Human prostate organoid generation and the identification of prostate development drivers using inductive rodent tissues.

The reactivation of developmental genes and pathways during adulthood may contribute to pathogenesis of diseases such as prostate cancer. Analysis of the mechanistic links between development and disease could be exploited to identify signalling pathways leading to disease in the prostate. However, the mechanisms underpinning prostate development require further characterisation to interrogate fully the link between development and disease. Previously, our group developed methods to produce prostate organoids using induced pluripotent stem cells (iPSCs). Here, we show that human iPSCs can be differentiated into prostate organoids using neonatal rat seminal vesicle mesenchyme in vitro. The organoids can be used to study prostate development or modified to study prostate cancer. We also elucidated molecular drivers of prostate induction through RNA-sequencing analyses of the rat urogenital sinus and neonatal seminal vesicles. We identified candidate drivers of prostate development evident in the inductive mesenchyme and epithelium involved with prostate specification. Our top candidates included Spx, Trib3, Snai1, Snai2, Nrg2 and Lrp4. This work lays the foundations for further interrogation of the reactivation of developmental genes in adulthood, leading to prostate disease.

Prostate Cancer Risk Stratification by Simple Scoring of the Current pT3 Lesions: A Proposal for a New Pathologic T-Staging System.

Cancer spread beyond the prostate, including extraprostatic extension (other than seminal vesicle or bladder invasion; EPE)/microscopic bladder neck invasion and seminal vesicle invasion (SVI) currently classified as pT3a and pT3b lesions, respectively, does not uniformly indicate poor oncologic outcomes. Accurate risk stratification of current pT3 disease is therefore required. We herein further determined the prognostic impact of these histopathologic lesions routinely assessed and reported by pathologists, particularly their combinations. We assessed consecutive 2892 patients undergoing radical prostatectomy for current pT2 (n = 1692), pT3a (n = 956), or pT3b (n = 244) disease at our institution between 2009 and 2018. Based on our preliminary findings, point(s) were given (1 point to focal EPE, microscopic bladder neck invasion, or unilateral SVI; 2 points to nonfocal/established EPE or bilateral SVI) and summed up in each case. Our cohort had 0 point (n = 1692, 58.5%; P0), 1 point (n = 243, 8.4%; P1), 2 points (n = 657, 22.7%; P2), 3 points (n = 192, 6.6%; P3), 4 points (n = 76, 2.6%; P4), and 5 points (n = 32, 1.1%; P5). Univariate analysis revealed associations of higher points with significantly worse biochemical progression-free survival, particularly when P4 and P5 were combined. In multivariable analysis (P0 as a reference), P1 (hazard ratio [HR], 1.57; P = .033), P2 (HR, 3.25; P < .001), P3 (HR, 4.01; P < .001), and P4 + P5 (HR, 5.99; P < .001) showed significance for the risk of postoperative progression. Meanwhile, Harrell C-indexes for the current pT staging, newly developed point system, and the Cancer of the Prostate Risk Assessment post-Surgical (CAPRA-S) score were 0.727 (95% CI, 0.706-0.748), 0.751 (95% CI, 0.729-0.773), and 0.774 (95% CI, 0.755-0.794), respectively, for predicting progression. We believe our data provide a logical rationale for a novel pathologic T-staging system based on the summed points, pT1a (0 point), pT1b (1 point), pT2 (2 points), pT3a (3 points), and pT3b (4 or 5 points), which more accurately stratifies the prognosis of prostate cancer.

Genomic analysis of primary epithelial neoplasms of the seminal vesicle identifies a subset of mucinous cystic tumours driven by KRAS mutations.

BACKGROUND: Carcinomas of the seminal vesicle are exceedingly rare, with a limited number of cases described in the literature. Reported cases span a relatively wide morphological spectrum, and their genomic features remain unexplored. DESIGN: In this study, we interrogated five primary epithelial neoplasms of the seminal vesicle using a targeted DNA sequencing platform (OncoPanel, 447 genes). RESULTS: The tumours included one adenocarcinoma with intestinal phenotype presenting after external beam radiation (for prostatic adenocarcinoma), one carcinoma with Müllerian-type clear cell phenotype, two mucinous tumours resembling low-grade mucinous neoplasms of the appendix (LAMN) and one mucinous cystadenoma. The post-radiation mucinous adenocarcinoma had genomic findings consistent with bi-allelic inactivation of TP53, as well as multiple copy-number changes with regional and chromosomal arm-level copy-number losses. The Müllerian-type clear cell carcinoma exhibited a complex copy-number profile with numerous regional and arm-level copy-number changes, as well as focal amplification events, including copy-number gain of 8q and amplification of a region within 20q13. Both low-grade mucinous tumours resembling LAMN harboured hot-spot gain-of-function KRAS variants (p.G12V and p.G13D) as the only genomic alteration. No genomic alterations were detected inthe lesion diagnosed as mucinous cystadenoma. CONCLUSION: Our results suggest that primary low-grade mucinous neoplasms of the seminal vesicle may represent a distinct entity equivalent to appendiceal counterparts, driven by gain-of-function variants of RAS GTPases. The remaining tumours showed genomic features that closely resembled those of neoplasms with comparable phenotypes and/or biological characteristics arising in other sites, suggesting that they could be managed similarly, with special considerations related to their anatomical location.

Seminal Vesicle-Derived Exosomes for the Regulation of Sperm Activity.

The seminal vesicle contributes to a large extent of the semen volume and composition. Removal of seminal vesicle or lack of seminal vesicle proteins leads to decreased fertility. Seminal plasma proteome revealed that seminal fluid contained a wide diversity of proteins. Many of them are known to modulate sperm capacitation and serve as capacitation inhibitors or decapacitation factors. Despite identifying secretory vesicles from the male reproductive tract, such as epididymosomes or prostasomes, isolation, identification, and characterization of seminal vesicle-derived exosomes are still unknown. This chapter aims to review the current understanding of the function of seminal vesicles on sperm physiology and male reproduction and provide ultracentrifugation-based isolation protocols for the isolation of seminal vesicle exosomes. Moreover, via proteomic analysis and functional categorization, a total of 726 proteins IDs were identified in the purified seminal vesicle exosomes fraction. Preliminary data showed seminal vesicle-derived exosomes inhibited sperm capacitation; however, more studies will be needed to reveal other functional involvements of seminal vesicle-derived exosomes on the sperm physiology and, more importantly, how these exosomes interact with sperm membrane to achieve their biological effects.

What's in a name? Is an anatomical term only a name?

The purpose of a standard terminology is to facilitate communication. Thus, changing the name of an anatomical structure or the meaning of an anatomical term undermines that aspiration and cuts connections with anatomy's long history. Two types of anatomical terms are the most vulnerable to logical arguments for revision-ones that are descriptive, but viewed, at least by some, as inaccurate, and ones that contain words that are polysemic or vague. A half dozen examples of each type are discussed, including ductus deferens, glandula seminalis, articulationes costochondrales, vulva and fascia. In general, traditional terms should be preserved, but judgments about which terms are traditional should be based on five centuries of modern anatomy, not just the past several decades.

Non-monotonic effects of Bisphenol A Dimethacrylate on male mouse reproductive system and fertility leads to impaired conceptive performance.

As an estrogenic agent, Bisphenol A Dimethacrylate (Bis-DMA) may incite alterations in both the reproductive tract and the neuroendocrine axis, and thus have the potential to affect the proper development, maturity and conceptive performance in animals. We investigated the consequences of 14 weeks of exposure to different concentrations of Bis-DMA on male mouse conceptive performance. Male mice were exposed to Bis-DMA (0, 0.1 mg/L, 1.0 mg/L or 10 mg/L) via drinking water, and the effects on fertility, reproductive organ weights, reproductive hormone levels, sperm counts and testicular histology were assessed. We clearly demonstrate that prolonged exposure of male mice to Bis-DMA negatively affects fertility and reproduction causing significant reductions in sperm counts, non-monotonic effects on serum LH and testosterone levels, increased seminal vesicle weights, lower number of embryonic implantations and viable fetuses, as well as, increased embryonal resorptions in females mated by Bis-DMA treated males. Furthermore, Bis-DMA caused abnormalities in testicular infrastructure with atrophic seminiferous tubules exhibiting intraepithelial vacuolization and disorganization, loss and shedding of germ cells into the lumen, and presence of apoptotic cells. Our data collectively suggest that Bis-DMA adversely affects male fertility and reproduction by interference with normal hormone signaling in the testis, inducing changes in testicular infrastructure and ultimately leading to impaired reproductive function and fertility.

[The role of seminal vesicles in male sexual function].

The seminal vesicle is an important accessory gland of the male reproductive system. In the past, some scholars focused more on its role in the fertilization process and neglected its relationship with male sexual function. Researches show that the seminal vesicle is involved in multiple processes such as sexual desire, penile erection, and ejaculation. Treatment of sexual dysfunction by medication targeting the seminal vesicle has achieved certain therapeutic effects. This article discusses the relationship between the seminal vesicle and sexual function in terms of physiopathology, clinical study and basic research, hoping to provide some new ideas on the clinical diagnosis and treatment of sexual dysfunction.

Long-Term Prognosis and Treatment Strategy of Persistent PSA After Radical Prostatectomy.

PURPOSE: Prostate-specific antigen (PSA) is thought to be undetectable (< 0.1 ng/mL) after radical prostatectomy (RP), and persistent PSA (≥ 0.1 ng/mL) is considered a failure of curative treatment. MATERIALS AND METHODS: The study population consisted of 135 patients, all of whom underwent RP for localized prostate cancer, and developed persistent PSA. We set the starting point at the timing of RP, and the endpoints were the development of castration-resistant prostate cancer (CRPC) and cancer-specific survival. RESULTS: Salvage radiation therapy (RT) and androgen deprivation therapy (ADT) were performed in 53 (39.3%) and 64 (47.4%) patients, respectively. Eighteen (13.3%) patients didn't receive any salvage treatment. During the median follow-up of 10.1 years, CRPC was observed in 23 patients, and 6 patients died due to prostate cancer. Kaplan-Meier curves demonstrated the 15-year CRPC-free and cancer-specific survivals were 79.5% and 92.7%, respectively. Cox multivariate analysis demonstrated that seminal vesicle invasion (SVI) (p = 0.007) and nadir PSA ≥1.0 ng/mL (p = 0.002) were independent risk factors for CRPC. Salvage RT demonstrated better cancer control (the 10-and 15-year CRPC-free survival was 94.1% and 94.1%) compared to ADT (75.9% and 58.5%, p = 0.017) after 1:1 propensity score matching. CONCLUSIONS: SVI and nadir PSA ≥1.0 ng/mL are independent risk factors for CRPC in patients with persistent PSA after RP. Salvage RT is considered to be the optimal treatment for this condition.

Senescent Tumor Cells Are Frequently Present at the Invasion Front: Implications for Improving Disease Control in Patients with Locally Advanced Prostate Cancer.

INTRODUCTION: Local tumor invasion is a critical factor for the outcome of men with prostate cancer. In particular, seminal vesicle invasion (SVI) has been reported to be associated with a more unfavorable prognosis. A better understanding of the functional state of invading prostate cancer cells is crucial to develop novel therapeutic strategies for patients with locally advanced disease. METHODS: The prognostic impact of local tumor progression was ascertained in over 1,000 men with prostate cancer. Prostate cancer specimens were stained by double-immunohistochemistry for the proliferation marker Ki-67 and the senescence marker p16INK4A. The migratory properties of senescent prostate cancer cells were analyzed in vitro using a wound healing assay and immunofluorescence microscopy for p16INK4A. RESULTS: We confirm the notion that patients with SVI have a more unfavorable prognosis than patients with extraprostatic extension alone. Surprisingly, we found that the tumor invasion front frequently harbors p16INK4A-positive and Ki-67-negative, i.e., senescent, tumor cells. While the intraprostatic tumor periphery was a hotspot for both proliferation and expression of p16INK4A, the area of SVI showed less proliferative activity but was at the same time a hotspot of cells with increased nuclear p16INK4A expression. Senescence was associated with an accelerated migration of prostate cancer cells in vitro. CONCLUSION: This proof-of-concept study shows that invading prostate cancer cells frequently show signs of cellular senescence. This finding may open new avenues for neoadjuvant and adjuvant treatment concepts in men with locally advanced prostate cancer.

Altered microbiota profile in seminal vesicles of men presenting with refractory hematospermia.

BACKGROUND: Currently, no recognized evidence is known about the bacterial communities found within seminal vesicles (SV) of men presenting with refractory hematospermia. METHODS AND RESULTS: Fifteen male patients with refractory hematospermia or anejaculation were enrolled, and 15 SV-Infection (SV-In) samples from SV with hemorrhage and/or stones, 11 SV-Control (SV-C) samples from SV with non-infection, and 14 Urine (Urine) samples from posterior urethra were obtained via transurethral seminal vesiculoscopy. Then the high-throughput 16 S rRNA gene sequencing method was performed to characterize the microbiota profile. Finally, a total of 1535 operational taxonomic units (OTUs) were found, 1295 OTUs were shared across three groups, 7 OTUs, 45 OTUs, and 48 OTUs were unique to SV-C group, SV-In group, and Urine group, respectively. The 5 top bacterial phyla (mean relative abundance) in all samples were Firmicutes (52.08%), Bacteroidetes (21.69%), Proteobacteria (12.72%), Actinobacteria (9.64%), and Fusobacteria (1.62%), the 5 top bacterial genera in all samples were Bacteroides (9.13%), Lactobacillus (5.38%), Bifidobacterium (5.35%), Faecalibacterium (5.10%), and Allobaculum (3.34%), of which Bifidobacterium had the highest level in SV-C samples and had a significant difference (P < 0.05) across all groups. Differential analysis showed genera Leuconostoc and LachnospiraceaeFCS020group were identified as biomarkers in the SV-In microbiota. CONCLUSION: Altered microbiota composition in seminal vesicles is related to refractory hematospermia in men, and the distribution of genus Leuconostoc or LachnospiraceaeFCS020group within seminal vesicles may interact with hematospermia. This study provides clues for the diagnosis and treatment of this urologic disorder.

A dominant negative mutation uncovers cooperative control of caudal Wolffian duct development by Sprouty genes.

The Wolffian ducts (WD) are paired epithelial tubules central to the development of the mammalian genitourinary tract. Outgrowths from the WD known as the ureteric buds (UB) generate the collecting ducts of the kidney. Later during development, the caudal portion of the WD will form the vas deferens, epididymis and seminal vesicle in males, and will degenerate in females. While the genetic pathways controlling the development of the UB are firmly established, less is known about those governing development of WD portions caudal to the UB. Sprouty proteins are inhibitors of receptor tyrosine kinase (RTK) signaling in vivo. We have recently shown that homozygous mutation of a conserved tyrosine (Tyr53) of Spry1 results in UB defects indistinguishable from that of Spry1 null mice. Here, we show that heterozygosity for the Spry1 Y53A allele causes caudal WD developmental defects consisting of ectopically branched seminal vesicles in males and persistent WD in females, without affecting kidney development. Detailed analysis reveals that this phenotype also occurs in Spry1+/- mice but with a much lower penetrance, indicating that removal of tyrosine 53 generates a dominant negative mutation in vivo. Supporting this notion, concomitant deletion of one allele of Spry1 and Spry2 also recapitulates the genital phenotype of Spry1Y53A/+ mice with high penetrance. Mechanistically, we show that unlike the effects of Spry1 in kidney development, these caudal WD defects are independent of Ret signaling, but can be completely rescued by lowering the genetic dosage of Fgf10. In conclusion, mutation of tyrosine 53 of Spry1 generates a dominant negative allele that uncovers fine-tuning of caudal WD development by Sprouty genes.

Proteomic Dissection of the Impact of Environmental Exposures on Mouse Seminal Vesicle Function.

Seminal vesicles are an integral part of the male reproductive accessory gland system. They produce a complex array of secretions containing bioactive constituents that support gamete function and promote reproductive success, with emerging evidence suggesting these secretions are influenced by our environment. Despite their significance, the biology of seminal vesicles remains poorly defined. Here, we complete the first proteomic assessment of mouse seminal vesicles and assess the impact of the reproductive toxicant acrylamide. Mice were administered acrylamide (25 mg/kg bw/day) or control daily for five consecutive days prior to collecting seminal vesicle tissue. A total of 5013 proteins were identified in the seminal vesicle proteome with bioinformatic analyses identifying cell proliferation, protein synthesis, cellular death, and survival pathways as prominent biological processes. Secreted proteins were among the most abundant, and several proteins are linked with seminal vesicle phenotypes. Analysis of the effect of acrylamide on the seminal vesicle proteome revealed 311 differentially regulated (FC ± 1.5, p ≤ 0.05, 205 up-regulated, 106 downregulated) proteins, orthogonally validated via immunoblotting and immunohistochemistry. Pathways that initiate protein synthesis to promote cellular survival were prominent among the dysregulated pathways, and rapamycin-insensitive companion of mTOR (RICTOR, p = 6.69E-07) was a top-ranked upstream driver. Oxidative stress was implicated as contributing to protein changes, with acrylamide causing an increase in 8-OHdG in seminal vesicle epithelial cells (fivefold increase, p = 0.016) and the surrounding smooth muscle layer (twofold increase, p = 0.043). Additionally, acrylamide treatment caused a reduction in seminal vesicle secretion weight (36% reduction, p = 0.009) and total protein content (25% reduction, p = 0.017). Together these findings support the interpretation that toxicant exposure influences male accessory gland physiology and highlights the need to consider the response of all male reproductive tract tissues when interpreting the impact of environmental stressors on male reproductive function.

Functions of Steroid Hormones in the Male Reproductive Tract as Revealed by Mouse Models.

Steroid hormones are capable of diffusing through cell membranes to bind with intracellular receptors to regulate numerous physiological processes. Three classes of steroid hormones, namely androgens, estrogens and glucocorticoids, contribute to the development of the reproductive system and the maintenance of fertility. During the past 30 years, mouse models have been produced in which the expression of genes encoding steroid hormone receptors has been enhanced, partially compromised or eliminated. These mouse models have revealed many of the physiological processes regulated by androgens, estrogens and to a more limited extent glucocorticoids in the testis and male accessory organs. In this review, advances provided by mouse models that have facilitated a better understanding of the molecular regulation of testis and reproductive tract processes by steroid hormones are discussed.

Elucidation of the protein composition of mouse seminal vesicle fluid.

The seminal vesicles are male accessory sex glands that contribute the major portion of the seminal plasma in which mammalian spermatozoa are bathed during ejaculation. In addition to conveying sperm through the ejaculatory duct, seminal vesicle secretions support sperm survival after ejaculation, and influence the female reproductive tract to promote receptivity to pregnancy. Analysis of seminal vesicle fluid (SVF) composition by proteomics has proven challenging, due to its highly biased protein signature with a small subset of dominant proteins and the difficulty of solubilizing this viscous fluid. As such, publicly available proteomic datasets identify only 85 SVF proteins in total. To address this limitation, we report a new preparative methodology involving sequential solubilization of mouse SVF in guanidine hydrochloride, acetone precipitation, and analysis by label-free mass spectrometry. Using this strategy, we identified 126 SVF proteins, including 83 previously undetected in SVF. Members of the seminal vesicle secretory protein family were the most abundant, accounting for 79% of all peptide spectrum matches. Functional analysis identified inflammation and formation of the vaginal plug as the two most prominent biological processes. Other notable processes included modulation of sperm function and regulation of the female reproductive tract immune environment. Together, these findings provide a robust methodological framework for future SVF studies and identify novel proteins with potential to influence both male and female reproductive physiology.

PDGFRα+ subepithelial interstitial cells act as a pacemaker to drive smooth muscle of the guinea pig seminal vesicle.

Smooth muscle cells (SMCs) of the guinea pig seminal vesicle (SV) develop spontaneous phasic contractions, Ca2+ flashes and electrical slow waves in a mucosa-dependent manner, and thus it was envisaged that pacemaker cells reside in the mucosa. Here, we aimed to identify the pacemaker cells in SV mucosa using intracellular microelectrode and fluorescence Ca2+ imaging techniques. Morphological characteristics of the mucosal pacemaker cells were also investigated using focused ion beam/scanning electron microscopy tomography and fluorescence immunohistochemistry. Two populations of mucosal cells developed spontaneous Ca2+ transients and electrical activity, namely basal epithelial cells (BECs) and subepithelial interstitial cells (SICs). Pancytokeratin-immunoreactive BECs were located on the apical side of the basement membrane (BM) and generated asynchronous, irregular spontaneous Ca2+ transients and spontaneous transient depolarisations (STDs). The spontaneous Ca2+ transients and STDs were not diminished by 10 µM nifedipine but abolished by 10 µM cyclopiazonic acid (CPA). Platelet-derived growth factor receptor α (PDGFRα)-immunoreactive SICs were distributed just beneath the basal side of the BM and developed synchronous Ca2+ oscillations and electrical slow waves, which were suppressed by 3 µM nifedipine and abolished by 10 µM CPA. In SV mucosal preparations in which some smooth muscle bundles remained attached, SICs and residual SMCs developed temporally correlated spontaneous Ca2+ transients. Neurobiotin injected into SICs spread not only to neighbouring SICs but also to neighbouring SMCs or vice versa. These results suggest that PDGFRα+ SICs electrotonically drive the spontaneous contractions of SV smooth muscle. KEY POINTS: In many visceral smooth muscle organs, spontaneous contractions are electrically driven by non-muscular pacemaker cells. In guinea pig seminal vesicles (SVs), as yet unidentified mucosal cells appear to drive neighbouring smooth muscle cells (SMCs). Two populations of spontaneously active cells are distributed in the SV mucosa. Basal epithelial cells (BECs) generate asynchronous, irregular spontaneous Ca2+ transients and spontaneous transient depolarisations (STDs). In contrast, subepithelial interstitial cells (SICs) develop synchronous Ca2+ oscillations and electrical slow waves. Pancytokeratin-immunoreactive (IR) BECs are located on the apical side of the basement membrane (BM), while platelet-derived growth factor receptor α (PDGFRα)-IR SICs are located on the basal side of the BM. Spontaneous Ca2+ transients in SICs are synchronised with those in SV SMCs. Dye-coupling between SICs and SMCs suggests that SICs act as pacemaker cells to drive the spontaneous contractions of SV smooth muscle.

Functional significance of mouse seminal vesicle sulfhydryl oxidase on sperm capacitation in vitro.

During ejaculation, cauda epididymal spermatozoa are suspended in a protein-rich solution of seminal plasma, which is composed of proteins mostly secreted from the seminal vesicle. These seminal proteins interact with the sperm cells and bring about changes in their physiology, so that they can become capacitated in order for the fertilization to take place. Sulfhydryl oxidase (SOX) is a member of the QSOX family and its expression is found to be high in the seminal vesicle secretion (SVS) of mouse. Previously, it has been reported to cross-link thiol-containing amino acids among major SVS proteins. However, its role in male reproduction is unclear. In this study, we determined the role of SOX on epididymal sperm maturation and also disclosed the binding effect of SOX on the sperm fertilizing ability in vitro. In order to achieve the above two objectives, we constructed a Sox clone (1.7 kb) using a pET-30a vector. His-tagged recombinant Sox was overexpressed in Shuffle Escherichia coli cells and purified using His-Trap column affinity chromatography along with hydrophobic interaction chromatography. The purified SOX was confirmed by western blot analysis and by its activity with DTT as a substrate. Results obtained from immunocytochemical staining clearly indicated that SOX possesses a binding site on the sperm acrosome. The influence of SOX on oxidation of sperm sulfhydryl to disulfides during epididymal sperm maturation was evaluated by a thiol-labeling agent, mBBr. The SOX protein binds onto the sperm cells and increases their progressive motility. The effect of SOX binding on reducing the [Ca2+]i concentration in the sperm head was determined using a calcium probe, Fluo-3 AM. The inhibitory influence of SOX on the sperm acrosome reaction was shown by using calcium ionophore A32187 to induce the acrosome reaction. The acrosome-reacted sperm were examined by staining with FITC-conjugated Arachis hypogaea (peanut) lectin. Furthermore, immunocytochemical analysis revealed that SOX remains bound to the sperm cells in the uterus but disappears in the oviduct during their transit in the female reproductive tract. The results from the above experiment revealed that SOX binding onto the sperm acrosome prevents sperm capacitation by affecting the [Ca2+]i concentration in the sperm head and the ionophore-induced acrosome reaction. Thus, the binding of SOX onto the sperm acrosome may possibly serve as a decapacitation factor in the uterus to prevent premature capacitation and acrosome reaction, thus preserving their fertilizing ability.

Spontaneous Findings in the Reproductive System of Sexually Mature Male Cynomolgus Macaques.

Sexually mature nonhuman primates are often used in nonclinical safety testing when evaluating biopharmaceuticals; however, there is limited information in historical control databases or in the published literature on the spontaneous findings in the male reproductive system. This review evaluated digital slides from the male reproductive tract (testes, epididymides, prostate, and seminal vesicles) in sexually mature cynomolgus macaques (Macaca fascicularis; n = 255) from vehicle control groups in nonclinical toxicology studies and compared the observations with body weight, organ weight, and geographical origin. The most common microscopic findings were hypospermatogenesis and tubular dilatation in the testes; inflammatory cell infiltrate, cellular debris, and decreased sperm in the epididymides; inflammatory cell infiltrate and acinar dilatation in the prostate; and corpora amylacea and atrophy in the seminal vesicles. There were a few correlative observations in animals when grouped by weight or geographical origin: animals with lower terminal body weights (<5 kg) often displayed features of late puberty despite having sperm in the epididymis, while animals originating from Mauritius had a lower incidence of inflammatory cell infiltrates than those from Southeast Asia/China. This review provides incidence, descriptions, and photomicrographs of the common spontaneous microscopic findings in the reproductive system of mature male cynomolgus macaques.

Zinner syndrome in children: clinical presentation, imaging findings, diagnosis, and outcome.

BACKGROUND: Zinner syndrome (ZS), the association of congenital seminal vesicle cyst (SVC) and ipsilateral kidney anomalies, is rarely diagnosed in childhood. This study aimed to assess presentation, imaging findings, management, and outcome of pediatric ZS. METHODS: Sixteen children with ZS were diagnosed and managed at our hospital from 2003 to 2021. We reviewed the medical records to collect data on initial symptoms, results of imaging studies, complications, operation, and follow-up. RESULTS: Ultrasound was used in all 16 cases as initial diagnostic tool. Fourteen patients were asymptomatic at diagnosis: these were transferred from obstetricians or pediatricians for evaluation of the prenatally or postnatally detected ultrasonic kidney anomalies. SVCs were incidentally noted on ultrasonography. The other two cases initially presented with urinary tract infection (UTI). Kidney anomalies included multicystic dysplastic kidney in 3 and kidney agenesis in 13 patients. Eleven (68.7%) patients had ipsilateral ectopic ureters entering SVC. Four (36.4%) patients had a reflux from urethra into SVC (urethro-cystic reflux) on voiding cystourethrography. Ten (62.5%) patients remained asymptomatic over a mean of 58 months (range, 7-216 months), two patients developed lower urinary tract dysfunction, and five patients had UTIs. Two boys needed SVC removal, and SVC had disappeared in two patients after 2.5-4 years of follow-up. CONCLUSIONS: Unilateral kidney hypodysplasia with ectopic ureter inserting into the ipsilateral SVC is a characteristic sign for diagnosis of ZS. In our case series, ZS was mainly asymptomatic. Urethro-cystic reflux was associated with UTIs in young infants. SVC removal was rarely required. A higher resolution version of the Graphical abstract is available as Supplementary information.

A common tumor in an uncommon site: epithelioid Leiomyoma arising from the seminal vesicle-a case report.

BACKGROUND: Leiomyoma of the seminal vesicle is a rare leiomyoma characterized by the formation of benign leiomyomatous tissue within the seminal vesicle. Although histologically benign, excessive size can lead to urinary system disease if left untreated. Herein, we report a case of a seminal vesicle epithelioid leiomyoma. CASE PRESENTATION: A 36-year-old Chinese man sought medical attention at our hospital for urination pain and hemospermia. CT showed a 5.3 cm × 5.0 cm seminal vesicle mass with a mixed density in the right seminal vesicle. The gross specimen showed light yellow, gray, and white tissues, with softness and hemorrhage in some places. Histologically, it showed classic spindle cell proliferation, with spindle cells arranged in fascicles, and mitosis was rare. Immunohistochemistry showed frequent expression of smooth muscle markers, such as calponin, SMA, and desmin. A diagnosis of epithelioid leiomyoma was proposed according to the immunohistochemical findings and morphology. The patient did not receive adjuvant therapy. There was no evidence of tumor recurrence in the 10 months after surgery. CONCLUSIONS: We report the first case of epithelioid leiomyoma in the seminal vesicle. This disease should be included in the differential diagnostic list of seminal vesicle tumors with epithelioid morphology.

Primary seminal vesicle epithelioid smooth muscle neoplasm of uncertain biologic potential.

We present the case of a 73-year-old male patient who presented with obstructive urinary symptoms, pelvic pressure, and hematuria. CT imaging revealed a heterogenous prostate enlargement, and MRI demonstrated the mass to be arising from the seminal vesicle. Prostate biopsies showed benign tissue. Surgical excision was completed and pathology revealed it to be an epithelioid smooth muscle neoplasm of uncertain biologic potential. This is only the second known case of such a seminal vesicle tumour. As soft tissue sarcomas of the seminal vesicle emerge in the literature, we may develop a better understanding of their biologic behaviour and prognostic potential.