Are telocytes related to maintenance of vascular homeostasis in normal and pathological aorta?

The telocyte (TC) is a new interstitial cell type described in a wide variety of organs and loose connective tissues around small vessels, but its presence in large arteries remains unexplored. TCs have small cell bodies and remarkably thin, long, moniliform processes called telopods (Tps). Using transmission electron microscopy and immunofluorescence, we identified TCs in normal human thoracic aortas and in those with aneurysm or acute dissection (TAAD). In normal aortas the TCs were distributed throughout the connective tissue of the adventitial layer, in its innermost portion and at the zone of transition with the medial layer, with their long axes oriented parallel to the external elastic lamellae, forming a three-dimensional network, without prevalence in the media layer. In contrast, TAAD TCs were present in the medial layer and in regions of neovascularization. The most important feature of the adventitia of diseased aortas was the presence of numerous contacts between TCs and stem cells, including vascular progenitor cells. Although the biologically functional correlations need to be elucidated, the morphological observations presented here provide strong evidence of the involvement of TCs in maintaining vascular homeostasis in pathological situations of tissue injury.

Prostatic morphological changes throughout life: Cytochemistry as a tool to reveal tissue aging markers.

The prostate undergoes normal or pathological morphological changes throughout life. An understanding of these changes is fundamental for the comprehension of aging-related pathological processes such as benign prostatic hyperplasia (BPH) and cancer. In the present study, we show some of these morphological changes, as well as histochemical techniques like Weigert's resorcin-fuchsin method, Picrosirius Red, and Gömöri's reticulin for use as tools in the study of prostate tissue under light microscopy. For this purpose, prostates of the Mongolian gerbil (n = 9), an experimental model that develops BPH spontaneously, were analyzed at three life stages: young (1 month old), adult (3 months old), and old (15 months old). The results showed that fibrillar components such as collagen, and reticular and elastic fibers, change throughout life. In young animals, the prostate has cuboidal epithelium surrounded by thin layers of smooth muscle, continuous collagen fibers, winding reticular fibers, and sporadic elastic fibers. With adulthood, the epithelium becomes columnar, encircled by compacted muscle cells among slender collagen fibers, elongated reticular fibers, and linear elastic fibers. In aging individuals, the prostate's epithelium stratifies, surrounded by thick muscle layers among dense collagen fibers, disordered reticular fibers, and elastic fibers in different planes. We also identified a few accumulations of lipid droplets and lipofuscin granules in adult animals and high accumulation in old animals evidenced by Oil red O and Gömöri-Halmi techniques, respectively. The histochemical techniques presented here have been demonstrated to be useful and accessible tools in prostate studies. RESEARCH HIGHLIGHTS: Cytochemical techniques to study prostate morphology. The prostate changes with age.

Aging effects in adrenal cortex of male Mongolian gerbil: A model for endocrine studies.

The adrenal gland produces steroid hormones that act in the homeostasis of organisms. During aging, alterations in the hormonal balance affect the adrenal glands, but these have not yet been fully described due to the lack of adequate animal models. The adrenal gland of the Mongolian gerbil has a morphology similar to the primate's adrenal gland, which makes it a possible animal model for endocrine studies. Therefore, the current study aimed to study the morphophysiology of the adrenal gland under the effect of aging. For this purpose, males Meriones unguiculatus, aged three, six, nine, twelve, and fifteen months were used. Morphometric, immunohistochemical, and hormonal analyses were performed. It was observed that during aging the adrenal gland presents hypertrophy of the fasciculata and reticularis zones. Lipofuscin accumulation was observed during aging, in addition to changes in proliferation, cell death, and cell receptors. The analyses also showed that the gerbil presents steroidogenic enzymes and the production of steroid hormones, such as DHEA, like that found in humans. The data provide the first comprehensive assessment of the morphophysiology of the Mongolian gerbil adrenal cortex during aging, indicating that this species is a possible experimental model for studies of the adrenal gland and aging.

Testicular regression and recrudescence in the bat Eptesicus furinalis: Morpho-physiological variations and hormonal signaling pathways.

Males of the bat Eptesicus furinalis show at least one process of testicular regression, in which the testes regress and temporarily interrupt the production of sperm, during its annual reproductive cycle. As the process of spermatogenesis is under hormonal control, mainly of pituitary and androgen hormones, our aim was to analyze the morphological variations and the hormonal control of the testes of E. furinalis during the four phases of its reproductive cycle. Testes of 18 adult males, divided into four sample groups (active, regressing, regressed, and recrudescence phases), were submitted to morphological, morphometric, and immunohistochemical analyzes. The results demonstrate that the processes of testicular regression and recrudescence of E. furinalis are under the control of pituitary, androgen and estrogen hormones. The regulation is exerted mainly through the activation and cross signaling of AR and FSHR in Sertoli cells and of LHR in Leydig cells. The testicular regression appears to be activated by an inhibition/reduction of AR expression in Sertoli cells, which inhibits the proliferation and differentiation of new spermatogonia and causes the deactivation of spermatogenesis. Conversely, the testicular recrudescence occurs by the increasing of the expression of LHR in Leydig cells, and AR and FSHR in Sertoli cells, which reactivates the testicular production of androgens and estrogens, the proliferation of spermatogonia and restarts the spermatogenesis.

The marked dextro-dominance causes accentuated morphophysiological variations in the female reproductive organs of the bat Molossus molossus.

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.

The Impact in Intestines and Microbiota in BALB/c Mice Through Consumption of Milk Fermented by Potentially Probiotic Lacticaseibacillus casei SJRP38 and Limosilactobacillus fermentum SJRP43.

The present study aimed to evaluate the effect of consumption of milk fermented by Lacticaseibacillus (Lc.) casei SJRP38 and Limosilactobacillus (Lm.) fermentum SJRP43 on bacterial translocation, stool analysis, and intestinal morphology of healthy BALB/c mice. Potentially probiotic lactic acid bacteria, Lc. casei SJRP38, and Lm. fermentum SJRP43 were evaluated and analyzed for translocation, fecal analysis, and intestinal morphology of four groups of mice: water control (WC), milk control (MC), milk fermented by Lc. casei SJRP38 (FMLC), and milk fermented by Lm. fermentum SJRP43 (FMLF), in co-culture with Streptococcus thermophilus ST080. The results of the animal assay indicate that the population of Lactobacilli and Bidobacterium sp. in the gastrointestinal tract of BALB/c mice was greater than 6.0 log10 CFU/g, and there was no evidence of bacteremia due to the low incidence of bacterial translocation. Ingesting fermented milk containing Lc. casei SJRP38 and Lm. fermentum SJRP43 was found to promote a healthier microbiota, as it led to a reduction in Clostridium sp. and an increase in Lactobacilli and Bifidobacterium sp. in feces. Furthermore, the dairy treatments (MC, FMLC, and FMLF) resulted in taller intestinal villi and an increase in the frequency of goblet cells in the intestines. Overall, the consumption of fermented milk containing Lc. casei SJRP38 and Lm. fermentum SJRP43 strains was deemed safe and demonstrated beneficial effects on the intestines of BALB/c mice.

Impacts of heavy metal exposure on the prostate of murine models: Mechanisms of toxicity.

Heavy metals are elements found into the environment mainly due to anthropogenic activities. Naturally occurring and higher released doses cause disorders in the prostate, which depends on appropriate hormonal regulation, and exposure to heavy metals may impair prostate homeostasis. The current work highlighted the main mechanisms of toxicity of different environmental heavy metal contaminants, such as aluminum, arsenic, cadmium, chromium, lead, mercury, and nickel, and their impacts found in the prostate morphophysiology of murine models. The repercussions triggered by heavy metals on the prostate include hormonal imbalance and oxidative damage, leading to morphological alterations, which can vary according to the chemical properties of each element, exposure time and concentration, and age. The information of altered biological pathways and its impacts on the prostate of exposed murines are related to human outcomes being useful in the real context of human exposure.

Stromal cell-derived factor 1 (SDF-1) increases the number of telocytes in ex vivo and in vitro assays.

Telocytes are interstitial cells that are present in various tissues, have long cytoplasmic projections known as telopodes, and are classified as CD34+ cells. Telopodes form extensive networks that permeate the stroma, and there is evidence that these networks connect several stromal cell types, giving them an important role in intercellular communication and the maintenance of tissue organisation. Data have also shown that these networks can be impaired and the number of telocytes reduced in association with many pathological conditions such as cancer and fibrosis. Thus, techniques that promote telocyte proliferation have become an important therapeutic target. In this study, ex vivo and in vitro assays were conducted to evaluate the impact on prostatic telocytes of SDF-1, a factor involved in the proliferation and migration of CD34+ cells. SDF-1 caused an increase in the number of telocytes in explants, as well as morphological changes that were possibly related to the proliferation of these cells. These changes involved the fusion of telopode segments, linked to an increase in cell body volume. In vitro assays also showed that SDF-1 enriched prostate stromal cells with telocytes. Altogether, the data indicate that SDF-1 may offer promising uses in therapies that aim to increase the number of telocytes. However, further studies are needed to confirm the efficiency of this factor in different tissues/pathological conditions.

Annual reproductive cycle of males of the great fruit-eating bat, Artibeus lituratus: Testicular variations, abiotic regulation and sperm analysis.

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.

The impacts of exposure to bisphenol A in the adult female prostate Meriones unguiculatus.

The female prostate is associated with the urogenital system and presents homology in morphological terms with the male prostate. Due to its responsiveness to endogenous hormones, this gland is under a constant risk of developing prostatic pathologies and neoplasia when exposed to certain exogenous compounds. Bisphenol A (BPA) is an endocrine disruptor found in different plastic and resin products. Studies have emphasized the effects of perinatal exposure to this compound on different hormone-responsive organs. However, there have been few studies highlighting the influence on female prostate morphology of perinatal exposure to BPA. The objective of this study was to describe the histopathological alterations caused by perinatal exposure to BPA (50 µg/kg) and 17-ß estradiol (E2) (35 µg/kg) in the prostate of adult female gerbils. The results showed that E2 and BPA induced proliferative lesions in the female prostate and acted along similar pathways by modulating steroid receptors in the epithelium. BPA was also found to be a pro-inflammatory and pro-angiogenic agent. The impacts of both agents were marked in the prostatic stroma. An increase in the thickness of the smooth muscle layer and a decrease in AR expression were observed, but no alterations in the expression of ERα and ERß, leading to estrogenic sensitivity of the prostate. However, a peculiar response of the female prostate was to diminish the collagen frequency under BPA exposure correlated to smooth muscle layer. These data therefore indicate the development of features related to estrogenic and non-estrogenic tissue repercussions by BPA perinatally exposure in gerbil female prostate.

Condyloma acuminata: An evaluation of the immune response at cellular and molecular levels.

Condyloma acuminata (CA) is a benign proliferative disease mainly affecting in non-keratinized epithelia. Most cases of CA are caused by low-risk human papillomavirus (HPV), mainly HPV 6 and 11. The aim of the current study was to highlight the candidate genes and pathways associated with immune alterations in individuals who did not spontaneously eliminate the virus and, thus, develop genital warts. Paraffin-embedded condyloma samples (n = 56) were analyzed by immunohistochemistry using antibodies against CD1a, FOXP3, CD3, CD4, CD8, and IFN-γ. The immunomarkers were chosen based on the evaluation of the innate and adaptive immune pathways using qPCR analysis of 92 immune-related genes, applying a TaqMan Array Immune Response assay in HPV 6 or HPV 11 positive samples (n = 27). Gene expression analysis revealed 31 differentially expressed genes in CA lesions. Gene expression validation revealed upregulation of GZMB, IFNG, IL12B, and IL8 and downregulation of NFATC4 and IL7 in CA samples. Immunohistochemical analysis showed increased FOXP3, IFN-γ, CD1a, and CD4 expression in CA than in the control tissue samples. In contrast, CD3 and CD8 expression was decreased in CA lesion samples. Increased levels of pro-inflammatory cytokines in HPV-positive patients compared with HPV-negative patients seem to reflect the elevated immunogenicity of HPV-positive CA lesions. Host defense against HPV begins during the early stages of the innate immune response and is followed by activation of T lymphocytes, which are mainly represented by CD4+ and regulatory T cells. The low CD8+ T cell count in CA may contribute to this recurrent behavior. Additional studies are needed to elucidate the mechanism of host defense against HPV infection in CA.

Bisphenol A disruption promotes mammary tumor microenvironment via phenotypic cell polarization and inflammatory response.

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.

Impairment of steroidogenesis and follicle development after bisphenol A exposure during pregnancy and lactation in the ovaries of Mongolian gerbils aged females.

The ovaries regulate fertility and hormonal control in females, and aging is a crucial factor in this process, when ovarian function is drastically impacted. Exogenous endocrine disruptors may accelerate this process, acting as the main agents in decreased female fertility and hormonal imbalance, since they impact different features related to reproduction. In the present study, we demonstrate the implications of exposure of adult mothers to the endocrine disruptor bisphenol A (BPA) during pregnancy and lactation on their ovarian function during the transition to later in life (aging). The follicle population of BPA exposed ovaries showed impairment in the development of follicles to the mature stages, with growing follicles being halted in the early stages. Atretic and early-atretic follicles were also enhanced. Expression of estrogen and androgen receptors in the follicle population demonstrated impairment in signaling function: ERß was highly expressed in follicles from BPA exposed females, which also showed a higher incidence of early atresia of developed follicles. ERß1 wild-type isoform was also enhanced in BPA-exposed ovaries, compared to its variant isoforms. In addition, steroidogenesis was targeted by BPA exposure: aromatase and 17-ß-HSD were reduced, whereas 5-α reductase was enhanced. This modulation was reflected in serum levels of estradiol and testosterone, which decreased in BPA-exposed females. Imbalances in steroidogenesis impair the development of follicles and play an important role in follicular atresia. Our study demonstrated that BPA exposure in two windows of susceptibility - gestation and lactation - had implications during aging, enhancing perimenopausal and infertile features.

Neonatal exposure to aluminum chloride predisposes adult and senile gerbils to the prostatic hyperplasia.

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.

The Mongolian Gerbil as a Useful Experimental Model in Reproductive Biology.

Ultimately, the Mongolian gerbils (Meriones unguiculatus) have acquired a relevant role in biological and biomedical experiments alongside other rodents. The use of gerbils in research has been mainly oriented to physiological and pharmacological studies, with special attention to nervous, digestive, and auditory systems as well as microbiology and parasitology. Ultimately, gerbils have also been applied for studying carcinogenesis in different organs and systems, since these animals show a natural propensity to develop spontaneous proliferative lesions, especially in steroid-responsive organs. This characteristic shed light on the reproductive aspects of this rodent model regarding morphological features in male and female individuals. This review of literature summarizes the significance of this model as an alternative to the use of inbred mice and rats in reproductive experimental research, highlighting recent findings. Gerbils have contributed to the expansion of knowledge in prostate biology in male and female individuals, providing studies related to prostatic morphogenesis and neoplasia. In the testes, spermiogenesis occurs in 15 steps, differently from other experimental models. Also, the complete maturation of the testis-epididymal complex occurs between the second and third months. Mammary gland alterations related to the estrous cycle and pregnancy were described, as well as its modulation under endogenous and exogenous estrogenic compounds. The ovaries frequently present ovarian cysts. Furthermore, this organ shows predominantly interstitial steroidogenic glands in the stroma, especially at aging. Adrenal gland shows a large size compared to other animals, presenting three distinct zones with a remarkable role in steroidogenesis.

Morphophysiology of the male reproductive accessory glands of the bat Pteronotus gymnonotus (Mormoopidae: Chiroptera).

Mormoopidae is an exclusive Neotropical family of bats, distributed from southern Mexico to northeastern Brazil. Possibly due to its endemic distribution and very low occurrence (rarity), descriptions of their reproductive accessory glands (RAGs) are still lacking. Thus, this study aims to characterize the male RAGs of Pteronotus gymnonotus (Mormoopidae: Chiroptera). Results demonstrate that the RAGs of P. gymnonotus is composed of a prostatic complex, comprising two regions (ventral and dorsal prostates); urethral (Littre) glands, a pair of bulbourethral and ampullary glands, with the absence of seminal vesicles. The ventral prostate has an atypical epithelium, due to its holocrine secretion; which contains numerous PAS-positive globular vesicles. The dorsal prostate has a cubic-to-columnar pseudostratified epithelium, containing fluid PAS-negative secretion. The ampullary glands present cubic-to-columnar pseudostratified epithelium, with secretion varying from granular and PAS-negative to fluid and PAS-positive. Urethral glands are dispersed in the submucosa of the urethra, while the bulbourethral glands are located in the penile root. Both glands have cubic-to-columnar pseudostratified epithelium with PAS-positive globular secretion. In conclusion, we propose that the RAGs of P. gymnonotus possibly evolved from a common emballonurid ancestor, shared with the families Phyllostomidae and Noctilionidae, but with the development of an exclusive apomorphy, the ampullary glands.

Comparative analysis of male reproductive accessory glands in bats Histiotus velatus (Vespertilionidae), Molossus rufus (Molossidae), and Peropteryx leucoptera (Emballonuridae).

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.

Proteoglycans orchestrate remodeling of prostatic cytoarchitecture after androgenic blockade in old gerbils.

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.

High-lipid nutritional environment in different ontogenetic periods induce developmental programming of rat prostate at aging.

In brief: Maternal obesity plus high-fat diet in breastfeeding induces stromal hyperplasia and diffuse acinar atrophy in the rat prostate at aging, related to dyslipidemia and testosterone reduction. The high-lipid nutritional environment from intrauterine and throughout life favors the development of prostatic intraepithelial neoplasia and aggravated degenerative alterations in the gland. Abstract: Maternal obesity and high-fat diet (HFD) affect permanently prostate histophysiology in adulthood, but the consequences during aging are unknown. Here, we evaluated the prostate alterations in middle-aged rats subjected to a high-lipid nutritional environment (HLE) in different ontogenetic periods. Wistar rats (56 weeks of age) were assigned into groups exposed to standard nutrition (C) or HLE during gestation (G), gestation and lactation (GL), from lactation onward (L), from weaning onward (W) and from gestation onward (AL). HLE in the periods after weaning consisted of HFD (20% fat), and during gestation and lactation it also included previous maternal obesity induced by the HFD. HLE increased total cholesterol and triglyceride levels in all groups and led to insulin resistance in GL and AL and obesity in L. Serum testosterone levels decreased ~67% in GL, ~146% in L and W, and ~233% in AL. Histological and stereological analysis revealed an increment of the stromal compartment and collagen fibers in the prostates of all HLE groups, as well as degenerative lesions, such as cell vacuolation and prostate concretions. HLE aggravated acinar atrophy in G, GL, and L, and in AL it reached more than 50% of the prostate area for most animals. The foci of prostatic intraepithelial neoplasia increased in AL. Tissue expression of androgen receptor did not vary among groups, except for a higher stromal expression for G and GL. Even when restricted to gestation and lactation, HLE induces diffuse acinar atrophy in the aging prostate and worsens degenerative and premalignant lesions when it continues throughout life.