OBJECTIVE: To investigate the genetic causal relationship of leukocyte telomere length (LTL) with prostatitis, orchitis and epididymitis by two-sample Mendelian randomization (MR). METHODS: Using LTL as the exposure factor and prostatitis, orchitis and epididymitis as outcome factors, we mined the Database of Genome-Wide Association Studies (GWAS). Then, we analyzed the causal relationship of LTL with prostatitis, orchitis and epididymitis by Mendelian randomization using inverse variance weighting (IVW) as the main method and weighted median and MR-Egger regression as auxiliary methods, determined the horizontal multiplicity by MR-Egger intercept test, and conducted sensitivity analysis using the leaving-one-out method. RESULTS: A total of 121 related single nucleotide polymorphisms (SNPs) were identified in this study. IVW showed LTL to be a risk factor for prostatitis (OR = 1.383, 95% CI: 1.044－1.832, P = 0.024), and for orchitis and epididymitis as well (OR = 1.770, 95% CI: 1.275－2.456, P = 0.000 6). CONCLUSION Genetic evidence from Mendelian randomized analysis indicates that shortening of LTL reduces the risk of prostatitis, orchitis and epididymitis.
Humans ; Male ; Mendelian Randomization Analysis ; Epididymitis/genetics* ; Prostatitis/genetics* ; Polymorphism, Single Nucleotide ; Leukocytes ; Orchitis/genetics* ; Genome-Wide Association Study ; Telomere ; Risk Factors

OBJECTIVE: To explore the role of the CMTM2 gene in regulating testicular spermatogenesis in the mouse model of experimental autoimmune orchitis (EAO). METHODS: We constructed an EAO model in CMTM2 knockout and wild-type (WT) mice, studied the immunological reproductive phenotype and examined the number, morphology and activity of the sperm generated in the CMTM2 knockout mice. We assessed the infiltration of macrophages and lymphocytes in the testis tissue sections and Leydig cells, and determined the expression levels of CMTM2 in the homozygous knockout (KO), heterozygous and WT mice by RT-PCR, Western blot and Northern blot. RESULTS: Statistically significant differences were observed in the long testicular axis and the number of sperm generated between the KO and WT mice after reaching adulthood (P<0.05). The total numbers of macrophages and lymphocytes were markedly increased, while sperm motility and the percentage of morphologically normal sperm remarkably decreased in the testis of the KO mouse model compared with those in the WT mouse model of EAO. CONCLUSION The CMTM2 gene, as a regulator of spermatogenesis, is highly expressed in adult male mice and plays an important role in the maintenance of spermatogenesis. Moreover, decreased expression products of the CMTM2 gene may weaken spermatogenesis under chronic inflammation conditions.
Animals ; Male ; Mice ; Orchitis/genetics* ; Spermatogenesis/genetics* ; Disease Models, Animal ; Testis/metabolism* ; Autoimmune Diseases/genetics* ; Mice, Knockout ; MARVEL Domain-Containing Proteins/genetics*

Male reproductive infections are known to shape the immunological homeostasis of the testes, leading to male infertility. However, the specific pathogenesis of these changes remains poorly understood. Exosomes released in the inflammatory microenvironment are important in communication between the local microenvironment and recipient cells. Here, we aim to identify the immunomodulatory properties of inflammatory testes-derived exosomes (IT-exos) and explore their underlying mechanisms in orchitis. IT-exos were isolated using a uropathogenic Escherichia coli (UPEC)-induced orchitis model and confirmed that IT-exos promoted proinflammatory M1 activation with increasing expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in vitro. We further used small RNA sequencing to identify the differential miRNA profiles in exosomes and primary testicular macrophages (TMs) from normal and UPEC-infected testes, respectively, and identified that miR-155-5p was highly enriched in IT-exos and TMs from inflammatory testes. Further study of bone marrow derived macrophages (BMDMs) transfected with miR-155-5p mimic showed that macrophages polarized to proinflammatory phenotype. In addition, the mice that were administrated IT-exos showed remarkable activation of TM1-like macrophages; however, IT-exos with silencing miR-155-5p showed a decrease in proinflammatory responses. Overall, we demonstrate that miR-155-5p delivered by IT-exos plays an important role in the activation of TM1 in UPEC-induced orchitis. Our study provides a new perspective on the immunological mechanisms underlying inflammation-related male infertility.
Humans ; Male ; Mice ; Animals ; Orchitis ; Uropathogenic Escherichia coli/metabolism* ; MicroRNAs/metabolism* ; Exosomes/metabolism* ; Macrophages/metabolism* ; Phenotype ; Infertility, Male/metabolism*

The aim of this work was to study effects of ketotifen fumarate (KF) on prevention of tissue damage in testes of rats with experimental autoimmune orchitis (EAO) and on the contralateral testis in a model of prolonged testicular cord torsion (TCT). Rats with EAO or TCT were injected intraperitoneally once daily with KF or saline solution (vehicle group). Incidence and severity of testicular damage were evaluated by histopathology using an EAO score or a Johnsen score. Mast cells (MC) were identified by histochemistry and quantified. In EAO model, KF significantly reduced severity of histopathological testicular damage compared to rats in the vehicle group. KF also reduced the number of testicular MC compared to vehicle group. Similarly, in TCT model, multifocal damage of the contralateral testis was observed 30 days after testicular torsion characterized by sloughing of the germinal epithelium, seminiferous tubule atrophy, and interstitial edema. Focal signs of inflammation and fibrosis of seminiferous tubular walls were also observed. In contrast, sections of contralateral testis of rats injected with KF and killed 30 days after surgery showed normal histological features. A significant decrease in the number of MC was observed in rats treated with KF compared to untreated animals. In conclusion, we demonstrated that treatment with KF reduced testicular inflammatory process and MC infiltrates in both EAO and TCT models. The results suggest a promising treatment for infertile male patients with testicular pathologies associated with inflammation and germ cell loss.
Animals ; Autoimmune Diseases/pathology* ; Cell Count ; Epididymis/pathology* ; Epididymitis/pathology* ; Histamine H1 Antagonists/pharmacology* ; Hypersensitivity, Delayed ; Immunity, Cellular/drug effects* ; Ketotifen/pharmacology* ; Male ; Mast Cells/pathology* ; Orchitis/pathology* ; Rats ; Severity of Illness Index ; Spermatic Cord Torsion/pathology* ; Testis/pathology* ; Vaccination

The search for ideal brucellosis vaccines remains active today. Currently, no licensed human or canine anti-brucellosis vaccines are available. In bovines, the most successful vaccine (S19) is only used in calves, as adult vaccination results in orchitis in male, prolonged infection, and possible abortion complications in pregnant female cattle. Another widely deployed vaccine (RB51) has a low protective efficacy. An ideal vaccine should exhibit a safe profile as well as enhance protective efficacy. However, currently available vaccines exhibit one or more major drawbacks. Smooth live attenuated vaccines suffer shortcomings such as residual virulence and serodiagnostic interference. Inactivated vaccines, in general, confer relatively low levels of protection. Recent developments to improve brucellosis vaccines include generation of knockout mutants by targeting genes involved in metabolism, virulence, and the lipopolysaccharide synthesis pathway, as well as generation of DNA vaccines, mucosal vaccines, and live vectored vaccines, have all produced varying degrees of success. Herein, we briefly review the bacteriology, pathogenesis, immunological implications, candidate vaccines, vaccinations, and models related to Brucella.
Adult ; Animals ; Bacteriology ; Brucella* ; Brucellosis ; Cattle ; Female ; Humans ; Male ; Metabolism ; Models, Animal ; Orchitis ; Vaccination ; Vaccines* ; Vaccines, Attenuated ; Vaccines, DNA ; Vaccines, Inactivated ; Virulence

Objective: To investigate the effect of micro-dissection testicular sperm extraction (microTESE) for patients with non-obstructive azoospermia (NOA) and the indications of the strategy. METHODS: This retrospective study included 196 cases of NOA undergoing microTESE in our center from September 2014 to March 2017. We recorded the sperm retrieval rate (SRR) and analyzed its correlation with the patients' age, testis volume, level of blood follicle-stimulating hormone (FSH), and etiological factors. RESULTS: Testicular sperm were successfully retrieved from 87 (44.4%) of the patients. No significant correlation was found between the SRR and the patients' age, testis volume, or blood FSH level (P >0.05). As regards etiological factors, the SRR was 100% (29/29) in the patients with orchitis, 66.7% (16/24) in those surgically treated for cryptorchidism, 55.6% (10/18) in those with other secondary testis lesions, 60.0% (3/5) in those with AZFc deletion, 40.9% (9/22) in those with severe idiopathic testicular atrophy, 21.4% (12/56) in those with idiopathic NOA, 20.5% (8/39) in those with Klinefelter's syndrome, and 0% (0/3) in those with other abnormal karyotypes. CONCLUSIONS MicroTESE is an effective strategy for sperm retrieval in NOA patients, and the SRR is correlated with etiological factors but not with the FSH level or testis volume of the patients.
Age Factors ; Azoospermia ; blood ; etiology ; Cryptorchidism ; blood ; complications ; Follicle Stimulating Hormone ; blood ; Humans ; Klinefelter Syndrome ; complications ; Male ; Microdissection ; methods ; Orchitis ; complications ; Retrospective Studies ; Sperm Retrieval ; statistics & numerical data ; Spermatozoa ; Testis ; anatomy & histology

OBJECTIVETo investigate the epidemiological characteristics, clinical manifestations, diagnosis, and treatment of Brucella orchitis, so as to provide reliable evidence for the prevention and treatment of the disease.

METHODSWe conducted retrospective statistical analyses on the medical records of 48 outpatients and 21 inpatients with Brucella orchitis.

RESULTSBrucella orchitis was diagnosed in 6.67% of the male patients with brucellosis (69/1 034). The disease exhibited typical epidemiological features, with a higher incidence rate among those in frequent contact with sheep and elderly people, in the period from April to July, and in the areas with sheep husbandry. All the Brucella orchitis patients had such local symptoms as testicular pain and swelling, more frequently involving both testes, and other most common symptoms included fever, chills, sweating, and painful joints. Based on IIEF-5, 45 of the patients suffered from severe erectile dysfunction, with their reproductive function temporarily affected in the course of the disease. Misdiagnosis easily occurred in the early stage of the disease. Therapeutic options mainly included doxycycline hydrochloride and rifampicin, administered orally or intravenously, which could effect a cure, though relapse might occur in some cases.

CONCLUSIONBru- cella orchitis has distinct epidemiological characteristics, with clinical manifestations of testicular pain and swelling. Though a transient disease, it affects the reproductive function of the patient before cured. It can be treated by combined oral and intravenous medication, with painkillers or ice bags for testicular pain and swelling.

Animals ; Brucella ; pathogenicity ; Brucellosis ; complications ; diagnosis ; therapy ; Humans ; Male ; Orchitis ; diagnosis ; microbiology ; therapy ; Retrospective Studies ; Sheep

Ultrasonography is the ideal noninvasive imaging modality for evaluation of scrotal abnormalities. It is capable of differentiating the most important etiologies of acute scrotal pain and swelling, including epididymitis and testicular torsion, and is the imaging modality of choice in acute scrotal trauma. In patients presenting with palpable abnormality or scrotal swelling, ultrasonography can detect, locate, and characterize both intratesticular and extratesticular masses and other abnormalities. A 12-17 MHz high frequency linear array transducer provides excellent anatomic detail of the testicles and surrounding structures. In addition, vascular perfusion can be easily assessed using color and spectral Doppler analysis. In most cases of scrotal disease, the combination of clinical history, physical examination, and information obtained with ultrasonography is sufficient for diagnostic decision-making. This review covers the normal scrotal anatomy as well as various testicular and scrotal lesions.
Adult* ; Epididymitis ; Humans ; Male ; Orchitis ; Perfusion ; Physical Examination ; Scrotum* ; Spermatic Cord Torsion ; Testis ; Transducers ; Ultrasonography*

Cysts ; Epididymitis ; Humans ; Male ; Orchitis ; Urinary Tract Infections

Of the chlamydia species that can cause infections in humans, C. trachomatis is responsible for lower urinary tract diseases in men and women. C. trachomatis infections are prevalent worldwide, but current research is focused on females, with the burden of disease and infertility sequelae considered to be a predominantly female problem. However, a role for this pathogen in the development of male urethritis, epididymitis, and orchitis is widely accepted. Also, it can cause complications such as chronic prostatitis and infertility. This review summarizes C. trachomatis infection in the male genitourinary tract, including urethritis, epididymitis, orchitis, and its complications, and addresses the microbiology, epidemiology, screening, clinical manifestations, diagnosis, and treatment.
Chlamydia ; Epididymitis ; Female ; Humans ; Infertility ; Male ; Mass Screening ; Orchitis ; Prostatitis ; Urethritis ; Urinary Tract ; Urologic Diseases