Rat Prostate Research Articles

The anti-inflammation, anti-oxidative and anti-fibrosis properties of swertiamarin in cigarette smoke exposure-induced prostate dysfunction in rats

Chronic cigarette smoke (CS) exposure induces prostate deficits. We previously found that swertiamarin had prostatic protective potential. This study was to investigate the possible protective effect of swertiamarin against CS-induced prostate dysfunction on human prostate epithelial cells, stromal cells and rats. Rat prostate collagen deposition and fibrosis were assessed by sirius red staining and measuring hydroxyproline content, as well as by qPCR and western blot analysis for fibrotic extracellular matrix components. Prostatic levels of oxidative stress and inflammatory-related factors were also analyzed. In order to explore its underling mechanisms, the activities of Hedgehog signaling pathway and epithelial-mesenchymal transition of human prostate cells and rat prostate tissue were estimated. It was found that swertiamarin ameliorated CS-induced prostatic collagen deposition, relieved oxidative stress and local inflammation, inhibited the activation of Hedgehog signaling pathway and attenuated epithelial-mesenchymal transition. It indicated that swertiamarin could ameliorate CS-induced prostatic fibrosis by inhibiting epithelial-mesenchymal transition and Hedgehog pathway.

Regulation of microRNAs by rape bee pollen on benign prostate hyperplasia in rats.

The miRNAs are dysregulated in BPH. Rape bee pollen (RBP) is used to improve benign prostatic hyperplasia (BPH). Whether RBP treats BPH by regulating the dysregulated miRNAs remains unclear. Here, we identified miRNAs regulated along with the improvement of BPH by RBP in posterior lobes of prostate in rats. Firstly, to screened miRNAs might relate to improvement of BPH by RBP, we compared differentially expressed miRNAs between BPH model group and RBP group by high-throughput sequencing. As a result, 10 known miRNAs and 17 novel miRNA were up-regulated in RBP group, and 6 known and 13 novel miRNAs were down-regulated. Secondly, among the known miRNAs, we identified those that might relate to BPH by RT-qPCR, while only rno-miR-184 was screened, so we compared it among normal control group, BPH model group and RBP group. The results showed that rno-miR-184 was significantly lower expressed in BPH group, but up-regulated along with the improvement of BPH by RBP. Moreover, expression level of rno-miR-184 was no difference between RBP group and normal control level. Therefore, we considered that RBP might improve BPH through regulating expression of miRNAs like rno-miR-184 in prostate in rats.

Impact of Single Dose Photons and Carbon Ions on Perfusion and Vascular Permeability: A Dynamic Contrast-Enhanced MRI Pilot Study in the Anaplastic Rat Prostate Tumor R3327-AT1.

We collected initial quantitative information on the effects of high-dose carbon (12C) ions compared to photons on vascular damage in anaplastic rat prostate tumors, with the goal of elucidating differences in response to high-LET radiation, using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Syngeneic R3327-AT1 rat prostate tumors received a single dose of either 16 or 37 Gy 12C ions or 37 or 85 Gy 6 MV photons (iso-absorbed and iso-effective doses, respectively). The animals underwent DCE-MRI prior to, and on days 3, 7, 14 and 21 postirradiation. The extended Tofts model was used for pharmacokinetic analysis. At day 21, tumors were dissected and histologically examined. The results of this work showed the following: 1. 12C ions led to stronger vascular changes compared to photons, independent of dose; 2. Tumor growth was comparable for all radiation doses and modalities until day 21; 3. Nonirradiated, rapidly growing control tumors showed a decrease in all pharmacokinetic parameters (area under the curve, Ktrans, ve, vp) over time; 4. 12C-ion-irradiated tumors showed an earlier increase in area under the curve and Ktrans than photon-irradiated tumors; 5. 12C-ion irradiation resulted in more homogeneous parameter maps and histology compared to photons; and 6. 12C-ion irradiation led to an increased microvascular density and decreased proliferation activity in a largely dose-independent manner compared to photons. Postirradiation changes related to 12C ions and photons were detected using DCE-MRI, and correlated with histological parameters in an anaplastic experimental prostate tumor. In summary, this pilot study demonstrated that exposure to 12C ions increased the perfusion and/or permeability faster and led to larger changes in DCE-MRI parameters resulting in increased vessel density and presumably less hypoxia at the end of the observation period when compared to photons. Within this study no differences were found between curative and sub-curative doses in either modality.

The Effect of the Aqueous Extract of Origanum vulgare on the Postnatal Development of the Rat Prostate

The Effect of the Aqueous Extract of Origanum vulgare on the Postnatal Development of the Rat Prostate

Short-term aromatase inhibition induces prostatic alterations in adult wistar rat: A biochemical, histopathological and immunohistochemical study

PurposeThis study aimed to evaluate the effects of estrogen reduction on amyloid deposition, some lipid metabolism and oxidative stress markers, PSA-like production and p63 expression in the prostate of the adult rat. MethodsAromatase inhibitor: Formestane (4-OHA), was administrated to male rats, at a dose of 0.1 mg/kg b.w./day, for 10 days. The control group (CONT) received the same volume of placebo injection (NaCl 0.9%). Results4-OHA treatment induced a significant accumulation of intraprostatic cholesterol (138.90 ± 17.64 vs 85.12 ± 2.87, p = 0.01); against an insignificant diminution of malondialdehyde (412.6 ± 54.35 vs 842.70 ± 336.50, p > 0.05) and glutathione (2.40 ± 0.23 vs 3.65 ± 0.88, p > 0.05). This was associated with a significant decrease of nitric oxide (31.76 ± 7.07 vs 179.40 ± 58.35, p = 0.024). Additionally, 4-OHA significantly increased the intraprostatic production of PSA-like (11.12 ± 2.78 vs 3.91 ± 0.43, p = 0.043). The prostatic histology revealed an amyloid deposition, in all prostatic lobes and a smooth muscle layer growth (p < 0.05); especially significant in the dorsal and lateral lobes. Theses lobes manifested a basal cells proliferation, with a 3-fold increase of p63 expression (p < 0.001). The ventral lobe presented epithelial atrophy (37.80 ± 16.20 vs 167.60 ± 5.16, p < 0.05); with occasional and significant proliferative foci (247.00 ± 9.573 vs 167.60 ± 5.16 p < 0.05). Discussion and conclusionAromatase inhibition, in the adult male rat, alters the prostatic function by reducing nitric oxide availability and inducing amyloid deposition along with limiting the differentiation of basal cells, through a lobe-specific p63-overexpression.

The Effects of 8-Week Endurance Training on Prostatic Autophagy and Benign Prostatic Hyperplasia of Rats

PURPOSE Benign prostatic hyperplasia (BPH) is a typical male adult disease in which the prostate is enlarged but not cancerous. Autophagy is a catabolic process of cellular constituents and a mechanism for cellular homeostasis of tissues. Currently, it is not established whether BPH is linked to autophagy or not and whether endurance exercise training, an autophagy activator, can ameliorate its disease symptoms. Therefore, the purpose of this study was to investigate whether BPH is closely related with autophagy dysregulation and induced autophagy by exercise training can relieve BPH. METHODS Forty-eight male wild-type SD rats (10-week old) were randomly divided into 4 groups: Sham, BPH-sedentary, BPH-exercise, and BPH-finasteride. For BPD induction, rats were castrated and testosterone (3 mg/kg/day) were administered daily for 2 months. During this period, rats performed five daily bouts of 25-minute treadmill running exercise per week or daily treated with finasteride dissolved in corn oil (10 mg/kg) by oral gavage for 8 weeks. Prostate weight, autophagy flux, serum and prostate levels of androgens and inflammatory factors were analyzed. The results were analyzed with one-way ANOVA. RESULTS In BPH rats, the ratio of prostate weight/body weight was significantly elevated, but autophagy flux was significantly decreased (p<.05). Eight-week exercise training failed to reduce the ratio and to increase autophagy flux in the prostate of BPH rats. However, 8-week running training significantly decreased the levels of DHT and proinflammatory factors (IL-1β and IL-6) in the serum and the prostate of BPH rats (p<.05). CONCLUSIONS This current study suggests that endurance exercise training may be beneficial for BPH not through the mechanisms involved in autophagy regulation but through alleviating hormonal and inflammatory factors. 색인어: ì „ë¦½ì„ ë¹„ëŒ€ì¦, 자가포식, ìš´ë™í›ˆë ¨, í ŒìŠ¤í† ìŠ¤í Œë¡ , 염증 Keywords: Benign prostatic hyperplasia, Autophagy, Exercise training, Testosterone, Inflammation

ICP-MS analysis of diet supplementation influence on the elemental content of rat prostate gland

Metabolism of numerous elements is involved in carcinogenesis. Among other, calcium and zinc metabolic pathways coincide with prostate cancer development. It is probable that the restoration of elemental loses can moderate or even stop prostate malignancy. For this reason, studies on elemental content in tissues taken from organisms with cancer are carried out to establish proper supplementation. ICP-MS is a well-established method for the analysis of such a kind of samples. The study aimed to investigate the influence of dietary supplementation on elemental content in the prostate gland of rats with implanted cancer cells. Tested animals were divided into six dietary groups: standard diet and supplementation with Ca, Fe, Zn, Cu, or Se. Every dietary group was divided into experimental group (with implanted cancer cells) and control group (without cancer cells). Prostate tissue was dried and treated with microwave-assisted mineral digestion. Total elemental content was quantified by ICP-MS. Student's t test and analysis of variance with post-hoc Tukey’s procedure were applied to compare treatment and dietary groups. The total content of selected elements (K, Na, Mg, Ca, Fe, Zn, Cu, Sr, Pb, and Se) was quantified, with statistically significant differences in Na, Mg, Ca, Zn, Sr, and Se contents between treatment groups and in Ca, Fe, Cu, Zn, Sr, and Pb contents between diet groups. High heterogeneity within group could be observed for Zn content in the tissue, confirming the crucial role of zinc in prostate gland metabolism and pointing its inter-individual variability.Graphic abstract

Membrane-initiated estrogen signaling in prostate cancer: A route to epithelial-to-mesenchymal transition.

The plasma membrane (PM) is considered as a major druggable site. More than 50% of the existing drugs target PM proteins. In the wake of emerging data indicating a key role of estrogens in prostate cancer (PCa) pathogenesis, the study was undertaken to explore whether the estrogen binding sites exist on the PM and if such sites are functionally relevant in PCa. Estradiol (E2) binding to the PM was detected in androgen-dependent (LNCaP), androgen-independent (PC3, DU145) PCa cell lines, nontumorigenic (RWPE1) prostate epithelial cell line, and rat prostate cells. Conventional estrogen receptors (nuclear estrogen receptors), known for their nuclear localization, were detected in the PM enriched extracts. This was indirectly confirmed by reduced localization of ERs on the PM of cells, silenced for the expression of their cognate genes. Further, unlike cell-permeable E2, stimulation with cell-impermeable estradiol (E2-BSA) did not induce proliferation in LNCaP cells. However, stimulation with E2-BSA led to alterations in the phosphorylation status of several kinases including GSK3 and AKT, along with the hyperphosphorylation of cytoskeletal proteins such as β-actin and cytokeratin 8 in LNCaP. This was accompanied by epithelial-to-mesenchymal (EMT) features such as increased migration and invasion; higher vimentin expression, and a concomitant decrease in the E-cadherin expression. These effects were not observed in RWPE1 cells. Interestingly, cell-permeable E2 failed to induce EMT in PCa cells. This in vitro study is the first to suggest that the PM-initiated estrogen signaling contributes to higher invasiveness in PCa cells. Plasma membrane ERs may act as novel targets for PCa therapeutics.

Effects of Black Raspberries and Their Constituents on Rat Prostate Carcinogenesis and Human Prostate Cancer Cell Growth In Vitro

Prostate cancer patients often use dietary supplements, such as black raspberries, which are a rich source of compounds with antioxidant and anticancer activity, particularly on gastrointestinal cancers. Feeding black raspberries inhibited mammary cancer induction in rats and growth of cancer cells in nude mice, indicating systemic bioavailability of bioactive compounds. We tested whether feeding black raspberries and its constituents would inhibit prostate cancer development. However, we did not find preventive effects in two rat prostate carcinogenesis models, even though the berry anthocyanin metabolite protocatechuic acid was detectable in their prostates. Black raspberry extract, the anthocyanin cyanidin-3-rutinoside and protocatechuic acid did not inhibit prostate cancer cell growth in vitro, but ellagic acid and its urolithin A metabolite did at high concentrations. Prostate cancer cell migration was not affected by these agents nor was growth in soft agar, except that ellagic acid reduced colony formation at physiological concentrations and protocatechuic acid at high concentrations. Low bioavailability of bioactive berry compounds and metabolites may limit exposure of tissues such as the prostate, since we found that cyanidin-3-rutinoside was not bioavailable to prostate cancer cells, but its aglycone cyanidin was and inhibited their growth. Thus, black raspberries are unlikely to prevent prostate cancer.

Prostate Cancer in World Trade Center Responders Demonstrates Evidence of an Inflammatory Cascade.

An excess incidence of prostate cancer has been identified among World Trade Center (WTC) responders. In this study, we hypothesized that WTC dust, which contained carcinogens and tumor-promoting agents, could facilitate prostate cancer development by inducing DNA damage, promoting cell proliferation, and causing chronic inflammation. We compared expression of immunologic and inflammatory genes using a NanoString assay on archived prostate tumors from WTC Health Program (WTCHP) patients and non-WTC patients with prostate cancer. Furthermore, to assess immediate and delayed responses of prostate tissue to acute WTC dust exposure via intratracheal inhalation, we performed RNA-seq on the prostate of normal rats that were exposed to moderate to high doses of WTC dust. WTC prostate cancer cases showed significant upregulation of genes involved in DNA damage and G2-M arrest. Cell-type enrichment analysis showed that Th17 cells, a subset of proinflammatory Th cells, were specifically upregulated in WTC patients. In rats exposed to WTC dust, we observed upregulation of gene transcripts of cell types involved in both adaptive immune response (dendritic cells and B cells) and inflammatory response (Th17 cells) in the prostate. Unexpectedly, genes in the cholesterol biosynthesis pathway were also significantly upregulated 30 days after acute dust exposure. Our results suggest that respiratory exposure to WTC dust can induce inflammatory and immune responses in prostate tissue. IMPLICATIONS: WTC-related prostate cancer displayed a distinct gene expression pattern that could be the result of exposure to specific carcinogens. Our data warrant further epidemiologic and cellular mechanistic studies to better understand the consequences of WTC dust exposure.Visual Overview: http://mcr.aacrjournals.org/content/molcanres/17/8/1605/F1.large.jpg.

Structural and functional abnormalities of penile cavernous endothelial cells result in erectile dysfunction at experimental autoimmune prostatitis rat

BackgroundThere is growing recognition of the association of CP/CPPS accompany with ED. However, the specific mechanism of action remains unclear. The aim of this study was to investigate structural and functional abnormalities of cavernous endothelial cells in EAP rat, which may result in the ED.Methodswe use rat prostate protein extract supplemented with immunoadjuvant to induce EAP rat, ICP and MAP were measured and inflammatory factor infiltration, Akt, eNOS, AR, nNOS and iNOS in the corpus cavernosum were tested. Subsequently, the normal rat and EAP rat cavernosum endothelial cells were purified by MACS, and the metabolism, oxidative stress, MMP, Akt, eNOS, AR and iNOS were evaluated.ResultsThe EAP rat model was successfully constructed. The ratio of max ICP/MAP in EAP rat was significantly lower and TNF-α infiltration in corpus cavernosum was significantly higher than normal rats. Besides, Akt, eNOS and AR were decreased, iNOS was significantly increased. The growth and metabolism of endothelial cells in the EAP rats corpus cavernosum decreased and inflammatory factor mRNA was increased and intracellular oxidative stress was also increased significantly. The MMP of EAP rats cavernosum endothelial cells decreased and the expression of Akt, eNOS and AR were also significantly decreased, iNOS was significantly increased.ConclusionThe prostate suffer local inflammatory infiltrate and promotes cytokines infiltrated into corpus cavernosum caused the oxidative stress increases and the metabolism or MMP decreases. In addition, AR, Akt and eNOS expression and phosphorylation are also reduced, thereby inhibiting the diastolic function of the corpus cavernosum, resulting in decreased erectile function.

Purple rice extract inhibits testosterone-induced rat prostatic hyperplasia and growth of human prostate cancer cell line by reduction of androgen receptor activation.

The preventive effects of purple rice crude ethanolic extract (PRE) were firstly investigated on testosterone-induced benign prostatic hyperplasia (BPH) in castrated rats. As compared to vehicle-treated rats, lower prostate weights were found in the BPH rats that received PRE 1g/kg bw. In addition, the PRE treatment down-regulated the androgen receptor (AR) expression in the dorsolateral prostate of those rats. In human prostate cancer cell line, LNCaP, PRE could reduce the cell growth, down-regulate the expression of AR and suppress prostate-specific antigen (PSA) secretion. Moreover, PRE also inhibited an activity of 5α-reductase from rat liver microsomes and the mutagenicity of Salmonella Typhimurium induced by standard mutagen. These results demonstrate that PRE altered testosterone-induced BPH in rats and retarded prostate cancer cell growth by modulating AR expression. It is therefore recommended that further investigation is undertaken into the chemopreventive potential of PRE in androgen-AR mediated diseases. PRACTICAL APPLICATIONS: This study revealed the mechanisms of purple rice extract on testosterone-induced rat benign prostatic hyperplasia. Such information, purple rice components show promise as an effective chemopreventive agent for prostatic hyperplasia prevention by alternating the influence of testosterone through its receptor. Thus, purple rice might be developed as food supplement for reduction of prostatic hyperplasia or cancer in elder men.

Electric Stimulation Hyperthermia Relieves Inflammation via the Suppressor of Cytokine Signaling 3-Toll Like Receptor 4 Pathway in a Prostatitis Rat Model.

PurposeChronic prostatitis (CP), including chronic pelvic pain syndrome (CPPS), is the most commonly encountered manifestation of prostatitis. The aim of this study was to evaluate the effect of electric stimulation hyperthermia treatment (ESHT) on CP/CPPS and to explore the underlying mechanism.Materials and MethodsRWPE-2 cells with lipopolysaccharide-induced inflammation and a prostatitis rat model induced by 17β-estradiol and dihydrotestosterone underwent sham, electric stimulation, or ESHT treatment. Four weeks later, cells, supernatants, and rat prostates were collected for analysis using immunohistochemistry, Western blots, and enzyme-linked immunosorbent assays.ResultsWe found that ESHT improved prostatitis in vivo and attenuated inflammation in vitro. ESHT significantly induced suppressor of cytokine signaling 3 (SOCS3) expression and subsequently promoted HSP70. It attenuated inflammation through decreased expression of toll-like receptor 4 (TLR4), nuclear factor kappa B, and subsequent inflammatory cytokines. ESHT also inhibited apoptosis and released growth factor in tissue affected by prostatitis.ConclusionsESHT improved CP/CPPS and reversed pathologic changes of prostatitis by inhibiting the SOCS3-TLR4 pathway.

Arsenic exposure during prepuberty alters prostate maturation in pubescent rats

Arsenic is a widely dispersed chemical compound in the environment and has been associated with the development of some diseases and different types of cancer. Little is known about the action of arsenic compounds on prostate development during prepuberty and puberty. This study evaluated prostate morphophysiology after sodium arsenite exposure during prepubertal period in rats. Male Wistar rats at PND23 were randomly distributed into three experimental groups (n = 10/group). The Ctrl group (filtered drinking water); As1 group (0.01 mg/L of NaAsO2); As2 group (10.0 mg/L of NaAsO2) that received the diluted solution in drinking water from PND23 to PND53. Histological and molecular analyzes showed developmental delay in the As1 group and important morphophysiological alterations in As2 group. The results showed that exposure to NaAsO2 during prepuberty compromised structural and functional maturation of the prostate in pubertal rats at both doses evaluated in this study.

Fatty Acids in Some Cooking Oils as Agents of Hormonal Manipulation in a Rat Model of Benign Prostate Cancer.

Anti-androgenic substances, mainly prostate 5α-reductase inhibitors, used in the treatment of benign prostatic hyperplasia (BPH) have been associated with side effects in man and animals. To reduce these side effects as well as suppress BPH development, the management of the condition has come to include dietary interventions. This study investigated the effect of some cooking oils on testosterone-induced hyperplasia of the prostate in rats. Male Sprague-dawley rats were distributed into eighteen groups (n=6) as A-R. A negative control group was injected subcutaneously with soya oil; while prostatic hyperplasia was induced subcutaneously in groups B-R with 3mg/kg testosterone daily for 14days. Group B was the positive control (BPH group) while groups C-R were also administered orally 800mg/kg of coconut, castor, canola, cottonseed, pomegranate, blackseed, sheabutter, olive oil, codliver, sardine, palm, repeatedly heated palm (RHPO), vegetable, repeatedly-heated vegetable (RHVO), sesame, and groundnut oils respectively, daily, for 14 days. Blood sample was drawn via retro-orbital sinus for the estimation of serum testosterone(T) and dihydrotestosterone (DHT) level and rats were thereafter euthanized to obtain the prostates for T and DHT determination as well as tissue weights. Data are mean ± SEM, compared by ANOVA. The oils significantly reduced the increase in prostate weight (PW) to body weight (BW) ratio induced by testosterone. Apart from the fact that all the oils reduced the PW:BW ratio, the blackseed, sheabutter, sardine, vegetable and groundnut oils suppressed the DHT level in the serum, while pomegranate, olive, RHPO reduced DHT level in the prostate compared to the BPH rats. This study suggests that blackseed, sheabutter, sardine, vegetable, groundnut, pomegranate, olive, and RHPO oils could inhibit testosterone-induced hyperplasia of the prostate and therefore may be beneficial in the management of BPH.

Anatomy and Imaging of Rat Prostate: Practical Monitoring in Experimental Cancer-Induced Protocols.

The rat has been frequently used as a model to study several human diseases, including cancer. In many research protocols using cancer models, researchers find it difficult to perform several of the most commonly used techniques and to compare their results. Although the protocols for the study of carcinogenesis are based on the macroscopic and microscopic anatomy of organs, few studies focus on the use of imaging. The use of imaging modalities to monitor the development of cancer avoids the need for intermediate sacrifice to assess the status of induced lesions, thus reducing the number of animals used in experiments. Our work intends to provide a complete and systematic overview of rat prostate anatomy and imaging, facilitating the monitoring of prostate cancer development through different imaging modalities, such as ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI).

Cell-Free DNA Plasma Levels Differ in Age-Specific Pattern in Healthy Rats and Castrates with Testosterone-Induced Benign Prostatic Hyperplasia.

The purpose of this work was to study changes in the level of cell-free DNA (cfDNA) in the blood of young and old rats in the normal state and with induced benign prostatic hyperplasia (BPH). Male Wistar rats were divided into 4 groups—young (3 months), old (20 months), intact, or with testosterone-induced BPH. Groups with BPH were subjected to surgical castration and administration of testosterone esters at a dose of 25 mg/kg for a total of 7 injections for 20 days. In intact animals, the level of cfDNA in old rats (2.00 ± 0.14 ng/μl) was significantly higher than that in the young (1.02 ± 0.30 ng/μl). The body and the prostate weights of old rats were 1.6 and 1.4 times larger than those of the young, without an increase in the prostate index (PI). The testosterone level in the blood of young rats was 1.6 times higher than that of old (6.20 ± 0.93 nmol/l vs. 3.77 ± 0.55 nmol/l; NS). In animals with BPH, the level of cfDNA in old rats (3.14 ± 0.76 ng/μl) was significantly higher than that in young rats (0.80 ± 0.14 ng/μl). The body and the prostate weights in old rats were 1.8 and 2.3 times larger, than those in young rats, with an increase in the PI. The level of testosterone in the blood of young (15.76 ± 0.51 nmol/l) and old (16.99 ± 1.1 nmol/l) rats was not significantly different. Morphological signs of BPH were observed in the prostate of both young and old rats. During the induction of BPH in the experiment, according to the level of cfDNA, cell death processes have not changed significantly in young rats but significantly increased in old rats. A similar trend was observed in the group of intact animals. The obtained data indicate that apoptosis processes are enhanced during the development of BPH despite the growth of tissues in the prostate itself.

Male reproductive tract antimicrobial expression in the extremes of ages of rats

Alterations in the global gene expression profile are considered to contribute to the various physiological and pathological changes during the course of ageing. Genes that code for the molecular components of the innate system are alter markedly as ageing occurs; and this may define the susceptibility of very young and very old individuals to reproductive tract infections. The expression pattern of genes that code for beta-defensins (effectors of innate immune response) in male reproductive tract tissues of different stages of ageing is not yet reported. Further, the induction of beta-defensins during endotoxin challenge and whether epigenetic modulators can influence the expression of these genes in different stages of ageing are not reported. We analyzed the basal mRNA levels of beta-defensins and defensin-like proteins (Sperm Associated Antigen 11 (SPAG11) family members), their induction during endotoxin challenge and modulation by epigenetic modifiers (Trichostatin A and Azacytidine) in the caput, cauda, testis, prostate and seminal vesicle of rats that represent early stage to late stages of life (20 day to 730 day old). We observed differential basal gene expression pattern in the male reproductive tract tissues and the induction by LPS was not consistent neither among the age groups not the tissues analyzed. Trichostatin A and Azacytidine also influenced antimicrobial gene expression and the pattern was not consistent in different tissues obtained from different age groups. Results of this study demonstrate that antimicrobial gene expression varies to a great extent during ageing and is strongly influenced by endotoxins and epigenetic modulators.

Chronic prostatitis alters the prostatic microenvironment and accelerates preneoplastic lesions in C57BL/6 mice

BackgroundChronic prostatitis has been supposed to be associated with preneoplastic lesions and cancer development. The objective of this study was to examine how chronic inflammation results in a prostatic microenvironment and gene mutation in C57BL/6 mice.MethodsImmune and bacterial prostatitis mouse models were created through abdominal subcutaneous injection of rat prostate extract protein immunization (EAP group) or transurethral instillation of uropathogenic E. coli 1677 (E. coli group). Prostate histology, serum cytokine level, and genome-wide exome (GWE) sequences were examined 1, 3, and 6 months after immunization or injection.ResultIn the EAP and E. coli groups, immune cell infiltrations were observed in the first and last months of the entire experiment. After 3 months, obvious proliferative inflammatory atrophy (PIA) and prostatic intraepithelial neoplasia (PIN) were observed accompanied with fibrosis hyperplasia in stroma. The decrease in basal cells (Cytokeratin (CK) 5+/p63+) and the accumulation of luminal epithelial cells (CK8+) in the PIA or PIN area indicated that the basal cells were damaged or transformed into different luminal cells. Hic1, Zfp148, and Mfge8 gene mutations were detected in chronic prostatitis somatic cells.ConclusionChronic prostatitis induced by prostate extract protein immunization or E. coli infection caused a reactive prostatic inflammation microenvironment and resulted in tissue damage, aberrant atrophy, hyperplasia, and somatic genome mutation.

Kangquan Recipe Regulates the Expression of BAMBI Protein via the TGF-β/Smad Signaling Pathway to Inhibit Benign Prostatic Hyperplasia in Rats.

Background Kangquan Recipe (KQR) is a traditional Chinese medicine compound made by our research group for the treatment of benign prostatic hyperplasia (BPH). Whether KQR can treat BPH as a single drug or play a role in the treatment of BPH in combination therapy needs further study. Aim of the Study To investigate the effect of KQR on the expression of TGF-β/Smad signaling pathway-related factors in rats with BPH. In-depth analysis revealed the relevant signal transduction mechanism by which KQR acts to treat BPH. Materials and Methods Forty-eight male Sprague-Dawley rats were randomly divided into six groups of 8 rats each. In addition to the control group, 40 rats were castrated and then injected with testosterone propionate to form a prostatic hyperplasia model. After 30 days, three groups received different concentrations of KQR (14 g/kg, 7 g/kg, and 3.5 g/kg), and the finasteride group received 0.5 mg/kg finasteride. The BPH group and the control group received the same volume of saline. All groups were treated for a total of 30 days. Rat body weight, prostate volume, wet weight, index, histology, and the mRNA and protein levels of TGF-β, TGF-βR1, TGF-βR2, p-Smad2, p-Smad3, BAMBI, E-cadherin, and N-cadherin in the prostate tissue were measured after the end of treatment. Results Compared with the control group, the BPH group had increased prostate wet weight, volume, and index, and the histology showed significant BPH. Compared with the BPH group, the three KQR groups and the finasteride group all had varying levels of reduction in the prostate wet weight, volume, and index of the prostate and varying degrees of improvement in the histological manifestations of BPH. KQR downregulates the mRNA and/or protein expression of TGF-β, TGF-βR1, TGF-βR2, p-Smad2, p-Smad3, and N-cadherin protein in prostate tissue and increases the mRNA and protein expression of BAMBI and E-cadherin protein. Conclusions In the model of BPH induced by testosterone propionate after castration, KQR can inhibit the conduction of the TGF-β/Smad signaling pathway by upregulating the expression of BAMBI protein and reversing EMT in rat prostate tissue.