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Human Reproduction Update Jul 2023Regulated cell death is a fundamental component of numerous physiological processes; spanning from organogenesis in utero, to normal cell turnover during adulthood, as... (Review)
Review
BACKGROUND
Regulated cell death is a fundamental component of numerous physiological processes; spanning from organogenesis in utero, to normal cell turnover during adulthood, as well as the elimination of infected or damaged cells throughout life. Quality control through regulation of cell death pathways is particularly important in the germline, which is responsible for the generation of offspring. Women are born with their entire supply of germ cells, housed in functional units known as follicles. Follicles contain an oocyte, as well as specialized somatic granulosa cells essential for oocyte survival. Follicle loss-via regulated cell death-occurs throughout follicle development and life, and can be accelerated following exposure to various environmental and lifestyle factors. It is thought that the elimination of damaged follicles is necessary to ensure that only the best quality oocytes are available for reproduction.
OBJECTIVE AND RATIONALE
Understanding the precise factors involved in triggering and executing follicle death is crucial to uncovering how follicle endowment is initially determined, as well as how follicle number is maintained throughout puberty, reproductive life, and ovarian ageing in women. Apoptosis is established as essential for ovarian homeostasis at all stages of development and life. However, involvement of other cell death pathways in the ovary is less established. This review aims to summarize the most recent literature on cell death regulators in the ovary, with a particular focus on non-apoptotic pathways and their functions throughout the discrete stages of ovarian development and reproductive life.
SEARCH METHODS
Comprehensive literature searches were carried out using PubMed and Google Scholar for human, animal, and cellular studies published until August 2022 using the following search terms: oogenesis, follicle formation, follicle atresia, oocyte loss, oocyte apoptosis, regulated cell death in the ovary, non-apoptotic cell death in the ovary, premature ovarian insufficiency, primordial follicles, oocyte quality control, granulosa cell death, autophagy in the ovary, autophagy in oocytes, necroptosis in the ovary, necroptosis in oocytes, pyroptosis in the ovary, pyroptosis in oocytes, parthanatos in the ovary, and parthanatos in oocytes.
OUTCOMES
Numerous regulated cell death pathways operate in mammalian cells, including apoptosis, autophagic cell death, necroptosis, and pyroptosis. However, our understanding of the distinct cell death mediators in each ovarian cell type and follicle class across the different stages of life remains the source of ongoing investigation. Here, we highlight recent evidence for the contribution of non-apoptotic pathways to ovarian development and function. In particular, we discuss the involvement of autophagy during follicle formation and the role of autophagic cell death, necroptosis, pyroptosis, and parthanatos during follicle atresia, particularly in response to physiological stressors (e.g. oxidative stress).
WIDER IMPLICATIONS
Improved knowledge of the roles of each regulated cell death pathway in the ovary is vital for understanding ovarian development, as well as maintenance of ovarian function throughout the lifespan. This information is pertinent not only to our understanding of endocrine health, reproductive health, and fertility in women but also to enable identification of novel fertility preservation targets.
Topics: Adult; Animals; Female; Humans; Apoptosis; Granulosa Cells; Mammals; Oocytes; Ovarian Follicle; Ovary; Regulated Cell Death; Homeostasis
PubMed: 36857094
DOI: 10.1093/humupd/dmad005 -
Journal of Assisted Reproduction and... Jun 2023The storage and release of calcium ions (Ca2 +) in oocyte maturation and fertilization are particularly noteworthy features of the endoplasmic reticulum (ER). The ER... (Review)
Review
The storage and release of calcium ions (Ca2 +) in oocyte maturation and fertilization are particularly noteworthy features of the endoplasmic reticulum (ER). The ER is the largest organelle in the cell composed of rough ER, smooth ER, and nuclear envelope, and is the main site of protein synthesis, transport and folding, and lipid and steroid synthesis. An appropriate calcium signaling response can initiate oocyte development and embryogenesis, and the ER is the central link that initiates calcium signaling. The transition from immature oocytes to zygotes also requires many coordinated organelle reorganizations and changes. Therefore, the purpose of this review is to generalize information on the function, structure, interaction with other organelles, and spatiotemporal localization of the ER in mammalian oocytes. Mechanisms related to maintaining ER homeostasis have been extensively studied in recent years. Resolving ER stress through the unfolded protein response (UPR) is one of them. We combined the clinical problems caused by the ER in in vitro maturation (IVM), and the mechanisms of ER have been identified by single-cell RNA-seq. This article systematically reviews the functions of ER and provides a reference for assisted reproductive technology (ART) research.
Topics: Animals; Oocytes; Unfolded Protein Response; Endoplasmic Reticulum Stress; Oogenesis; Endoplasmic Reticulum; Mammals
PubMed: 37171741
DOI: 10.1007/s10815-023-02782-3 -
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 -
Journal of Assisted Reproduction and... Oct 2023The biggest cell in the human body, the oocyte, encloses almost the complete machinery to start life. Despite all the research performed to date, defining oocyte quality... (Review)
Review
The biggest cell in the human body, the oocyte, encloses almost the complete machinery to start life. Despite all the research performed to date, defining oocyte quality is still a major goal of reproductive science. It is the consensus that mature oocytes are transcriptionally silent although, during their growth, the cell goes through stages of active transcription and translation, which will endow the oocyte with the competence to undergo nuclear maturation, and the oocyte and embryo to initiate timely translation before the embryonic genome is fully activated (cytoplasmic maturation). A systematic search was conducted across three electronic databases and the literature was critically appraised using the KMET score system. The aim was to identify quantitative differences in transcriptome of human oocytes that may link to patient demographics that could affect oocyte competence. Data was analysed following the principles of thematic analysis. Differences in the transcriptome were identified with respect to age or pathological conditions and affected chromosome mis segregation, perturbations of the nuclear envelope, premature maturation, and alterations in metabolic pathways-amongst others-in human oocytes.
Topics: Humans; Oocytes; Oogenesis; Transcriptome; Cytoplasm; RNA, Messenger
PubMed: 37558907
DOI: 10.1007/s10815-023-02906-9 -
International Journal of Molecular... Aug 2022Worldwide, infertility affects between 10 and 15% of reproductive-aged couples. Female infertility represents an increasing health issue, principally in developing... (Review)
Review
Worldwide, infertility affects between 10 and 15% of reproductive-aged couples. Female infertility represents an increasing health issue, principally in developing countries, as the current inclinations of delaying pregnancy beyond 35 years of age significantly decrease fertility rates. Female infertility, commonly imputable to ovulation disorders, can be influenced by several factors, including congenital malformations, hormonal dysfunction, and individual lifestyle choices, such as smoking cigarettes, stress, drug use and physical activity. Moreover, diet-related elements play an important role in the regulation of ovulation. Modern types of diet that encourage a high fat intake exert a particularly negative effect on ovulation, affecting the safety of gametes and the implantation of a healthy embryo. Identifying and understanding the cellular and molecular mechanisms responsible for diet-associated infertility might help clarify the confounding multifaceted elements of infertility and uncover novel, potentially curative treatments. In this view, this systematic revision of literature will summarize the current body of knowledge of the potential effect of high-fat diet (HFD) exposure on oocyte and follicular quality and consequent female reproductive function, with particular reference to molecular mechanisms and pathways. Inflammation, oxidative stress, gene expression and epigenetics represent the main mechanisms associated with mammal folliculogenesis and oogenesis.
Topics: Animals; Diet, High-Fat; Female; Humans; Infertility, Female; Mammals; Oocytes; Oogenesis; Ovulation; Pregnancy
PubMed: 36012154
DOI: 10.3390/ijms23168890 -
Reproductive Biomedicine Online Oct 2022Ovarian tissue cryopreservation and subsequent autotransplantation is a successful technique for fertility preservation in oncological patients. However, there are... (Review)
Review
Ovarian tissue cryopreservation and subsequent autotransplantation is a successful technique for fertility preservation in oncological patients. However, there are concerns regarding safety, as the graft may contain malignant cells that could lead to the reintroduction of cancer. To circumvent this problem several experimental strategies are being pursued. This systematic review was conducted to provide an overview of the strategies aiming to safely use cryopreserved human ovarian tissue to restore fertility after cancer. Thirty-one studies were included, covering five different experimental strategies: (i) in-vitro maturation of oocytes, (ii) constructing an artificial ovary as a scaffold for reseeding pre-antral follicles, (iii) purging strategies aimed at the eradication of contaminating malignant cells, (iv) maturation of oocytes by xenotransplantation, and (v) stem cell-based oogenesis. These strategies to circumvent the reintroduction of cancer cells through ovarian tissue autotransplantation are being developed, but so far have not reached the stage of clinical trials. Further research is required to establish their risks and effectiveness while the ethical aspects associated with these strategies also need to be discussed. Despite the fact that these experimental procedures are still under development, they might provide safe fertility restoration options for oncological patients in the future.
Topics: Cryopreservation; Female; Fertility Preservation; Humans; Neoplasms; Oocytes; Oogenesis; Ovary
PubMed: 35945106
DOI: 10.1016/j.rbmo.2022.05.020 -
Fertility and Sterility Jun 2015To systematically review the reporting of MII (MII) oocyte development after xenotransplantation of human ovarian tissue. (Review)
Review
Xenotransplantation of cryopreserved human ovarian tissue--a systematic review of MII oocyte maturation and discussion of it as a realistic option for restoring fertility after cancer treatment.
OBJECTIVE
To systematically review the reporting of MII (MII) oocyte development after xenotransplantation of human ovarian tissue.
DESIGN
Systematic review in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA).
SETTING
Not applicable.
PATIENT(S)
Not applicable.
INTERVENTION(S)
Formation of MII oocytes after xenotransplantation of human ovarian tissue.
MAIN OUTCOME MEASURE(S)
Any outcome reported in Pubmed.
RESULT(S)
Six publications were identified that report on formation of MII oocytes after xenotransplantation of human ovarian tissue.
CONCLUSION(S)
Xenografting of human ovarian tissue has proved to be a useful model for examining ovarian function and follicle development in vivo. With human follicles that have matured through xenografting, the possibility of cancer transmission and relapse can also be eliminated, because cancer cells are not able to penetrate the zona pellucida. The reported studies have demonstrated that xenografted ovarian tissue from a range of species, including humans, can produce antral follicles that contain mature (MII) oocytes, and it has been shown that mice oocytes have the potential to give rise to live young. Although some ethical questions remain unresolved, xenotransplantation may be a promising method for restoring fertility. This review furthermore describes the value of xenotransplantation as a tool in reproductive biology and discusses the ethical and potential safety issues regarding ovarian tissue xenotransplantation as a means of recovering fertility.
Topics: Animals; Cell Survival; Cells, Cultured; Cryopreservation; Female; Fertility Preservation; Humans; Mice; Mice, SCID; Neoplasms; Oocyte Retrieval; Oocytes; Oogenesis; Transplantation, Heterologous
PubMed: 25881879
DOI: 10.1016/j.fertnstert.2015.03.001 -
Journal of Assisted Reproduction and... Jan 2022Does existing scientific literature suggest an impact of oocyte dysmorphisms on biological or clinical outcomes of assisted reproduction treatments?
PURPOSE
Does existing scientific literature suggest an impact of oocyte dysmorphisms on biological or clinical outcomes of assisted reproduction treatments?
METHODS
Studies of interest were selected from an initial cohort of 6651 potentially relevant records retrieved. PubMed was systematically searched for peer-reviewed original papers and reviews identified by keywords and medical subject heading (MeSH) terms. The most relevant publications were critically evaluated to identify criteria for oocyte morphological evaluation and IVF outcomes. For each morphological abnormality, we generated an oocyte literature score (OLS) through the following procedure: (a) papers showing a negative, absence of, or positive correlation between a given abnormality and IVF outcome were scored 1, 0, and - 1, respectively; (b) the sum of these scores was expressed as a fraction of all analyzed papers; (c) the obtained fraction was multiplied by 10 and converted into decimal number.
RESULT
We identified eleven different dysmorphisms, of which six were extracytoplasmic (COC, zona pellucida, perivitelline space, polar body 1, shape, giant size) and five intracytoplasmic (vacuoles, refractile bodies, SER clusters, granularity, color). Among the extracytoplasmic dysmorphisms, abnormal morphology of the COC generated an OLS of 8.33, indicating a large prevalence (5/6) of studies associated with a negative outcome. Three intracytoplasmic dysmorphisms (vacuoles, SER clusters, and granularity) produced OLS of 7.14, 7.78, and 6.25, respectively, suggestive of a majority of studies reporting a negative outcome.
CONCLUSION
COC morphology, vacuoles, SER clusters, and granularity produced OLS suggestive of a prevalence of studies reporting a negative outcome.
Topics: Humans; Oocytes; Oogenesis; Zona Pellucida
PubMed: 34993709
DOI: 10.1007/s10815-021-02370-3