Rat Prostate Research Articles

Old Rats Are More Susceptible to Induction of Benign Prostatic Hyperplasia (BPH) at Comparative to Young Mature.

The aim of the experiments was to find out the factors on which age-related sensitivity to the occurrence of BPH depends. 45 Male Wistar rats aged 3 and 24 months were used. In each age group, there were intact rats and animals with induced BPH (by surgical castration + testosterone injections, 25 mg/kg x 7). On the 36th day of the experiment, blood was taken from rats to determine serum testosterone, cholesterol, triglycerides and glucose; then, the animals were autopsied, their prostates were weighed, and their morphology was studied. Young mature intact rats had much higher testosterone levels (6.2±0.93 nmol/l) than old intact (3.8±0.55 nmol/l), while the ratio of prostate weight was inverse. The weight of the prostate and prostatic index in old rats with induced BPH was significantly higher not only in comparison with the old intact rats but also with young animals after BPH induction. Morphologically, the inflammatory foci were determined not only in the prostates of old rats, which induced BPH, but also in intact animals. Besides, in old intact rats, the foci of prostate hyperplasia were often noted. Our experimental model indicates the important role of non-bacterial prostatitis in the pathogenesis of BPH. No metabolic disorders in BPH induction were revealed. The sensitivity of the prostate of old rats to BPH development is increasing despite the low concentrations of testosterone in the body. Age sensitivity to BPH is probably determined by a higher expression of androgen receptors in old animals.

High-grade tumours promote growth of other less-malignant tumours in the same prostate.

Prostate cancer is a multifocal disease, but if and how individual prostate tumours influence each other is largely unknown. We therefore explored signs of direct or indirect tumour–tumour interactions in experimental models and patient samples. Low‐metastatic AT1 and high‐metastatic MatLyLu (MLL) Dunning rat prostate cancer cells were injected into separate lobes of the ventral prostate of immunocompetent rats. AT1 tumours growing in the same prostate as MLL tumours had increased tumour size and proliferation compared to AT1 tumours growing alone. In addition, the vasculature and macrophage density surrounding the AT1 tumours were increased by MLL tumour closeness. In patient prostatectomy samples, selected to contain an index tumour [tumour with the highest grade, International Society of Urological Pathology (ISUP) grade 1, 2, 3 or 4] and a low‐grade satellite tumour (ISUP grade 1), cell proliferation in low‐grade satellite tumours gradually increased with increasing histological grade of the index tumour. The density of blood vessels and CD68+ macrophages also increased around the low‐grade satellite tumour if a high‐grade index tumour was present. This suggests that high‐grade tumours, by changing the prostate microenvironment, may increase the aggressiveness of low‐grade lesions in the organ. Future studies are needed to explore the mechanisms behind tumour–tumour interactions and their clinical importance. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Glutaminolysis is a metabolic route essential for survival and growth of prostate cancer cells and a target of 5α-dihydrotestosterone regulation.

Resistance to androgen-deprivation therapies and progression to so-called castrate-resistant prostate cancer (CRPC) remain challenges in prostate cancer (PCa) management and treatment. Among other alterations, CRPC has been associated with metabolic reprogramming driven by androgens. Here, we investigated the role of androgens in regulating glutaminolysis in PCa cells and determined the relevance of this metabolic route in controlling the survival and growth of androgen-sensitive (LNCaP) and CRPC (DU145 and PC3) cells. PCa cells (LNCaP, DU145 and PC3) and 3-month old rats were treated with 5α-dihydrotestosterone (DHT). Alternatively, LNCaP cells were exposed to the glutaminase inhibitor BPTES, alone or in combination with the anti-androgen bicalutamide. Biochemical, Western blot and extracellular flux assays were used to evaluate the viability, proliferation, migration and metabolism of PCa cells in response to DHT treatment or glutaminase inhibition. We found that DHT up-regulated the expression of the glutamine transporter ASCT2 and glutaminase, both in vitro in LNCaP cells and in vivo in rat prostate cells. BPTES diminished the viability and migration of PCa cells, while increasing caspase-3 activity. CRPC cells were found to be more dependent on glutamine and more sensitive to glutaminase inhibition. BPTES and bicalutamide co-treatment had an additive effect on suppressing LNCaP cell viability. Finally, we found that inhibition of glutaminolysis differentially affected glycolysis and lipid metabolism in both androgen-sensitive and CRPC cells. Our data reveal glutaminolysis as a central metabolic route controlling PCa cell fate and highlight the relevance of targeting glutaminase for CRPC treatment.

Altered expression of genes identified in rats with prostatic chronic inflammation in a prostate spheroid model treated by estradiol/testosterone.

Rats are the standard model for male reproductive toxicity testing. Rat prostates are physiologically and anatomically different from those of humans. Drug and chemical toxicity testing would benefit from an in vitro model of human prostate cells. Recently, spheroids derived by three-dimensional culture of human cell lines have been used for assessing drug and chemical toxicity in vitro as they mimic in vivo environments more closely than two-dimensional culture. However, forming consistently sized, uniform spheroids is technically challenging for toxicity testing. The purpose of this study was to identify potential genetic markers for assessing prostatic toxicity in spheroids. We formed prostate spheroids using agarose-coated plates seeded with human primary prostate epithelial cells. Prostate spheroids were treated with either 17β-estradiol (E2) or testosterone (T) on days 2-7 of culture. Samples were harvested on culture day 7. qPCR was used to examine gene expression levels previously identified in rats with chronic inflammation exposed to estradiol benzoate, E2 and/or T. Changes in some gene expression levels were observed in the spheroids treated with E2 or T. We found that treatment with 1 nM E2 and/or 10 μM T significantly altered spheroid proliferation and viability, as well as the expression levels of genes including Nanog homeobox (NANOG), C-C motif chemokine ligand 2 (CCL2) and bone morphogenetic protein receptor type 2 (BMPR2). Further studies using biologically active molecules with prostatic toxicity are needed to verify the results and to determine whether gene expression changes in the spheroid are specific to E2 or T treatment.

Human Tissue Kallikrein 1 Is Downregulated in Elderly Human Prostates and Possesses Potential In Vitro Antioxidative and Antifibrotic Effects in Rodent Prostates.

Objective The aim of the present study was to investigate the protective effects and mechanisms of KLK1 on aging-related prostate alterations and search clues about the application of KLK1 to the treatment of human BPH. Methods Thirty-six rats including 26 male wild-type SD rats and 10 transgenic rats were fed to 3- or 18-month-old and divided into three groups: young WTR (yWTR) as the control (n = 16), aged WTR (aWTR) (n = 10), and aged TGR (aTGR) (n = 10). The prostates of the three groups of rats (10 rats per group) were harvested to evaluate the levels of KLK1 expression, oxidative stress, fibrosis, and involved signaling pathways, such as NO/cGMP, COX-2/PTGIS/cAMP, and TGF-β1/RhoA/ROCK1, via quantitative PCR, Western blot, histological examinations, and ELISA. Moreover, the remaining 6 yWTRs were sacrificed to obtain primary prostate fibroblast and aortic endothelial cells, and a coculture system was built with the cells for the verification of above signaling pathways in vitro. And the direct effects of bradykinin on prostate cells were detected by MTT experiment. Prostate specimens of 47 patients (age from 48 to 92 years) undergoing BPH surgery were collected after approval. Histological examinations and KLK1 IHC were preformed to analyze the relationship between KLK1 expression and age and prostate fibrosis. Results The human KLK1 gene only existed and was expressed in aTGR. The prostate of young rats expressed more KLK1 than the aged and the expression of KLK1 in prostate decreased with age in humans (r = −0.347, P = 0.018). Compared to the aWTR group, the yWTR and aTGR groups showed milder fibrosis, less oxidative stress, upregulated NO/cGMP, and COX-2/PTGIS/cAMP signaling pathways and inhibited TGF-β1/RhoA/ROCK1 signaling pathway. In the coculture system, KLK1 suppressed TGF-β1-mediated fibroblast-to-myofibroblast transdifferentiation via cleaving LMWK to produce the BK which upregulate eNOS expression and NO production in endothelial cells. BK not only slightly stimulated the proliferation ability of prostatic stromal cells but also upregulated iNOS and inhibited TGF-β1 expression in them. Conclusion KLK1 protects prostate from oxidative stress and fibrosis via amplified NO/cGMP signal in aged rats. The decrease of KLK1 expression with aging is laying the groundwork for the application of KLK1 to the treatment of human BPH. The current experimental data showed that the side effects of KLK1 on the prostate cell were not obvious.

Functional Impact of Acidosis-Regulated MicroRNAs on the Migration and Adhesion of Tumor Cells.

Tumor tissue shows special features in metabolism in contrast to healthy tissue. Besides a distinctive oxygen deficiency, tumors often show a reduced extracellular pH (acidosis) resulting from an intensified glycolysis not only under hypoxic but also under normoxic conditions (Warburg effect). As shown in previous studies, cell migration is increased in AT1 prostate carcinoma cells after incubation at pH6.6, and this leads to an increased number of lung metastases in vivo. However, the signaling pathway causing these functional changes is still unknown. Possible mediators could be acidosis-regulated microRNAs (miR-7, miR-183, miR-203, miR-215). The aim of the study was therefore to analyze whether a change in the expression of these microRNAs has an impact on the tumor cell migration and adhesion. Studies were performed with AT1 rat prostate cancer cells which were incubated for 24h at pH7.4 or 6.6. Keeping AT1 tumor cells at low pH increased the migratory capacity by about 100%. But also the decrease of miR-203 and miR-215 expression (at normal pH) led to an increase in migration velocity by 50%. In contrast, cell adhesion was increased by about 75% at low pH. However, an increase in miR-215 expression at pH6.6 reduced the adhesion by trend. These results clearly indicated that the extracellular pH has an impact on migration and adhesion of tumor cells. In this mechanism, pH-regulated microRNAs could play a role since changes in the expression of these microRNAs (especially miR-203) are also able to modulate the migratory behavior.

Periodontitis Exacerbates Benign Prostatic Hyperplasia through Regulation of Oxidative Stress and Inflammation.

Epidemiological studies demonstrate that men with periodontitis are also susceptible to benign prostatic hyperplasia (BPH) and that periodontal treatment can improve the prostatic symptom. However, molecular links of this relationship are largely unknown. The goal of the current study was to elucidate the effects of experimental periodontitis on the hyperplasia of prostate and whether oxidative stress and inflammation participated in this process. For this purpose, ligature-induced periodontitis, testosterone-induced BPH, and the composite models in rats were established. Four weeks later, all the rats were sacrificed and the following items were measured: alveolar bone loss and histological examination of periodontal tissues were taken to assess the establishment of periodontitis model, prostate index and histological examination of prostate tissues were taken to test the establishment of the BPH model, inflammatory cytokines in plasma were assessed, and Bax/Bcl-2 proteins related to cell apoptosis were analyzed via western blot analysis. To further investigate whether oxidative stress participates in the aggravation of BPH, in vitro models were also conducted to measure the production of intracellular reactive oxygen species (ROS) and hydrogen peroxide (H2O2) concentration. We found that simultaneous periodontitis and BPH synergistically aggravated prostate histological changes, significantly increased Ki67 proliferation, and reduced apoptosis in rat prostate tissues. Also, our results showed that periodontal ligation induced increased Bcl-2 protein expression, whereas Bax expression was decreased in BPH rats than in normal rats. Compared with the control group, periodontitis and BPH both significantly enhanced inflammatory cytokine levels of TNF-α, IL-6, IL-1β, and CRP. Furthermore, Porphyromonas gingivalis lipopolysaccharide induced enhanced generation of intracellular expression of ROS and H2O2 in BPH-1 cells. Our experimental evidence demonstrated that periodontitis might promote BPH development through regulation of oxidative stress and inflammatory process, thus providing new strategies for prevention and treatment of BPH.

Increased oxidative stress and cancer biomarkers in the ventral prostate of older rats submitted to maternal malnutrition

The concept of Developmental Origins of Health and Disease (DOHaD) states that exposure to malnutrition early in life increase the incidence of non-communicable chronic diseases throughout the lifespan. In this study, a reduction in serum testosterone and an increase in estrogen levels were shown in older rats born to protein malnourished dams (6% protein in the diet) during gestation and lactation. Intraprostatic levels of reduced glutathione were decreased, while tissue expression of glutathione S-transferase pi and sulfiredoxin-1 were increased in these animals. Strong immunostaining for alfametilacil CoA racemase (AMACR), vascular endothelial growth factor-A (VEGF-A), and aquaporin-1 (AQP1) was also observed. In silico analysis confirmed commonly deregulated proteins in the ventral prostate of old rats and patients with prostate cancer. In conclusion, the increase in oxidative stress associated with an imbalance of sex hormones may contribute to prostate carcinogenesis in offspring, highlighting early-life malnutrition as a key risk factor for this malignance.

Rauwolfia vomitoria extract suppresses benign prostatic hyperplasia by reducing expression of androgen receptor and 5α-reductase in a rat model

ObjectiveHerbal medicine is an important therapeutic option for benign prostatic hyperplasia (BPH), a common disease in older men that can seriously affect their quality of life. Currently, it is crucial to develop agents with strong efficacy and few side effects. Herein we investigated the effects of the extract of Rauwolfia vomitoria, a shrub grown in West Africa, on BPH. MethodsRats with testosterone-induced BPH were treated with R. vomitoria. Prostates were histologically analyzed by Hematoxylin and eosin staining. Proliferation index and the expression levels of androgen receptor and its associated proteins were quantified through immunohistochemistry and immunoblotting. Androgen receptor target genes were examined by quantitative real-time polymerase chain reaction. The sperm count and body weight of rats were also measured. ResultsThe oral administration of R. vomitoria extract significantly reduced the prostate weight and prostate weight index in BPH rats, supported by the decreased thickness of the prostate epithelial layer and increased lumen size. Similar effects were observed in the BPH rats treated with the reference drug, finasteride. R. vomitoria extract significantly reduced the testosterone-induced proliferation markers, including proliferating cell nuclear antigen and cyclin D1, in the prostate glands of BPH rats; it also reduced levels of androgen receptor, its associated protein steroid 5α-reductase 1 and its downstream target genes (FK506-binding protein 5 and matrix metalloproteinase 2). Notably, compared with the finasteride group, R. vomitoria extract did not significantly reduce sperm count. ConclusionR. vomitoria suppresses testosterone-induced BPH development. Due to its milder side effects, R. vomitoria could be a promising therapeutic agent for BPH.

Effect of Streptozotocin Induced Diabetes on the Adult Rat Prostate and the Possible Protective Role of Vitamin E

Background: Diabetes mellitus (DM), a disorder of metabolism, has adverse effects on all organ systems including reproductive organs due to insulin deficiency. The aim of the present work was to study the impact of Streptozotocin (STZ)-induced diabetes and the potential protective role of vitamin E on the adult rat prostate. Materials and Methods: Forty adult male albino rats were divided equally into 4 groups (10 rats per group). First group was control negative, while the second group was control positive. Rats in the 3rd group were received streptozotocin dissolved in a citrate buffer by intraperitoneal injection at a dose of 40 mg/kg body weight once daily. 2 weeks after confirmation of diabetes induction rats were sacrificed. Rats in the fourth group after induction of diabetes were fed with vitamin E supplemented diet for 15 days then the rats were sacrificed. The prostatic lobes were dissected out and processed for histological and immuno-histochemical examinations. Hormonal assay was performed and Statistical analysis was done.Results: No structural differences were found between the two control groups. The diabetic group showed thinning of acinar epithelial lining; sever cellular infiltration and areas of exudate in interstitial tissue. By immunohistochemical staining, apparent decrease of the acinar cells with positive immunostaining androgen receptor reaction was observed. Also decreased serum testosterone level in diabetic group was noticed. Supplementation of vitamin E was found to improve most of the prostatic changes associated with DM.Conclusion: Supplementation of vitamin E improves the prostatic changes produced by DM.

Хронический простатит: инфекционный или неинфекционный? (экспериментальное исследование)

Introduction. The pathogenesis of chronic prostatitis remains unclear. The aim of this study was to study the pathogenesis and frequency of infectious and non-infectious prostatitis and the effectiveness of prostatilen in its prevention in the experiment. Materials and methods. Experimental work was carried out on 82 male Wistar rats 5–8 months of age (weight 250–400 g). To initiate inflammation of the prostate gland, rats of the 1st and 2nd groups (30 in each) were injected into the rectum with 1 ml of a mixture of turpentine and Dimexide in a ratio of 1:4 to a depth of 2.5 cm. For rats of the 3rd group (n=17) prostatilen was intramuscularly injected daily for five days at a dose of 0.1 mg/100 g of weight. The day after the last injection into the rectum, they were also injected with a pathogenic mixture to initiate prostatitis. In the 4th group (n=5) there were control animals, which were injected intramuscularly with physiological sodium chloride solution for five days before the initiation of prostatitis. Rats were removed from the experiment by guillotinization, in the 1st group the next day, and in the 2nd group 28 days after the initiation of inflammation, and for rats of the 3rd and 4th groups – 5 days after the last injection (prostatilen or physiological solution respectively). The prostate gland and seminal vesicles were used as the test material for the culture and histological examination. Results. In the experiment, microorganisms were isolated in 23.4% of cases in the 1st group, and in 92.1% of cases in the 2nd group. Among the identified microorganisms, Staphylococcus aureus prevailed in the 1st group, and S. urealiticus in the 2nd group. The presence of mixed flora was found in 18.2% in the 1st group and in 20% in the 2nd group. During macro- and microscopic examination of the prostate gland of rats of the 3rd group, we did not find signs of its active inflammation, and during bacteriological examination, microorganisms were not detected. Conclusion. Chronic inflammation of the prostate gland initially develops as aseptic, but later the prostatitis becomes infectious. This can be confirmed by modern means and methods of laboratory diagnostics of bacterial flora in prostate exprimat in patients with chronic prostatitis. The data obtained from experimental studies confirm the ability of prostatilen to prevent the development of the inflammatory process in the prostate gland, which makes it possible to recommend it in clinical conditions for the complex therapy of patients with chronic prostatitis, as well as in means of preventing this disease.

Phenolic Content and Antimicrobial and Anti-Inflammatory Effects of Solidago virga-aurea, Phyllanthus niruri, Epilobium angustifolium, Peumus boldus, and Ononis spinosa Extracts

Prostatitis is an inflammatory condition that is related to multiple infectious agents, including bacteria and fungi. Traditional herbal extracts proved efficacious in controlling clinical symptoms associated with prostatitis. In this context, the aim of the present study was to explore the efficacy of extracts from Solidago virga-aurea, Ononis spinosa, Peumus boldus, Epilobium angustifolium, and Phyllanthus niruri against bacterial (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus cereus) and fungi strains (Candida albicans; C. tropicalis) involved in prostatitis. Additionally, anti-mycotic effects were tested against multiple species of dermatophytes (Trichophyton rubrum, T. tonsurans, T. erinacei, Arthroderma crocatum, A. quadrifidum, A. gypseum, A. currey, and A. insingulare). Antioxidant effects were also evaluated in isolated rat prostates challenged with lipopolysaccharide (LPS), and phytochemical analyses were conducted to identify and quantify selected phenolic compounds, in the extracts. Finally, a bioinformatics analysis was conducted to predict putative human and microbial enzymes targeted by extracts’ phytocompounds and underlying the observed bio-pharmacological effects. The phytochemical analysis highlighted that rutin levels could be crucial for explaining the highest antibacterial activity of P. boldus extract, especially against E. coli and B. cereus. On the other hand, in the E. angustifolium extract, catechin concentration could partially explain the highest efficacy of this extract in reducing lipid peroxidation, in isolated rat prostates stimulated with LPS. Concluding, the results of the present study showed moderate antimicrobial and anti-inflammatory effects induced by water extracts of S. virga-aurea, P. boldus, E. angustifolium, P. niruri, and O. spinosa that could be related, at least partially, to the phenolic composition of the phytocomplex.

PH-0477: Effectiveness of fractionated carbon ion treatments in three rat prostate tumors

PH-0477: Effectiveness of fractionated carbon ion treatments in three rat prostate tumors

PH-0476: Impact of single dose photon or 12C-ion irradiation on rat prostate tumors assessed by DCE-MRI

PH-0476: Impact of single dose photon or 12C-ion irradiation on rat prostate tumors assessed by DCE-MRI

Effect of Atorvastatin on 7,12-Dimethylbenz (α) Anthracene and Testosterone-induced Prostatic Intraepithelial Neoplasia in the Prostate of Wistar Rats: Role of TRPM7

Effect of Atorvastatin on 7,12-Dimethylbenz (α) Anthracene and Testosterone-induced Prostatic Intraepithelial Neoplasia in the Prostate of Wistar Rats: Role of TRPM7

Clinicopathological and immunohistochemical evaluation of lonidamine-entrapped lipid–polymer hybrid nanoparticles in treatment of benign prostatic hyperplasia: An experimental rat model

Benign prostatic hyperplasia (BPH) is a progressive proliferative disease, the incidence of which is constantly increasing due to aging of population. In this research, a hexokinase-II enzyme inhibiting agent, lonidamine – the use of which is limited in BPH treatment due to high hepatic toxicity observed after three months of treatment – was selected as an active agent, based on its mechanism of action in treating BPH. The aim of this study was to evaluate in vivo therapeutic efficacy and hepatic toxicity of lipid–polymer hybrid nanoparticles of lonidamine in a rat BPH model created in rat prostates. After local injections of hybrid nanoparticles of lonidamine were administered to the rat prostates, hyperplasic structures of prostates were evaluated in terms of prostatic index values, immunohistochemical evaluations, and histopathological findings. Liver blood enzyme values were also determined to specify hepatic toxicity. Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) reaction and histopathological methods to determine intravital degenerative destruction in liver. Through this study, lonidamine-loaded hybrid nanoparticles were found to reduce the hepatic toxicity and increase therapeutic efficiency of lonidamine. Therefore, lonidamine-entrapped hybrid nanoparticles may provide a promising, and very safe, drug delivery strategy in the treatment of BPH.

Melatonin ameliorates degenerative alterations caused by age in the rat prostate and mitigates high-fat diet damages.

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 (∼32% 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.

Identification of potential molecular pathways involved in prostate carcinogenesis in offspring exposed to maternal malnutrition.

The developmental origins of health and disease concept links adult diseases with early-life exposure to inappropriate environmental conditions. Intrauterine and postnatal malnutrition may lead to an increased incidence of type 2 diabetes, obesity, and cardiovascular diseases. Maternal malnutrition (MM) has also been associated with prostate carcinogenesis. However, the molecular mechanisms associated with this condition remain poorly understood. Using a proteomic analysis, we demonstrated that MM changed the levels of proteins associated with growth factors, estrogen signaling, detoxification, and energy metabolism in the prostate of both young and old rats. These animals also showed increased levels of molecular markers of endoplasmic reticulum function and histones. We further performed an in silico analysis that identified commonly deregulated proteins in the ventral prostate of old rats submitted to MM with a mouse model and patients with prostate cancer. In conclusion, our results demonstrated that estrogenic signaling pathways, endoplasmic reticulum functions, energy metabolism, and molecular sensors of protein folding and Ca2+ homeostasis, besides histone, and RAS-GTPase family appear to be involved in this process. Knowledge of these factors may raise discussions regarding the role of maternal dietary intervention as a public policy for the lifelong prevention of chronic diseases.

Fetal programming by high-fat diet promoted the decreased of the prostate in adult Wistar albino rats

We investigated the effect of a high-fat diet on body metabolism and ventral prostate morphology in 4-months-old offspring. The mother was fed with a control (C) or a high-fat (HF) diet during gestation and lactation. At weaning, the offspring diet remained the same (C/C, n = 8; HF/HF, n = 8) or it was switched (C/HF, n = 8; HF/C, n = 9). Biometry, blood pressure (BP), glucose, lipid metabolism and ventral prostate were evaluated. Triacylglycerol of HF/C increased, and the C/HF group had decreased HDL-c levels (P = 0.0005 and P = 0.0100, respectively). All groups on the HF diet presented hyperglycemia (P = 0.0064). Serum testosterone diminished in the C/HF group (P = 0.0218). The HF diet, regardless of the period, reduced prostatic acinar area (P < 0.0001). The epithelium height was smaller in HF/C and HF/HF groups compared with C/C and C/HF (P < 0.0001), and the volume density of epithelium was lower in HF/C group compared with the C/C and C/HF (P = 0.0024). The volume density of smooth muscle cells diminished in C/HF and HF/C (P = 0.0013), and the volume density of connective tissue was reduced in HF/C and HF/HF (P < 0.0001). High-fat diet intake during prenatal and postnatal life leads to prostatic atrophy, which may impair prostate secretory activity and contractility, and thus disturb reproductive function in adulthood.

Voiding Dysfunction in Old Male Rats Associated With Enlarged Prostate and Irregular Afferent-Triggered Reflex Responses.

PurposeThis study was conducted to evaluate the hypothesis that an enlarged prostate in old rats may lead to complications associated with voiding dysfunction involving ionotropic P2X2/3-type purinergic receptorsMethodsIntact animals were divided into male young (MYR; 8–10 weeks old) and male old (MOR; 20 months old) rats. The animals underwent simultaneous detrusor electromyography (EMG) and suprapubic cystometry (CMG) under urethane anesthesia. Immunofluorescence techniques were used to evaluate prostatic autonomic innervation and P2X3R expression in bladder urothelial cells. The functional role of P2X3R was characterized by intramuscular application of AF-353, a selective P2X2/3R antagonist.ResultsThe prostate index significantly increased in MOR, suggestive of an enlarged prostate affecting micturition patterns. Significant EMG and CMG differences were found between MYR and MOR. Higher immunoreactivity for P2X2/3R in the urothelial layer and for prostatic neurofilaments was seen in MOR. Systemic inhibition of P2X2/3R had minimal effects on MYR responsiveness, but improved voiding function in MOR with a marked decrease of intravesical pressure and bladder contractile responses.ConclusionsThe data support the hypothesis that an enlarged prostate in MOR may contribute to voiding dysfunction involving activation of P2X2/3R, which enhances a prostate-bladder reflex. This reflex may increase bladder afferent transmission and activation of increased prostate innervation, leading to voiding dysfunction.