Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Germ Cells”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 217 records · Page 12Linked to original sources
PubMed1991

Effect of an acute exposure of rat testes to gamma rays on germ cells and on Sertoli and Leydig cell functions.

Germ cells and Sertoli and Leydig cell functions were studied from 7 to 180 days after an acute exposure of 2-month-old rat testes to 9 Gy of gamma rays. Body weight, testis and epididymal weights were recorded. Sertoli cell parameters (androgen-binding protein, ABP, in caput epididymis and plasma follicle stimulating hormone, FSH) and Leydig cell parameters (plasma luteinizing hormone, LH, testosterone and prostate and seminal vesicle weights) were determined together with the number of germ cells and Sertoli cells. Irradiation did not affect body weight but significantly reduced testicular and epididymal weights from day 7 and day 15 post-irradiation respectively. The cells killed by irradiation were mainly spermatogonia and preleptotene spermatocytes engaged in replicating their DNA at the time of exposure, but all spermatocytes seemed damaged as they gave abnormal descendent cells. By day 34, only elongated spermatids remained in a few tubules and thereafter very little regeneration of the seminiferous epithelium occurred, except for one rat which showed a better regeneration. Levels of ABP decreased by day 15 when the germ cell depletion had reached the pachytene spermatocytes, whereas FSH and LH levels rose when the number of elongated spermatids decreased. Levels of testosterone and the weight of the seminal vesicles did not change; occasionally, the prostate weight was slightly reduced. These results support our hypothesis that pachytene spermatocytes and elongated spermatids are involved in influencing some aspects of Sertoli cell function in the adult rat.

Animals↗
PubMed2005

Contribution of germ cells to the differentiation and maturation of the ovary: insights from models of germ cell depletion.

In mammals, the role played by germ cells in ovarian differentiation and folliculogenesis has been the focus of an increasing number of studies over the last decades. From these studies, it has emerged that bidirectional communication between germ cells and surrounding companion cells is required as soon as the initial assembly of follicles. Models of germ cell depletion that arise from both spontaneous and experimentally induced mutations as well as irradiation or chemical treatments have been helpful in deciphering the role played by germ cells from the onset of ovarian differentiation onward. This review reports current knowledge and proposes novel hypotheses that can be formulated from these models about the contribution of germ cells to ovarian differentiation and folliculogenesis. In particular, it promotes the idea that the influence of germ cells on companion somatic cells varies within both ovarian differentiation and folliculogenesis.

Animals↗
PubMedDate not supplied

HLA class I antigens are expressed by Sertoli cells of intratubular germ cell neoplasia.

Five frozen samples from seminomas and one from a combined seminoma/embryonal carcinoma and surrounding tissue were examined for the presence of HLA class I molecules using an antibody directed against a monomorphic epitope of the 45 kDa long chain of HLA-A, -B and -C molecules. Only tubules with intratubular germ cell neoplasia stained positively, while normal seminiferous tubules and invasive tumor cells stained negatively. The immunohistology with anti-HLA class I antibody was compared to that with anti-beta 2-microglobulin antibody which reacts with the light nonpolymorphic chain of all HLA class I molecules. Immunohistology with these two antibodies was indistinguishable. This result combined with immunohistology using anti-PLAP indicates that the stained cells are Sertoli cells. The results are discussed in relation to lymphocytic infiltration and immune surveillance of seminomas.

Alkaline Phosphatase↗
PubMed1997

Germ cell nuclear antigen (GCNA1) expression does not require a gonadal environment or steroidogenic factor 1: examination of GCNA1 in ectopic germ cells and in Ftz-F1 null mice.

The germ cell lineage is first recognized as a population of mitotically proliferating primordial germ cells that migrate toward the gonadal ridge. Shortly after arriving at the gonadal ridge, the germ cells begin to initiate a commitment to gamete production in the developing gonad. The mechanisms controlling this transition are poorly understood. We recently reported that a mouse germ cell nuclear antigen 1 (GCNA1) is initially detected in both male and female germ cells as they reach the gonad at 11.5 days postcoitum (dpc). GCNA1 is continually expressed in germ cells through all stages of gametogenesis until the diplotene/dictyate stage of meiosis I. Since GCNA1 expression commences soon after primordial germ cells arrive at the gonadal ridge, we wanted to determine whether the gonadal environment was essential for induction of GCNA1 expression. By examining GCNA1 expression in germ cells that migrate ectopically into the adrenal gland, we determined that both the gonadal and adrenal gland environments allow GCNA1 expression. We also examined GCNA1 expression Ftz-F1 null mice, which were born lacking gonads and adrenal glands. During embryonic development in the Ftz-F1 null mice, the gonad and most germ cells undergo apoptotic degeneration at about 12.5 dpc. While most of the germ cells undergo apoptosis without expressing GCNA1, a few surviving germs cells, especially outside the involuting gonad clearly express GCNA1. Thus, although the Ftz-F1 gene is essential for gonadal and adrenal development, induction of GCNA1 expression in germ cells does not require Ftz-F1 gene products. The finding that germ cell GCNA1 expression is not restricted to the gonadal environment and is not dependent on the Ftz-F1 gene products suggests that GCNA1 expression may be initiated in the germ cell lineage by autonomous means.

Animals↗
PubMed2002

Clinical pattern and therapeutic results achieved in 1490 patients with germ-cell tumours of the testis: the experience of the Spanish Germ-Cell Cancer Group (GG).

OBJECTIVE: To describe the clinical characteristics and treatment results obtained with the application of a homogeneous treatment protocol in 1490 patients with germ-cell tumours (GCT) registered in the 55 hospitals belonging to the Spanish Germ-Cell Cancer Group (GG) during the period between January 1994 and April 2001. METHODS: In general, surveillance was the common policy for stage I patients without local poor prognosis factors, whereas they received adjuvant chemotherapy in case those factor were present. Chemotherapy schedules used in advanced cases were cisplatin and etoposide (EP) for seminoma and BEP or BOMP-EPI in non-seminoma, according to whether the patient was in the good or poor prognosis IGCCCG (International Germ-Cell Cancer Collaborative Group) group. Excision of residual masses was mandatory in non-seminomatous germ-cell tumour (NSGCT). RESULTS: Initial local symptomatology was increased testis size in 90% of cases. Sonography was an excellent diagnostic tool to suggest tumour. Non-seminoma (64.2%) was more frequent than seminoma (35.8%). Approximately 10% had the antecedent of cryptorchidism. Non-seminoma patients were 7 years younger than seminoma. Right testis was involved predominantly. Pre-orchidectomy tumour markers were elevated in 21% of seminoma (betaHGC) and 79% in non-seminoma (alphaFP and/or betaHGC). Scrotum violation occurred in only 1.8%. There were significant differences among stage I and the IGCCCG prognosis groups related to a longer interval between the first symptom and orchiectomy. Eighteen percent of non-seminomatous germ-cell tumour belonged to the poor prognosis IGCCCG group. With a median follow-up to 33 months, this series has achieved a 3 year overall survival of 98% for seminoma and 94% for non-seminoma. Only 10% of excised residual masses present after chemotherapy contained malignant cells. CONCLUSION: Spanish GCT have a similar clinical pattern to that described in the other occidental countries except for a slight increased proportion of non-seminoma upon seminoma. Co-operative groups as GG are unique structures to obtain quick and wide experience on the treatment of testis tumours, contributing to achieve a high cure rate.

Adolescent↗
PubMed2001

Long-term quality of life and neuropsychologic functioning for patients with CNS germ-cell tumors: from the First International CNS Germ-Cell Tumor Study.

This study evaluated the quality of life and neuropsychologic functioning among patients enrolled between 1989 and 1993 in the First International CNS Germ-Cell Tumor Study. Quality-of-life questionnaires (Short Form-36 or Child Health Questionnaire) were completed on 43 patients at median follow-up of 6.1 years after diagnosis (range, 4.5-8.8 years), and intellectual and academic testing was performed on 22 patients. Psychosocial and physical functioning of patients aged 19 years and older at follow-up was within the average range, whereas the same functioning for patients aged 18 years and younger, as reported by their parents at follow-up, was low average and borderline, respectively. Overall psychosocial and physical health summary scores were positively correlated with age at diagnosis for both groups combined. Those who received CNS radiation therapy (n = 29) reported significantly worse physical health, but similar psychosocial health, compared with those treated without radiation. Neuropsychologic testing indicated full-scale and verbal IQ, reading, spelling, and math skills in the average range, and performance IQ in the low average range. Intelligence and math skills were positively correlated with age at diagnosis. Those with germinomas significantly outperformed those with nongerminomatous/ mixed tumors on all neuropsychological measures administered. Younger patients diagnosed with CNS germ-cell tumors are at increased risk for psychosocial and physical problems as well as neuropsychologic deficits. Exposure to irradiation adversely affects overall physical functioning, whereas tumor pathology appears to be a salient neurocognitive risk factor. Collaborative and randomized studies are required to further elucidate the late effects arising from factors such as age at diagnosis, tumor histology, level of irradiation therapy, and chemotherapy toxicity among these young and potentially curable patients.

Adolescent↗
PubMed2002

The status of high-dose chemotherapy with hematopoietic stem cell transplantation in germ cell tumor patients.

BACKGROUND AND OBJECTIVES: Germ cell tumors (GCTs) are very chemosensitive cancers, in which high-dose chemotherapy (HDCT) has been investigated as salvage therapy or as first-line treatment in poor prognosis patients. This paper presents an update of available information in order to define the status of HDCT in GCT patients. INFORMATION SOURCES: The authors have been working in this field, contributing to international clinical trials and to peer-reviewed journals with original papers. The material examined in this review includes articles published in journals covered by MedLine, reviews from journals with high impact factor, and unpublished data from the European Group for Blood and Marrow Transplantation (EBMT) registry. STATE OF THE ART AND PERSPECTIVES: The delineation of prognostic factors associated with a poor probability of survival after HDCT contributed to the selection of patients who are likely to get an advantage from HDCT and those who should be spared from dose-intensive treatment. HDCT as first-line therapy for poor prognosis GCT (IGCCCG classification), and in a salvage setting in good risk GCT (prognostic index from Beyer et al.77), has been associated with a very high rate of complete remissions and long-term disease-free survivors. However, it is important to wait for the results of ongoing randomized trials for the validation of these findings. Other strategies are required for patients with refractory GCTs. Several new treatment options are currently emerging for this subset of patients.

Adult↗
PubMed2006

Avian germplasm preservation: embryonic stem cells or primordial germ cells?

Presently, avian genetic resources are best maintained as living collections of birds. Unfortunately, these stocks have been under constant pressure to be destroyed because of the decline in the number of Poultry Science Departments and pressures to cut costs at land grant institutions. Cryopreservation of semen is often suggested as a means to bank avian germplasm. However, this is only applicable for single-gene traits and does not allow for full reconstitution of the genetics of the original line. Over the last 15 yr, advances in the manipulation of the early chick embryo, manipulation of primordial germ cells (PGC), and the culture of embryonic stem cells (ESC) suggests that cryopreservation of blastodermal cells, ESC, or PGC might offer a means to preserve the entire genome of highly selected, specialized stocks of poultry. Freezing each of these cell types is possible with varying degrees of efficiency. Similarly, the effectiveness of generating germ line chimeras using blastodermal cells, ESC, or PGC also varies greatly. Other factors that must be considered include the choice of the recipient lines to develop the germ line chimeras and the number of individuals needed to reconstitute the line. Finally, the low efficiency rate of reconstitution and the high cost associated with current technologies makes these approaches prohibitive. Significant challenges remain to be overcome before the entire genome of poultry stocks can be routinely cryoperserved and reconstituted.

Animals↗
PubMed2006

Germline transmission of genetically modified primordial germ cells.

Primordial germ cells (PGCs) are the precursors of sperm and eggs. In most animals, segregation of the germ line from the somatic lineages is one of the earliest events in development; in avian embryos, PGCs are first identified in an extra-embryonic region, the germinal crescent, after approximately 18 h of incubation. After 50-55 h of development, PGCs migrate to the gonad and subsequently produce functional sperm and oocytes. So far, cultures of PGCs that remain restricted to the germ line have not been reported in any species. Here we show that chicken PGCs can be isolated, cultured and genetically modified while maintaining their commitment to the germ line. Furthermore, we show that chicken PGCs can be induced in vitro to differentiate into embryonic germ cells that contribute to somatic tissues. Retention of the commitment of PGCs to the germ line after extended periods in culture and after genetic modification combined with their capacity to acquire somatic competence in vitro provides a new model for developmental biology. The utility of the model is enhanced by the accessibility of the avian embryo, which facilitates access to the earliest stages of development and supplies a facile route for the reintroduction of PGCs into the embryonic vasculature. In addition, these attributes create new opportunities to manipulate the genome of chickens for agricultural and pharmaceutical applications.

Animals↗
PubMed2002

Sertoli cell vacuolization and abnormal germ cell adhesion in mice deficient in an inositol polyphosphate 5-phosphatase.

The dynamic nature of cellular interactions during differentiation of germ cells and their translocation from the basement membrane to the lumen of the seminiferous tubules requires the existence of complex and well-regulated cellular adhesion mechanisms in the testis. Successful migration of the developing germ cells is characterized by dynamic breakage and reformation of cadherin-containing adherens junctions between the germ cells and Sertoli cells, the polarized somatic cells of the testis that support and nourish the developing gametes. Here, we demonstrate the accumulation of abnormally swollen, actin-coated, endosome-like structures that contain intact adherens junctions and stain positive for N-cadherin and beta-catenin in the Sertoli cell cytosol of mice deficient in Inpp5b, an inositol polyphosphate 5-phosphatase. Simultaneous to the formation of these abnormal structures, developing germ cells are prematurely released from the seminiferous epithelium and sloughed into the epididymis. Our results demonstrate a role for Inpp5b in the regulation of cell adhesion in the testis and in the formation of junctional complexes with neighboring cells, and they emphasize the important and essential role of phosphoinositides in spermatogenesis.

Animals↗
PubMed2001

Sequential detection of alphafetoprotein-bearing cells in blood stem cell fraction of germ cell tumour patients.

High-dose chemotherapy with peripheral blood stem cell (PBSC) transplantation in advanced germ cell tumour (GCT) patients is widely applied. The aims of this study were: (1) To examine the presence of alphafetoprotein (AFP) bearing tumour cells in PBSC harvests from advanced GCT patients obtained after multiple cycles of induction chemotherapy. (2) To determine whether induction chemotherapy contributed to in vivo purging of the tumour. We evaluated cryopreserved PBSC samples from 5 patients with advanced stage II/III AFP producing GCT. PBSC were separated after the first, second and third cycles of induction chemotherapy. Those samples were analysed using the nested reverse transcription polymerase chain reaction (RT-PCR) method to detect AFP mRNA. Although, in all patients, AFP mRNA was detected in PBSC samples after the first or second cycle of induction chemotherapy, but was not detected in 3 of 4 samples after the third cycle of chemotherapy. Although it is not clear whether tumour cells contaminating PBSC fraction contribute to disease relapse, PBSC harvested after at least 3 cycles of induction chemotherapy might be recommended to avoid such a possibility.

Adult↗
PubMed1989

[Differentiation of human germ cell tumor cells].

Human germ cell tumors are an excellent model for investigating the mechanism of human early embryogenesis as well as cellular differentiation. Three human EC cell lines, NCR-G 2, 3 and 4 were newly established from testicular mixed embryonal carcinomas in vitro, G3 and G4 cells were capable of somatic cell differentiation. The G3 cells demonstrated the most noticeable antigenetical changes with the administration of retinoic acid. SSEA-1 appeared on some cells whereas expression of HLA-A, B, C as well as 2H2, 2D7 and 5D4 antigens tended to be reduced in G3 cell line. 2H2, 2D7 and 5D4 antigens which we recently produced were immature human EC specific cell surface antigens, defined by mouse monoclonal antibodies, obtained immunization with G2 cells. The production of hCG, high molecular weight cytokeratin and intercellular matrices such as type IV collagen and laminin were inducible in G3 cells. Thus, G3 cells are thought to be one of the most pluripotent human EC cells. These findings clearly indicate that the EC cell lines we established provide an opportunity to study differentiation mechanism of human germ cell tumors and also human somatic cells.

Animals↗
PubMed2026

Overlapping genetic etiology of pediatric and adult germ cell tumors.

BACKGROUND: Germ cell tumors are heterogeneous neoplasms arising from primordial germ cells. Although genome-wide association studies have identified numerous susceptibility loci for adult testicular germ cell tumors, the heritable basis of pediatric testicular germ cell tumors and germ cell tumors that arise outside the testes remain poorly understood. METHODS: We conducted a multi-ancestry genome-wide association study of pediatric germ cell tumors, including 1927 cases from the Germ Cell Tumor Epidemiology Study and 10 601 controls. Cases were diagnosed with testicular (n = 678), ovarian (n = 441), intracranial (n = 435), and extragonadal (n = 373) germ cell tumor between the ages of 0 and 19 years. RESULTS: We identified 4 loci reaching genome-wide significance, including variants near BAK1 (chr 6: rs3831846), SPRY4 (chr 5: rs12515244), DMRT1 (chromosome [chr] 9: rs10815910), and DEPTOR (chr 8: rs13277786). Additional genome-wide statistically significant associations were identified in subgroup analyses, including 6 loci for intracranial germ cell tumors (rs2758612 [PMF1/BGLAP], rs9854760 [PLCL2], rs6851498 [KIT], rs11816992 on chromosome 10, rs3830273 [TFAM], and rs13054014 [LZTR1]), 1 locus for testicular germ cell tumor (rs1907702 [KITLG]), and 1 locus for males (rs4610628 [MAD1L1]). After Bonferroni correction, 18 of 78 previously reported testicular germ cell tumor loci were significantly associated with germ cell tumor overall or in at least 1 subgroup with a particularly strong correlation between testicular germ cell tumor and intracranial germ cell tumor effect estimates (rho = 0.63, P = 5.5 × 10-10). Expression quantitative trait locus (QTL) analyses identified candidate genes in the regions identified on chromosome 6 (BAK1, LINC003366, and ITPR3) and chromosome 8 (DEPTOR and RP11-760H22.2). CONCLUSIONS: Our data support a role for germline genetic variation in the development of germ cell tumors in locations outside the testes and highlight shared genetic architecture across age group and tumor location.

Humans↗
PubMed1995

Response to high-dose cisplatin and etoposide in advanced germ cell tumors in children: results of the Brazilian Germ Cell Tumor Study.

A trial was undertaken to assess the efficacy and toxicity of high-dose cisplatin and etoposide in children with newly diagnosed advanced malignant germ cell tumors. A total of eleven children and adolescents were treated with courses of high dose cisplatin 30 mg/m2/day and etoposide 120 mg/m2/day in five day cycles at 21 day intervals. There were eight girls and three boys, aged between 1 and 16 years (median: 120 months). Of nine unresectable tumors, six were in complete remission after three cycles and were completely resected. All patients are alive (median follow-up 17 months). Preliminary results shows that high dose cisplatin and etoposide is effective in controlling advanced malignant germ cell tumor.

Adolescent↗
PubMed2005

Paclitaxel-based high-dose chemotherapy with autologous stem cell rescue for relapsed germ cell cancer.

We evaluated the antitumor activity of tandem cycles of high-dose chemotherapy with autologous peripheral stem cell transplantation (aPSCT) in relapsed germ cell tumors by using high-dose paclitaxel, carboplatin, etoposide, and ifosfamide. Thirty-three patients were entered, and 31 underwent protocol therapy. Paclitaxel 350 mg/m2 (5 patients) or 425 mg/m2 (26 patients) by 24-hour continuous intravenous infusion was followed by 3 daily doses of carboplatin and either etoposide (cycle 1) or ifosfamide/mesna (cycle 2). The carboplatin dose had a calculated area under the curve of 7 mg-min/mL, and the daily dose of etoposide was 20 mg/kg (cycle 1). Ifosfamide 3 g/m2/d for 3 days (with mesna uroprotection) was substituted for etoposide in cycle 2. Each cycle was supported by granulocyte colony-stimulating factor-mobilized peripheral blood stem cells. Thirty-one patients were evaluable for response, toxicity, and long-term disease control. Two patients did not undergo aPSCT because of rapid disease progression. Nineteen patients received both cycles of aPSCT, 8 progressed after cycle 1, 3 refused the second cycle, and 1 died of fungal infection during cycle 1. Twelve patients remain relapse free at a median of 67 months from the initiation of therapy. Whereas the International Germ Cell Cancer Collaborative Group category at the time of initial diagnosis did not seem to predict outcome, the patient's probability of achieving durable remission was significantly associated with the Beyer prognostic score at the time of protocol entry. Regimens containing the most active agents in relapsed nonseminomatous germ cell tumors, including high-dose paclitaxel, are well tolerated and have promising activity even in patients with poor-risk features who do not achieve durable remissions with standard therapy. The Beyer prognostic system is a valuable predictor for patients undergoing aPSCT.

Adolescent↗
PubMed1997

In vivo analysis of germ cell apoptosis reveals the existence of stage-specific 'social' control of germ cell death in the seminiferous epithelium.

It has become clear in recent years that programmed cell death is regulated during development by signals from other cells. Nevertheless, compared to the 'social' control of cell proliferation, relatively little is known about the 'social' control of cell death in other systems. Since in a previous study we showed that induced germ cell apoptosis occurs at specific stages of the spermatogenic cycle, in this study we aimed to ascertain the existence of supracellular control of germ cell death during spermatogenesis. Therefore, the TUNEL technique has been used to analyse whether all of the different germ cell types are induced to die at these specific stages in animals injected intratesticularly with one of several inducers of apoptosis. Our findings suggest that all of the investigated agents trigger apoptosis in all the diverse progenies of germ cells existing at stages I, XII or XIV of the spermatogenic cycle. In contrast, at most other stages the number of apoptotic cells was similar to that found in control animals. These data are consistent with the existence of an intercellular control of germ cell death during spermatogenesis. We conclude that the seminiferous epithelium provides a suitable in vivo model to study the mechanisms underlying the 'social' control of apoptosis.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

Changes in protooncogene expression correlated with general and sex-specific differentiation in murine primordial germ cells.

Primordial germ cells (PGCs) of the mouse undergo key developmental transitions during embryonic days 12-15. On day 12 they complete migration into the gonads. They cease mitotic proliferation on day 13 and subsequently enter sex-specific pathways of development. The molecular mechanisms controlling these transitions are poorly understood, yet they are crucial to production of normal gametes later in life. We have used the polymerase chain reaction (PCR) to directly compare levels of expression of several protooncogenes proposed to be involved in control of cell proliferation and differentiation in proliferating and differentiating PCGs of both sexes over a 4 day time course. We report here that mRNA levels for nuclear protooncogenes c-myc, c-fos, and c-jun increase dramatically in both sexes from little or no detectable expression on day 12 to high expression on days 13-15. We observe c-kit message on day 12 in combined PGCs of both sexes, in female but not male PGCs on day 13, and in both sexes on day 14, c-kit mRNA is undetectable on day 15 in either sex, c-mos is not expressed at detectable levels on day 12 in either sex, but increases gradually in female PGCs to very high levels on day 15. In male PGCs, c-mos is expressed at high levels on days 13-15. Our results are consistent with a role for protooncogenes c-myc, c-fos and c-jun in mediating the initial differentiation of PGCs of both sexes that occurs upon colonization of the gonad. Because c-kit and c-mos are expressed differentially in male and female day 13-15 germ cells, they may play roles in initiating or mediating progress along the sex-specific pathways of development that PGCs embark upon at this time.

Animals↗