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Physiological Reviews Oct 2023Mammalian eggs (oocytes) are formed during fetal life and establish associations with somatic cells to form primordial follicles that create a store of germ cells (the... (Review)
Review
Mammalian eggs (oocytes) are formed during fetal life and establish associations with somatic cells to form primordial follicles that create a store of germ cells (the primordial pool). The size of this pool is influenced by key events during the formation of germ cells and by factors that influence the subsequent activation of follicle growth. These regulatory pathways must ensure that the reserve of oocytes within primordial follicles in humans lasts for up to 50 years, yet only approximately 0.1% will ever be ovulated with the rest undergoing degeneration. This review outlines the mechanisms and regulatory pathways that govern the processes of oocyte and follicle formation and later growth, within the ovarian stroma, through to ovulation with particular reference to human oocytes/follicles. In addition, the effects of aging on female reproductive capacity through changes in oocyte number and quality are emphasized, with both the cellular mechanisms and clinical implications discussed. Finally, the details of current developments in culture systems that support all stages of follicle growth to generate mature oocytes in vitro and emerging prospects for making new oocytes from stem cells are outlined.
Topics: Animals; Humans; Female; Oocytes; Ovarian Follicle; Ovary; Oogenesis; Mammals; Aging
PubMed: 37171807
DOI: 10.1152/physrev.00032.2022 -
Fertility and Sterility May 2021Cryopreservation of ovarian tissue to preserve the fertility of girls and young women at high risk of sterility is now widely practiced. Pieces of cryopreserved ovarian... (Review)
Review
Cryopreservation of ovarian tissue to preserve the fertility of girls and young women at high risk of sterility is now widely practiced. Pieces of cryopreserved ovarian cortex can be thawed and autografted to restore fertility, but because of the risks of reintroduction of the cancer, transplantation may not be possible for girls and women with blood-borne leukemias or cancers with a high risk of ovarian metastasis. Cryopreserved ovarian tissue contains mainly primordial follicles but also provides access to immature oocytes from small antral follicles, which may be matured in vitro to provide an additional source of mature oocytes. So in cases in which transplantation is contraindicated, fertility restoration could be safely achieved in the laboratory either by in vitro maturation (IVM) of oocytes aspirated from growing follicles or by the complete in vitro growth (IVG) and maturation (IVM) of primordial follicles to produce fertile metaphase II (MII) oocytes. The development of IVM and IVG methods to support all stages of oocytes available within ovarian tissue will maximize the potential for all patients undergoing fertility preservation.
Topics: Cryopreservation; Female; Fertility Preservation; Humans; In Vitro Oocyte Maturation Techniques; Oocytes; Oogenesis; Ovarian Follicle
PubMed: 33823993
DOI: 10.1016/j.fertnstert.2021.03.004 -
Genes Oct 2022Various pathogenic factors can lead to oogenesis failure and seriously affect both female reproductive health and fertility. Genetic factors play an important role in... (Review)
Review
Various pathogenic factors can lead to oogenesis failure and seriously affect both female reproductive health and fertility. Genetic factors play an important role in folliculogenesis and oocyte maturation but still need to be clarified. Oocyte maturation is a well-organized complex process, regulated by a large number of genes. Pathogenic variants in these genes as well as aneuploidy, defects in mitochondrial genome, and other genetic and epigenetic factors can result in unexplained infertility, early pregnancy loss, and recurrent failures of IVF/ICSI programs due to poor ovarian response to stimulation, oocyte maturation arrest, poor gamete quality, fertilization failure, or early embryonic developmental arrest. In this paper, we review the main genes, as well as provide a description of the defects in the mitochondrial genome, associated with female infertility.
Topics: Pregnancy; Humans; Female; Fertilization in Vitro; Oogenesis; Oocytes; Infertility, Female; Embryonic Development
PubMed: 36360157
DOI: 10.3390/genes13111920 -
International Journal of Molecular... May 2023The quality and maturation of an oocyte not only play decisive roles in fertilization and embryo success, but also have long-term impacts on the later growth and... (Review)
Review
The quality and maturation of an oocyte not only play decisive roles in fertilization and embryo success, but also have long-term impacts on the later growth and development of the fetus. Female fertility declines with age, reflecting a decline in oocyte quantity. However, the meiosis of oocytes involves a complex and orderly regulatory process whose mechanisms have not yet been fully elucidated. This review therefore mainly focuses on the regulation mechanism of oocyte maturation, including folliculogenesis, oogenesis, and the interactions between granulosa cells and oocytes, plus in vitro technology and nuclear/cytoplasm maturation in oocytes. Additionally, we have reviewed advances made in the single-cell mRNA sequencing technology related to oocyte maturation in order to improve our understanding of the mechanism of oocyte maturation and to provide a theoretical basis for subsequent research into oocyte maturation.
Topics: Animals; Female; Oogenesis; Oocytes; Mammals; Meiosis; Granulosa Cells
PubMed: 37240406
DOI: 10.3390/ijms24109059 -
Nature Nov 2016The female germ line undergoes a unique sequence of differentiation processes that confers totipotency to the egg. The reconstitution of these events in vitro using...
The female germ line undergoes a unique sequence of differentiation processes that confers totipotency to the egg. The reconstitution of these events in vitro using pluripotent stem cells is a key achievement in reproductive biology and regenerative medicine. Here we report successful reconstitution in vitro of the entire process of oogenesis from mouse pluripotent stem cells. Fully potent mature oocytes were generated in culture from embryonic stem cells and from induced pluripotent stem cells derived from both embryonic fibroblasts and adult tail tip fibroblasts. Moreover, pluripotent stem cell lines were re-derived from the eggs that were generated in vitro, thereby reconstituting the full female germline cycle in a dish. This culture system will provide a platform for elucidating the molecular mechanisms underlying totipotency and the production of oocytes of other mammalian species in culture.
Topics: Animals; Cell Line; Embryo, Mammalian; Female; Fertilization; In Vitro Techniques; Male; Meiosis; Mice; Mouse Embryonic Stem Cells; Oocytes; Oogenesis; Pluripotent Stem Cells; Transcriptome
PubMed: 27750280
DOI: 10.1038/nature20104 -
Molecular Cell Nov 2020Well-balanced and timed metabolism is essential for making a high-quality egg. However, the metabolic framework that supports oocyte development remains poorly...
Well-balanced and timed metabolism is essential for making a high-quality egg. However, the metabolic framework that supports oocyte development remains poorly understood. Here, we obtained the temporal metabolome profiles of mouse oocytes during in vivo maturation by isolating large number of cells at key stages. In parallel, quantitative proteomic analyses were conducted to bolster the metabolomic data, synergistically depicting the global metabolic patterns in oocytes. In particular, we discovered the metabolic features during meiotic maturation, such as the fall in polyunsaturated fatty acids (PUFAs) level and the active serine-glycine-one-carbon (SGOC) pathway. Using functional approaches, we further identified the key targets mediating the action of PUFA arachidonic acid (ARA) on meiotic maturation and demonstrated the control of epigenetic marks in maturing oocytes by SGOC network. Our data serve as a broad resource on the dynamics occurring in metabolome and proteome during oocyte maturation.
Topics: Animals; Epigenesis, Genetic; Fatty Acids, Unsaturated; Female; Meiosis; Metabolome; Mice; Mice, Inbred C57BL; Oocytes; Oogenesis; Proteome; Proteomics
PubMed: 33068521
DOI: 10.1016/j.molcel.2020.09.022 -
Human Reproduction Update 2016Extracellular vesicles (EVs) are membrane-bound vesicles, found in biofluids, that carry and transfer regulatory molecules, such as microRNAs (miRNAs) and proteins, and... (Review)
Review
BACKGROUND
Extracellular vesicles (EVs) are membrane-bound vesicles, found in biofluids, that carry and transfer regulatory molecules, such as microRNAs (miRNAs) and proteins, and may mediate intercellular communication between cells and tissues. EVs have been isolated from a wide variety of biofluids, including plasma, urine, and, relevant to this review, seminal, follicular and uterine luminal fluid. We conducted a systematic search of the literature to review and present the currently available evidence on the possible roles of EVs in follicular growth, resumption of oocyte development and maturation (meiosis), sperm maturation, fertilization and embryo implantation.
METHODS
MEDLINE, Embase and Web of Science databases were searched using keywords pertaining to EVs, including 'extracellular vesicles', 'microvesicles', 'microparticles' and 'exosomes', combined with a range of terms associated with the period of development between fertilization and implantation, including 'oocyte', 'sperm', 'semen', 'fertilization', 'implantation', 'embryo', 'follicular fluid', 'epididymal fluid' and 'seminal fluid'. Relevant research articles published in English (both animal and human studies) were reviewed with no restrictions on publication date (i.e. from earliest database dates to July 2015). References from these articles were used to obtain additional articles.
RESULTS
A total of 1556 records were retrieved from the three databases. After removing duplicates and irrelevant titles, we reviewed the abstracts of 201 articles, which included 92 relevant articles. Both animal and human studies unequivocally identified various types of EVs in seminal, follicular and ULFs. Several studies provided evidence for the roles of EVs in these biofluids. In men, EVs in seminal fluid were linked with post-testicular sperm maturation, including sperm motility acquisition and reduction of oxidative stress. In women, EVs in follicular fluid were shown to contain miRNAs with potential roles in follicular growth, resumption of oocyte meiosis, steroidogenesis and prevention of polyspermy after fertilization. EVs were also detected in the media of cultured embryos, suggesting that EVs released from embryos and the uterus may mediate embryo-endometrium cross-talk during implantation. It is important to note that many of the biologically plausible functions of EVs in reproduction discussed in the current literature have not yet been substantiated by conclusive experimental evidence.
CONCLUSIONS
A detailed understanding of the contributions of EVs in the series of events from gametogenesis to fertilization and then on to implantation, in both normal and pathological cases, may enable the development of valuable tools to advance reproductive health. Because of the early stage of the field, it is unsurprising that the current literature includes not only growing experimental evidence, but also as-yet unproven hypotheses pertaining to the roles of EVs in key reproductive processes. In this review, we present a comprehensive survey of the rapidly expanding literature on this subject, highlighting both relevant findings and gaps in knowledge.
Topics: Animals; Cell Communication; Embryo Implantation; Extracellular Vesicles; Female; Fertilization; Humans; Male; Oocytes; Oogenesis; Pregnancy; Semen; Spermatogenesis
PubMed: 26663221
DOI: 10.1093/humupd/dmv055 -
The Journal of Reproduction and... Feb 2020Oocyte quality is affected by many factors, among which the environment of growth and maturation seems to be crucial. Studies show that well balanced oocyte energy... (Review)
Review
Oocyte quality is affected by many factors, among which the environment of growth and maturation seems to be crucial. Studies show that well balanced oocyte energy metabolism has a significant impact on several elements of cytoplasmic and nuclear maturation as well as further embryo developmental competence. Therefore homeostasis between metabolism of glucose and fatty acids in the oocyte is being widely described nowadays. This review aims to discuss the follicular (in vivo) or maturation media (in vitro) environments with regard to glucose and fatty acid metabolism, as the main sources of the energy for the oocyte. A great emphasis is given on the balance between those two metabolic pathways and its further impact on female fertility.
Topics: Animals; Energy Metabolism; Fatty Acids; Female; Humans; In Vitro Oocyte Maturation Techniques; Lipid Metabolism; Oocytes; Oogenesis; Ovarian Follicle
PubMed: 31787727
DOI: 10.1262/jrd.2019-102 -
Nature Communications Aug 2022The combined use of transcriptome and translatome as indicators of gene expression profiles is usually more accurate than the use of transcriptomes alone, especially in...
The combined use of transcriptome and translatome as indicators of gene expression profiles is usually more accurate than the use of transcriptomes alone, especially in cell types governed by translational regulation, such as mammalian oocytes. Here, we developed a dual-omics methodology that includes both transcriptome and translatome sequencing (T&T-seq) of single-cell oocyte samples, and we used it to characterize the transcriptomes and translatomes during mouse and human oocyte maturation. T&T-seq analysis revealed distinct translational expression patterns between mouse and human oocytes and delineated a sequential gene expression regulation from the cytoplasm to the nucleus during human oocyte maturation. By these means, we also identified a functional role of OOSP2 inducing factor in human oocyte maturation, as human recombinant OOSP2 induced in vitro maturation of human oocytes, which was blocked by anti-OOSP2. Single-oocyte T&T-seq analyses further elucidated that OOSP2 induces specific signaling pathways, including small GTPases, through translational regulation.
Topics: Animals; Gene Expression Profiling; Gene Expression Regulation; Humans; Mammals; Mice; Oocytes; Oogenesis; Transcriptome
PubMed: 36042231
DOI: 10.1038/s41467-022-32791-2 -
ELife Feb 2023An in vitro model of human ovarian follicles would greatly benefit the study of female reproduction. Ovarian development requires the combination of germ cells and...
An in vitro model of human ovarian follicles would greatly benefit the study of female reproduction. Ovarian development requires the combination of germ cells and several types of somatic cells. Among these, granulosa cells play a key role in follicle formation and support for oogenesis. Whereas efficient protocols exist for generating human primordial germ cell-like cells (hPGCLCs) from human induced pluripotent stem cells (hiPSCs), a method of generating granulosa cells has been elusive. Here, we report that simultaneous overexpression of two transcription factors (TFs) can direct the differentiation of hiPSCs to granulosa-like cells. We elucidate the regulatory effects of several granulosa-related TFs and establish that overexpression of NR5A1 and either RUNX1 or RUNX2 is sufficient to generate granulosa-like cells. Our granulosa-like cells have transcriptomes similar to human fetal ovarian cells and recapitulate key ovarian phenotypes including follicle formation and steroidogenesis. When aggregated with hPGCLCs, our cells form ovary-like organoids (ovaroids) and support hPGCLC development from the premigratory to the gonadal stage as measured by induction of DAZL expression. This model system will provide unique opportunities for studying human ovarian biology and may enable the development of therapies for female reproductive health.
Topics: Humans; Female; Transcription Factors; Induced Pluripotent Stem Cells; Ovary; Oogenesis; Cell Differentiation
PubMed: 36803359
DOI: 10.7554/eLife.83291