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ELife Nov 2022Recent studies show that pre-follicular mouse oogenesis takes place in germline cysts, highly conserved groups of oogonial cells connected by intercellular bridges that...
Recent studies show that pre-follicular mouse oogenesis takes place in germline cysts, highly conserved groups of oogonial cells connected by intercellular bridges that develop as nurse cells as well as an oocyte. Long studied in and insect gametogenesis, female germline cysts acquire cytoskeletal polarity and traffic centrosomes and organelles between nurse cells and the oocyte to form the Balbiani body, a conserved marker of polarity. Mouse oocyte development and nurse cell dumping are supported by dynamic, cell-specific programs of germline gene expression. High levels of perinatal germ cell death in this species primarily result from programmed nurse cell turnover after transfer rather than defective oocyte production. The striking evolutionary conservation of early oogenesis mechanisms between distant animal groups strongly suggests that gametogenesis and early embryonic development in vertebrates and invertebrates share even more in common than currently believed.
Topics: Female; Pregnancy; Mice; Animals; Drosophila; Oogenesis; Germ Cells; Oocytes; Gametogenesis
PubMed: 36445738
DOI: 10.7554/eLife.83230 -
Biomolecules Jun 2017Amyloids are traditionally considered pathological protein aggregates that play causative roles in neurodegenerative disease, diabetes and prionopathies. However,... (Review)
Review
Amyloids are traditionally considered pathological protein aggregates that play causative roles in neurodegenerative disease, diabetes and prionopathies. However, increasing evidence indicates that in many biological systems nonpathological amyloids are formed for functional purposes. In this review, we will specifically describe amyloids that carry out biological roles in sexual reproduction including the processes of gametogenesis, germline specification, sperm maturation and fertilization. Several of these functional amyloids are evolutionarily conserved across several taxa, including human, emphasizing the critical role amyloids perform in reproduction. Evidence will also be presented suggesting that, if altered, some functional amyloids may become pathological.
Topics: Amyloid; Animals; Female; Fertilization; Gametogenesis; Humans; Male; Reproduction; Spermatozoa; Zona Pellucida
PubMed: 28661450
DOI: 10.3390/biom7030046 -
Cells Jul 2019During gametogenesis and early embryonic development, the chromatin architecture changes dramatically, and both the transcriptomic and epigenomic landscape are... (Review)
Review
During gametogenesis and early embryonic development, the chromatin architecture changes dramatically, and both the transcriptomic and epigenomic landscape are comprehensively reprogrammed. Understanding these processes is the holy grail in developmental biology and a key step towards evolution. The 3D conformation of chromatin plays a central role in the organization and function of nuclei. Recently, the dynamics of chromatin structures have been profiled in many model and non-model systems, from insects to mammals, resulting in an interesting comparison. In this review, we first introduce the research methods of 3D chromatin structure with low-input material suitable for embryonic study. Then, the dynamics of 3D chromatin architectures during gametogenesis and early embryonic development is summarized and compared between species. Finally, we discuss the possible mechanisms for triggering the formation of genome 3D conformation in early development.
Topics: Animals; Chromatin; Embryonic Development; Gametogenesis; Genome; Humans; Molecular Conformation; Single-Cell Analysis
PubMed: 31362461
DOI: 10.3390/cells8080788 -
The International Journal of... 2015Cell death is prominent in gametogenesis and shapes and sculpts embryos. In non-mammalian embryos one sees little or no cell death prior to the maternal-zygotic... (Review)
Review
Cell death is prominent in gametogenesis and shapes and sculpts embryos. In non-mammalian embryos one sees little or no cell death prior to the maternal-zygotic transition, but, in mammalian embryos, characteristic deaths of one or two cells occur at the end of compaction and are apparently necessary for the separation of the trophoblast from the inner cell mass. Considerable sculpting of the embryo occurs by cell deaths during organogenesis, and appropriate cell numbers, especially in the CNS and in the immune system, are generated by massive overproduction of cells and selection of a few, with death of the rest. The timing, identity, and genetic control of specific cells that die have been well documented in Caenorhabditis, but in other embryos the stochastic nature of the deaths limit our ability to do more than identify the regions in which cells will die. Complete disruption of the cell death machinery can be lethal, but many mutations of the regulatory machinery yield only modest or no phenotypes, indicating substantial redundancy and compensation of regulatory mechanisms. Most of the deaths are apoptotic and are identified by techniques used to recognize apoptosis, but techniques identifying lysosomes (whether in dying or involuting cells or in the phagocytes that invade the tissue) also reveal patterns of cell death. Aberrant cell deaths that produce known phenotypes are typically localized, indicating that the mechanism of activating a programmed death in a specific region, rather than the mechanism of death, is aberrant. These results lead us to conclude that we need to know much more about the conversations among cells that lead cells to commit suicide.
Topics: Animals; Apoptosis; Autophagy; Caenorhabditis; Embryo, Mammalian; Embryo, Nonmammalian; Gametogenesis; Gene Expression Regulation, Developmental; Germ Cells; Lysosomes; Mice; Organogenesis
PubMed: 26374521
DOI: 10.1387/ijdb.150220zz -
Human Reproduction Update May 2022The pathways of gametogenesis encompass elaborate cellular specialization accompanied by precise partitioning of the genome content in order to produce fully matured...
The pathways of gametogenesis encompass elaborate cellular specialization accompanied by precise partitioning of the genome content in order to produce fully matured spermatozoa and oocytes. Transcription factors are an important class of molecules that function in gametogenesis to regulate intrinsic gene expression programs, play essential roles in specifying (or determining) germ cell fate and assist in guiding full maturation of germ cells and maintenance of their populations. Moreover, in order to reinforce or redirect cell fate in vitro, it is transcription factors that are most frequently induced, over-expressed or activated. Many reviews have focused on the molecular development and genetics of gametogenesis, in vivo and in vitro, in model organisms and in humans, including several recent comprehensive reviews: here, we focus specifically on the role of transcription factors. Recent advances in stem cell biology and multi-omic studies have enabled deeper investigation into the unique transcriptional mechanisms of human reproductive development. Moreover, as methods continually improve, in vitro differentiation of germ cells can provide the platform for robust gain- and loss-of-function genetic analyses. These analyses are delineating unique and shared human germ cell transcriptional network components that, together with somatic lineage specifiers and pluripotency transcription factors, function in transitions from pluripotent stem cells to gametes. This grand theme review offers additional insight into human infertility and reproductive disorders that are linked predominantly to defects in the transcription factor networks and thus may potentially contribute to the development of novel treatments for infertility.
Topics: Cell Differentiation; Gametogenesis; Gene Expression Regulation; Germ Cells; Humans; Infertility; Male; Pluripotent Stem Cells; Transcription Factors; Transcription, Genetic
PubMed: 35297982
DOI: 10.1093/humupd/dmac002 -
Genetics Feb 2018Gametogenesis represents the most dramatic cellular differentiation pathways in both female and male flies. At the genome level, meiosis ensures that diploid germ cells... (Review)
Review
Gametogenesis represents the most dramatic cellular differentiation pathways in both female and male flies. At the genome level, meiosis ensures that diploid germ cells become haploid gametes. At the epigenome level, extensive changes are required to turn on and shut off gene expression in a precise spatiotemporally controlled manner. Research applying conventional molecular genetics and cell biology, in combination with rapidly advancing genomic tools have helped us to investigate (1) how germ cells maintain lineage specificity throughout their adult reproductive lifetime; (2) what molecular mechanisms ensure proper oogenesis and spermatogenesis, as well as protect genome integrity of the germline; (3) how signaling pathways contribute to germline-soma communication; and (4) if such communication is important. In this chapter, we highlight recent discoveries that have improved our understanding of these questions. On the other hand, restarting a new life cycle upon fertilization is a unique challenge faced by gametes, raising questions that involve intergenerational and transgenerational epigenetic inheritance. Therefore, we also discuss new developments that link changes during gametogenesis to early embryonic development-a rapidly growing field that promises to bring more understanding to some fundamental questions regarding metazoan development.
Topics: Animals; Cell Differentiation; Cell Self Renewal; Epigenesis, Genetic; Gametogenesis; Gene Expression Regulation, Developmental; Genome; Germ Cells; Humans; Meiosis; Mitosis; RNA, Small Interfering; Signal Transduction
PubMed: 29378808
DOI: 10.1534/genetics.117.300208 -
Cell Stem Cell Jun 2016The germ cell lineage originates early in development and undergoes a series of complex developmental processes that culminate in the generation of fully matured... (Review)
Review
The germ cell lineage originates early in development and undergoes a series of complex developmental processes that culminate in the generation of fully matured gametes, the spermatozoa and the oocytes. Remarkably, researchers have been recapitulating these developmental pathways using mouse and human pluripotent stem cells (PSCs). With further studies, including those involving non-human primate models, human gametogenesis may be fully reconstituted from PSCs, which would profoundly facilitate our understanding of human germ cell development and infertility. Here we discuss groundbreaking studies that lay the foundation for this achievement, the current state of the field, and challenges for deriving gametes from hPSCs.
Topics: Animals; Biological Assay; Ethics, Research; Gametogenesis; Germ Cells; Humans; Pluripotent Stem Cells
PubMed: 27257761
DOI: 10.1016/j.stem.2016.05.001 -
Seminars in Cell & Developmental Biology Nov 2022Gametes are cells that have the unique ability to give rise to new individuals as well as transmit (epi)genetic information across generations. Generation of... (Review)
Review
Gametes are cells that have the unique ability to give rise to new individuals as well as transmit (epi)genetic information across generations. Generation of functionally competent gametes, oocytes and sperm cells, depends to some extent on several fundamental processes that occur during fetal development. Direct studies on human fetal germ cells remain hindered by ethical considerations and inaccessibility to human fetal material. Therefore, the majority of our current knowledge of germ cell development still comes from an invaluable body of research performed using different mammalian species. During the last decade, our understanding of human fetal germ cells has increased due to the successful use of human pluripotent stem cells to model aspects of human early gametogenesis and advancements on single-cell omics. Together, this has contributed to determine the cell types and associated molecular signatures in the developing human gonads. In this review, we will put in perspective the knowledge obtained from several mammalian models (mouse, monkey, pig). Moreover, we will discuss the main events during human fetal (female) early gametogenesis and how the dysregulation of this highly complex and lengthy process can link to infertility later in life.
Topics: Animals; Cell Differentiation; Female; Gametogenesis; Germ Cells; Humans; Infertility; Male; Mammals; Mice; Semen; Swine
PubMed: 35431137
DOI: 10.1016/j.semcdb.2022.03.035 -
PLoS Computational Biology Feb 2023From insects to mammals, oocytes and sperm develop within germline cysts comprising cells connected by intercellular bridges (ICBs). In numerous insects, formation of...
From insects to mammals, oocytes and sperm develop within germline cysts comprising cells connected by intercellular bridges (ICBs). In numerous insects, formation of the cyst is accompanied by growth of the fusome-a membranous organelle that permeates the cyst. Fusome composition and function are best understood in Drosophila melanogaster: during oogenesis, the fusome dictates cyst topology and size and facilitates oocyte selection, while during spermatogenesis, the fusome synchronizes the cyst's response to DNA damage. Despite its distinct and sex-specific roles during insect gametogenesis, elucidating fusome growth and inheritance in females and its structure and connectivity in males has remained challenging. Here, we take advantage of advances in three-dimensional (3D) confocal microscopy and computational image processing tools to reconstruct the topology, growth, and distribution of the fusome in both sexes. In females, our experimental findings inform a theoretical model for fusome assembly and inheritance and suggest that oocyte selection proceeds through an 'equivalency with a bias' mechanism. In males, we find that cell divisions can deviate from the maximally branched pattern observed in females, leading to greater topological variability. Our work consolidates existing disjointed experimental observations and contributes a readily generalizable computational approach for quantitative studies of gametogenesis within and across species.
Topics: Animals; Female; Male; Drosophila melanogaster; Semen; Oocytes; Oogenesis; Cell Division; Mammals
PubMed: 36821548
DOI: 10.1371/journal.pcbi.1010875 -
Protein & Cell Jan 2023RBM46 is a germ cell-specific RNA-binding protein required for gametogenesis, but the targets and molecular functions of RBM46 remain unknown. Here, we demonstrate that...
RBM46 is a germ cell-specific RNA-binding protein required for gametogenesis, but the targets and molecular functions of RBM46 remain unknown. Here, we demonstrate that RBM46 binds at specific motifs in the 3'UTRs of mRNAs encoding multiple meiotic cohesin subunits and show that RBM46 is required for normal synaptonemal complex formation during meiosis initiation. Using a recently reported, high-resolution technique known as LACE-seq and working with low-input cells, we profiled the targets of RBM46 at single-nucleotide resolution in leptotene and zygotene stage gametes. We found that RBM46 preferentially binds target mRNAs containing GCCUAU/GUUCGA motifs in their 3'UTRs regions. In knockout mice, the RBM46-target cohesin subunits displayed unaltered mRNA levels but had reduced translation, resulting in the failed assembly of axial elements, synapsis disruption, and meiotic arrest. Our study thus provides mechanistic insights into the molecular functions of RBM46 in gametogenesis and illustrates the power of LACE-seq for investigations of RNA-binding protein functions when working with low-abundance input materials.
Topics: Animals; Mice; 3' Untranslated Regions; Cell Cycle Proteins; Gametogenesis; Meiosis; Nuclear Proteins; RNA-Binding Proteins; Cohesins
PubMed: 36726756
DOI: 10.1093/procel/pwac040