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Frontiers in Cell and Developmental... 2023Meiosis is a specialized cell division that generates haploid gametes and is critical for successful sexual reproduction. During the extended meiotic prophase I,... (Review)
Review
Meiosis is a specialized cell division that generates haploid gametes and is critical for successful sexual reproduction. During the extended meiotic prophase I, homologous chromosomes progressively pair, synapse and desynapse. These chromosomal dynamics are tightly integrated with meiotic recombination (MR), during which programmed DNA double-strand breaks (DSBs) are formed and subsequently repaired. Consequently, parental chromosome arms reciprocally exchange, ultimately ensuring accurate homolog segregation and genetic diversity in the offspring. Surveillance mechanisms carefully monitor the MR and homologous chromosome synapsis during meiotic prophase I to avoid producing aberrant chromosomes and defective gametes. Errors in these critical processes would lead to aneuploidy and/or genetic instability. Studies of mutation in mouse models, coupled with advances in genomic technologies, lead us to more clearly understand how meiosis is controlled and how meiotic errors are linked to mammalian infertility. Here, we review the genetic regulations of these major meiotic events in mice and highlight our current understanding of their surveillance mechanisms. Furthermore, we summarize meiotic prophase genes, the mutations that activate the surveillance system leading to meiotic prophase arrest in mouse models, and their corresponding genetic variants identified in human infertile patients. Finally, we discuss their value for the diagnosis of causes of meiosis-based infertility in humans.
PubMed: 36910159
DOI: 10.3389/fcell.2023.1127440 -
Developmental Cell Dec 2023During meiosis, the chromatin and transcriptome undergo prominent switches. Although recent studies have explored the genome reorganization during spermatogenesis, the...
During meiosis, the chromatin and transcriptome undergo prominent switches. Although recent studies have explored the genome reorganization during spermatogenesis, the chromatin remodeling in oogenesis and characteristics of homologous pairing remain largely elusive. We comprehensively compared chromatin structures and transcriptomes at successive substages of meiotic prophase in both female and male mice using low-input high-through chromosome conformation capture (Hi-C) and RNA sequencing (RNA-seq). Compartments and topologically associating domains (TADs) gradually disappeared and slowly recovered in both sexes. We found that homologs adopted different sex-conserved pairing strategies prior to and after the leptotene-to-zygotene transition, changing from long interspersed nuclear element (LINE)-enriched compartments B to short interspersed nuclear element (SINE)-enriched compartments A. We complemented marker genes and predicted the sex-specific meiotic sterile genes for each substage. This study provides valuable insights into the similarities and distinctions between sexes in chromosome architecture, homologous pairing, and transcriptome during meiotic prophase of both oogenesis and spermatogenesis.
Topics: Male; Female; Mice; Animals; Meiosis; Spermatogenesis; Prophase; Meiotic Prophase I; Chromatin; Oogenesis; Chromosome Pairing
PubMed: 37963468
DOI: 10.1016/j.devcel.2023.10.009 -
Progress in Molecular and Subcellular... 2017In sexually reproducing organisms the germ line is the cellular lineage that gives rise to gametes. All germ cells originate from germline stem cells that divide... (Review)
Review
In sexually reproducing organisms the germ line is the cellular lineage that gives rise to gametes. All germ cells originate from germline stem cells that divide asymmetrically to generate gonial pre-cursors, which are amplified in number by mitotic divisions, undergo meiosis and eventually differentiate into mature gametes (haploid eggs and sperm). Information transmitted with gametes is inherited by offspring, and potentially by subsequent generations, instructing in organismal development and beyond. Meiosis comprises one round of DNA replication, followed by two rounds of chromosome segregation; homologous chromosomes segregate in the first division (meiosis I) and sister chromatids segregate in the second division (meiosis II). Important mechanistic features of meiosis occur in substages of prophase I and are critical for genetic recombination, including pairing and synapsis of homologous chromosomes (at leptotene and zygotene), crossing-over (at pachytene), and the appearance of chiasmata (at diplotene/diakinesis). Another unique feature of meiosis is the altered centromere/kinetochore geometry at metaphase I, such that sister kinetochores face the same spindle pole (mono-orientation) and stay together at anaphase I. This chapter reviews centromere dynamics in germ cells, focusing on centromere function and assembly in meiotic cell cycles, as well as centromere inheritance in zygotes. Centromeres are functionally defined by the presence of the histone H3 variant CENP-A, the epigenetic determinant of centromere identity. In most eukaryotes, it is well established that CENP-A function is essential for chromosome segregation in mitosis. CENP-A function in meiosis is less well understood and emerging insights into the differential regulation of meiotic and mitotic CENP-A are discussed.
Topics: Centromere; Chromosome Segregation; Female; Germ Cells; Humans; Kinetochores; Male; Meiosis
PubMed: 28840245
DOI: 10.1007/978-3-319-58592-5_15 -
Frontiers in Cell and Developmental... 2017Chromosome dynamics during meiotic prophase I are associated with a series of major events such as chromosomal reorganization and condensation, pairing/synapsis and... (Review)
Review
Chromosome dynamics during meiotic prophase I are associated with a series of major events such as chromosomal reorganization and condensation, pairing/synapsis and recombination of the homologs, and chromosome movements at the nuclear envelope (NE). The NE is the barrier separating the nucleus from the cytoplasm and thus plays a central role in NE-associated chromosomal movements during meiosis. Previous studies have shown in various species that NE-linked chromosome dynamics are actually driven by the cytoskeleton. The linker of nucleoskeleton and cytoskeleton (LINC) complexes are important constituents of the NE that facilitate in the transfer of cytoskeletal forces across the NE to individual chromosomes. The LINCs consist of the inner and outer NE proteins Sad1/UNC-84 (SUN), and Klarsicht/Anc-1/Syne (KASH) domain proteins. Meiosis-specific adaptations of the LINC components and unique modifications of the NE are required during chromosomal movements. Nonetheless, the actual role of the NE in chromosomic dynamic movements in plants remains elusive. This review summarizes the findings of recent studies on meiosis-specific constituents and modifications of the NE and corresponding nucleoplasmic/cytoplasmic adaptors being involved in NE-associated movement of meiotic chromosomes, as well as describes the potential molecular network of transferring cytoplasm-derived forces into meiotic chromosomes in model organisms. It helps to gain a better understanding of the NE-associated meiotic chromosomal movements in plants.
PubMed: 29376050
DOI: 10.3389/fcell.2017.00121 -
Frontiers in Cell and Developmental... 2023Actin is a multi-functional protein that is involved in numerous cellular processes including cytoskeleton regulation, cell migration, and cellular integrity. In these... (Review)
Review
Actin is a multi-functional protein that is involved in numerous cellular processes including cytoskeleton regulation, cell migration, and cellular integrity. In these processes, actin's role in respect to its structure, complex mechanical, and protein-binding properties has been studied primarily in the cytoplasmic and cellular membrane compartments. However, its role in somatic cell nuclei has recently become evident where it participates in transcription, chromatin remodeling, and DNA damage repair. What remains enigmatic is the involvement of nuclear actin in physiological processes that lead to the generation of germ cells, in general, and primary spermatocytes, in particular. Here, we will discuss the possible role and nuclear localization of actin during meiotic prophase I and its interaction with chromatin remodeling complexes, the latter being essential for the control of pairing of homologous chromosomes, cross-over formation, and recombination. It is our hope that this perspective article will extend the scope of actin's nuclear function in germ cells undergoing meiotic division.
PubMed: 38078006
DOI: 10.3389/fcell.2023.1295452 -
Cell Cycle (Georgetown, Tex.) Aug 2021A central player in meiotic chromosome dynamics is the conserved Polo-like kinase (PLK) family. PLKs are dynamically localized to distinct structures during meiotic... (Review)
Review
A central player in meiotic chromosome dynamics is the conserved Polo-like kinase (PLK) family. PLKs are dynamically localized to distinct structures during meiotic prophase and phosphorylate a diverse group of substrates to control homolog pairing, synapsis, and meiotic recombination. In a recent study, we uncovered the mechanisms that control the targeting of a meiosis-specific PLK-2 in . In early meiotic prophase, PLK-2 localizes to special chromosome regions known as pairing centers and drives homolog pairing and synapsis. PLK-2 then relocates to the synaptonemal complex (SC) after crossover designation and mediates chromosome remodeling required for homolog separation. What controls this intricate targeting of PLK-2 in space and time? We discuss recent findings and remaining questions for the future.
Topics: Animals; Binding Sites; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Chromosome Pairing; Chromosomes; Gene Expression Regulation; Meiosis; Meiotic Prophase I; Phosphorylation; Protein Binding; Protein Serine-Threonine Kinases; Signal Transduction
PubMed: 34266376
DOI: 10.1080/15384101.2021.1953232 -
Frontiers in Cell and Developmental... 2021Meiosis is the basis of sexual reproduction. In female mammals, meiosis of oocytes starts before birth and sustains at the dictyate stage of meiotic prophase I before... (Review)
Review
Meiosis is the basis of sexual reproduction. In female mammals, meiosis of oocytes starts before birth and sustains at the dictyate stage of meiotic prophase I before gonadotropins-induced ovulation happens. Once meiosis gets started, the oocytes undergo the leptotene, zygotene, and pachytene stages, and then arrest at the dictyate stage. During each estrus cycle in mammals, or menstrual cycle in humans, a small portion of oocytes within preovulatory follicles may resume meiosis. It is crucial for females to supply high quality mature oocytes for sustaining fertility, which is generally achieved by fine-tuning oocyte meiotic arrest and resumption progression. Anything that disturbs the process may result in failure of oogenesis and seriously affect both the fertility and the health of females. Therefore, uncovering the regulatory network of oocyte meiosis progression illuminates not only how the foundations of mammalian reproduction are laid, but how mis-regulation of these steps result in infertility. In order to provide an overview of the recently uncovered cellular and molecular mechanism during oocyte maturation, especially epigenetic modification, the progress of the regulatory network of oocyte meiosis progression including meiosis arrest and meiosis resumption induced by gonadotropins is summarized. Then, advances in the epigenetic aspects, such as histone acetylation, phosphorylation, methylation, glycosylation, ubiquitination, and SUMOylation related to the quality of oocyte maturation are reviewed.
PubMed: 33842483
DOI: 10.3389/fcell.2021.654028 -
ELife Jan 2021Protein modification by SUMO helps orchestrate the elaborate events of meiosis to faithfully produce haploid gametes. To date, only a handful of meiotic SUMO targets...
Protein modification by SUMO helps orchestrate the elaborate events of meiosis to faithfully produce haploid gametes. To date, only a handful of meiotic SUMO targets have been identified. Here, we delineate a multidimensional SUMO-modified meiotic proteome in budding yeast, identifying 2747 conjugation sites in 775 targets, and defining their relative levels and dynamics. Modified sites cluster in disordered regions and only a minority match consensus motifs. Target identities and modification dynamics imply that SUMOylation regulates all levels of chromosome organization and each step of meiotic prophase I. Execution-point analysis confirms these inferences, revealing functions for SUMO in S-phase, the initiation of recombination, chromosome synapsis and crossing over. K15-linked SUMO chains become prominent as chromosomes synapse and recombine, consistent with roles in these processes. SUMO also modifies ubiquitin, forming hybrid oligomers with potential to modulate ubiquitin signaling. We conclude that SUMO plays diverse and unanticipated roles in regulating meiotic chromosome metabolism.
Topics: Chromosome Pairing; Meiosis; Prophase; SUMO-1 Protein; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Sumoylation
PubMed: 33502312
DOI: 10.7554/eLife.57720 -
Reproductive Biology and Endocrinology... Oct 2023In human female primordial germ cells, the transition from mitosis to meiosis begins from the fetal stage. In germ cells, meiosis is arrested at the diplotene stage of... (Review)
Review
In human female primordial germ cells, the transition from mitosis to meiosis begins from the fetal stage. In germ cells, meiosis is arrested at the diplotene stage of prophase in meiosis I (MI) after synapsis and recombination of homologous chromosomes, which cannot be segregated. Within the follicle, the maintenance of oocyte meiotic arrest is primarily attributed to high cytoplasmic concentrations of cyclic adenosine monophosphate (cAMP). Depending on the specific species, oocytes can remain arrested for extended periods of time, ranging from months to even years. During estrus phase in animals or the menstrual cycle in humans, the resumption of meiosis occurs in certain oocytes due to a surge of luteinizing hormone (LH) levels. Any factor interfering with this process may lead to impaired oocyte maturation, which in turn affects female reproductive function. Nevertheless, the precise molecular mechanisms underlying this phenomenon has not been systematically summarized yet. To provide a comprehensive understanding of the recently uncovered regulatory network involved in oocyte development and maturation, the progress of the cellular and molecular mechanisms of oocyte nuclear maturation including meiosis arrest and meiosis resumption is summarized. Additionally, the advancements in understanding the molecular cytoplasmic events occurring in oocytes, such as maternal mRNA degradation, posttranslational regulation, and organelle distribution associated with the quality of oocyte maturation, are reviewed. Therefore, understanding the pathways regulating oocyte meiotic arrest and resumption will provide detailed insight into female reproductive system and provide a theoretical basis for further research and potential approaches for novel disease treatments.
Topics: Animals; Female; Humans; Oogenesis; Oocytes; Meiosis; Meiotic Prophase I; Ovarian Follicle
PubMed: 37784186
DOI: 10.1186/s12958-023-01143-0 -
Results and Problems in Cell... 2017Generation of healthy oocytes requires coordinated regulation of multiple cellular events and signaling pathways. Oocytes undergo a unique developmental growth and... (Review)
Review
Generation of healthy oocytes requires coordinated regulation of multiple cellular events and signaling pathways. Oocytes undergo a unique developmental growth and differentiation pattern interspersed with long periods of arrest. Oocytes from almost all species arrest in prophase I of oogenesis that allows for long period of growth and differentiation essential for normal oocyte development. Depending on species, oocytes that transit from prophase I to meiosis I also arrest at meiosis I for fairly long periods of time and then undergo a second arrest at meiosis II that is completed upon fertilization. While there are species-specific differences in C. elegans, D. melanogaster, and mammalian oocytes in stages of prophase I, meiosis I, or meiosis II arrest, in all cases cell signaling pathways coordinate the developmental events controlling oocyte growth and differentiation to regulate these crucial phases of transition. In particular, the ERK MAP kinase signaling pathway, cyclic AMP second messengers, and the cell cycle regulators CDK1/cyclin B are key signaling pathways that seem evolutionarily conserved in their control of oocyte growth and meiotic maturation across species. Here, I identify the common themes and differences in the regulation of key meiotic events during oocyte growth and maturation.
Topics: Animals; Female; Humans; Meiosis; Meiotic Prophase I; Oocytes; Oogenesis; Signal Transduction
PubMed: 28247047
DOI: 10.1007/978-3-319-44820-6_4