect the female prostate. Therefore, although diseases involving the female prostate are rare, the susceptibility of this organ to develop lesions must be considered, especially in our recent years in which the exposure to endocrine-disrupting chemicals has greatly increased. Finally, further studies will be necessary to enhance our understanding about this gland, mainly of the developmental, evolutionary, and biological functions.
Assuntos
Próstata/patologia , Próstata/fisiologia , Animais , Feminino , Humanos/embriologia , Masculino , Camundongos/embriologia , Sistema UrogenitalRESUMO
Parabens are xenoestrogens widely employed in cosmetics, foodstuffs, and pharmaceutical products. These chemicals are known to disrupt hormone-dependent organs, due to their binding affinity for hormonal receptors. Although recent studies have evaluated the endocrine-disrupting potential of parabens in several reproductive organs, few have investigated the effects of these chemicals in the prostate. The aim of this work was to evaluate the effects of oral exposure to methylparaben (500 mg/kg/day) for 3, 7, and 21 days on male and female adult gerbil prostate. For this purpose, we employed biometrical, morphological, and immunohistochemical analyses. The results showed that methylparaben caused morphological changes in gerbil prostates in all experimental groups. These animals displayed similar alterations such as prostate epithelial hyperplasia, increased cell proliferation, and a higher frequency of AR-positive cells. However, the prostate of the female gerbil showed additional changes such as stromal inflammatory infiltration, intraepithelial neoplasia foci, and an increase in AR-positive frequency. Altogether, these data show that methylparaben was responsible for disrupting estrogenic and androgenic receptors, suggesting that parabens may have estrogenic and antiandrogenic effects in the prostate.
Assuntos
Disruptores Endócrinos/toxicidade , Gerbillinae , Músculo Liso/efeitos dos fármacos , Parabenos/toxicidade , Próstata/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Administração Oral , Animais , Feminino , Masculino , Músculo Liso/metabolismo , Músculo Liso/patologia , Próstata/metabolismo , Próstata/patologia , Receptores Androgênicos/metabolismoRESUMO
The development of the prostate gland in females has not yet been clearly elucidated, and the sexual dimorphism associated with such gland development in general is far from being understood. In the present study, we used tridimensional (3D) reconstructions and histochemical and immunohistochemical techniques to describe the sexual dimorphism and its causes in the early postnatal development of the prostate in male and female Mongolian gerbils (Meriones unguiculatus). We observed that the female prostate was smaller, had fewer branches throughout the development, and underwent differentiation earlier than that in males. Also, the expression of the estrogen receptor 1 (ESR1 or ER-alpha) and fibroblast growth factor 10 (FGF10) was decreased in the periductal region, and the expression of the androgen receptor (AR) was increased in the epithelium. All together, these changes decreased proliferation and branching and led to an earlier prematuration of the female prostate. These new data shed light on the underlying mechanisms involved with the sexual dimorphism in the development of the prostate. Anat Rec, 299:1130-1139, 2016. © 2016 Wiley Periodicals, Inc.
Assuntos
Diferenciação Celular , Receptor alfa de Estrogênio/metabolismo , Organogênese/fisiologia , Próstata/crescimento & desenvolvimento , Receptores Androgênicos/metabolismo , Caracteres Sexuais , Animais , Feminino , Gerbillinae , Técnicas Imunoenzimáticas , Masculino , Próstata/metabolismoRESUMO
The development of the prostate in male rodents, which involves complex epithelial-mesenchymal interactions between the urogenital sinus epithelium (UGE) and the urogenital sinus mesenchyme (UGM), has been deeply studied. In females, however, this process is not very clear. In this study, the postnatal development of the prostate in female Mongolian gerbils employing three-dimensional (3D) reconstructions, histochemical, and immunohistochemical techniques was characterized. It was observed that prostatic branching and differentiation in females was induced by a single mesenchyme localized at a ventrolateral position, which was named as ventrolateral mesenchyme (VLM); furthermore, the canalization of solid buds began on the third postnatal day (P3) and the branching morphogenesis on P5. We observed secretions in the acini at the end of the first month, and, on P45, the acini were completely differentiated. The strong cell proliferation phase in the first week coincided with the mesenchymal expression of estrogen receptor 1 (ESR1). The expression of androgen receptor (AR) paralleled cell differentiation, and, on P30, immunolabelling with p63 was restricted to basal cells. This study serves as a baseline parameter for future research on disruptions that could affect the development of the female prostate.
Assuntos
Gerbillinae/embriologia , Próstata/embriologia , Animais , Diferenciação Celular , Receptor alfa de Estrogênio/metabolismo , Feminino , Gerbillinae/metabolismo , Masculino , Próstata/citologia , Próstata/metabolismo , Receptores Androgênicos/metabolismoRESUMO
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.
Assuntos
Suscetibilidade a Doenças/embriologia , Etinilestradiol/farmacologia , Efeitos Tardios da Exposição Pré-Natal/patologia , Próstata/efeitos dos fármacos , Neoplasia Prostática Intraepitelial/patologia , Neoplasias da Próstata/metabolismo , Envelhecimento/fisiologia , Animais , Animais Recém-Nascidos , Suscetibilidade a Doenças/metabolismo , Estradiol/metabolismo , Estradiol/farmacologia , Feminino , Gerbillinae/crescimento & desenvolvimento , Masculino , Gravidez , Próstata/metabolismo , Neoplasia Prostática Intraepitelial/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Receptores Androgênicos/metabolismo , Testosterona/metabolismo , Testosterona/farmacologiaRESUMO
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.