Germ Cell Research Articles (Page 10)

ABSTRACTMalignant germ cell tumors (GCTs) spreading to the central nervous system (CNS) are uncommon, particularly when it comes to spinal cord metastases, which are extremely rare. This report details a case involving a metastatic cervical spinal cord GCT in a patient who had previously been diagnosed with a primary malignant GCT of the right testicle 3 years earlier. The patient experienced progressive cervical pain, and imaging revealed a mass in the cervical spinal cord area. Histopathological analysis confirmed that the mass was a malignant GCT, indicating it was a metastatic spread from the original testicular tumor. This case underscores the rarity of spinal cord metastases resulting from GCTs and emphasizes the necessity of considering metastatic disease in patients with a history of GCTs when they present with neurological symptoms (as often the earliest and most common presenting features).

Effect of two artificial photoperiods on male domestic cat reproduction.

An overview of malignant ovarian tumors in children.

The primordial follicle (PF) pool (also known as ovarian reserve) is the only source of functional eggs during the reproductive lifespan, which formed at embryonic stage in most female mammals and is no longer renewed. CCAAT/enhancer binding protein beta (C/EBPβ) is a transcription factor (TF) and widely expressed in adult ovarian granulosa cells, but its role in the early ovarian development remains unclear. Here, we showed that C/EBPβ was enhanced during PF formation process in mice, and underwent nuclear translocation in germ cells along with the PF assembly (PFA) process. Importantly, the in vitro knockdown of C/EBPβ could inhibit the related proteins expression, resulting in the obstruction of PF formation. Mechanistically, the chromatin accessibility analysis revealed that C/EBPβ binds to the promoter region of the histone acetylase encoding gene Ep300 to promotes its expression, and enhance neurotrophic tyrosine receptor kinase (NTRK) signaling (required for PF formation) by maintaining chromatin accessibility of Furin promoter region. Interestingly, our results verified that the nuclear translocation of C/EBPβ is regulated by its phosphorylation level, and Lamin B1 acts as a "gatekeeper" molecule for the process. In summary, this report suggests that C/EBPβ is a key regulator for the establishment of ovarian reserve in mice.

Purpose: This study aimed to evaluate the therapeutic potential of Bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, in combination with the standard Bleomycin, Etoposide, and Cisplatin (BEP) regimen for the treatment of testicular germ cell tumors (TGCTs). The primary focus was to investigate its ability to enhance treatment efficacy while reducing cytotoxic side effects. Materials and Methods: The half-maximal inhibitory concentration (IC₅₀) of the BEP regimen was determined in the 1618-K human TGCT cell line and subsequently combined with varying concentrations of Bevacizumab. Cell viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Expression levels of VEGF, Bax, Bcl-2, and Caspase-3 were analyzed by immunohistochemistry. Results: Bevacizumab significantly reduced cell viability in a dose-dependent manner. Bax expression in Group 2 (2.05 ± 1.04) was significantly lower than in the control group (8.63 ± 2.57;). Caspase-3 expression in Group 2 (0.49 ± 0.08) was markedly decreased compared with the control (5.10 ± 3.82), and a similar reduction was also observed in Group 3. Despite the absence of substantial changes in apoptotic markers, the reduction in cell viability suggests that Bevacizumab may act through alternative mechanisms. Conclusion: By targeting tumor vascularity, Bevacizumab may enhance the therapeutic efficacy of the BEP regimen in TGCT treatment. These findings support the potential role of Bevacizumab as an adjunctive agent in TGCT therapy and highlight the need for further validation through in vivo studies.

Diabetes mellitus (DM) has been linked to reproductive impairments. Medicinal plants have shown potential in alleviating diabetes-induced reproductive dysfunction in male. The Primary aim of the study was to assess the influence of an extract derived from Cassia fistula pod on reproductive hormone levels and testicular dysfunction in diabetic rats. A streptozotocin (STZ) dose (60 mg/kg b.wt.) was intraperitoneally (i.p.) injected to Wistar male rats to induce diabetes. 36 male rats were randomly assigned to six different groups: a healthy control group, a diabetic control group, three diabetic groups administered varying amount of Cassia fistula extract (100, 250, 500 mg/kg body weight per day), and a diabetic group receiving glibenclamide (5 mg/kg body weight per day). The treatment was given every day for 60 consecutive days. Levels of reproductive hormones including follicle-stimulating hormone (FSH), testosterone and luteinizing hormone (LH), along with oxidative stress in testicular tissue, were assessed. Histomorphometric and histopathological alterations in the testes were also examined. Diabetic control group exhibited significant decline in testicular weight, the testicular germ cells population, seminiferous tubular diameter and reproductive hormones like testosterone, FSH and LH as compared to control rats. Additionally, significant rise in lipid peroxidation (TBARS) alongside a simultaneous reduction in SOD and CAT activities as well as ascorbic acid and glutathione levels within the testicular tissues were observed compared to control rats. The administration of Cassia fistula extract or glibenclamide via oral route in diabetic rat led to improvements in serum insulin and reproductive hormone concentrations. Additionally, a reversal of histopathological and histomorphometric changes was noted relative to the diabetic reference group. Furthermore, the administration with the extract decreased lipid peroxidation and increased antioxidant levels in testicular tissue in comparison to the untreated diabetic rats. The outcomes of this research reveal that the hydroalcoholic extract from Cassia fistula pod exhibits significant antioxidant activities and can also modulate testicular dysfunction in diabetic male rats.

Germ cell tumours of the testis: 10-year survival data from a tertiary care centre in India

A single institutional study on survival and fertility outcomes in malignant ovarian germ cell tumour patients

Testicular microlithiasis (TM) is a pathological condition characterized by diffuse calcifications within the seminiferous tubules. Its clinical significance remains controversial. While some studies regard TM a benign imaging finding, others suggest potential associations with impaired fertility and an increased risk of testicular malignancy. This studyaims to systematically review the existing evidence regarding the relationship between TM and male fertility, incorporating both imaging and physiological perspectives. A systematic review was conducted in accordance with PRISMA guidelines. We searched the PubMed, Embase, and CNKI databases from 2003 to 2025 using the keywords "testicular microlithiasis" in combination with "fertility," "spermatogenesis," and "semen analysis." The inclusion criteria comprised clinical studies evaluating TM in the context of male fertility, including imaging techniques, physiological mechanisms, case-control studies, cohort studies, cross-sectional studies, and narrative reviews. Conference abstracts and animal studies were excluded from the review. After rigorous screening, 66 high-quality studies were included for synthesis and analysis. The prevalence of TM was significantly higher in infertile men (5.54%) compared to the fertile population (1.47%), reinforcing the potential link between TM and male infertility. Bilateral TM was strongly associated with reduced testicular volume, lower sperm retrieval rates, and abnormal semen parameters, indicating a more pronounced detrimental effect on reproductive function. Imaging and physiological data suggest that scrotal ultrasonography, used as the primary diagnostic tool, frequently reveals an elevated testicular resistive index (RI) in patients with TM. Concurrent findings include damage to the seminiferous tubules, aberrant expression of fertility-related genes such as KITLG and BMP7, and dysregulation of the testicular microenvironment, which may underlie impaired spermatogenesis. Additionally, in high-risk populations, TM has been linked to an increased risk of testicular germ cell tumors. Individuals with bilateral TM and testicular atrophy should be classified as high-risk and closely monitored through routine ultrasound evaluations. Assisted reproductive technologies, such as microdissection testicular sperm extraction (micro-TESE), may be necessary to optimize fertility outcomes. Future research should prioritize large-scale prospective cohort studies and interdisciplinary approaches to elucidate the molecular mechanisms underlying TM and to advance personalized treatment strategies.

Germline-competent embryonic stem (ES) cells have been successfully derived from mice and rats, but not from other species. Here we report the development of culture conditions for deriving ES cells from chickens and seven other avian species. Chicken ES cells express core pluripotency markers and can differentiate into cells of all embryonic germ layers, as well as extra-embryonic lineages. Notably, chicken ES cells contribute to high rates of chimerism when injected into chicken embryos and give rise to germ cells both in vitro and in ovo, confirming their germline competence. In addition, we demonstrated that ES cell self-renewal pathways are conserved among avian species, allowing ES cells from multiple avian species to be established using optimized chicken ES cell culture conditions. The establishment of authentic avian ES cells lays the groundwork for future applications in genetic engineering and the conservation of avian biodiversity.

Background: Genitourinary syndrome of menopause (GSM) is one of the common complications in women which occurs after post menopause. Women with genitourinary syndrome experiences vaginal dryness, irritation and dyspareunia regarding treatment, vaginal estrogen was given but new treatments are introduced because of its effectiveness and the side effects of hormones cause by traditional management. Professional experts continue to debate which therapy method works better between vaginal estrogen and laser therapy therefore current research needs to be established for a complete review of evidence. Objectives: This comprehensive review investigates how vaginal estrogen performs in relation to laser therapy when treating postmenopausal atrophy and also addresses their safety aspects. The review examines important symptomatic changes together with patient satisfaction and identifies safety complications of both interventions. Methodology: A comprehensive search of studies between 2015 and 2024 was conducted within PubMed along with Scopus and Web of Science and the Cochrane Library databases. Two types of studies including Randomized Controlled Trials (RCTs) and Cohort studies and Systematic Reviews evaluated vaginal estrogen versus laser therapy for Germ Cell Mastitis. Researchers evaluated symptom relief together with vaginal health index scores and histological changes and adverse events in their analyses. The researchers used PRISMA standards to perform both data extraction and risk of bias assessment. Results: Both vaginal estrogen and laser treatment show equivalent potential in subsiding GSM symptoms by decreasing vaginal dryness together with dyspareunia and urinary discomfort. Maximum symptom relief was witnessed more in laser therapy as compared to estrogen therapy. People expressed equal satisfaction with GSM treatment when using laser therapy or vaginal estrogen although laser therapy demanded multiple procedures at a higher initial expense. Users of both laser therapy and vaginal estrogen experienced low frequencies of adverse events yet laser treatment resulted in increased reports of immediate discomfort and localized skin irritation. Conclusion: The treatment options of vaginal estrogen and laser therapy provide effective relief from GSM symptoms without causing significant side effects. Laser therapy stands as a suitable non-hormonal treatment option after estrogen in patients which are recommended by doctors to avoid hormonal treatments due to medical reasons. Additional research needs to provide detailed performance guidelines that help decide which therapy method is more suitable.

piRNA biogenesis occurs in the intermitochondrial cement (IMC) in mammalian germ cells. The mechanisms by which IMC components engage mitochondria to form an efficient piRNA biogenesis machinery remain elusive. Here, we demonstrate that PIWI proteins orchestrate the assembly and disassembly of the piRNA biogenesis machinery in mice. The mitochondrial-anchored protein ASZ1 specifically interacts with PIWIL2 and recruits PIWIL2 to IMC granules. Sequentially, piRNAs competitively bind PIWIL2, leading to ASZ1-PIWIL2 dissociation. In fetal male germ cells, ASZ1-PIWIL2-TDRD1 forms a seed complex to initiate the assembly of the piRNA biogenesis machinery. During postnatal meiosis, the TDRKH-PIWIL1-TDRD1 complex synergizes with the ASZ1-PIWIL2-TDRD1 complex to induce substantial IMC assembly and pachytene piRNA biogenesis through TDRD1-mediated phase separation. PIWI proteins act as bridges, tethering non-mitochondrial proteins to mitochondrial-anchored proteins in IMC granules with the assistance of TDRD1. Together, our findings establish the pivotal role of PIWI proteins in governing the spatiotemporal dynamics of piRNA biogenesis machinery during mammalian spermatogenesis.

Mammalian spermatogenesis comprises three phases: the mitotic phase of spermatogonia (involving self-renewal and proliferation), the meiotic phase of spermatocytes (producing haploid round spermatids), and the spermiogenic phase (transforming round spermatids into spermatozoa). This process depends critically on maintaining a normal transcriptome and proteome. While recent studies demonstrated that conditional knockout of Exosc10 in male germ cells prior to meiosis disrupts meiosis, causing spermatogenic defects and male infertility, the role of EXOSC10 in spermatogonial maintenance remained unknown. This study reveals the critical role of EXOSC10 in maintaining mouse spermatogonia. Knockout of Exosc10 in embryonic (E15.5) male germ cells using Ddx4-Cre mice disrupts spermatogonial maintenance. This is manifested by reduced germ cell proliferation, arrested spermatogenesis, failed sperm production, and consequent male infertility. Transcriptomic and proteomic analyses confirmed that Exosc10 deficiency disrupts the expression of genes and proteins associated with spermatogenesis, ribosome biogenesis, germline stem cell maintenance, and regulation of reproductive processes, thereby impairing spermatogonial maintenance and blocking spermatogenesis. In summary, this study highlights that EXOSC10 safeguards normal sperm production and male fertility by maintaining the transcriptome and proteome essential for spermatogenesis, particularly at the spermatogonial stage.

BackgroundThe endoscopic endonasal approach (EEA) is the mainstay of resection for lesions in the retroinfundibular area and the prepontine and interpeduncular cisterns. Owing to the anatomical barrier of structures such as the pituitary gland (PG)/pituitary stalk (PS), dorsum sellae (DS) and posterior clinoid process (PCPs), sufficient tumour resection often requires displacement of the pituitary gland and varying degrees of bony resection.MethodsWe retrospectively studied the clinical data of 23 patients, from June 2016 to February 2023,who underwent endoscopic endonasal intradural pituitary gland transposition (PGT) as well as dorsectomy and posterior clinoidectomy for the treatment of lesions involving the retroinfundibular area, prepontine cistern and interpeduncular cisterns. Outcomes, including postoperative complications and the extent of tumour resection (EOR), were evaluated.ResultsAmong the 23 patients with tumours, 16 had craniopharyngiomas, 3 had germ cell tumours, 2 had epidermoid cysts, and 2 had gliomas. Fifteen patients underwent unilateral PGT and ipsilateral dorsectomy, and 8 patients underwent ipsilateral posterior clinoidectomy. Ten patients with visual impairment improved, and none of the patients experienced cranial nerve palsy postoperatively. Fourteen patients developed hypopituitarism, and 8 patients experienced diabetes insipidus (DI) postoperatively, 6 and 4 of theses patients recovered after 2–4 weeks of replacement therapy. Twelve patients with intraoperative high-flow CSF leakage underwent an average of 7 days of early postoperative lumbar drain (LD). Among them, 4 patients developed an infection, which was cured by 10 days of antibiotic treatment combined with LD. None of the patients experienced constant CSF leakage at the discharge. Gross total resection (GTR) was achieved in 19 tumour patients, and near-total resection (NTR) was achieved in 4 patients. The average follow-up period was 26 months, and magnetic resonance imaging (MRI) revealed no tumour recurrence in 22 patients.ConclusionTumours of the retroinfundibular area, prepontine and interpeduncular cisterns can be safely removed via the PGT technique. The intradural PGT technique combined with flexible dorsectomy and posterior clinoidectomy has obvious advantages, including less intraoperative bleeding, more effective pituitary transposition, and good preservation of pituitary function. Owing to the complexity of these regions, this technique should be performed by experienced endoneurosurgeons.

Comparing incidence patterns over time and between populations stimulates aetiological research and informs health policy. With this report, we provide the first comprehensive assessment and interpretation of 40 years of childhood cancer registration data and observed incidence patterns and time trends in Germany. We identified all incident childhood cancer cases diagnosed before the age of 15 years between 1980 and 2019 from the German Childhood Cancer Registry (N = 65,163) and examined incidence patterns and temporal trends. Over the entire period (1980-2019), boys were more frequently diagnosed than girls, children aged <5 years had the highest age-specific incidence rates and age-standardised incidence rates (ASR) were highest for leukaemias and CNS tumours. Trend analyses indicated a statistically significant increase in ASRs for childhood cancer overall (from 122.8/million in 1980-1989 to 173.4/million in 2010-2019) as well as across diagnostic groups and age groups. The steepest increase (on average 4.9% per annum for all cancer diagnoses combined) occurred in the initial years of registration (1980-1987), mostly driven by the sharp increase in the reporting of CNS tumours diagnoses, soft tissue sarcoma and germ cell tumours. Since the 1990s, temporal patterns were more heterogeneous across diagnostic groups; yet overall, less pronounced than during the build-up phase of the registry. Various factors have influenced the observed incidence patterns in Germany over the 40-year registration period. The steep increase in ASRs during the early years is primarily attributable to improvements in case reporting and registration. Explanations for the more recent temporal patterns remain speculative.

Germ cell tumors (GCT) in men usually arise in the gonads, presenting as a testicular mass. GCT may rarely involve the gastrointestinal tract due to metastasis from the testicular tumor. GCT arising from an undescended testis and presenting primarily with gastrointestinal symptoms is extremely rare. We hereby present a primary testicular seminoma in a 51-year-old gentleman, presenting with gastrointestinal symptoms. Sigmoidoscopy showed a large ulcero-infiltrative growth (7 × 6 × 3 cm) in the cecum and proximal ascending colon. The growth was biopsied with a clinical suspicion of a primary colonic adenocarcinoma. The biopsy showed infiltration by a seminoma. A thorough clinicoradiological evaluation revealed right cryptorchidism in the patient. He later underwent right hemicolectomy which revealed an adherent remnant cryptorchid testis at ileocecal junction and colonic infiltration by seminoma. Though challenging to diagnose seminoma at an unusual site, accurate biopsy diagnosis can play a decisive role in planning the timely surgery and adjuvant chemotherapeutic options.

Dermoid cyst (cystic teratoma) is a benign germ cell tumour showing well differentiated derivatives of all three germs cell layers. Ovaries remain the commonest site. Paravaginal dermoid cyst is a rare occurrence. A 48years’ female presented with paravaginal cyst, (9.11x7) cm. The diagnosis of a suspected ovarian tumor was made and an exploratory laparotomy was done. On dissection, the lower margin could not be identified. So lower limit of the cyst was dissected through vaginal approach. Transvaginal excision of dermoid cyst under anaesthesia remains treatment of choice. Retrospective diagnosis on histopathological examination remains confirmatory as it may be missed on sonography if teeth are not present in dermoid cyst. Bangladesh J Obstet Gynaecol, 2024; Vol. 39(2): 120-123

Medicinal plants remain central to traditional healthcare, yet their increasing integration into modern pharmacology necessitates robust toxicological evaluation. Origanum majorana L. (sweet marjoram), widely used in culinary and folk medicine, contains diverse secondary metabolites with both therapeutic and potential genotoxic activities. Despite its popularity, systematic in vivo and in vitro safety assessments remain limited. This study aimed to comprehensively evaluate the acute oral toxicity, cytotoxicity, and genotoxicity of O. majorana methanolic extract, providing baseline toxicological data to support its safe traditional use and potential pharmaceutical applications. The methanol extract of O. majorana leaves was tested in NIH-3T3 fibroblasts for cytotoxicity and genotoxicity. In vivo acute oral toxicity was assessed in rats according to OECD Guideline 420, with animals monitored over 14 days for clinical signs, hematological and biochemical alterations, and histopathological changes. The extract preserved fibroblast viability above 90% across all tested concentrations (10-200 µg/mL), indicating absence of cytotoxicity. However, comet and micronucleus assays revealed dose-dependent DNA damage, suggesting genotoxic potential at higher exposures. In vivo, no mortality or overt systemic toxicity was observed at doses up to 2000 mg/kg. Hematological analyses showed immunomodulatory shifts (increased neutrophils and monocytes, reduced eosinophils), while biochemical profiles indicated hepatoprotective and cardioprotective effects, with reduced ALT, AST, and LDH levels. Histopathological evaluation revealed only mild, focal changes consistent with adaptive rather than irreversible responses. O. majorana extract demonstrates a favorable acute safety profile with preserved hepatic and renal function, hematological modulation, and absence of in vitro cytotoxicity. Nevertheless, dose-dependent genotoxicity warrants caution for concentrated formulations. According to GHS classification, the extract aligns with Category 5 (acute oral toxicity, lowest hazard) and Category 2 (germ cell mutagenicity). These findings underscore the importance of dose management and further long-term genotoxicity studies before translational applications in nutraceutical or biomedical fields.

Primordial germ cells (PGCs) are common precursors of all male and female germline cells. PGCs arise in peri-implantation mammalian embryos and become gender-specific germ cell precursors upon sexual differentiation of the gonadal anlage. The in vitro model commonly known as PGC-Like Cells (PGCLCs), generated from human pluripotent stem cells, is a useful surrogate of the human embryonic PGCs, providing a unique opportunity to explore human gametogenesis in vitro. The protocol presented here supports long-term in vitro expansion of human PGCLCs. Freshly isolated PGCLCs are maintained initially on a STO feeder layer and then expanded in a feeder-free condition on basement membrane extract. The long-term culture PGCLCs (LTC-PGCLCs) can be Fluorescence-Activated Cell Sorting (FACS)-enriched as CD38-positive cells and are readily amplified to tens of millions of cells as pure, feeder-free, and serum-free monotonous culture without apparent limitations such as senescence. It is practically feasible to obtain a pure population of more than 1 million human PGCLCs from a few thousand freshly isolated PGCLCs. The human LTC-PGCLC cell culture is a useful and convenient in vitro model to study human germ cell biology and differentiation into the downstream germline cells.

CRISPR-Cas9-based editing in germ cells like PGCs, spermatogonial stem cells, oocytes, and early embryos can poten tially correct heritable genetic disorders, preventing their transmission to future generations. Additionally, CRISPR based gene editing in germ cells can enhance fertility by repairing mutations linked to infertility. Despite its potential, germline editing presents significant challenges like off-target effects, unintended mutations, and mosaicism, raising concerns about safety and long-term consequences. Advances in base and prime editing techniques aim to improve precision and reduce unwanted mutations. Ongoing research focuses on enhancing editing efficiency, understanding the implications of heritable changes, and developing ethical frameworks to govern its use. This review emphasizes genome editing in germ cells to revolutionize animal breeding, ensuring more sustainable agricultural practices and long-term benefits for society. As the field progresses, balancing scientific innovation with ethical responsibility will be crucial in determining the future of CRISPR-based germline editing.