Researches on the testicular dysgenesis syndrome (TDS) have flourished in the recent decade, and a widely accepted view on its pathogenesis is that environmental endocrine disrupting chemicals (EDCs) act on Leydig cells and/or testicular Sertoli cells, resulting in abnormal development of the testis and leading to the symptoms of TDS. Molecular biological studies suggest a correlation of TDS etiology with insulin-like factor 3 (INSL-3), androgen receptor (AR), P27kip, WT-1 and Müllerian inhibiting substance (MIS). This review focuses on the progress in current researches on the etiology and mechanism of TDS.
Cryptorchidism ; Gonadal Dysgenesis ; etiology ; genetics ; Humans ; Male ; Testicular Diseases ; etiology ; genetics ; Testicular Neoplasms

Humans ; Male ; RNA ; analysis ; Telomerase ; genetics ; Testicular Neoplasms ; genetics

Testicular germ cell tumor (TGCT) is a most common testicular malignancy with an increasing incidence, and its pathogenesis and mechanisms are not yet clear. The next generation sequencing has become the main tool to uncover the underlying mechanisms of TGCT. The differential gene expressions, gene mutation, predisposing gene-dominated signaling pathways, and changes of the relevant genes in the sex chromosome are largely involved in the occurrence and development of TGCT. Studies on the genomics of TGCT contribute a lot to identifying the pivotal pathogenic genes and paving a theoretical ground for the early screening and targeted therapy of TGCT. This paper summarizes the advances in the studies of the genomics of TGCT so as to reveal thetmechanisms of the disease at the genetic level.
Genomics ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Neoplasms, Germ Cell and Embryonal ; genetics ; Testicular Neoplasms ; genetics

Objective: To investigate the clinicopathological features, immunophenotype and prognosis of nuclear protein in testis (NUT) midline carcinoma. Methods: Twenty-four resection cases of NUT midline carcinoma diagnosed at the Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China from January 2018 to September 2022, were collected, and retrospectively analyzed for their clinicopathological characteristics. Relevant literature was reviewed. Results: All 24 cases of NUT midline carcinoma occurred in the chest or head and neck, including 14 men and 10 women, with a median age of 40 years. Histological examination showed that the tumors were poorly differentiated, with solid nested or sheet-like arrangement, small to medium-sized cells, sparse cytoplasm and coarse granular chromatin, including 5 cases with abrupt squamous epithelial differentiation. Immunohistochemistry showed that all 24 cases were positive for NUT protein, while 16 cases were p63 positive, 19 cases were p40 positive, 15 out of 18 cases were CK5/6 positive. Follow-up data were obtained for 21 patients (follow-up time range, 1-21 months), of which 11 survived, 10 died, and 3 were lost to follow-up. Conclusions: NUT midline carcinoma is a rare and highly aggressive malignancy with unique histological, immunophenotypic and molecular features. It has a poor prognosis.
Male ; Humans ; Female ; Adult ; Neoplasm Proteins/genetics* ; Nuclear Proteins/genetics* ; Retrospective Studies ; Carcinoma/surgery* ; Testicular Neoplasms

Primary testicular carcinoid tumor, occupying 0.23% of testicular neoplasm, is a rare and indolent neoplasm with the potential for distant metastasis. We present two cases of primary pure carcinoid tumor of the testis. Both patients were 36 years old. Physical examination revealed testicular mass with and without tenderness. The preoperative serum levels of beta-human chorionic gonadotropin and alpha-fetoprotein were normal and neither patient had carcinoid syndrome. The tumors measured 7.5x6x4 cm and 5.5x5x4 cm in size. Histologically, immunohistochemically and ultrastructurally, the tumors showed typical features of the carcinoid tumor. Case 1 showed extensive tumor necrosis and vascular invasion. DNA flow cytometric analysis showed aneuploidy with DNA index of 1.47 and S+G2M of 14.0% in case 1 and tetraploidy with DNA index of 1.96 and S+G2M of 22.1% in case 2. Both patients have been well without any signs of metastasis after operation for 24 months in case 1 and for 16 months in case 2.
Adult ; Carcinoid Tumor/pathology ; Carcinoid Tumor/metabolism ; Carcinoid Tumor/genetics* ; Case Report ; DNA, Neoplasm/analysis* ; Flow Cytometry/methods* ; Human ; Immunohistochemistry ; Male ; Testicular Neoplasms/pathology ; Testicular Neoplasms/metabolism ; Testicular Neoplasms/genetics*

OBJECTIVE: To analyze the clinical and genetic characteristics of a 46,XX case of testicular disease with prostate germ cell tumor and explore its pathogenesis. METHODS: The clinical features and pathological examination of the patient were reviewed, and the genetic basis was analyzed by chromosome karyotyping analysis and fluorescence in situ hybridization. RESULTS: The patient had slightly short stature, small testicles and large breast. Serum alpha fetoprotein was significantly increased, along with increased follicle stimulating hormone, luteinizing hormone and prolactine, and lower level of testosterone. The karyotype was 46,XX. Fluorescence in situ hybridization has identified the presence of SRY gene at the end of short arm of one X chromosome. The pathological diagnosis was primary germ cell tumor of prostate, mainly of yolk sac tumor type. CONCLUSION A rare case of 46,XX testicular disorder of sex development combined with germ cell tumor of the prostate was diagnosed, which has enriched the phenotype spectrum of the disease and provided clues for the treatment of the disease.
Humans ; In Situ Hybridization, Fluorescence ; Male ; Neoplasms, Germ Cell and Embryonal/genetics* ; Prostate ; Sexual Development ; Testicular Diseases

Testicular microlithiasis (TM) is one of the symptoms of testicular dysgenesis syndrome (TDS). TM is particularly interesting as an informative marker of testicular germ cell tumors (TGCTs). KIT ligand gene (KITLG), BCL2 antagonist/killer 1 (BAK1), and sprouty RTK signaling antagonist 4 (SPRY4) genes are associated with a high risk of TGCTs, whereas bone morphogenetic protein 7 gene (BMP7), transforming growth factor beta receptor 3 gene (TGFBR3), and homeobox D cluster genes (HOXD) are related to TDS. Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, we investigated allele and genotype frequencies for KITLG (rs995030, rs1508595), SPRY4 (rs4624820, rs6897876), BAK1 (rs210138), BMP7 (rs388286), TGFBR3 (rs12082710), and HOXD (rs17198432) in 142 TGCT patients, 137 TM patients, and 153 fertile men (control group). We found significant differences in the KITLG GG_rs995030 genotype in TM (P = 0.01) and TGCT patients (P = 0.0005) compared with the control. We also revealed strong associations between KITLG_rs1508595 and TM (G allele, P = 0.003; GG genotype, P = 0.01) and between KITLG_rs1508595 and TGCTs (G allele, P = 0.0001; GG genotype, P = 0.0007). Moreover, there was a significant difference in BMP7_rs388286 between the TGCT group and the control (T allele, P = 0.00004; TT genotype, P = 0.00006) and between the TM group and the control (T allele, P = 0.04). HOXD also demonstrated a strong association with TGCTs (rs17198432 A allele, P = 0.0001; AA genotype, P = 0.001). Furthermore, significant differences were found between the TGCT group and the control in the BAK1_rs210138 G allele (P = 0.03) and the GG genotype (P = 0.01). KITLG and BMP7 genes, associated with the development of TGCTs, may also be related to TM. In summary, the KITLG GG_rs995030, GG_rs1508595, BMP7 TT_rs388286, HOXD AA_rs17198432, and BAK1 GG_rs210138 genotypes were associated with a high risk of TGCT development.
Adolescent ; Adult ; Calculi/genetics* ; Case-Control Studies ; Cohort Studies ; DNA/genetics* ; Gene Frequency ; Genetic Predisposition to Disease ; Gonadal Dysgenesis/genetics* ; Humans ; Male ; Neoplasms, Germ Cell and Embryonal/genetics* ; Polymerase Chain Reaction ; Testicular Diseases/genetics* ; Testicular Neoplasms/genetics* ; Ultrasonography ; Young Adult

TSPY1 (testis-specific protein, Y-linked 1) gene family, located in male-specific region of Y-chromosome (MSY), has the maximum number of copies organized as a long tandem repeat array in protein-coding gene families of human genome. TSPY1 is identified to be the most important candidate gene for gonadoblastoma, and its coding protein can promote the proliferation and differentiation of tumor cells. Recently, TSPY1 gene family is also proposed to play an important role in spermatogenesis. In this review, the structure characteristics of the gene family were illustrated, and the functional studies of TSPY1 in the process of tumorigenesis and spermatogenesis were discussed.
Cell Cycle Proteins ; genetics ; Chromosomes, Human, Y ; genetics ; Gene Dosage ; Genetic Predisposition to Disease ; genetics ; Gonadoblastoma ; genetics ; Humans ; Male ; Spermatogenesis ; genetics ; Testicular Neoplasms ; genetics

Adolescent ; Adult ; Biomarkers, Tumor ; genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Neoplasm Metastasis ; Neoplasms, Germ Cell and Embryonal ; diagnosis ; genetics ; pathology ; Octamer Transcription Factor-3 ; genetics ; Ovarian Neoplasms ; diagnosis ; genetics ; pathology ; Testicular Neoplasms ; diagnosis ; genetics ; pathology

OBJECTIVE: To explore the inhibitory role of spermatogenesis-associated gene 12 (SPATA12) on tumor cell proliferation and its possible mechanism. METHODS: The expression pattern of SPATA12 in testicular tumors was investigated by in situ hybridization analysis using tissue microarrays. The effects of SPATA12 on tumor cell proliferation and colony formation was detected by 3-(4.5-dimethylthiazol-2- yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and colonyforming assays, respectively. The changes of expression level of cell cycle genes in tumor cells were detected by reverse transcription polymerase chain reaction(RTPCR). RESULTS: In situ hybridization analysis showed that the SPATA12 was highly expressed in normal adult testis, but lacking in testicular tumors such as seminoma. MTT assay and colony-forming assay indicated that the exogenous expression of SPATA12 could suppress both tumor cell proliferation and colony formation. RT-PCR showed that the expression of cyclin A1 gene was markedly suppressed and the level of cyclin D1 was somewhat reduced following SPATA12 transfection. However, no obvious changes were observed in mRNA expression of cyclin B1 or cyclin E1 after SPATA12 transfection. CONCLUSION SPATA12 could be an inhibitor during the development of tumor via regulation of cell cycle genes.
Cell Line, Tumor ; Cell Proliferation ; Genes, Tumor Suppressor ; Genes, cdc ; HeLa Cells ; Homeodomain Proteins ; genetics ; metabolism ; Humans ; Male ; Testicular Neoplasms ; genetics ; pathology ; Transfection