Chronic Prostatitis Affects Male Reproductive Health and Is Associated with Systemic and Local Epigenetic Inactivation of C-X-C Motif Chemokine 12 Receptor C-X-C Chemokine Receptor Type 4

Schagdarsurengin, Undraga; Teuchert, L.M.; Hagenkötter, Christina; Nesheim, Nils; Dansranjavin, Temuujin; Schuppe, Hans‐Christian; Gies, Sabrina; Pilatz, Adrian; Weidner, W.; Wagenlehner, Florian M. E.

doi:10.1159/000452251

Cited by 20 publications

(19 citation statements)

References 34 publications

(44 reference statements)

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“…The decline of semen quality in patients with CP has been gradually confirmed in the past years. One of the possible pathogenic mechanisms is the inactivation of systemic and local epigenetic C-X-C chemokine receptor type 4 (CXCR4) due to promoter hypermethylation [19]. Decreased sperm motility in CP patients was also found in our study.…”

Section: Discussionsupporting

confidence: 74%

Clinical Evaluation of Urine Prostatic Exosomal Protein in the Diagnosis of Chronic Prostatitis

Li¹,

Jiang²,

Liu³

et al. 2017

Urol Int

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Objective: To evaluate the clinical potential of urine prostatic exosomal protein (PSEP) as a diagnostic biomarker of chronic prostatitis (CP). Materials andmethods: Using an enzyme-linked immunosorbent assay kit, urine PSEP levels were detected in 103 control cases as well as 283 cases of CP, with 82 cases fulfilling the definition of the USA National Institutes of Health category II (NIH-II), 108 cases of NIH-IIIa and 93 cases of NIH-IIIb. The values of age, body mass index, prostate volume, serum prostatic specific antigen (PSA) urine PSEP levels, and seminal parameters were analyzed. Results: The PSEP levels were significantly higher in patients of NIH-II (2.09 [2.35] ng/mL), NIH-IIIa (1.80 [2.95] ng/mL) and NIH-IIIb (1.64 [2.48] ng/mL) compared to the value of 0.24 (0.76) ng/mL in the controls. ROC identified a cutoff value of 1.387 ng/mL, with a sensitivity of 59.0% and specificity of 94.2%. The area under the ROC curve was 0.833. PSEP levels positively correlated with serum PSA levels in the NIH-IIIb group, and with EPS WBC count in the NIH-IIIa group, and with semen WBC count in each CP subgroups but negatively correlated with sperm motility in both the NIH-IIIa group and the NIH-IIIb group. Conclusion: Urine PSEP could be a potential biomarker for CP.

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Section: Discussionsupporting

confidence: 74%

Clinical Evaluation of Urine Prostatic Exosomal Protein in the Diagnosis of Chronic Prostatitis

Li¹,

Jiang²,

Liu³

et al. 2017

Urol Int

View full text Add to dashboard Cite

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“…In particular, significant impairments in ejaculate volume, sperm concentration, total number, motility, morphology and vitality of sperm cells and pH-value could be evaluated in CP/CPPS patients in comparison to healthy controls ( Supplementary Figure 1 ). These subsequent results confirmed our previously described and discussed observations in CP/CPPS patients [ 25 ] and emphasized again the relation between CP/CPPS and impaired semen parameters.…”

Section: Resultssupporting

confidence: 92%

“…Moreover, in CP/CPPS patients, but not in controls, a significant correlation between estradiol levels in seminal plasma and in blood was detected, indicating a CP/CPPS specific systemic and local deregulation of E 2. These novel findings in CP/CPPS patients demonstrate that estrogen and estrogen receptors’ deregulation may play an important role in the chronification of prostatitis and, together with our previous results [ 25 ], suggest that semen is a suitable source for development of diagnostic biomarkers for CP/CPPS.…”

Section: Discussionsupporting

confidence: 77%

“…Human semen contains besides spermatozoa and immature germ cells also a variety of somatic cells, including epithelial cells from the male tract and leukocytes. Our previous study demonstrated that ejaculated somatic cells from CP/CPPS patients exhibited epigenetic aberrations in CXCR4 gene, a chemokine receptor often dysregulated in human tumors [ 25 ]. In order to get a more detailed profile of the white blood cells in ejaculates, we performed the peroxidase-positive leukocyte test and, additionally, an analysis of the expression of genes typical for inflammatory cells.…”

Section: Resultsmentioning

confidence: 99%

“…Administration of the histone deactelyase (HDAC) inhibitor MS-275 led to EAP attenuation in a rat model [ 24 ], highlighting the epigenetic dimensions of the inflammatory response as a possible target for epigenetic drugs. Our group recently reported epigenetic inactivation of CXCR4 (C-X-C motif receptor of the chemokine CXCL12/SDF1) in CP/CPPS patients’ liquid biopsies [ 25 ], showing that CP/CPPS is accompanied by systemic and organ-specific epigenetic changes. Here, we extend upon this and examine in a prospective analytical comparative study whether epigenetic aberrations of the sex hormone receptor genes ESR1 , ESR2 and AR (androgen receptor) occur in CP/CPPS and associate with the clinical phenotype.…”

Section: Introductionmentioning

confidence: 99%

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Elevated seminal plasma estradiol and epigenetic inactivation of ESR1 and ESR2 is associated with CP/CPPS

et al. 2018

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Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is associated with urinary tract symptoms and hormonal imbalances amongst others. The heterogeneous clinical presentation, unexplored molecular background and lack of prostate biopsies complicate therapy. Here, using liquid biopsies, we performed a comprehensive translational study on men diagnosed with CP/CPPS type III (n = 50; median age 39.8, range 23–65) and age-matched controls (n = 61; median age 36.8, range 20–69), considering biochemical parameters of blood and ejaculates, and epigenetic regulation of the estrogen receptor genes (ESR1 and ESR2) in leukocytes isolated from blood (systemic regulation) and in somatic cells isolated from ejaculates (local regulation). We found elevated 17β-estradiol (E2) levels in seminal plasma, but not in blood plasma, that was significantly associated with CP/CPPS and impaired urinary tract symptoms. In ejaculated somatic cells of CP/CPPS patients we found that ESR1 and ESR2 were both significantly higher methylated in CpG-promoters and expressionally down-regulated in comparison to controls. Mast cells are reported to contribute to CP/CPPS and are estrogen responsive. Consistent with this, we found that E2 –treatment of human mast cell lines (HMC-1 and LAD2) resulted in altered cytokine and chemokine expression. Interestingly, in HMC-1 cells, possessing epigenetically inactivated ESR1 and ESR2, E2 –treatment led to a reduced transcription of a number of inflammatory genes. Overall, these data suggest that elevated local E2 levels associate with an epigenetic down-regulation of the estrogen receptors and have a prominent role in CP/CPPS. Investigating E2 levels in semen could therefore serve as a promising biomarker to select patients for estrogen targeted therapy.

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Post‐prostatic‐massage urine exosomes of men with chronic prostatitis/chronic pelvic pain syndrome carry prostate‐cancer‐typical microRNAs and activate proto‐oncogenes

et al. 2022

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Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) has a high prevalence of up to 15% and accounts for 90-95% of prostatitis diagnoses, and yet its etiopathogenesis and link to prostate cancer (PCa) are still unclear. Here, we investigated microRNAs in exosomes isolated from blood and post-prostatic-massage urine of CP/CPPS type IIIb patients and healthy men. THP-1 monocytes (human leukemia monocytic cell line) were treated with exosomes and subjected to mRNA arrays "Cancer Inflammation and Immunity Crosstalk" and "Transcription Factors." Using The Cancer Genome Atlas, the expression of CP/CPPS-associated microRNAs was analyzed in PCa and normal prostate tissue. In silico functional studies were carried out to explore the disease ontology of CP/CPPS. In CP/CPPS, urine exosomes exhibited significant upregulation of eight PCa-specific microRNAs (e.g., hsa-miR-501, hsa-miR-20a, and hsa-miR-106), whose target genes were significantly enriched for GO terms, hallmark gene sets, and pathways specific for carcinogenesis. In THP-1 monocytes, CP/CPPS-derived urine exosomes induced upregulation of PCa-associated proinflammatory genes (e.g., CCR2 and TLR2) and proto-oncogene transcription factors (e.g., MYB and JUNB). In contrast, CP/CPPS-derived blood exosomes exhibited molecular properties similar to those of healthy men. Thus, CP/CPPS exhibits molecular changes that constitute a risk for PCa and should be considered in the development of PCa biomarkers and cancer screening programs.

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Chronic Prostatitis Affects Male Reproductive Health and Is Associated with Systemic and Local Epigenetic Inactivation of C-X-C Motif Chemokine 12 Receptor C-X-C Chemokine Receptor Type 4

Cited by 20 publications

References 34 publications

Clinical Evaluation of Urine Prostatic Exosomal Protein in the Diagnosis of Chronic Prostatitis

Clinical Evaluation of Urine Prostatic Exosomal Protein in the Diagnosis of Chronic Prostatitis

Elevated seminal plasma estradiol and epigenetic inactivation of ESR1 and ESR2 is associated with CP/CPPS

Post‐prostatic‐massage urine exosomes of men with chronic prostatitis/chronic pelvic pain syndrome carry prostate‐cancer‐typical microRNAs and activate proto‐oncogenes

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