RESUMEN
Paradoxical sleep deprivation (PSD) presents different effects on metabolism and neurological functions. In addition, over long duration, sleep restriction (SR) can promote permanent changes. The prostate is an endocrine-dependent organ with homeostatic regulation directly related to hormone levels. Our study proposed to demonstrate the experimental prostatic effects of PSD (96 h), PSD with recovery (PSR - 96/96 h), and sleep restriction (SR - 30 PSD cycles/recovery). PSD and SR promoted decrease in serum testosterone and significant increase in serum and intraprostatic corticosterone. In agreement, androgen receptors (AR) were less expressed and glucocorticoid receptors (GR) were enhanced in PSR and SR. Thus, the prostate, especially under SR, demonstrates a castration-like effect due to loss of responsiveness and sensitization by androgens. SR triggered an important inflammatory response through enhancement of serum and intraprostatic pro- (IL-1α, IL-6, TNF-α) and anti-inflammatory (IL-10) cytokines. Furthermore, the respective receptors of anti-inflammatory cytokines (IL-1RI and TNF-R) were highly expressed in the prostatic epithelium and stroma. PSR can partially restore prostate homeostasis, as it restores testosterone and the prostate proliferation index, in addition to promoting balance in the inflammatory response that is considered protective. PSD and SR are key factors in the endocrine axis that coordinate prostatic homeostasis, and significant changes in these factors have consequences on prostate functionality.
Asunto(s)
Gerbillinae , Próstata , Receptores Androgénicos , Privación de Sueño , Testosterona , Animales , Masculino , Privación de Sueño/metabolismo , Privación de Sueño/patología , Próstata/metabolismo , Próstata/patología , Testosterona/sangre , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Receptores de Glucocorticoides/metabolismo , Receptores de Glucocorticoides/genética , Corticosterona/sangre , Citocinas/metabolismo , Inflamación/metabolismo , Inflamación/patología , Castración , Andrógenos/metabolismoRESUMEN
The aim of this study was to evaluate the effects of chrysin on the ventral prostate of spontaneously hypertensive rats (SHR). Ten-week-old male Wistar and SHR rats received 100 mg/kg/day of chrysin (TW and TSHR) or 200 µL/day of the dilution vehicle (CW and CSHR) for 70 days. After the treatment, the animals were euthanized and the prostates were dissected out, fixed, and processed for further morphological, immunohistochemical, and biochemical analyses. Blood was collected for serological analysis. Chrysin did not interfere with the blood pressure. Morphologically, the epithelial height increased in TW and decreased in TSHR. Stereology showed an increase in the epithelial and stromal relative frequency, and a decrease in the lumen of TW, whereas the epithelium in TSHR was reduced. Normal alveoli decreased, and hyperplastic alveoli had an increment in TW, whereas in TSHR normal alveoli increased and intense hyperplasia decreased. The secretion area was reduced in TW. Immunohistochemical analysis showed a smaller number of PCNA-positive cells in TW. Finally, the biochemical analysis showed a reduction in malondialdehyde, carbonylated proteins, superoxide dismutase, and catalase in TW and TSHR. We concluded that the chrysin effect is dependent on the context in which this flavonoid is employed. In normal conditions, the anabolic potential of the chrysin was favored, disrupting the morphology of the prostate. However, when used in animals predisposed to develop hyperplasia, this flavonoid attenuates the hyperplastic status, improving the morphology of the gland.
Asunto(s)
Flavonoides , Próstata , Hiperplasia Prostática , Animales , Masculino , Ratas , Presión Sanguínea/efectos de los fármacos , Flavonoides/farmacología , Próstata/efectos de los fármacos , Próstata/patología , Próstata/metabolismo , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/patología , Hiperplasia Prostática/metabolismo , Ratas Endogámicas SHR , Ratas Wistar , Superóxido Dismutasa/metabolismoRESUMEN
Molossus molossus is an insectivorous molossid bat that is important in the control of nocturnal insects. It is the nominal and the most representative species of the family. However, there are few studies about its reproduction. Thus, this study aimed to evaluate variations of its female reproductive organs during the different reproductive phases. Twenty adult females, divided into four sample groups (non-reproductive, early and advanced pregnancy and lactation), were submitted to morphological and morphometric analyses. Results show that the female reproductive system of M. molossus is composed of ovaries, a short bicornuate uterus, slightly convoluted uterine tubes and vagina. The system presents a distinct morphofunctional asymmetry, with a marked dextro-dominance. The right ovaries of all analyzed groups (NON, P1, P2, and LAC) showed follicles at different stages of development, a large number of interstitial glands and a small, but persistent corpus luteum. Ovulation is simple, unilateral and preferential, occurring exclusively in the right ovary. Follicular development in the left ovary usually does not pass the secondary stage. Implantation is fundic and preferential, occurring exclusively in the right uterine horn. The placenta is formed with two distinct chorioallantoic portions, one diffuse endotheliochorial, which covers the entire uterine cavity and regresses in the final stages of pregnancy, and the principal discoidal hemochorial portion, formed in the implantation site. The uterine cervix presents a pseudostratified epithelium, while the vagina has a little keratinized stratified epithelium, which does not accentually vary in the different reproductive stages, but can disrupt and shed in some cases.
Asunto(s)
Quirópteros , Embarazo , Animales , Femenino , Quirópteros/anatomía & histología , Útero , Reproducción/fisiología , Placenta , VaginaRESUMEN
Artibeus lituratus is one of the most well-known bat species in the Neotropics, probably due to its high abundance and the ability to inhabit urban areas. It plays an important ecological role in the ecosystem due to its ability to disperse seeds, which contributes to the regeneration of degraded areas. Actually, the species has been used as an important experimental model for ecotoxicological studies of the impact of pesticides on male reproduction. Despite that, the reproductive pattern of A. lituratus is still controversial due to inconsistent descriptions of the reproductive cycle. Thus, the aim of the present work was to evaluate the annual variations of the testicular parameters and sperm quality of A. lituratus and analyze their responses to annual variations in abiotic factors in the Cerrado area in Brazil. Testes of five specimens were collected each month for one year (12 sample groups) and submitted to histological, morphometric, and immunohistochemical analyses. Analyses of the sperm quality were also performed. Results demonstrate that A. lituratus presents a continuously active process of spermatogenesis throughout the year, with two significant peaks in spermatogenic production (September-October and March), which indicates a bimodal polyestric pattern of reproduction. These reproductive peaks seem to be related to an increase in proliferation and, consequently, in the number of spermatogonia. Conversely, seasonal variations in testicular parameters are correlated with annual fluctuations in rainfall and photoperiod but not with temperature. In general, the species presents smaller spermatogenic indexes with a similar sperm quantity and quality to other bat species.
Asunto(s)
Quirópteros , Testículo , Masculino , Animales , Quirópteros/metabolismo , Frutas , Ecosistema , Semillas , Reproducción/fisiología , Espermatozoides , Estaciones del AñoRESUMEN
Inflammation in the established tumor microenvironment (TME) is often associated with a poor prognosis of breast cancer. Bisphenol A (BPA) is an endocrine-disrupting chemical that acts as inflammatory promoter and tumoral facilitator in mammary tissue. Previous studies demonstrated the onset of mammary carcinogenesis at aging when BPA exposure occurred in windows of development/susceptibility. We aim to investigate the inflammatory repercussions of BPA in TME in mammary gland (MG) during neoplastic development in aging. Female Mongolian gerbils were exposed to low (50 µg/kg) or high BPA (5000 µg/kg) doses during pregnancy and lactation. They were euthanized at 18 months of age (aging) and the MG were collected for inflammatory markers and histopathological analysis. Contrarily to control MG, BPA induced carcinogenic development mediated by COX-2 and p-STAT3 expression. BPA was also able to promote macrophage and mast cell (MC) polarization in tumoral phenotype, evidenced by pathways for recruitment and activation of these inflammatory cells and tissue invasiveness triggered by tumor necrosis factor-alpha and transforming growth factor-beta 1 (TGF-ß1). Increase of tumor-associated macrophages, M1 (CD68 + iNOS+) and M2 (CD163+) expressing pro-tumoral mediators and metalloproteases was observed; this aspect greatly contributed to stromal remodeling and invasion of neoplastic cells. In addition, the MC population drastically increased in BPA-exposed MG. Tryptase-positive MCs increased in disrupted MG and expressed TGF-ß1, contributing to EMT process during carcinogenesis mediated by BPA. BPA exposure interfered in inflammatory response by releasing and enhancing the expression of mediators that contribute to tumor growth and recruitment of inflammatory cells that promote a malignant profile.
Asunto(s)
Factor de Crecimiento Transformador beta1 , Microambiente Tumoral , Embarazo , Femenino , Humanos , Compuestos de Bencidrilo , Carcinogénesis , FenotipoRESUMEN
Despite the high number of species and wide geographic dispersion, reproductive accessory glands (RAGs) of bats have traditionally received little attention in the literature, with some species not even having a basic description of their composition and structure. Thus, this study aimed to analyze and compare the composition, anatomy, and histology of male RAGs of bat species belonging to three of the largest (cosmopolitan) bat families: Vespertilionidae (Histiotus velatus), Molossidae (Molossus rufus), and Emballonuridae (Peropteryx leucoptera), in order to understand the variations in the bat RAGs. The results showed that the RAGs of H. velatus, M. rufus, and P. leucoptera are composed of an intra-abdominal prostatic complex, associated with the urethra, urethral glands, and a pair of inguinal bulbourethral glands; without ampullary glands or seminal vesicles. The prostatic complex can be composed of two (M. rufus and P. leucoptera) or three (H. velatus) prostatic regions, and can be compact (P. leucoptera), semi-lobed (M. rufus), or multilobed (H. velatus). Each prostatic region has unique and distinct characteristics, with the ventral region presenting a holocrine nature, exclusive to bats; while the dorsal and/or dorsolateral regions have similar characteristics to the ventral prostate of rats and to the human peripheral zone.
Asunto(s)
Quirópteros , Humanos , Masculino , Animales , Ratas , Quirópteros/anatomía & histología , Próstata/anatomía & histología , Glándulas Bulbouretrales/anatomía & histología , Uretra , ReproducciónRESUMEN
BACKGROUND: The aim of this study was to evaluate modifications in proteoglycan morphology and composition in the prostatic stroma of 18-month-old gerbils after surgical castration, in association or not with an androgenic blockade. METHODS: The animals (n = 5) were sorted into groups subjected or not to antiandrogen treatment (flutamide 10 mg/kg/day) administered for the total postsurgery period and euthanized at 7- or 30-day postcastration; the control group consisted of intact animals. Tissue analysis included immunohistochemical assessment (perlecan and chondroitin sulfate) and proteoglycan morphology was analyzed by transmission electron microscopy. RESULTS: Chondroitin sulfate frequency was increased 7 days postcastration with an androgenic blockade. The presence of these carbohydrates was rare after 30 days of androgenic blockade treatment. There was a significant increase in the amount of perlecan in the prostate stroma from groups subjected to castration plus flutamide for 7 or 30 days. Ultrastructural analysis showed that the incidence of areas occupied by proteoglycans and basement membrane was altered by treatment. In addition, androgenic blockade results in changes in the amount, thickness, and morphology of these structures. At 30 days postcastration, with or without flutamide treatment, larger proteoglycans were common. CONCLUSIONS: In this study, in particular, the decrease in chondroitin sulfate after the longer period might be understood as a prostatic response to androgenic deprivation, while the high frequency and permanence of perlecan led to the assumption that its modulation could be androgen-independent. Length and form alterations in proteoglycans as well as associations among them and with the basement membrane were dynamic events in the prostate microenvironment.
Asunto(s)
Flutamida , Próstata , Masculino , Animales , Flutamida/farmacología , Gerbillinae , Andrógenos/farmacología , Sulfatos de Condroitina/farmacología , OrquiectomíaRESUMEN
BACKGROUND: In vitro studies evidenced antitumor effects of omega-3 polyunsaturated fatty acids ([n-3] PUFAs), but their effects on prostate cancer (PCa) remain controversial in epidemiological studies. Here we investigated whether an (n-3) PUFA-enriched diet affects tumor progression in transgenic adenocarcinoma of the mouse prostate (TRAMP), at early (12 weeks age) and advanced stages (20 weeks age). METHODS: TRAMP mice were fed with standard rodent diet (C12, C20) or (n-3) PUFA-enriched diet containing 10% fish oil (T12, T20). A group of 8 weeks age animals fed standard diet was also used for comparison (C8). The ventral prostate was processed for histopathological and immunohistochemical analyses and serum samples submitted to biochemical assays. RESULTS: At early stages, (n-3) PUFA increased the frequency of normal epithelium (3.8-fold) and decreased the frequency of high-grade intraepithelial neoplasia (3.3-fold) and in situ carcinoma (1.9-fold) in the gland, maintaining prostate pathological status similar to C8 group. At advanced stages, 50% of the animals developed a large primary tumor in both C20 and T20, and tumor weight did not differ (C20: 2.2 ± 2.4; T20: 2.8 ± 2.9 g). The ventral prostate of T12 and of T20 animals that did not develop primary tumors showed lower cell proliferation, tissue expressions of androgen (AR) and glucocorticoid (GR) receptors, than their respective controls. For these animals, (n-3) PUFA also avoided an increase in the number of T-lymphocytes, collagen fibers, and αSMA immunoreactivity, and preserved stromal gland microenvironment. (n-3) PUFA also lowered serum triglycerides and cholesterol, regulating the lipid metabolism of TRAMP mice. CONCLUSIONS: (n-3) PUFAs had a protective effect at early stages of PCa, delaying tumor progression in TRAMP mice, in parallel with reductions in cell proliferation, AR, and GR and maintenance of the stromal compartment of the gland. However, (n-3) PUFAs did not prevent the development of primary tumors for the T20 group, reinforcing the need for further investigation at advanced stages of disease.
Asunto(s)
Adenocarcinoma , Ácidos Grasos Omega-3 , Neoplasias de la Próstata , Humanos , Masculino , Ratones , Animales , Ratones Transgénicos , Próstata/patología , Neoplasias de la Próstata/patología , Adenocarcinoma/patología , Ácidos Grasos Omega-3/farmacología , Procesos Neoplásicos , Ácidos Grasos Insaturados/metabolismo , Microambiente TumoralRESUMEN
The prostate is not an organ exclusive to the male. It is also found in females of several species, including humans, in which part of the Skene gland is homologous to the male prostate. Evidence is accumulating that changes in the stroma are central to tumorigenesis. Equally, telocytes, a recently discovered type of interstitial cell, are essential for the maintenance of stromal organization. However, it is still uncertain whether there are telocytes in the female prostate and if they play a role in tumorigenesis. The present study used ultrastructural and immunofluorescence techniques to investigate the presence of telocytes in the prostate of Mongolian gerbil females, a rodent model that often has a functional prostate in females, as well as to assess the impact of a combination of N-ethyl-N-nitrosourea, testosterone, and estradiol on telocytes. The results point to the presence of telocytes in the female prostate in the perialveolar and interalveolar regions, and reveal that these cells are absent in regions of benign and premalignant lesions in the gland, in which the perialveolar smooth muscle is altered. Additionally, telocytes are also closely associated with infiltrated immune cells in the stroma. Our data suggest that telocytes are important for both the maintenance of smooth muscle and prostatic epithelium integrity, which indicates a protective role against the advancement of tumorigenesis. But telocytes are also associated with immune cells and a proinflammatory/proangiogenic role for these cells cannot be ruled out, implying that telocytes have a complex role in prostatic tumorigenesis in females.
Asunto(s)
Próstata , Telocitos , Animales , Antígenos CD34/metabolismo , Carcinogénesis/metabolismo , Femenino , Gerbillinae/metabolismo , Humanos , Masculino , Próstata/metabolismo , Telocitos/metabolismoRESUMEN
The presence of the prostate in female mammals has long been known. However, pieces of information related to its development are still lacking. The aim of this study was to explore the budding dynamic during the initial prostate development in female gerbils. Pregnant females were timed, the fetuses were euthanized, and the urogenital sinus was dissected out between the embryonic days 20 and 24 (E20-E24 groups). Newborn pups (1-day-old; P1 group) underwent the same procedures. The female prostate development was based on epithelial buds which arose far from the paraurethral mesenchyme (PAM). The epithelial buds reached the PAM at prenatal day 24, crossing a small gap in the smooth muscle layer between the periurethral mesenchyme (PEM) and the PAM. Steroid nuclear receptors such as the androgen receptor and estrogen receptor alpha were localized in the PEM through the urethral wall, although some epithelial labeling was also present in the urogenital sinus epithelium (UGE). P63-positive cells were found only in the UGE, becoming restricted to the basal compartment after the 23rd prenatal day. The results showed that the gerbil female prostate exhibits a distinct budding pattern as compared to the male prostate development.
Asunto(s)
Próstata , Sistema Urogenital , Animales , Epitelio , Femenino , Gerbillinae , Humanos , Recién Nacido , Masculino , Mesodermo , EmbarazoRESUMEN
Advances in prostatic stroma studies over the past few decades have demonstrated that the stroma not only supports and nourishes the gland's secretory epithelium but also participates in key aspects of morphogenesis, in the prostate's hormonal metabolism, and in the functionality of the secretory epithelium. Furthermore, the stroma is implicated in the onset and progression of prostate cancer through the formation of the so-called reactive stroma, which corresponds to a tumorigenesis-permissive microenvironment. Prostatic stromal cells are interconnected and exchange paracrine signals among themselves in a gland that is highly sensitive to endocrine hormones. There is a growing body of evidence that telocytes, recently detected interstitial cells that are also present in the prostate, are involved in stromal organization, so that their processes form a network of interconnections with both the epithelium and the other stromal cells. The present review provides an update on the different types of prostate stromal cells, their interrelationships and implications for prostate development, physiology and pathological conditions.
Asunto(s)
Próstata/patología , Células del Estroma/patología , Animales , Humanos , Masculino , Comunicación Paracrina/fisiología , Neoplasias de la Próstata/patologíaRESUMEN
This study evaluated such as exposure to ethinylestradiol during the prenatal (18th-22nd day) and pubertal (42nd-49th day) periods acts on the male ventral prostate and female prostate of 12-month old gerbils. We performed the analysis to serum hormone levels for estradiol and testosterone. The prostates were submitted to morphometric and immunohistochemical analyses. Exposure to ethinylestradiol during these developmental periods decreased the testosterone serum levels in males and increased the estradiol serum levels in females. Morphologically, prostate intraepithelial neoplasia and disorders in the arrangement of the fibrous components were observed in the prostate glands of both sexes of gerbil exposed to ethinylestradiol during development periods. In the male prostate, the ethinylestradiol promoted decreased in the frequency of positive epithelial cell for androgen receptor (AR) and increased the frequency of positive stromal cell for estrogen receptor α. However, in the female prostate, this synthetic estrogen caused AR upregulation and increased cell proliferation. This study shows that the exposure to ethinylestradiol during development phases alters the morphology and the hormonal signaling in the male and female prostates of old gerbils, confirming the action of ethinylestradiol as endocrine disruptor.
Asunto(s)
Células Epiteliales/citología , Etinilestradiol/farmacología , Efectos Tardíos de la Exposición Prenatal/patología , Próstata/anatomía & histología , Animales , Animales Recién Nacidos , Proliferación Celular , Células Epiteliales/efectos de los fármacos , Estrógenos/farmacología , Etinilestradiol/administración & dosificación , Etinilestradiol/toxicidad , Femenino , Gerbillinae , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Próstata/efectos de los fármacosRESUMEN
The prostate is an important gland that contributes to the male reproductive process, producing secretions that are essential for maintaining ideal conditions for the survival of sperm. Studies indicate a wide variation in the occurrence, morphology, and physiology of this gland in mammals, especially in bats, with this variation being related not only to the number of regions and their degree of compaction/lobulation but also to fluctuations in their functioning throughout the year. Thus, the aim of this study was to evaluate the annual morphological and physiological variations of the male prostate of Artibeus lituratus and analyze their responses to annual abiotic variations and hormonal control. Sixty sexually adult males of A. lituratus were analyzed in this study, with five specimens collected monthly. Blood samples were submitted to serum hormone measurements and the prostates were morphologically, morphometrically, and immunohistochemically analyzed. The results indicated that the two prostatic regions (ventral and dorsal) of A. lituratus had different morphology, as well as different physiology and regulation. Annual fluctuations in abiotic factors seemed to influence the dorsal region more than the ventral region. Conversely, variations on testicular factors, such as testosterone and estradiol, influenced the ventral region more than the dorsal region. Despite these differences, both prostatic regions were strongly synchronized to the main reproductive peak of the species in September. The holocrine pattern of the ventral prostate was not directly affected by abiotic factors or by factors released by the testes.
Asunto(s)
Quirópteros , Próstata , Animales , Masculino , Reproducción , Estaciones del Año , TestículoRESUMEN
Myotis nigricans is a species of bat from the Vespertilionidae family that is endemic of the Neotropical region. Its insectivorous feeding habit plus its large range of prey species, great geographical dispersion, wide colonies, and anthropomorphized behavior make this species an important ecological agent that acts in the control of nocturnal insects. Reproductively, M. nigricans presents geographic variations, having different patterns of reproduction according to its geographical location. Despite these extremely interesting characteristics, no more detailed study of the hormonal control of the reproduction of this species has been conducted. Therefore, the aim of the present study was to evaluate the variations in serum hormone concentrations and in uterine hormonal control of this bat during its different reproductive phases. Twenty adult females were collected, divided into four (4) sample groups, according to the reproductive status (nonreproductive, initial, and advanced pregnancy and lactating), and submitted to hormone dosage and immunohistochemical analyses. The results demonstrated that the uterus of M. nigricans is strongly regulated by the interaction/cross-talk between serum concentrations of estradiol (E2) and progesterone with their respective hormone receptors. Significant increases in the concentration of E2 and progesterone are needed to regulate the early pregnancy. The persistence of the corpus luteum throughout pregnancy is necessary, since its placenta does not express aromatase. The expressions of ERα and PR appear to be synchronized in order to coordinate a large portion of the processes that occur inside the uterus of M. nigricans during pregnancy and lactation.
Asunto(s)
Estradiol/metabolismo , Progesterona/metabolismo , Útero/fisiopatología , Animales , Quirópteros , Femenino , Embarazo , ReproducciónRESUMEN
Imbalance of sexual steroids milieu and oxidative stress are often observed during aging and correlated to prostate disorders. Likewise, high-fat intake has been related to prostate damage and tumor development. Melatonin (MLT) is an antioxidant whose secretion decreases in elderly and is also suggested to protect the gland. This study evaluated the impact of a long-term high-fat diet during aging on prostate morphology and antioxidant system of rats and tested the effects of MLT supplementation under these conditions. Male rats were assigned into four groups: control, treated with MLT, high-fat diet and high-fat diet treated with MLT. The high-fat diet was provided from the 24th week of age, MLT from the 48th (100 µg/kg/day) and rats were euthanized at the 62nd week. The high-fat diet increased body weight, retroperitoneal fatness, glycaemia, and circulating estrogen levels. It aggravated the aging effects, leading to epithelial atrophy (â¼32% reduction of epithelial height) and collagen fibers increase (83%). MLT alone did not alter biometric and physiological parameters, except for the prostate weight decrease, whereas it alleviated biometric as well as ameliorated acinar atrophy induced by high-lipid intake. Systemic oxidative stress increased, and prostatic glutathione peroxidase activity decreased fivefold with the high-fat diet despite the indole. Regardless of the diet, MLT triggered epithelial desquamation, reduced androgen receptor-positive cells, increased smooth muscle layer thickness (12%), decreased at least 50% corpora amylacea formation, and stimulated prostatic gluthatione-S-transferase activity. In conclusion, MLT partially recovered prostate damage induced by aging and the long-term high-fat diet and ameliorated degenerative prostate alterations.
Asunto(s)
Melatonina/farmacología , Próstata/patología , Células Acinares/efectos de los fármacos , Células Acinares/patología , Adiposidad/efectos de los fármacos , Animales , Colágeno/metabolismo , Dieta Alta en Grasa , Epitelio/efectos de los fármacos , Epitelio/patología , Masculino , Estrés Oxidativo/efectos de los fármacos , Antígeno Nuclear de Célula en Proliferación/metabolismo , Próstata/efectos de los fármacos , Ratas , Receptores Androgénicos/metabolismo , Espacio Retroperitoneal/patologíaRESUMEN
The postlactational involution of the mammary gland is a complex process. It involves the collapse of the alveoli and the remodeling of the extracellular matrix, which in turn implies a complex set of interrelations between the epithelial, stromal, and extracellular matrix elements. The telocytes, a new type of CD34-positive stromal cell that differs from fibroblasts in morphological terms and gene expression, were detected in the stroma of several tissues, including the mammary gland; however, their function remains elusive. The present study employed three-dimensional reconstructions and immunohistochemical, ultrastructural, and immunofluorescence techniques in histological sections of the mammary gland of the Mongolian gerbil during lactation and postlactational involution to evaluate the presence of telocytes and to investigate a possible function for these cells. By means of immunofluorescence assays for CD34 and c-kit, major markers of telocytes, and also through morphological and ultrastructural evidences, telocytes were observed to surround the mammary ducts and collapsing alveoli. It was also found that these cells are associated with matrix metalloproteinase 9, which indicates that telocytes can play a role in extracellular matrix digestion, as well as vascular endothelial growth factor, a factor that promotes angiogenesis. Together, these data indicate that telocytes are a distinct cell type in the mammary gland and, for the first time, show that these cells possibly play a role in tissue remodeling and angiogenesis during the postlactional involution of the mammary gland.
Asunto(s)
Lactancia/metabolismo , Glándulas Mamarias Animales/fisiología , Telocitos/metabolismo , Animales , Antígenos CD34/metabolismo , Matriz Extracelular/metabolismo , Femenino , Expresión Génica/genética , Gerbillinae/metabolismo , Glándulas Mamarias Animales/metabolismo , Neovascularización Patológica/metabolismo , Células del Estroma/metabolismo , Telocitos/fisiología , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Telocytes are cells present in the stroma of various tissues including the prostate. The detection of telocytes is still very much dependent on obtaining ultrastructural data that show the presence of telopodes, which are cytoplasmic projections that alternate between dilated regions, the podoms, and thin segments, the podomers. These structures are the distinctive characteristics of the telocytes. Thus, in vitro assays are important for the study of telocytes, which are more easily identified in culture, which also enables the experimental manipulation of these cells. The isolation of telocytes per se does not allow the analysis of the behavior of these cells in relation to other cell types in a given organ. In this sense, in the prostate, explants could be a useful tool for the study of telocytes. The present study obtained prostatic explants and evaluated the influence of recombinant proteins, scattering factor (SCF) and stromal-derived factor 1 (SDF-1), which could impact on the migration of CD34-positive cells. Telocytes migrate out of explants and SDF-1 stimulates the proliferation and formation of telocyte networks in vitro. Telocytes are not smooth muscle cell progenitors in the prostate; on the contrary, they are CD90- and CD44-negative cells and, hence, have limited progenitor capacity. The present study demonstrated that explants are useful tools to elucidate the nature of telocytes and their functions.
Asunto(s)
Quimiocina CXCL12/metabolismo , Factor de Crecimiento de Hepatocito/metabolismo , Telocitos/metabolismo , Animales , Antígenos CD34/metabolismo , Técnicas de Cultivo de Célula/métodos , Gerbillinae , Masculino , Próstata/metabolismo , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Telocitos/fisiologíaRESUMEN
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.
Asunto(s)
Etinilestradiol/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Próstata/efectos de los fármacos , Animales , Epitelio/metabolismo , Receptor alfa de Estrógeno/metabolismo , Estrógenos/metabolismo , Etinilestradiol/metabolismo , Femenino , Gerbillinae/metabolismo , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Receptores Androgénicos/efectos de los fármacos , Receptores Androgénicos/metabolismo , Testosterona/metabolismoRESUMEN
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.
Asunto(s)
Finasterida/toxicidad , Gerbillinae/crecimiento & desarrollo , Próstata , Animales , Femenino , Masculino , Próstata/efectos de los fármacos , Próstata/crecimiento & desarrollo , Receptores Androgénicos/metabolismo , Testosterona/sangreRESUMEN
Artibeus lituratus is a frugivorous bat that directly assists in the restoration of degraded habitats through the effective dispersion of seeds and fruits. Given its great importance, this work aimed to evaluate the uterine hormonal control of A. lituratus during its different reproductive phases. The uteri of 30 sexually mature adult females, five specimens for each of the six sample groups (NON, nonreproductive; P1, initial pregnancy; P2, intermediate pregnancy; P3, advanced pregnancy; LAC, lactating; P + LAC, pregnant-lactating), were submitted to analyses of serum estradiol and progesterone concentrations, in addition to immunohistochemical analyses. Both estradiol and progesterone, gradually increased during pregnancy, with a marked significant increase in P3 females. Both returned to low levels in LAC-females; however, estradiol levels decreased further in P + LAC-females, while progesterone increased in the same group. In general, signs indicative of aromatase expression were observed in the endometrium of all analyzed groups and in the placenta of bats in the gestation groups. Similarly, ERα and PR were expressed in the myometrium, endometrium and placenta at varying levels of intensity. The results indicate that the uterine microenvironment of A. lituratus is directly regulated by serum concentrations of estradiol and progesterone, and fluctuations in these concentrations control morphological and physiological changes of this organ during different phases of the reproductive cycle. RESEARCH HIGHLIGHTS: Increases in serum concentrations of estradiol and progesterone coordinate the gestational period of A. lituratus. Estradiol activates ERα, stimulating cell proliferation in the uterus, in addition to activating the expression of PR, which trigger the quiescence of the myometrium and stimulation of the secretion and differentiation of the endometrium. Results showed several similarities to humans, indicating the use of A. lituratus as an animal model in reproductive studies.