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European Journal of Obstetrics,... Aug 2021To synthesize the evidence on Sertoli-Leydig cell tumour (SLCT) relapses, and identify the clinicopathological characteristics and prognosis of patients with recurrent... (Review)
Review
OBJECTIVE
To synthesize the evidence on Sertoli-Leydig cell tumour (SLCT) relapses, and identify the clinicopathological characteristics and prognosis of patients with recurrent SLCT.
METHODS
A literature search was undertaken of all published cases of SLCT relapse found in PubMed, Embase and Web of Science databases between January 1998 and January 2021. All articles in English reporting at least one case of SLCT relapse and mentioning the relapse location or the follow-up data were included. All reported data on relapsed cases were extracted. Student's t-test and Chi-squared test were used for the descriptive analysis, and the Kaplan-Meier statistical method was applied for survival analysis.
RESULTS
Eighty-five patients from 33 articles were included in this review. The median age was 20 years (range 3-76 years) with a median time to relapse of 14 months (range 1-168 months). Forty-eight percent (36/75) of relapses were local and 52% (39/75) were distant. In the subgroup of conservative primary surgery, contralateral ovarian SLCT events (metachronous or recurrent) were more frequent in the paediatric population than in the adult population (58.3 vs 18.2%; p = 0.005). Eleven cases had multiple relapses. Twenty-one percent (12/57) of cases were treated with conservative surgery after recurrence, and 64.9% (37/57) of cases were treated with radical surgery which tends to have a better 2-year survival rate (78.5% vs 61.0%; p = 0.177). Overall median survival was 48 months after recurrence (95% confidence interval ±21.0 months) with overall 5-year survival of 38.9%. The mean survival time was significantly higher for patients diagnosed at an early stage (I and II) compared with patients diagnosed at an advanced stage (p = 0.003).
DISCUSSION
The results showed that SLCT relapses have a poor prognosis and occur mainly in young patients, soon after the initial diagnosis. The majority of SLCT relapses are located in the abdominopelvic region. Contralateral ovarian SLCT events (metachronous or recurrent) occurred more frequently in paediatric cases. Multi-modal treatment with surgery and chemotherapy appears to be the best approach. The best chemotherapeutic regimen has yet to be defined.
Topics: Adult; Child; Child, Preschool; Female; Humans; Infant; Male; Neoplasm Recurrence, Local; Ovarian Neoplasms; Prognosis; Sertoli-Leydig Cell Tumor
PubMed: 34245994
DOI: 10.1016/j.ejogrb.2021.06.036 -
Andrologia Oct 2020We performed this systematic review to evaluate the possibility of an impact of SARS-CoV-2 infection on male fertility. SARS-CoV-2 enters the cells with the help of...
We performed this systematic review to evaluate the possibility of an impact of SARS-CoV-2 infection on male fertility. SARS-CoV-2 enters the cells with the help of ACE2; therefore, testicular expression of ACE2 was analysed from transcriptome sequencing studies and our unpublished data. Literature suggested that SARS-CoV-1 (2002-2004 SARS) had a significant adverse impact on testicular architecture, suggesting a high possibility of the impact of SARS-CoV-2 as well. Out of two studies on semen samples from COVID-19 affected patients, one reported the presence of SARS-CoV-2 in the semen samples while the other denied it, raising conflict about its presence in the semen samples and the possibility of sexual transmission. Our transcriptome sequencing studies on rat testicular germ cells showed ACE expression in rat testicular germ cells. We also found ACE2 expression in transcriptome sequencing data for human spermatozoa, corroborating its presence in the testicular germ cells. Transcriptome sequencing data from literature search revealed ACE2 expression in the germ, Sertoli and Leydig cells. The presence of ACE2 on almost all testicular cells and the report of a significant impact of previous SARS coronavirus on testes suggest that SARS-CoV-2 is highly likely to affect testicular tissue, semen parameters and male fertility.
Topics: Angiotensin-Converting Enzyme 2; Animals; Betacoronavirus; COVID-19; Coronavirus Infections; Gene Expression Profiling; Humans; Infertility, Male; Male; Models, Animal; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Rats; SARS-CoV-2; Semen; Spermatozoa; Spike Glycoprotein, Coronavirus; Testis
PubMed: 32578263
DOI: 10.1111/and.13712 -
Transplantation and Cellular Therapy Aug 2022Male gonadal dysfunction is a frequent late effect after pediatric hematopoietic stem cell transplantation (HSCT) that can lead to disturbances in pubertal development,...
Male gonadal dysfunction is a frequent late effect after pediatric hematopoietic stem cell transplantation (HSCT) that can lead to disturbances in pubertal development, sexual dysfunction, and infertility. However, no systematic review exists regarding prevalence and risk factors in relation to different treatment regimens. We aimed to systematically evaluate the current evidence regarding the prevalence of male gonadal dysfunction after pediatric HSCT, related risk factors, and the diagnostic value of surrogate markers of spermatogenesis in this patient group. We searched PubMed and Embase using a combination of text words and subject terms. The eligibility screening was conducted using predefined criteria. Data were extracted corresponding to the Leydig cell compartment involved in testosterone production and the germ cell compartment involved in spermatogenesis, respectively. Subsequently, data synthesis was performed. Of 2369 identified records, 25 studies were eligible. The studies were heterogeneous in terms of included diagnoses, gonadotoxic therapy, follow-up time, and definitions of gonadal dysfunction. The data synthesis revealed a preserved Leydig cell function in patients treated with non-total body irradiation (TBI) regimens, whereas the evidence regarding the impact of TBI conditioning on Leydig cell function was conflicting. Based on surrogate markers of spermatogenesis and only limited data on semen quality, the germ cell compartment was affected in half of the patients treated with non-TBI regimens and in nearly all patients treated with TBI conditioning. Testicular irradiation as part of front-line therapy before referral to HSCT led to complete Leydig cell failure and germ cell failure. Evidence regarding the impact of diagnosis, pubertal stage at HSCT, and chronic graft-versus-host disease is limited, as is the evidence of the diagnostic value of surrogate markers of spermatogenesis. Testicular irradiation as part of front-line therapy and TBI conditioning are the main risk factors associated with male gonadal dysfunction after pediatric HSCT; however, impaired spermatogenesis is also observed in half of the patients treated with non-TBI regimens. Methodological shortcomings limit existing evidence, and future studies should include semen quality analyses, follow-up into late adulthood, and evaluation of the cumulative exposure to gonadotoxic therapy.
Topics: Adult; Child; Gonadal Disorders; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Male; Semen Analysis; Transplantation Conditioning; Whole-Body Irradiation
PubMed: 35644480
DOI: 10.1016/j.jtct.2022.05.036 -
Cancers Jul 2023The objective of this review was to summarize the applications of sonoelastography in testicular tumor identification and inquire about their test performances. Two... (Review)
Review
The objective of this review was to summarize the applications of sonoelastography in testicular tumor identification and inquire about their test performances. Two authors independently searched English journal articles and full conference papers from CINAHL, Embase, IEEE Xplore, PubMed, Scopus, and Web of Science from inception and organized them into a PIRO (patient, index test, reference test, outcome) framework. Eleven studies ( = 11) were eligible for data synthesis, nine of which ( = 9) utilized strain elastography and two ( = 2) employed shear-wave elastography. Meta-analyses were performed on the distinction between neoplasm (tumor) and non-neoplasm (non-tumor) from four study arms and between malignancy and benignity from seven study arms. The pooled sensitivity of classifying malignancy and benignity was 86.0% (95%CI, 79.7% to 90.6%). There was substantial heterogeneity in the classification of neoplasm and non-neoplasm and in the specificity of classifying malignancy and benignity, which could not be addressed by the subgroup analysis of sonoelastography techniques. Heterogeneity might be associated with the high risk of bias and applicability concern, including a wide spectrum of testicular pathologies and verification bias in the reference tests. Key technical obstacles in the index test were manual compression in strain elastography, qualitative observation of non-standardized color codes, and locating the Regions of Interest (ROI), in addition to decisions in feature extractions. Future research may focus on multiparametric sonoelastography using deep learning models and ensemble learning. A decision model on the benefits-risks of surgical exploration (reference test) could also be developed to direct the test-and-treat strategy for testicular tumors.
PubMed: 37568585
DOI: 10.3390/cancers15153770 -
Chemico-biological Interactions Aug 2022The use of nanoscale materials for different biomedical applications has grown a lot in the last years and raised several concerns about toxic effects on human health.... (Review)
Review
The use of nanoscale materials for different biomedical applications has grown a lot in the last years and raised several concerns about toxic effects on human health. Several studies have shown that different types of NPs may exert toxic effects on organs such as the brain, the liver and the kidney. However, The toxicological effects of inorganic NPs on reproductive organs only recently has attracted attention. This systematic review selected data published in the last twelve years assessing rodent-male in vitro and in vivo reproductive toxicity caused by different types of inorganic nanoparticles (AgNPs, AuNPs, IONPs, ZnONPs, TiO2NPs and NiNPs). Structural and functional alterations were commonly observed in Sertoli, Leydig, germ and sperm cells in vitro and in vivo. Oxidative stress, apoptosis, and/or necrosis were the most common findings after inorganic nanoparticle exposure. The toxicity of different NPs depends strongly on their physicochemical characteristics and intrinsic properties. Although a broad overview of the toxicity of different inorganic NPs was found in the papers evaluated, the results are highly variable due to the lack of standardization of protocols, regarding NPs sizes, concentration/doses, and routes of administration. Despite focusing on the effect of different nanoparticles on male reproduction, the mechanisms and pathways related to cellular and/or organ toxicity were poorly discussed. Understanding the specific molecular interactions between NPs and male testicular cells is crucial for developing nanobiotechnologies related to reproductive medicine.
Topics: Animals; Gold; Humans; Male; Metal Nanoparticles; Nanoparticles; Oxidative Stress; Reproduction; Rodentia; Semen
PubMed: 35764125
DOI: 10.1016/j.cbi.2022.110023 -
Ecotoxicology and Environmental Safety Sep 2021Zearalenone (ZEA) is an oestrogen-like mycotoxin produced by Fusarium fungi, which has a considerable impact on human and animal health and results in substantial... (Meta-Analysis)
Meta-Analysis
Zearalenone (ZEA) is an oestrogen-like mycotoxin produced by Fusarium fungi, which has a considerable impact on human and animal health and results in substantial economic losses worldwide. This study aimed to demonstrate the reproductive injury induced by ZEA in rodents. We conducted a rigorous meta-analysis of the related literature via PubMed, Embase, and Web of Science. The scope of the study includes the following: development of reproductive organs, serum testosterone, oestradiol, and luteinizing hormone (LH) levels; parameters of Leydig cells; and parameters of semen. In total, 19 articles were reviewed. Compared with the control group, the increased relative epididymis weight, increased serum oestradiol level, and decreased LH levels in the prenatally exposed group were observed. In pubertal and adult rodents, the relative testicular weight, serum oestradiol level, Leydig cell number, and percentage of ST (+) Leydig cells decreased under ZEA exposure. In rodents at all ages, decreased serum testosterone level, sperm concentration, sperm motility rate, and increased serum deformity rate were observed in exposed groups compared with control groups. Although subgroup analysis failed to identify a clear dose-response relationship between ZEA exposure and reproductive system damage in male rodents, we still managed to confirm that zearalenone could decrease the serum testosterone level at the dosage of 50 mg/kg*day, 1.4 mg/kg*day, and 84 mg/kg*day, of prenatal, pubertal, and mature rodents respectively; pubertal zearalenone exposure impairs the quality and quantity of sperms of rodents at the dosage of 1.4 mg/kg*day and mature zearalenone exposure has the same effect at the dosage of 84 mg/kg*day. In conclusion, we found that ZEA exposure can cause considerable damage to the reproductive system of rodents of all ages. While the exact underlying mechanism of ZEA-induced toxicity in the reproductive system remains largely unknown, the theories of oestrogen-like effects and oxidative stress damage are promising.
Topics: Animals; Estrogens; Male; Reproduction; Zearalenone
PubMed: 34175827
DOI: 10.1016/j.ecoenv.2021.112457 -
Asian Journal of Surgery Dec 2021Testis-sparing surgery (TSS) has been increasingly used for treating a variety of testicular tumors (TTs) in children. However, the indications and feasibility... (Meta-Analysis)
Meta-Analysis Review
Testis-sparing surgery (TSS) has been increasingly used for treating a variety of testicular tumors (TTs) in children. However, the indications and feasibility associated with TSS remain uncertain. This study aimed to present the clinical outcomes of TSS in children with TTs. The PubMed, Cochrane Library, and Embase databases were reviewed for relevant articles on the clinical outcomes of TSS in children. Recurrence rate, benign rate, rate of TSS and its 95% confidence interval (CI) were calculated. A total of nine relevant studies with 320 patients were included in this study. The recurrence rate was 5.8% (95% CI: 2.3%-14.1%), benign rate was 70.9% (95% CI: 56.3%-82.1%), the rate of TSS (RTSS) was 36.2% (95% CI: 26.1%-47.8%), RTSS in benign tumor was 48.4% (95% CI: 34.3%-62.9%) and rate of elevated AFP was 29.3% (95% CI: 19.7%-41.3%) in children with TTs. Regarding the distribution of TTs, 159 (49.6%) were teratomas, 74 (23.1%) were yolk sac tumors, 36 (11.3%) were epidermoid cysts, 3 (0.9%) were rhabdomyosarcomas, 7 (2.2%) were leydig cell tumor, 6 (1.8%) were sex-cord stromal tumor, 8(2.5%) were mixed malignant germ cell tumors, 3(0.9%) were hemangioma, and 4(1.3%) were adrenal rest tumors. The findings of this meta-analysis suggested that most of the TTs in children were benign, and the most common histologic subtype was teratoma. TSS should be provided to children with benign lesions. This study confirmed that very low rates of tumor recurrence were observed in children with TTs.
Topics: Epidermal Cyst; Humans; Male; Testicular Neoplasms
PubMed: 33893031
DOI: 10.1016/j.asjsur.2021.03.016 -
Journal of Clinical Medicine Feb 2024Androgen insensitivity syndrome (AIS) is a rare Mendelian disorder caused by mutations of the androgen receptor () gene on the long arm of the X chromosome. As a result...
Androgen Insensitivity Syndrome with Bilateral Gonadal Sertoli Cell Lesions, Sertoli-Leydig Cell Tumor, and Paratesticular Leiomyoma: A Case Report and First Systematic Literature Review.
Androgen insensitivity syndrome (AIS) is a rare Mendelian disorder caused by mutations of the androgen receptor () gene on the long arm of the X chromosome. As a result of the mutation, the receptor becomes resistant to androgens, and hence, karyotypically male patients (46,XY) carry a female phenotype. Their cryptorchid gonads are prone to the development of several types of tumors (germ cell, sex cord stromal, and others). Here, we report a 15-year-old female-looking patient with primary amenorrhea who underwent laparoscopic gonadectomy. Histologically, the patient's gonads showed Sertoli cell hamartomas (SCHs) and adenomas (SCAs) with areas of Sertoli-Leydig cell tumors (SLCTs) and a left-sided paratesticular leiomyoma. Rudimentary Fallopian tubes were also present. The patient's karyotype was 46,XY without any evidence of aberrations. Molecular genetic analysis of the left gonad revealed two likely germline mutations-a pathogenic frameshift deletion in the gene (c.77delT) and a likely pathogenic missense variant in the gene (p.A94V). Strikingly, no somatic mutations, fusions, or copy number variations were found. We also performed the first systematic literature review (PRISMA guidelines; screened databases: PubMed, Scopus, Web of Science; ended on 7 December 2023) of the reported cases of patients with AIS showing benign or malignant Sertoli cell lesions/tumors in their gonads ( = 225; age: 4-84, mean 32 years), including Sertoli cell hyperplasia (1%), Sertoli cell nodules (6%), SCHs (31%), SCAs (36%), Sertoli cell tumors (SCTs) (16%), and SLCTs (4%). The few cases ( = 14, 6%; six SCAs, four SCTs, two SLCTs, and two SCHs) with available follow-up (2-49, mean 17 months) showed no evidence of disease (13/14, 93%) or died of other causes (1/14, 7%) despite the histological diagnosis. Smooth muscle lesions/proliferations were identified in 19 (8%) cases (including clearly reported rudimentary uterine remnants, 3 cases; leiomyomas, 4 cases). Rudimentary Fallopian tube(s) were described in nine (4%) cases. Conclusion: AIS may be associated with sex cord/stromal tumors and, rarely, mesenchymal tumors such as leiomyomas. True malignant sex cord tumors can arise in these patients. Larger series with longer follow-ups are needed to estimate the exact prognostic relevance of tumor histology in AIS.
PubMed: 38398243
DOI: 10.3390/jcm13040929 -
Andrology Mar 2023Men with Klinefelter Syndrome develop some degree of seminiferous tubule degeneration, hyalinization, and fibrosis by adulthood. However, the pathophysiology surrounding... (Review)
Review
BACKGROUND
Men with Klinefelter Syndrome develop some degree of seminiferous tubule degeneration, hyalinization, and fibrosis by adulthood. However, the pathophysiology surrounding testicular fibrosis in Klinefelter Syndrome patients remains incompletely understood.
OBJECTIVES
To perform a systematic review of literature studying the mechanisms of fibrosis initiation or propagation in Klinefelter Syndrome testes.
MATERIALS/METHODS
PubMed was searched systematically for articles specific to Klinefelter Syndrome and the process of fibrosis. Articles that did not contain original data or specifically addressed the target material were excluded. Additional references were extracted when pertinent from the reference lists of included studies.
RESULTS
Primary search yielded 139 articles for abstract review, which was narrowed to 16 for full-text review. Following full-text review, eight contained original data and met topic criteria, with one paper added from reference review for a total of nine papers.
DISCUSSION
The date range for included papers was 1992-2022. The proposed mechanisms of fibrosis mainly were centered around the impact of altered Sertoli cells on germ cells, the hormonal impact on Leydig cells, the inflammation mediated by mast cells, or the fibrous extracellular matrix deposition by peritubular myoid cells. Additionally, discussions of the role of the altered microvasculature and the specific proteins involved in the blood-testis barrier or the seminiferous tubule architecture are reviewed. Recent papers have incorporated advanced sequencing and offer future directions for targeted gene expression analysis. Still, much of the published data consists solely of immunohistological assessment by age range, creating difficulties in extrapolating causality.
CONCLUSION
The specific initiating factors of fibrosis of the seminiferous tubules and the propagation mechanisms unique to Klinefelter Syndrome remain incompletely understood with a relative paucity of data. Nonetheless, academic interest is increasing in this field as it may further elucidate the pathophysiology behind Klinefelter syndrome.
Topics: Male; Humans; Adult; Klinefelter Syndrome; Testis; Seminiferous Tubules; Sertoli Cells; Fibrosis
PubMed: 36252136
DOI: 10.1111/andr.13327 -
Evidence-based Complementary and... 2021Isoflavone is a phytoestrogen found in different types of food that can act as endocrine disrupters leading to testicular dysfunction. Currently, fragmented data on the... (Review)
Review
Isoflavone is a phytoestrogen found in different types of food that can act as endocrine disrupters leading to testicular dysfunction. Currently, fragmented data on the action of this compound in the testicles make it difficult to assess its effects to define a safe dose. Thus, we systematically reviewed the preclinical evidence of the impact of isoflavone on testicular function. We also determined which form (aglycones or glycosylated) was the most used, which allowed us to understand the main biological processes involved in testicular function after isoflavone exposure. This systematic review was carried out according to the PRISMA guidelines using a structured search on the biomedical databases MEDLINE (PubMed), Scopus, and Web of Science, recovering and analyzing 22 original studies. The bias analysis and the quality of the studies were assessed by the criteria described in the risk of bias tool developed by SYRCLE (Systematic Review Centre for Laboratory Animal Experimentation). The aglycones and glycosylated isoflavones proved to be harmful to the reproductive health, and the glycosylates at doses of 50, 100, 146, 200, 300, 500, and 600 mg/kg, in addition to 190 and 1000 mg/L, appear to be even more harmful. The main testicular pathologies resulting from the use of isoflavones are associated with Leydig cells resulting from changes in molecular functions and cellular components. The most used isoflavone to evaluate testicular changes was the genistein/daidzein conjugate. The consumption of high doses of isoflavones promotes changes in the functioning of Leydig cells, inducing testicular changes and leading to infertility in murine models.
PubMed: 33628321
DOI: 10.1155/2021/8853172