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Keywords = testicular enlargement

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18 pages, 4817 KB  
Article
Prenatal Bisphenol B Exposure Induces Adult Male Offspring Reproductive Dysfunction via ERα Inhibition-Triggered MHC I-Mediated Testicular Immunological Responses
by Nannan Chen, Xiaotian Li, Shenrui Zhou, Xin Peng, Senlin Xue, Yuetong Liu, Tingwang Jiang and Wei Yan
Toxics 2025, 13(6), 423; https://doi.org/10.3390/toxics13060423 - 22 May 2025
Cited by 1 | Viewed by 1681
Abstract
As an emerging endocrine-disrupting agent and structural analog of bisphenol A (BPA), bisphenol B (BPB) raises significant concerns due to its potential to induce male reproductive toxicity. Despite its presence in maternal bodily fluids, the effects of BPB exposure on the reproductive system [...] Read more.
As an emerging endocrine-disrupting agent and structural analog of bisphenol A (BPA), bisphenol B (BPB) raises significant concerns due to its potential to induce male reproductive toxicity. Despite its presence in maternal bodily fluids, the effects of BPB exposure on the reproductive system and its mechanisms in adult male offspring are poorly understood. By establishing a maternal BPB exposure model in mice, we found that the exposure reduced the relative weights of seminal vesicles and preputial glands, decreased the thickness of the seminiferous epithelium, enlarged the lumen area of seminiferous tubules, and lowered testosterone concentration and synthesis, as well as sperm count in 10-week-old male offspring. Bioinformatic analyses revealed that the differentially expressed genes were significantly associated with major histocompatibility complex I (MHC I)-mediated immunological processes, including immune system processes, antigen processing and presentation of exogenous peptide antigens via MHC class I, and interleukin-2 production. Importantly, molecular docking proposed a potential mechanistic model wherein BPB bound to estrogen receptor α (ERα) suppressed its testicular expression and triggered MHC class I gene overexpression, potentially promoting macrophage infiltration, CD4+/CD8+ T cell activation, and pro-inflammatory cytokine production. Our findings provide critical insights into the adverse effects of maternal BPB exposure on male reproductive development, suggesting that impairments in testicular morphology and spermatogenesis may be attributed to MHC I-mediated immunological responses and hormonal imbalances resulting from inhibited ERα signaling. These results underscore not only the toxicological risks associated with BPB but also potential therapeutic targets for mitigating male reproductive dysfunction. Full article
(This article belongs to the Section Emerging Contaminants)
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16 pages, 9727 KB  
Article
Teratoma Development in 129.MOLF-Chr19 Mice Elicits Two Waves of Immune Cell Infiltration
by Lucas Klaus, Sybille D. Reichardt, Maria Neif, Lutz Walter, Fabian A. Gayer and Holger M. Reichardt
Int. J. Mol. Sci. 2024, 25(23), 12750; https://doi.org/10.3390/ijms252312750 - 27 Nov 2024
Viewed by 1500
Abstract
Teratomas are a highly differentiated type of testicular germ cell tumors (TGCTs), the most common type of solid cancer in young men. Prominent inflammatory infiltrates are a hallmark of TGCTs, although their compositions and dynamics in teratomas remain elusive. Here, we reached out [...] Read more.
Teratomas are a highly differentiated type of testicular germ cell tumors (TGCTs), the most common type of solid cancer in young men. Prominent inflammatory infiltrates are a hallmark of TGCTs, although their compositions and dynamics in teratomas remain elusive. Here, we reached out to characterize the infiltrating immune cells and their activation and polarization state by using high-throughput gene expression analysis of 129.MOLF-Chr19 mice that spontaneously develop testicular teratomas. We showed that inconspicuous testes without any apparent alterations in size or morphology can be clustered into three groups based on their expression of stemness and immune genes, supporting a model in which initial oncogenic transformation elicits a first wave of T-cell infiltration. Moderately and severely enlarged tumorous testes then displayed a progressive infiltration with T cells, monocytes/macrophages, and B cells. Importantly, T cells seem to adopt an inactive state caused by an overexpression of immune checkpoint molecules and the polarization of monocytes/macrophages to an anti-inflammatory phenotype. Our findings are supported by the analysis of metabolic gene expression, which unveiled alterations indicative of tumor growth and immune cell infiltration. Collectively, testicular teratomas, at least in mice, are characterized by a diverse inflammatory infiltrate containing T cells that putatively become inactivated, allowing the tumors to further grow. We believe that these findings may provide a rationale for the development of new immunomodulatory therapies for TGCTs. Full article
(This article belongs to the Special Issue Current Research on Cancer Biology and Therapeutics: Third Edition)
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7 pages, 2099 KB  
Case Report
Synchronous Seminoma of Testis and Renal Cell Carcinoma: A Rare Case Report
by Stasys Auskalnis, Rasa Janciauskiene, Urte Rimsaite, Aurelija Alksnyte and Rasa Ugenskiene
Medicina 2024, 60(9), 1553; https://doi.org/10.3390/medicina60091553 - 23 Sep 2024
Cited by 2 | Viewed by 2112 | Correction
Abstract
Background and Objectives: Seminoma is the most common solid malignant tumour in young men. Clear-cell kidney carcinoma is the most common malignancy of the genitourinary tract. However, the synchronous occurrence of both of these tumours is rare. Case presentation: We present the [...] Read more.
Background and Objectives: Seminoma is the most common solid malignant tumour in young men. Clear-cell kidney carcinoma is the most common malignancy of the genitourinary tract. However, the synchronous occurrence of both of these tumours is rare. Case presentation: We present the case of a 36-year-old patient who presented to a medical facility at the end of 2019 with an enlarged right testicle. A unilateral orchofuniculectomy was performed, and a mass measuring 30 cm was removed. During histological examination, testicular seminoma pT2, R0, was diagnosed. An abdominal computed tomography (CT) scan showed a 6.4 cm × 6.8 cm × 6.7 cm tumour in the right kidney and a metastatic-like lesion in the right adrenal gland. A right nephrectomy and an adrenalectomy and paraaortic and paracaval lymphadenectomies were performed. A histological evaluation confirmed the presence of clear-cell renal carcinoma pT2aR0 G2, adrenal hyperplasia, and seminoma metastases in the removed lymph node. Chemotherapy with a Bleomycin, Etoposide, and Cisplatin (BEP) regimen was carried out. Three years after the last cycle of chemotherapy, a follow-up CT scan showed metastases in the left kidney, the right ischium, and the right lung. A well-differentiated clear-cell carcinoma G1 of the left kidney and metastasis of clear-cell carcinoma G2 in the right ischium were confirmed after the biopsy, and no tumour lesions were found in the lung tissue specimen. Treatment with targeted therapy with Sunitinib was started because the risk was favourable according to the Heng criteria. Genetic testing was performed, and the following genes were analysed: VHL, BAP1, CHEK2, FH, MET, MUTYH, APC, and STK11. The testing did not reveal any pathogenic or potentially pathogenic mutations or sequence changes of unknown clinical significance in the genes analysed. Conclusions: According to the authors, the occurrence of synchronous primary tumours is linked to one’s genetic predisposition. DNA sequencing of tumour tissue could provide more information on the corresponding aetiopathogenesis. Full article
(This article belongs to the Section Oncology)
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21 pages, 7687 KB  
Article
Alterations in the Hypothalamic–Pituitary–Adrenal Axis as a Response to Experimental Autoimmune Encephalomyelitis in Dark Agouti Rats of Both Sexes
by Ana Milosevic, Katarina Milosevic, Anica Zivkovic, Irena Lavrnja, Danijela Savic, Ivana Bjelobaba and Marija M. Janjic
Biomolecules 2024, 14(8), 1020; https://doi.org/10.3390/biom14081020 - 17 Aug 2024
Cited by 2 | Viewed by 1891
Abstract
Multiple sclerosis (MS) is a chronic inflammatory disease that affects the central nervous system, usually diagnosed during the reproductive period. Both MS and its commonly used animal model, experimental autoimmune encephalomyelitis (EAE), exhibit sex-specific features regarding disease progression and disturbances in the neuroendocrine [...] Read more.
Multiple sclerosis (MS) is a chronic inflammatory disease that affects the central nervous system, usually diagnosed during the reproductive period. Both MS and its commonly used animal model, experimental autoimmune encephalomyelitis (EAE), exhibit sex-specific features regarding disease progression and disturbances in the neuroendocrine and endocrine systems. This study investigates the hypothalamic–pituitary–adrenal (HPA) axis response of male and female Dark Agouti rats during EAE. At the onset of EAE, Crh expression in the hypothalamus of both sexes is decreased, while males show reduced plasma adrenocorticotropic hormone levels. Adrenal gland activity is increased during EAE in both males and females, as evidenced by enlarged adrenal glands and increased StAR gene and protein expression. However, only male rats show increased serum and adrenal corticosterone levels, and an increased volume of the adrenal cortex. Adrenal 3β-HSD protein and progesterone levels are elevated in males only. Serum progesterone levels of male rats are also increased, although testicular progesterone levels are decreased during the disease, implying that the adrenal gland is the source of elevated serum progesterone levels in males. Our results demonstrate a sex difference in the response of the HPA axis at the adrenal level, with male rats showing a more pronounced induction during EAE. Full article
(This article belongs to the Special Issue Role of Neuroactive Steroids in Health and Disease: 2nd Edition)
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11 pages, 230 KB  
Article
Seminological, Hormonal and Ultrasonographic Features of Male Factor Infertility Due to Genetic Causes: Results from a Large Monocentric Retrospective Study
by Rossella Mazzilli, Simona Petrucci, Virginia Zamponi, Bianca Golisano, Giulia Pecora, Camilla Mancini, Gerardo Salerno, Laura Alesi, Ilaria De Santis, Fabio Libi, Carla Rossi, Marina Borro, Salvatore Raffa, Vincenzo Visco, Giuseppe Defeudis, Maria Piane and Antongiulio Faggiano
J. Clin. Med. 2024, 13(15), 4399; https://doi.org/10.3390/jcm13154399 - 27 Jul 2024
Cited by 1 | Viewed by 1665
Abstract
Objectives: Evaluate the prevalence of genetic factors in a large population of infertile subjects and define the seminological, hormonal, and ultrasonographic features for each alteration. Methods: This single-center retrospective study included male partners of infertile couples undergoing genetic investigations due to oligozoospermia [...] Read more.
Objectives: Evaluate the prevalence of genetic factors in a large population of infertile subjects and define the seminological, hormonal, and ultrasonographic features for each alteration. Methods: This single-center retrospective study included male partners of infertile couples undergoing genetic investigations due to oligozoospermia or azoospermia evaluated from January 2012 to January 2022. The genetic investigations consist of karyotype, CFTR gene mutations plus variant of the IVS8-5T polymorphic trait, Y chromosome microdeletion, and Next Generation Sequencing panel to analyze genes implicated in congenital hypogonadotropic hypogonadism (CHH). Results: Overall, 15.4% (72/466) of patients received a diagnosis of genetic cause of infertility. Specifically, 23 patients (31.9%) harbor mutations in the CFTR gene, 22 (30.6%) have a 47, XXY karyotype, 14 (19.4%) patients show a Y chromosome microdeletion, 7 (9.7%) have structural chromosomal anomalies, and 6 (8.3%) have CHH. Overall, 80.6% of patients were azoospermic and 19.4% oligozoospermic (sperm concentration 3.5 ± 3.8 million/mL). Almost all patients presented hormonal alterations related to the specific genotype, while the main ultrasound alterations were testicular hypoplasia, calcifications/microcalcifications, and enlarged/hyperechoic epididymis. Conclusions: The prevalence of genetic abnormalities in males of infertile couples was 15.4% in our Center. CFTR gene disease-causing variants resulted in more frequent, with various clinical features, highlighting the complexity and heterogeneity of the presentation. Other investigations are needed to understand if conditions like ring chromosomes and other translocations are related to infertility or are incidental factors. Full article
19 pages, 1309 KB  
Article
Cohort Profile: Chongqing Pubertal Timing and Environment Study in China with 15 Follow-Ups since 2014
by Di Wu, Jie Luo, Qin Zhang, Shudan Liu, Xuan Xi, Wenyi Wu, Yuanke Zhou, Yu Tian, Yujie Wang, Zongwei He, Jie Zhang, Hong Wang and Qin Liu
Future 2024, 2(3), 107-125; https://doi.org/10.3390/future2030009 - 4 Jul 2024
Cited by 5 | Viewed by 4816
Abstract
Background: Puberty is a life milestone that marks the transition from childhood to adulthood. An ambispective Chongqing Pubertal Timing (CQPT) cohort was started in 2014 to understand pubertal timing and identify environmental risk factors. Methods: A total of 1429 children and adolescents were [...] Read more.
Background: Puberty is a life milestone that marks the transition from childhood to adulthood. An ambispective Chongqing Pubertal Timing (CQPT) cohort was started in 2014 to understand pubertal timing and identify environmental risk factors. Methods: A total of 1429 children and adolescents were recruited and have been followed up once every 6 months for 8 years in a district of Chongqing, China. Data were collected via questionnaires for social and family environment, health conditions, gestational and maternal information, and in-person physical examinations by trained medical school graduate students in follow-ups. Environmental exposures of polycyclic aromatic hydrocarbons (PAHs), neonicotinoids, and heavy metals in urine samples were measured at different time points. Results: The mean ages at pubertal onset were 10.20 for thelarche, 11.62 for pubic hair development, and 11.84 for menarche in girls, and 11.16 for genital development, 11.66 for testicular enlargement, and 12.71 for first spermatorrhea in boys. Four OH-PAHs were associated with delayed timing of menarche, thelarche, pubic hair, and axillary hair development in girls, and thiacloprid was found to potentially impact genital stages in boys and axillary hair development in girls. Conclusions: We built a cohort to provide evidence of regional pubertal timing of boys and girls and the significant environmental factors. Further health outcomes, especially mental health and women’s health and its long-term health implications, will be followed. Full article
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35 pages, 17814 KB  
Review
Diagnostic Approach to Equine Testicular Disorders
by Muhammad-Salman Waqas, Eduardo Arroyo and Ahmed Tibary
Vet. Sci. 2024, 11(6), 243; https://doi.org/10.3390/vetsci11060243 - 29 May 2024
Cited by 5 | Viewed by 10719
Abstract
Management of breeding stallions is crucial to equine reproduction. The longevity of the breeding career is the ultimate objective, whether the stallion is used for natural cover or for semen collection and artificial insemination. Stud farm veterinarians should be aware of the techniques [...] Read more.
Management of breeding stallions is crucial to equine reproduction. The longevity of the breeding career is the ultimate objective, whether the stallion is used for natural cover or for semen collection and artificial insemination. Stud farm veterinarians should be aware of the techniques used to evaluate testicular function and the diagnostic approach to testicular disorders in cases of emergency. This paper presents the clinical methods used to evaluate testicular health, including palpation, ultrasonography, biopsy, and fine-needle aspiration. The discussion of testicular disorders is broken down into four categories: congenital disorders (cryptorchidism, monorchidism, and testicular hypoplasia), differential diagnosis of scrotal enlargement, differential diagnosis of causes of progressive testicular enlargement, and differential diagnosis of testicular asymmetry or reduction in size with an emphasis on testicular degeneration. The sudden increase in testicular size is often accompanied by severe clinical signs and is a major cause for referral of stallion for surgery. Testicular disorders are illustrated with clinical cases seen by the authors. Full article
(This article belongs to the Special Issue Recent Findings in Equine Reproduction and Neonatology)
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18 pages, 1290 KB  
Systematic Review
Testicular Metastasis from Renal Cell Carcinoma: A Systematic Review
by Anna Pliszka, Sebastian Rajda, Agata Wawrzyniak, Jerzy Walocha, Michał Polguj, Grzegorz Wysiadecki, Edward Clarke, Michał Golberg, Michał Zarzecki and Krzysztof Balawender
J. Clin. Med. 2023, 12(17), 5636; https://doi.org/10.3390/jcm12175636 - 29 Aug 2023
Cited by 9 | Viewed by 4009
Abstract
Approximately one-third of renal cell carcinoma (RCC) is recognized in its metastatic stage. This systematic review aimed to summarize knowledge on the occurrence and treatment of testicular RCC metastasis. The literature search was performed by two authors independently, with the use of main [...] Read more.
Approximately one-third of renal cell carcinoma (RCC) is recognized in its metastatic stage. This systematic review aimed to summarize knowledge on the occurrence and treatment of testicular RCC metastasis. The literature search was performed by two authors independently, with the use of main electronic medical databases (Science Direct, Web of Science, and PubMed) until March 2023 to identify relevant articles that could potentially contribute to this review. Neither language nor publication dates were set as limits. Although we found a total of 51 case reports, only 31 of them contained all the required information. Testicular metastasis in patients with RCC suggests a late stage of the disease. Moreover, it usually does not present typical systemic or specific symptoms except for swelling and enlargement of the affected testis. Knowledge of the possibility of such variants of RCC metastases will allow a clinician to make an appropriate diagnosis and implement adequate treatment without delay, which is crucial in the management of neoplastic disease. Full article
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14 pages, 382 KB  
Review
Updating the Landscape for Functioning Gonadotroph Tumors
by Georgia Ntali and Cristina Capatina
Medicina 2022, 58(8), 1071; https://doi.org/10.3390/medicina58081071 - 8 Aug 2022
Cited by 16 | Viewed by 5306
Abstract
Functioning gonadotroph adenomas (FGAs) are rare tumors, as the overwhelming majority of gonadotroph tumors are clinically silent. Literature is based on case reports and small case series. Gonadotroph tumors are poorly differentiated and produce and secrete hormones inefficiently, but in exceptional cases, they [...] Read more.
Functioning gonadotroph adenomas (FGAs) are rare tumors, as the overwhelming majority of gonadotroph tumors are clinically silent. Literature is based on case reports and small case series. Gonadotroph tumors are poorly differentiated and produce and secrete hormones inefficiently, but in exceptional cases, they cause clinical syndromes due to hypersecretion of intact gonadotropins. The clinical spectrum of endocrine dysfunction includes an exaggerated response of ovaries characterized as ovarian hyperstimulation syndrome (OHSS) in premenopausal females and adolescent girls, testicular enlargement in males, and isosexual precocious puberty in children. Transsphenoidal surgery and removal of tumor reduces hormonal hypersecretion, improves endocrine dysfunction, and provides tissue for further analysis. Medical therapies (somatostatin analogues, dopamine agonists, GnRH agonists/antagonists) are partially or totally ineffective in many cases, especially with respect to antitumor effect. This review aims to update recent literature on these rare functioning tumors and highlight their therapeutic management. Full article
(This article belongs to the Special Issue New Therapeutic Horizons for Pituitary Tumors)
14 pages, 67774 KB  
Case Report
Ultrasound Examination of Unilateral Seminoma in a Salernitano Stallion
by Brunella Anna Giangaspero, Roberta Bucci, Francesca Del Signore, Massimo Vignoli, Jasmine Hattab, Gina Rosaria Quaglione, Lucio Petrizzi and Augusto Carluccio
Animals 2022, 12(7), 936; https://doi.org/10.3390/ani12070936 - 6 Apr 2022
Cited by 4 | Viewed by 4123
Abstract
An 18-year-old Salernitano stallion developed a progressive enlargement of the left testicle over eight months. An ultrasound evaluation was performed, along with a hormonal profile. A histopathological evaluation of the testis was performed after unilateral orchiectomy. On B-mode ultrasound examination, testicular parenchyma was [...] Read more.
An 18-year-old Salernitano stallion developed a progressive enlargement of the left testicle over eight months. An ultrasound evaluation was performed, along with a hormonal profile. A histopathological evaluation of the testis was performed after unilateral orchiectomy. On B-mode ultrasound examination, testicular parenchyma was characterized by the loss of internal structure, with the presence of multiple coalescing, nodular, well-defined and heterogeneous lesions with capsule deformity, appearing with an irregular profile. On dissection, the testicular parenchyma bulged over the cut section, confirming the increase in size. Microscopically, the lesion consisted mainly of large, densely packed, polygonal-to-round-shaped neoplastic cells. Mitotic figures were plentiful and frequently atypical; further microscopic features included apoptosis and necrosis. At immunohistochemistry, the entire neoplasm showed strong and diffuse immunolabeling for vimentin, while CD117-specific immunoreactivity was only observed in scattered clusters of neoplastic cells. Based on the gross, microscopic and IHC findings, a diagnosis of diffuse seminoma was made. Three months later, a follow-up examination showed no evidence of recurrence and the preservation of reproductive abilities. The case presented shows an unusual ultrasonographic pattern for seminoma and the basis of the correlation between the characteristics of the sonoelastographic examination and histological diagnosis. Full article
(This article belongs to the Special Issue Veterinary and Comparative Reproductive Pathology)
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8 pages, 2596 KB  
Case Report
Varicocele in an Adult Ram: Histopathological Examination and Sperm Quality Evaluation
by Athina Basioura, Georgia D. Brellou, Ioannis Tsakmakidis, Ioannis Vlemmas, Constantin M. Boscos and Nektarios Giadinis
Vet. Sci. 2022, 9(2), 86; https://doi.org/10.3390/vetsci9020086 - 17 Feb 2022
Viewed by 7301
Abstract
Varicocele is a common pathological condition of testis that is related to male fertility problems. A 3-year age Chios ram had an abnormally enlarged scrotal area, was excluded from reproductive duties, and was euthanized with the owners’ permission. The main pathological finding was [...] Read more.
Varicocele is a common pathological condition of testis that is related to male fertility problems. A 3-year age Chios ram had an abnormally enlarged scrotal area, was excluded from reproductive duties, and was euthanized with the owners’ permission. The main pathological finding was the presence of bilateral multinodular spermatic cord enlargement with laminated vascular thrombi. Histopathological examination revealed commonly mineralized thrombi within the lumen of veins of the pampiniform plexus, inflammation and testicular degeneration. The epididymides were transported to the laboratory and each cauda region was sliced and washed (8 mL water for injection/epididymis), and the epididymal sperm samples were collected. Sperm motility variables (CASA), viability (eosin-nigrosine), morphology (SpermBlue®), and DNA integrity (Acridine Orange Test, AOT) were assessed. The total and progressive motility were low in semen samples of both sides (30.00% and 1.00% vs. 42.60% and 2.50% for left and right epididymis, respectively). Low viability values were observed for both sides (26.00% vs. 23.00% for left and right epididymis, respectively), while sperm morphological abnormalities were within normal limits. No sperm with DNA damage were detected. The results of this case report indicate that varicocele is associated with testis dysfunction and degradation of ram semen quality, mainly affecting motility and kinematics. Full article
(This article belongs to the Section Veterinary Reproduction and Obstetrics)
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