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The Biochemical Journal Dec 2022Reproductive success of metazoans relies on germ cells. These cells develop early during embryogenesis, divide and undergo meiosis in the adult to make sperm and... (Review)
Review
Reproductive success of metazoans relies on germ cells. These cells develop early during embryogenesis, divide and undergo meiosis in the adult to make sperm and oocytes. Unlike somatic cells, germ cells are immortal and transfer their genetic material to new generations. They are also totipotent, as they differentiate into different somatic cell types. The maintenance of immortality and totipotency of germ cells depends on extensive post-transcriptional and post-translational regulation coupled with epigenetic remodeling, processes that begin with the onset of embryogenesis [1, 2]. At the heart of this regulation lie germ granules, membraneless ribonucleoprotein condensates that are specific to the germline cytoplasm called the germ plasm. They are a hallmark of all germ cells and contain several proteins and RNAs that are conserved across species. Interestingly, germ granules are often structured and tend to change through development. In this review, we describe how the structure of germ granules becomes established and discuss possible functional outcomes these structures have during development.
Topics: Male; Animals; Semen; Oocytes; Germ Cells; Cytoplasm; Ribonucleoproteins
PubMed: 36534469
DOI: 10.1042/BCJ20210815 -
Biochemical Society Transactions Oct 2022Animals constantly encounter environmental and physiological stressors that threaten survival and fertility. Somatic stress responses and germ cell arrest/repair... (Review)
Review
Animals constantly encounter environmental and physiological stressors that threaten survival and fertility. Somatic stress responses and germ cell arrest/repair mechanisms are employed to withstand such challenges. The Caenorhabditis elegans germline combats stress by initiating mitotic germ cell quiescence to preserve genome integrity, and by removing meiotic germ cells to prevent inheritance of damaged DNA or to tolerate lack of germline nutrient supply. Here, we review examples of germline recovery from distinct stressors - acute starvation and defective splicing - where quiescent mitotic germ cells resume proliferation to repopulate a germ line following apoptotic removal of meiotic germ cells. These protective mechanisms reveal the plastic nature of germline stem cells.
Topics: Animals; Caenorhabditis elegans; Cell Survival; Germ Cells; Cell Division; Caenorhabditis elegans Proteins
PubMed: 36196981
DOI: 10.1042/BST20220878 -
Traffic (Copenhagen, Denmark) Sep 2019Germ granules are hallmarks of all germ cells. Early ultrastructural studies in Drosophila first described these membraneless granules in the oocyte and early embryo as... (Review)
Review
Germ granules are hallmarks of all germ cells. Early ultrastructural studies in Drosophila first described these membraneless granules in the oocyte and early embryo as filled with amorphous to fibrillar material mixed with RNA. Genetic studies identified key protein components and specific mRNAs that regulate germ cell-specific functions. More recently these ultrastructural studies have been complemented by biophysical analysis describing germ granules as phase-transitioned condensates. In this review, we provide an overview that connects the composition of germ granules with their function in controlling germ cell specification, formation and migration, and illuminate these mysterious condensates as the gatekeepers of the next generation.
Topics: Animals; Cytoplasmic Granules; Drosophila Proteins; Drosophila melanogaster; Gametogenesis; Germ Cells; RNA
PubMed: 31218815
DOI: 10.1111/tra.12674 -
Current Opinion in Insect Science Apr 2022Germ plasm is a substance capable of driving naive cells toward the germ cell fate. Germ plasm has had multiple independent origins, and takes on diverse forms and... (Review)
Review
Germ plasm is a substance capable of driving naive cells toward the germ cell fate. Germ plasm has had multiple independent origins, and takes on diverse forms and functions throughout animals, including in insects. We describe here recent advances in the understanding of the evolution of germ plasm in insects. A major theme that has emerged is the complex and convoluted interactions of germ plasm with symbiotic bacteria within the germline, including at the very origin of oskar, the gene required for assembling germ plasm in insects. Major advancements have also been made in understanding the basic molecular arrangement of germ plasm in insects. These advances demonstrate that further analysis of insect germ plasm will be fruitful in illuminating diverse aspects of evolutionary and developmental biology.
Topics: Animals; Drosophila Proteins; Germ Cells; Insecta
PubMed: 35123121
DOI: 10.1016/j.cois.2022.100883 -
Sexual Development : Genetics,... 2022Whether to produce sperm or eggs is the most basic and important choice from the perspective of germ cell development and differentiation. However, the induction... (Review)
Review
BACKGROUND
Whether to produce sperm or eggs is the most basic and important choice from the perspective of germ cell development and differentiation. However, the induction mechanism has not received much attention until relatively recently. This is because the issue of sexual differentiation has generally been considered a theme of somatic cells to make a testis or ovary. Basically, the sex of individual somatic cells and germ cells matches. Therefore, the sex of germ cells is thought to follow the sex of somatic cells once determined. However, researchers realized that a big, open question remained: What somatic cell signals actually induce the sexual differentiation of germ cells and what is the sex determinant in germ cells?
SUMMARY
In vitro experiments demonstrated that 2 somatic signals (BMP and RA) act directly on germ cells to induce oogonia. Therefore, these 2 signals may be referred to as oogonia inducers. From the viewpoint of germ cells, an independent experiment identified SMAD4 and STRA8, which are directly downstream of BMP and RA, respectively, acting in germ cells as female determinants. However, what about male? If these factors are female determinants, their absence may result in the induction of spermatogonia. This may be true in vivo because germ cells enter a male pathway if they do not receive these signals even in the ovary. However, this has not been confirmed in an in vitro culture system. There should be signals required for germ cells to enter a male pathway.
KEY MESSAGES
The important message is that although testis-specific factors secreted from the testis are considered to include male-inducing factors for germ cells, this may not be the case, and the male-inducing factor, if it exists, also exists in the ovary.
PubMed: 35263749
DOI: 10.1159/000520976 -
Development (Cambridge, England) Jan 2023A hallmark of all germ cells is the presence of germ granules: assemblies of proteins and RNA that lack a delineating membrane and are proposed to form via condensation....
A hallmark of all germ cells is the presence of germ granules: assemblies of proteins and RNA that lack a delineating membrane and are proposed to form via condensation. Germ granules across organisms share several conserved components, including factors required for germ cell fate determination and maintenance, and are thought to be linked to germ cell development. The molecular functions of germ granules, however, remain incompletely understood. In this Development at a Glance article, we survey germ granules across organisms and developmental stages, and highlight emerging themes regarding granule regulation, dynamics and proposed functions.
Topics: Animals; Caenorhabditis elegans; Germ Cell Ribonucleoprotein Granules; Germ Cells; RNA-Binding Proteins; RNA; Cytoplasmic Granules
PubMed: 36715566
DOI: 10.1242/dev.201037 -
Advances in Experimental Medicine and... 2016Germ cell tumors (GCTs) are malignant cancers that arise from embryonic precursors known as Primordial Germ Cells. GCTs occur in neonates, children, adolescents and... (Review)
Review
Germ cell tumors (GCTs) are malignant cancers that arise from embryonic precursors known as Primordial Germ Cells. GCTs occur in neonates, children, adolescents and young adults and can occur in the testis, the ovary or extragonadal sites. Because GCTs arise from pluripotent cells, the tumors can exhibit a wide range of different histologies. Current cisplatin-based combination therapies cures most patients, however at the cost of significant toxicity to normal tissues. While GWAS studies and genomic analysis of human GCTs have uncovered somatic mutations and loci that might confer tumor susceptibility, little is still known about the exact mechanisms that drive tumor development, and animal models that faithfully recapitulate all the different GCT subtypes are lacking. Here, we summarize current understanding of germline development in humans and zebrafish, describe the biology of human germ cell tumors, and discuss progress and prospects for zebrafish GCT models that may contribute to better understanding of human GCTs.
Topics: Animals; Cell Differentiation; Disease Models, Animal; Humans; Neoplasms, Germ Cell and Embryonal; Zebrafish
PubMed: 27165367
DOI: 10.1007/978-3-319-30654-4_21 -
Andrology Jan 2015
Topics: Animals; Biomedical Research; Cooperative Behavior; Humans; International Cooperation; Male; Neoplasms, Germ Cell and Embryonal; Prognosis; Risk Factors; Testicular Neoplasms
PubMed: 25711179
DOI: 10.1111/andr.12010 -
Annals of Oncology : Official Journal... Oct 2018
Topics: Aftercare; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Europe; Female; Humans; Incidence; Long-Term Care; Medical Oncology; Neoplasm Staging; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Ovariectomy; Ovary; Societies, Medical; Survivorship; Treatment Outcome
PubMed: 29697741
DOI: 10.1093/annonc/mdy001 -
The Lancet. Oncology Apr 2016Management of paediatric extracranial germ-cell tumours carries a unique set of challenges. Germ-cell tumours are a heterogeneous group of neoplasms that present across... (Review)
Review
Management of paediatric extracranial germ-cell tumours carries a unique set of challenges. Germ-cell tumours are a heterogeneous group of neoplasms that present across a wide age range and vary in site, histology, and clinical behaviour. Patients with germ-cell tumours are managed by a diverse array of specialists. Thus, staging, risk stratification, and treatment approaches for germ-cell tumours have evolved disparately along several trajectories. Paediatric germ-cell tumours differ from the adolescent and adult disease in many ways, leading to complexities in applying age-appropriate, evidence-based care. Suboptimal outcomes remain for several groups of patients, including adolescents, and patients with extragonadal tumours, high tumour markers at diagnosis, or platinum-resistant disease. Survivors have significant long-term toxicities. The challenge moving forward will be to translate new insights from molecular studies and collaborative clinical data into improved patient outcomes. Future trials will be characterised by improved risk-stratification systems, biomarkers for response and toxic effects, rational reduction of therapy for low-risk patients and novel approaches for poor-risk patients, and improved international collaboration across paediatric and adult cooperative research groups.
Topics: Adolescent; Adult; Biomarkers, Tumor; Child; Female; Humans; Male; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Pediatrics; Survivors; Testicular Neoplasms
PubMed: 27300675
DOI: 10.1016/S1470-2045(15)00545-8