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Medical Ultrasonography Aug 2022To develop a decision tree model using US features to differentiate testicular torsion and other conditions of acute scrotum and to investigate predictive parameters of...
AIMS
To develop a decision tree model using US features to differentiate testicular torsion and other conditions of acute scrotum and to investigate predictive parameters of unsalvageable testis in testicular torsion.
MATERIALS AND METHODS
Scrotal US was reviewed in patients aged <30 years who presented with acute scrotum from 2014 to 2020. US findings of whirlpool sign, testicular volume ratio, heterogeneous echotexture, testicular vascularity, epididymis enlargement and/or hyperemia, and avascular nodule were evaluated and compared. A decision tree model was created using the conditional inference tree analysis and the accuracy was calculated. Univariate logistic regression analysis was performed to find out the predictive US features of unsalvageable testes.
RESULTS
Total of 381 patients (13.2±7.2 years old; range, 1 day-30 years) were included. Thirty-four patients were diagnosed with testicular torsion, and the others with orchitis or epididymo-orchitis (n=59), epididymitis (n=264), and appendage torsion (n=24). In the conditional inference tree analysis, whirlpool sign, avascular nodule, and increased testicular vascularity were the most significant discriminators (p<0.001), and the whirlpool sign was the first discriminator. The overall accuracy of the conditional inference tree was 91.1% (95% confidence interval [CI], 87.8-93.7%). Heterogeneous echotexture (odds ratio [OR], 74.99; 95% CI, 2.75-2046.26; p=0.01) and symptom-to-operation time >24 h (OR, 49.28; 95% CI, 1.92-1262.03; p=0.02) were significant predictors of unsalvageable testis.
CONCLUSIONS
Conditional inference tree analysis showed that the whirlpool sign of the spermatic cord, avascular nodule, and altered testicular vascularity were significant discriminators. Heterogeneous echotexture and symptom-to-operation delay were important prognostic factors for unsalvageable testis.
Topics: Adolescent; Adult; Child; Epididymitis; Humans; Male; Orchitis; Scrotum; Spermatic Cord Torsion; Testis; Young Adult
PubMed: 35437523
DOI: 10.11152/mu-3507 -
Oxidative Medicine and Cellular... 2021In the past two decades, testicular tissue grafting and xenografting have been well established, with the production of fertilization-competent sperm in some studies....
In the past two decades, testicular tissue grafting and xenografting have been well established, with the production of fertilization-competent sperm in some studies. However, few studies have been carried out to observe the development of grafted prepubertal testicular tissue of rats and compare the biological differences between in situ testis and grafted testis. In this study, we established the prepubertal testicular tissue xenografting model using a 22-day-old rat and evaluated certain parameters, including testicular histology, testosterone production, and ultrastructure of the grafted testes. We also assessed gene expression of cell proliferation markers, testicular cell markers, and antioxidative defense system. Our results showed that 47 days after transplantation, intratesticular testosterone concentration was not significantly altered; however, cell proliferation, spermatogenesis, and Sertoli cell markers in the transplanted testes were significantly disrupted compared with the control group, accompanied by aggravated apoptosis and oxidative damage. Moreover, the transplanted testes showed smaller tubular diameter and disrupted spermatogenic epithelium with apparent vacuoles, distorted and degenerated germ cells with obscure nuclear margin, and no spermatids in the center of the tubules. Although testis xenografting has been extensively tested and attained great achievement in other species, the prepubertal rat testicular tissue xenografting to immunodeficient mice exhibited obvious spermatogenesis arrest and oxidative damage. The protocol still needs further optimization, and there are still some unknown factors in prepubertal rat testes transplantation.
Topics: Animals; Gene Expression Profiling; Gene Expression Regulation; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Oxidative Stress; Rats; Rats, Sprague-Dawley; Sertoli Cells; Spermatogenesis; Testis; Transplantation, Heterologous
PubMed: 34840665
DOI: 10.1155/2021/1699990 -
Cell Reports Apr 2024The continuous regeneration of spermatogonial stem cells (SSCs) underpins spermatogenesis and lifelong male fertility, but the developmental origins of the SSC pool...
The continuous regeneration of spermatogonial stem cells (SSCs) underpins spermatogenesis and lifelong male fertility, but the developmental origins of the SSC pool remain unclear. Here, we document that hnRNPU is essential for establishing the SSC pool. In male mice, conditional loss of hnRNPU in prospermatogonia (ProSG) arrests spermatogenesis and results in sterility. hnRNPU-deficient ProSG fails to differentiate and migrate to the basement membrane to establish SSC pool in infancy. Moreover, hnRNPU deletion leads to the accumulation of ProSG and disrupts the process of T1-ProSG to T2-ProSG transition. Single-cell transcriptional analyses reveal that germ cells are in a mitotically quiescent state and lose their unique identity upon hnRNPU depletion. We further show that hnRNPU could bind to Vrk1, Slx4, and Dazl transcripts that have been identified to suffer aberrant alternative splicing in hnRNPU-deficient testes. These observations offer important insights into SSC pool establishment and may have translational implications for male fertility.
Topics: Animals; Male; Mice; Adult Germline Stem Cells; Alternative Splicing; Cell Differentiation; Spermatogenesis; Spermatogonia; Stem Cells; Testis; Heterogeneous-Nuclear Ribonucleoprotein U
PubMed: 38625792
DOI: 10.1016/j.celrep.2024.114113 -
Aging Feb 2024The male reproductive system experiences degradation with age, predominantly impacting the testes. Testicular aging can result in failure to produce physiological...
The male reproductive system experiences degradation with age, predominantly impacting the testes. Testicular aging can result in failure to produce physiological testosterone levels, normal sperm concentrations, or both. However, we cannot predict the onset of testicular aging in advance. Using single-cell RNA sequencing (scRNA-seq) from Gene Expression Omnibus (GEO) database, we conducted cell-cell communication network of human testis between older and young group, indicating Leydig cells' potential role in spermatogenesis microenvironment of aging testis. And we depicted the senescence-Associated Secretory Phenotype (SASP) features of aging testis by identifying differentially expressed senescence-associated secretory phenotype (SASP)-related genes between two group. Notably, mainly expressed in Leydig cells of those differentially expressed SASP-related genes in aging testis. Furthermore, protein located in the interstitial compartment of older mice confirmed by immunofluorescence and highly expressed in both human seminal plasma and mouse testis in the older group confirmed through Western blot. Together, our findings suggest that may be a new biomarker of testicular aging.
Topics: Humans; Male; Mice; Animals; Testis; Senescence-Associated Secretory Phenotype; Semen; Aging; Gene Expression Profiling; Cellular Senescence; Phenotype
PubMed: 38349859
DOI: 10.18632/aging.205538 -
Cells May 2021Aging of human testis and associated cellular changes is difficult to assess. Therefore, we used a translational, non-human primate model to get insights into underlying...
Aging of human testis and associated cellular changes is difficult to assess. Therefore, we used a translational, non-human primate model to get insights into underlying cellular and biochemical processes. Using proteomics and immunohistochemistry, we analyzed testicular tissue of young (age 2 to 3) and old (age 10 to 12) common marmosets (). Using a mass spectrometry-based proteomics approach, we identified 63,124 peptides, which could be assigned to 5924 proteins. Among them, we found proteins specific for germ cells and somatic cells, such as Leydig and Sertoli cells. Quantitative analysis showed 31 differentially abundant proteins, of which 29 proteins were more abundant in older animals. An increased abundance of anti-proliferative proteins, among them CDKN2A, indicate reduced cell proliferation in old testes. Additionally, an increased abundance of several small leucine rich repeat proteoglycans and other extracellular matrix proteins was observed, which may be related to impaired cell migration and fibrotic events. Furthermore, an increased abundance of proteins with inhibitory roles in smooth muscle cell contraction like CNN1 indicates functional alterations in testicular peritubular cells and may mirror a reduced capacity of these cells to contract in old testes.
Topics: Aging; Animals; Callithrix; Male; Proteome; Testis
PubMed: 34074003
DOI: 10.3390/cells10061306 -
PLoS Genetics Feb 2022The mammalian nuclear hormone receptors LRH1 (NR5A2) and SF1 (NR5A1) are close paralogs that can bind the same DNA motif and play crucial roles in gonadal development...
The mammalian nuclear hormone receptors LRH1 (NR5A2) and SF1 (NR5A1) are close paralogs that can bind the same DNA motif and play crucial roles in gonadal development and function. Lrh1 is essential for follicle development in the ovary and has been proposed to regulate steroidogenesis in the testis. Lrh1 expression in the testis is highly elevated by loss of the sex regulator Dmrt1, which triggers male-to-female transdifferentiation of Sertoli cells. While Sf1 has a well-defined and crucial role in testis development, no function for Lrh1 in the male gonad has been reported. Here we use conditional genetics to examine Lrh1 requirements both in gonadal cell fate reprogramming and in normal development of the three major cell lineages of the mouse testis. We find that loss of Lrh1 suppresses sexual transdifferentiation, confirming that Lrh1 can act as a key driver in reprogramming sexual cell fate. In otherwise wild-type testes, we find that Lrh1 is dispensable in Leydig cells but is required in Sertoli cells for their proliferation, for seminiferous tubule morphogenesis, for maintenance of the blood-testis barrier, for feedback regulation of androgen production, and for support of spermatogenesis. Expression profiling identified misexpressed genes likely underlying most aspects of the Sertoli cell phenotype. In the germ line we found that Lrh1 is required for maintenance of functional spermatogonia, and hence mutants progressively lose spermatogenesis. Reduced expression of the RNA binding factor Nxf2 likely contributes to the SSC defect. Unexpectedly, however, over time the Lrh1 mutant germ line recovered abundant spermatogenesis and fertility. This finding indicates that severe germ line depletion triggers a response allowing mutant spermatogonia to recover the ability to undergo complete spermatogenesis. Our results demonstrate that Lrh1, like Sf1, is an essential regulator of testis development and function but has a very distinct repertoire of functions.
Topics: Animals; Female; Male; Mammals; Mice; Sertoli Cells; Sex Differentiation; Spermatogenesis; Spermatogonia; Testis
PubMed: 35192609
DOI: 10.1371/journal.pgen.1010088 -
BMC Urology Feb 2021Splenogondal fusion (SGF) is a rare congenital anomaly characterized by abnormal association between the splenic tissue and the gonads or mesonephric remnants. SGF that... (Review)
Review
BACKGROUND
Splenogondal fusion (SGF) is a rare congenital anomaly characterized by abnormal association between the splenic tissue and the gonads or mesonephric remnants. SGF that requires separate two-stage laparoscopic staged Fowler-Stephen orchiopexy on both the left and right sides is extremely rare. SGF could be misdiagnosed as testicular malignancy and leads to unnecessary orchiectomy.
CASE PRESENTATION
This is a case of an 8-month old male infant presented with bilateral cryptorchidism, B-mode ultrasound visualized the left and right testes in the lower abdominal cavity and the upper margin of the left testicle as a hypoechoic mass extending to the spleen, indicating an undescended right testis and possible SGF on the left side. Single-site laparoscopic examination confirmed the diagnosis of SGF on the left side and an undescended right testis. As both testes were high and the right spermatic vessel was poorly developed and short, a routine single stage orchiopexy would be difficult and risky, therefore, separate two-stage laparoscopic staged Fowler-Stephen orchiopexies for both sides were implemented. Stage 1 of the staged Fowler-Stephen orchiopexy for the right side was performed first without treating the left side, Stage 2 for the right side, separation of the left testis from the spleen as well as Stage 1 for the left side were performed 7 months later, and Stage 2 for the left side was performed 7 months after that. Follow-up ultrasound 1 year after the surgery revealed no obvious abnormalities in the shapes of the testes or their blood supply. This treatment strategy prevented unnecessary orchiectomy.
CONCLUSIONS
We reported a rare case of SGF that needed separate two-stage laparoscopic staged Fowler-Stephen orchiopexies for both sides, and a review of the recent literature. SGF is a rare congenital anomaly often diagnosed incidentally during exploration/surgery for scrotal swelling/mass, cryptorchidism or inguinal hernia in young patients. Surgeons, especially pediatric surgeons should be aware of this rare condition to avoid unnecessary, life-altering radical orchiectomy. When routine single stage orchiopexy is not feasible or risky for either side, separate two-stage laparoscopic staged Fowler-Stephen orchiopexies could be performed on both the left and right sides to avoid unnecessary orchiectomy.
Topics: Abnormalities, Multiple; Cryptorchidism; Humans; Infant; Male; Orchiopexy; Spleen; Testis
PubMed: 33536002
DOI: 10.1186/s12894-021-00781-z -
Microbiology Spectrum Jun 2022Analysis of dissemination and colonization of sex organs in rodents is of significant value as it queries the possibility of mammal-to-mammal venereal transmission. The...
Analysis of dissemination and colonization of sex organs in rodents is of significant value as it queries the possibility of mammal-to-mammal venereal transmission. The aim of our study was to evaluate the presence and viability of Leptospira interrogans in testes of mice using models of infection that we previously developed. Using sublethal and lethal doses of bioluminescent strains of L. interrogans serovars Manilae and Copenhageni, we visualized the presence of leptospires in testes of C57BL/6 mice as early as 30 min and up to days 3-4 postinfection. This was confirmed by qPCR for the Copenhageni serovar after lethal infection of C3H/HeJ mice. In this model, no histopathological changes were noticed in testis. We further studied persistence of serovar Copenhageni in C3H/HeJ testes after lethal and sublethal infection, with different doses of leptospires. No viable leptospires were recovered from testes of lethally infected mice. However, we found live culturable in testes of 19/19 (100%) sublethally infected mice at the acute phase but not at 15 days postinfection, which corresponds to the chronic phase of renal colonization. The data suggest that colonization of testes with live and potentially infectious leptospires is transient and limited to the spirochetemic phase of infection. Further studies are necessary to evaluate if presence of in testes of mice leads to excretion in semen and to venereal transmission to female mice. Analysis of venereal transmission of is important to determine if direct animal to animal transmission occurs, which could impact measures to prevent and treat leptospirosis. The goal of this study was to determine if live colonize mouse testes. We found that colonization of mouse testes with live was transient and limited to the acute spirochetemic phase of infection and that transient colonization of the testes was insufficient to cause histopathological changes.
Topics: Animals; Female; Leptospira; Leptospira interrogans; Leptospirosis; Male; Mammals; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Testis
PubMed: 35446113
DOI: 10.1128/spectrum.02775-21 -
The Journal of Veterinary Medical... Oct 2022Cryptorchidism is defined as the failure of the testis to descend into the scrotal position. Bulls with cryptorchidism have problems in both meat quality and husbandry...
Cryptorchidism is defined as the failure of the testis to descend into the scrotal position. Bulls with cryptorchidism have problems in both meat quality and husbandry management; thus, it is greatly important to accurately identify the retained testis and remove it during the early stage. Abdominal computed tomography (CT) was performed under general anesthesia in 34 bulls aged 3-9 months with cryptorchidism. All bulls underwent laparoscopic or incision approach for cryptorchidectomy, and 40 testes were dissected. The detection rates of retained testes were 64.5% in the abdominal cavity and 100% in the subcutaneous inguinal region, and the total detection rate was 72.5%. Furthermore, all cases in this study were suspected to have intra-abdominal cryptorchidism in primary care, but CT revealed that 22.5% of cases had cryptorchidism in the subcutaneous inguinal region. The CT value (mean ± standard deviation) of the retained testes was 20.96 ± 7.54 Hounsfield Unit, and the CT value and size of the retained testes showed a positive weak correlation with bovine age. Therefore, there is the demerit that general anesthesia and a huge device are necessary; nevertheless, CT is suggested to be useful in identifying the location of retained testes and selecting an appropriate surgical approach in bulls with cryptorchidism. Moreover, CT findings suggested that the maturation of the retained testes might depend not on the descending process but on age.
Topics: Animals; Cattle; Cattle Diseases; Cryptorchidism; Laparoscopy; Male; Scrotum; Testis; Tomography; Tomography, X-Ray Computed
PubMed: 36058877
DOI: 10.1292/jvms.22-0124 -
Scientific Reports Nov 2019Male meiotic germ cell including the spermatozoa represent a great challenge to the immune system, as they appear long after the establishment of normal immune tolerance...
Male meiotic germ cell including the spermatozoa represent a great challenge to the immune system, as they appear long after the establishment of normal immune tolerance mechanisms. The capacity of the testes to tolerate autoantigenic germ cells as well as survival of allogeneic organ engrafted in the testicular interstitium have led to consider the testis an immunologically privileged site. Disruption of this immune privilege following trauma, tumor, or autoimmune orchitis often results in male infertility. Strong evidence indicates that indoleamine 2,3-dioxygenase (IDO) has been implicated in fetal and allograft tolerance, tumor immune resistance, and regulation of autoimmune diseases. IDO and tryptophan 2,3-dioxygenase (TDO) catalyze the same rate-limiting step of tryptophan metabolism along a common pathway, which leads to tryptophan starvation and generation of catabolites collectively known as kynurenines. However, the relevance of tryptophan metabolism in testis pathophysiology has not yet been explored. Here we assessed the in vivo role of IDO/TDO in experimental autoimmune orchitis (EAO), a model of autoimmune testicular inflammation and immunologically impaired spermatogenesis. EAO was induced in adult Wistar rats with testicular homogenate and adjuvants. Control (C) rats injected with saline and adjuvants and normal untreated rats (N) were also studied. mRNA expression of IDO decreased in whole testes and in isolated Sertoli cells during EAO. TDO and IDO localization and level of expression in the testis were analyzed by immunostaining and Western blot. TDO is expressed in granulomas from EAO rats, and similar protein levels were observed in N, C, and EAO groups. IDO was detected in mononuclear and endothelial cells and reduced IDO expression was detected in EAO group compared to N and C rats. This phenomenon was concomitant with a significant reduction of IDO activity in EAO testis measured by tryptophan and kynurenine concentrations (HPLC). Finally, in vivo inhibition of IDO with 1-methyl-tryptophan increased severity of the disease, demonstrating down regulation of IDO-based tolerance when testicular immune regulation was disrupted. We present evidence that an IDO-based mechanism is involved in testicular immune privilege.
Topics: Animals; Autoimmune Diseases; Disease Models, Animal; Epididymis; Immune Privilege; Indoleamine-Pyrrole 2,3,-Dioxygenase; Kynurenine; Lymph Nodes; Male; Orchitis; Rats; Rats, Wistar; Sertoli Cells; Severity of Illness Index; Testis; Tryptophan; Tryptophan Oxygenase
PubMed: 31685866
DOI: 10.1038/s41598-019-52192-8