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Science (New York, N.Y.) Jun 2022A hallmark of meiosis is chromosomal pairing, which requires telomere tethering and rotation on the nuclear envelope through microtubules, driving chromosome homology...
A hallmark of meiosis is chromosomal pairing, which requires telomere tethering and rotation on the nuclear envelope through microtubules, driving chromosome homology searches. Telomere pulling toward the centrosome forms the "zygotene chromosomal bouquet." Here, we identified the "zygotene cilium" in oocytes. This cilium provides a cable system for the bouquet machinery and extends throughout the germline cyst. Using zebrafish mutants and live manipulations, we demonstrate that the cilium anchors the centrosome to counterbalance telomere pulling. The cilium is essential for bouquet and synaptonemal complex formation, oogenesis, ovarian development, and fertility. Thus, a cilium represents a conserved player in zebrafish and mouse meiosis, which sheds light on reproductive aspects in ciliopathies and suggests that cilia can control chromosomal dynamics.
Topics: Animals; Centromere; Chromosome Pairing; Cilia; Female; Fertility; Mice; Morphogenesis; Oocytes; Oogenesis; Ovary; Telomere; Zebrafish
PubMed: 35549308
DOI: 10.1126/science.abh3104 -
Biochemical Society Transactions Apr 2024A large number of mRNAs of maternal origin are produced during oogenesis and deposited in the oocyte. Since transcription stops at the onset of meiosis during oogenesis... (Review)
Review
A large number of mRNAs of maternal origin are produced during oogenesis and deposited in the oocyte. Since transcription stops at the onset of meiosis during oogenesis and does not resume until later in embryogenesis, maternal mRNAs are the only templates for protein synthesis during this period. To ensure that a protein is made in the right place at the right time, the translation of maternal mRNAs must be activated at a specific stage of development. Here we summarize our current understanding of the sophisticated mechanisms that contribute to the temporal repression of maternal mRNAs, termed maternal mRNA dormancy. We discuss mechanisms at the level of the RNA itself, such as the regulation of polyadenine tail length and RNA modifications, as well as at the level of RNA-binding proteins, which often block the assembly of translation initiation complexes at the 5' end of an mRNA or recruit mRNAs to specific subcellular compartments. We also review microRNAs and other mechanisms that contribute to repressing translation, such as ribosome dormancy. Importantly, the mechanisms responsible for mRNA dormancy during the oocyte-to-embryo transition are also relevant to cellular quiescence in other biological contexts.
Topics: Animals; Humans; Oocytes; Oogenesis; RNA, Messenger; MicroRNAs; RNA, Messenger, Stored; RNA-Binding Proteins; Protein Biosynthesis; Gene Expression Regulation, Developmental; Female; Embryonic Development
PubMed: 38477334
DOI: 10.1042/BST20231122 -
International Journal of Molecular... Apr 2023It is a well-known fact that the reproductive organs in women, especially oocytes, are exposed to numerous regulatory pathways and environmental stimuli. The maternal... (Review)
Review
It is a well-known fact that the reproductive organs in women, especially oocytes, are exposed to numerous regulatory pathways and environmental stimuli. The maternal age is one cornerstone that influences the process of oocyte fertilization. More precisely, the longer a given oocyte is in the waiting-line to be ovulated from menarche to menopause, the longer the duration from oogenesis to fertilization, and therefore, the lower the chances of success to form a viable embryo. The age of menarche in girls ranges from 10 to 16 years, and the age of menopause in women ranges from approximately 45 to 55 years. Researchers are paying attention to the regulatory pathways that are impacting the oocyte at the very beginning during oogenesis in fetal life to discover genes and proteins that could be crucial for the oocyte's lifespan. Due to the general trend in industrialized countries in the last three decades, women are giving birth to their first child in their thirties. Therefore, maternal age has become an important factor impacting oocytes developmental competence, since the higher a woman's age, the higher the chances of miscarriage due to several causes, such as aneuploidy. Meiotic failures during oogenesis, such as, for instance, chromosome segregation failures or chromosomal non-disjunction, are influencing the latter-mentioned aging-related phenomenon too. These errors early in life of women can lead to sub- or infertility. It cannot be neglected that oogenesis is a precisely orchestrated process, during which the oogonia and primary oocytes are formed, and RNA synthesis takes place. These RNAs are crucial for oocyte growth and maturation. In this review, we intend to describe the relevance of regulatory pathways during the oogenesis in women. Furthermore, we focus on molecular pathways of oocyte developmental competence with regard to maternal effects during embryogenesis. On the background of transcriptional mechanisms that enable the transition from a silenced oocyte to a transcriptionally active embryo, we will briefly discuss the potential of induced pluripotent stem cells.
Topics: Pregnancy; Female; Humans; Maternal Age; Oogenesis; Oocytes; Ovulation; Stem Cells
PubMed: 37047809
DOI: 10.3390/ijms24076837 -
Cell Reports Nov 2023Although single-cell multi-omics technologies are undergoing rapid development, simultaneous transcriptome and proteome analysis of a single-cell individual still faces...
Although single-cell multi-omics technologies are undergoing rapid development, simultaneous transcriptome and proteome analysis of a single-cell individual still faces great challenges. Here, we developed a single-cell simultaneous transcriptome and proteome (scSTAP) analysis platform based on microfluidics, high-throughput sequencing, and mass spectrometry technology to achieve deep and joint quantitative analysis of transcriptome and proteome at the single-cell level, providing an important resource for understanding the relationship between transcription and translation in cells. This platform was applied to analyze single mouse oocytes at different meiotic maturation stages, reaching an average quantification depth of 19,948 genes and 2,663 protein groups in single mouse oocytes. In particular, we analyzed the correlation of individual RNA and protein pairs, as well as the meiosis regulatory network with unprecedented depth, and identified 30 transcript-protein pairs as specific oocyte maturational signatures, which could be productive for exploring transcriptional and translational regulatory features during oocyte meiosis.
Topics: Animals; Mice; Transcriptome; Proteome; Oocytes; Oogenesis; Gene Expression Profiling; Meiosis
PubMed: 37976159
DOI: 10.1016/j.celrep.2023.113455 -
Journal of Insect Science (Online) Nov 2020Oviposition-related genes have remained a consistent focus of insect molecular biology. Previous research has gradually clarified our mechanistic understanding of... (Review)
Review
Oviposition-related genes have remained a consistent focus of insect molecular biology. Previous research has gradually clarified our mechanistic understanding of oviposition-related genes, including those related to oviposition-gland-related genes, oogenesis-related genes, oviposition-site-selection-related genes, and genes related to ovulation and hatching. Moreover, some of this research has revealed how the expression of single oviposition-related genes affects the expression of related genes, and more importantly, how individual node genes function to link the expression of upstream and downstream genes. However, the research to date is not sufficient to completely explain the overall interactions among the genes of the insect oviposition system. Through a literature review of a large number of studies, this review provides references for future research on oviposition-related genes in insects and the use of RNAi or CRISPR/Cas9 technology to verify the functions of oviposition-related genes and to prevent and control harmful insects.
Topics: Animals; CRISPR-Cas Systems; Egg Proteins; Female; Gene Expression; Genes, Insect; Insect Control; Insecta; Oogenesis; Oviposition; RNA Interference; Receptors, Cell Surface; Vitellogenins
PubMed: 33367730
DOI: 10.1093/jisesa/ieaa137 -
Cold Spring Harbor Protocols Apr 2020The oocyte is a unique model system, allowing both the study of complex biological processes within a cellular context through expression of exogenous mRNAs and...
The oocyte is a unique model system, allowing both the study of complex biological processes within a cellular context through expression of exogenous mRNAs and proteins, and the study of the cell, molecular, and developmental biology of the oocyte itself. During oogenesis, oocytes grow dramatically in size, with a mature oocyte having a diameter of ∼1.3 mm, and become highly polarized, localizing many mRNAs and proteins. Thus, the mature oocyte is a repository of maternal mRNAs and proteins that will direct early embryogenesis prior to zygotic genome transcription. Importantly, the oocyte also has the capacity to translate exogenous microinjected RNAs, which has enabled breakthroughs in a wide range of areas including cell biology, developmental biology, molecular biology, and physiology. This introduction outlines how oocytes can be used to study a variety of important biological questions.
Topics: Animals; Cell Cycle; Cell Polarity; Female; Gene Expression Regulation, Developmental; Molecular Biology; Oocytes; Oogenesis; RNA, Messenger; Xenopus laevis
PubMed: 31980467
DOI: 10.1101/pdb.top095844 -
Genes Aug 2021All mammalian oocytes and eggs are surrounded by a relatively thick extracellular matrix (ECM), the zona pellucida (ZP), that plays vital roles during oogenesis,... (Review)
Review
All mammalian oocytes and eggs are surrounded by a relatively thick extracellular matrix (ECM), the zona pellucida (ZP), that plays vital roles during oogenesis, fertilization, and preimplantation development. Unlike ECM surrounding somatic cells, the ZP is composed of only a few glycosylated proteins, ZP1-4, that are unique to oocytes and eggs. ZP1-4 have a large region of polypeptide, the ZP domain (ZPD), consisting of two subdomains, ZP-N and ZP-C, separated by a short linker region, that plays an essential role in polymerization of nascent ZP proteins into crosslinked fibrils. Both subdomains adopt immunoglobulin (Ig)-like folds for their 3-dimensional structure. Mouse and human genes are encoded by single-copy genes located on different chromosomes and are highly expressed in the ovary by growing oocytes during late stages of oogenesis. Genes encoding ZP proteins are conserved among mammals, and their expression is regulated by -acting sequences located close to the transcription start-site and by the same/similar -acting factors. Nascent ZP proteins are synthesized, packaged into vesicles, secreted into the extracellular space, and assembled into long, crosslinked fibrils that have a structural repeat, a ZP2-ZP3 dimer, and constitute the ZP matrix. Fibrils are oriented differently with respect to the oolemma in the inner and outer layers of the ZP. Sequence elements in the ZPD and the carboxy-terminal propeptide of ZP1-4 regulate secretion and assembly of nascent ZP proteins. The presence of both ZP2 and ZP3 is required to assemble ZP fibrils and ZP1 and ZP4 are used to crosslink the fibrils. Inactivation of mouse genes by gene targeting has a detrimental effect on ZP formation around growing oocytes and female fertility. Gene sequence variations in human genes due to point, missense, or frameshift mutations also have a detrimental effect on ZP formation and female fertility. The latter mutations provide additional support for the role of ZPD subdomains and other regions of ZP polypeptide in polymerization of human ZP proteins into fibrils and matrix.
Topics: Animals; Female; Fertility; Humans; Mammals; Mice; Oocytes; Oogenesis; Zona Pellucida
PubMed: 34440440
DOI: 10.3390/genes12081266 -
The EMBO Journal May 2023Human in vitro oogenesis provides a framework for clarifying the mechanism of human oogenesis. To create its benchmark, it is vital to promote in vitro oogenesis using a...
Human in vitro oogenesis provides a framework for clarifying the mechanism of human oogenesis. To create its benchmark, it is vital to promote in vitro oogenesis using a model physiologically close to humans. Here, we establish a foundation for in vitro oogenesis in cynomolgus (cy) monkeys (Macaca fascicularis): cy female embryonic stem cells harboring one active and one inactive X chromosome (Xa and Xi, respectively) differentiate robustly into primordial germ cell-like cells, which in xenogeneic reconstituted ovaries develop efficiently into oogonia and, remarkably, further into meiotic oocytes at the zygotene stage. This differentiation entails comprehensive epigenetic reprogramming, including Xi reprogramming, yet Xa and Xi remain epigenetically asymmetric with, as partly observed in vivo, incomplete Xi reactivation. In humans and monkeys, the Xi epigenome in pluripotent stem cells functions as an Xi-reprogramming determinant. We further show that developmental pathway over-activations with suboptimal up-regulation of relevant meiotic genes impede in vitro meiotic progression. Cy in vitro oogenesis exhibits critical homology with the human system, including with respect to bottlenecks, providing a salient model for advancing human in vitro oogenesis.
Topics: Animals; Female; Humans; Macaca fascicularis; Oocytes; Oogenesis; Ovary; Embryonic Stem Cells
PubMed: 36929479
DOI: 10.15252/embj.2022112962 -
Journal of Assisted Reproduction and... Jul 2018Mammalian oogenesis and folliculogenesis share a dynamic connection that is critical for gamete development. For maintenance of quiescence or follicular activation,... (Review)
Review
PURPOSE
Mammalian oogenesis and folliculogenesis share a dynamic connection that is critical for gamete development. For maintenance of quiescence or follicular activation, follicles must respond to soluble signals (growth factors and hormones) and physical stresses, including mechanical forces and osmotic shifts. Likewise, mechanical processes are involved in cortical tension and cell polarity in oocytes. Our objective was to examine the contribution and influence of biomechanical signaling in female mammalian gametogenesis.
METHODS
We performed a systematic review to assess and summarize the effects of mechanical signaling and mechanotransduction in oocyte maturation and folliculogenesis and to explore possible clinical applications. The review identified 2568 publications of which 122 met the inclusion criteria.
RESULTS
The integration of mechanical and cell signaling pathways in gametogenesis is complex. Follicular activation or quiescence are influenced by mechanical signaling through the Hippo and Akt pathways involving the yes-associated protein (YAP), transcriptional coactivator with PDZ-binding motif (TAZ), phosphatase and tensin homolog deleted from chromosome 10 (PTEN) gene, the mammalian target of rapamycin (mTOR), and forkhead box O3 (FOXO3) gene.
CONCLUSIONS
There is overwhelming evidence that mechanical signaling plays a crucial role in development of the ovary, follicle, and oocyte throughout gametogenesis. Emerging data suggest the complexities of mechanotransduction and the biomechanics of oocytes and follicles are integral to understanding of primary ovarian insufficiency, ovarian aging, polycystic ovary syndrome, and applications of fertility preservation.
Topics: Animals; Female; Humans; Mechanotransduction, Cellular; Oocytes; Oogenesis; Ovarian Follicle; Ovary; Signal Transduction
PubMed: 29691711
DOI: 10.1007/s10815-018-1180-y -
The EMBO Journal Dec 2023Recent studies have reported the differentiation of pluripotent cells into oocytes in vitro. However, the developmental competence of in vitro-generated oocytes remains...
Recent studies have reported the differentiation of pluripotent cells into oocytes in vitro. However, the developmental competence of in vitro-generated oocytes remains low. Here, we perform a comprehensive comparison of mouse germ cell development in vitro over all culture steps versus in vivo with the goal to understand mechanisms underlying poor oocyte quality. We show that the in vitro differentiation of primordial germ cells to growing oocytes and subsequent follicle growth is critical for competence for preimplantation development. Systematic transcriptome analysis of single oocytes that were subjected to different culture steps identifies genes that are normally upregulated during oocyte growth to be susceptible for misregulation during in vitro oogenesis. Many misregulated genes are Polycomb targets. Deregulation of Polycomb repression is therefore a key cause and the earliest defect known in in vitro oocyte differentiation. Conversely, structurally normal in vitro-derived oocytes fail at zygotic genome activation and show abnormal acquisition of 5-hydroxymethylcytosine on maternal chromosomes. Our data identify epigenetic regulation at an early stage of oogenesis limiting developmental competence and suggest opportunities for future improvements.
Topics: Female; Animals; Mice; Epigenesis, Genetic; Oocytes; Ovarian Follicle; Oogenesis; Germ Cells
PubMed: 37850882
DOI: 10.15252/embj.2023113955