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Cells Sep 2021With the nucleus as an exception, mitochondria are the only animal cell organelles containing their own genetic information, called mitochondrial DNA (mtDNA). During... (Review)
Review
With the nucleus as an exception, mitochondria are the only animal cell organelles containing their own genetic information, called mitochondrial DNA (mtDNA). During oocyte maturation, the mtDNA copy number dramatically increases and the distribution of mitochondria changes significantly. As oocyte maturation requires a large amount of ATP for continuous transcription and translation, the availability of the right number of functional mitochondria is crucial. There is a correlation between the quality of oocytes and both the amount of mtDNA and the amount of ATP. Suboptimal conditions of in vitro maturation (IVM) might lead to changes in the mitochondrial morphology as well as alternations in the expression of genes encoding proteins associated with mitochondrial function. Dysfunctional mitochondria have a lower ability to counteract reactive oxygen species (ROS) production which leads to oxidative stress. The mitochondrial function might be improved with the application of antioxidants and significant expectations are laid on the development of new IVM systems supplemented with mitochondria-targeted reagents. Different types of antioxidants have been tested already on animal models and human rescue IVM oocytes, showing promising results. This review focuses on the recent observations on oocytes' intracellular mitochondrial distribution and on mitochondrial genomes during their maturation, both in vivo and in vitro. Recent mitochondrial supplementation studies, aiming to improve oocyte developmental potential, are summarized.
Topics: Animals; Antioxidants; Humans; Mitochondria; Oocytes; Oogenesis; Oxidative Stress; Reactive Oxygen Species
PubMed: 34572133
DOI: 10.3390/cells10092484 -
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 -
Biology of Reproduction Sep 2019About 10% of women of reproductive age are unable to conceive or carry a pregnancy to term. Female factors alone account for at least 35% of all infertility cases and... (Review)
Review
About 10% of women of reproductive age are unable to conceive or carry a pregnancy to term. Female factors alone account for at least 35% of all infertility cases and comprise a wide range of causes affecting ovarian development, maturation of oocytes, and fertilization competence, as well as the potential of a fertilized egg for preimplantation development, implantation, and fetal growth. Genetic abnormalities leading to infertility in females comprise large chromosome abnormalities, submicroscopic chromosome deletion and duplications, and DNA sequence variations in the genes that control numerous biological processes implicated in oogenesis, maintenance of ovarian reserve, hormonal signaling, and anatomical and functional development of female reproductive organs. Despite the great number of genes implicated in reproductive physiology by the study of animal models, only a subset of these genes is associated with human infertility. In this review, we mainly focus on genetic alterations identified in humans and summarize recent knowledge on the molecular pathways of oocyte development and maturation, the crucial role of maternal-effect factors during embryogenesis, and genetic conditions associated with ovarian dysgenesis, primary ovarian insufficiency, early embryonic lethality, and infertility.
Topics: Animals; Disease Models, Animal; Embryonic Development; Female; Humans; Infertility, Female; Maternal-Fetal Relations; Oogenesis; Ovarian Reserve; Pregnancy; Primary Ovarian Insufficiency; Reproduction; Signal Transduction
PubMed: 31077289
DOI: 10.1093/biolre/ioz084 -
Genes Jun 2021From fetal life until senescence, the ovary is an extremely active tissue undergoing continuous structural and functional changes. These ever-changing events are best... (Review)
Review
From fetal life until senescence, the ovary is an extremely active tissue undergoing continuous structural and functional changes. These ever-changing events are best summarized by a quotation attributed to Plato when describing motion in space and time-'nothing ever is but is always becoming…'. With respect to the ovary, these changes include, at the beginning, the processes of follicular formation and thereafter those of follicular growth and atresia, steroidogenesis, oocyte maturation, and decisions relating to the number of mature oocytes that are ovulated for fertilization and the role of the corpus luteum. The aims of this review are to offer some examples of these complex and hitherto unknown processes. The ones herein have been elucidated from studies undertaken in vitro or from normal in vivo events, natural genetic mutations or after experimental inactivation of gene function. Specifically, this review offers insights concerning the initiation of follicular growth, pathologies relating to poly-ovular follicles, the consequences of premature loss of germ cells or oocytes loss, the roles of (anti-Müllerian hormone) and (bone morphogenetic protein) genes in regulating follicular growth and ovulation rate together with species differences in maintaining luteal function during pregnancy. Collectively, the evidence suggests that the oocyte is a key organizer of normal ovarian function. It has been shown to influence the phenotype of the adjacent somatic cells, the growth and maturation of the follicle, and to determine the ovulation rate. When germ cells or oocytes are lost prematurely, the ovary becomes disorganized and a wide range of pathologies may arise.
Topics: Animals; Biological Evolution; Female; Humans; Oogenesis; Ovary; Ovulation
PubMed: 34207147
DOI: 10.3390/genes12060928 -
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 -
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 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 -
International Journal of Molecular... Jun 2020Each follicle represents the basic functional unit of the ovary. From its very initial stage of development, the follicle consists of an oocyte surrounded by somatic... (Review)
Review
Each follicle represents the basic functional unit of the ovary. From its very initial stage of development, the follicle consists of an oocyte surrounded by somatic cells. The oocyte grows and matures to become fertilizable and the somatic cells proliferate and differentiate into the major suppliers of steroid sex hormones as well as generators of other local regulators. The process by which a follicle forms, proceeds through several growing stages, develops to eventually release the mature oocyte, and turns into a corpus luteum (CL) is known as "folliculogenesis". The task of this review is to define the different stages of folliculogenesis culminating at ovulation and CL formation, and to summarize the most recent information regarding the newly identified factors that regulate the specific stages of this highly intricated process. This information comprises of either novel regulators involved in ovarian biology, such as , Phoenixin/GPR73, C1QTNF, and α-SNAP, or recently identified members of signaling pathways previously reported in this context, namely PKB/Akt, HIPPO, and Notch.
Topics: Animals; Female; Gonadal Steroid Hormones; Humans; Oogenesis; Ovarian Follicle; Ovulation; Signal Transduction
PubMed: 32604954
DOI: 10.3390/ijms21124565 -
Journal of Assisted Reproduction and... Jun 2021Oocyte in vitro maturation (IVM) is an assisted reproductive technology designed to obtain mature oocytes following culture of immature cumulus-oocyte complexes... (Review)
Review
Oocyte in vitro maturation (IVM) is an assisted reproductive technology designed to obtain mature oocytes following culture of immature cumulus-oocyte complexes collected from antral follicles. Although IVM has been practiced for decades and is no longer considered experimental, the uptake of IVM in clinical practice is currently limited. The purpose of this review is to ensure reproductive medicine professionals understand the appropriate use of IVM drawn from the best available evidence supporting its clinical potential and safety in selected patient groups. This group of scientists and fertility specialists, with expertise in IVM in the ART laboratory and/or clinic, explore here the development of IVM towards acquisition of a non-experimental status and, in addition, critically appraise the current and future role of IVM in human ART.
Topics: Female; Humans; In Vitro Oocyte Maturation Techniques; Meiosis; Oocytes; Oogenesis; Ovarian Follicle; Polycystic Ovary Syndrome; Reproductive Techniques, Assisted
PubMed: 34218388
DOI: 10.1007/s10815-021-02263-5