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Frontiers in Cell and Developmental... 2021Premature ovarian insufficiency (POI) is the loss of normal ovarian function before the age of 40 years, a condition that affects approximately 1% of women under 40... (Review)
Review
Premature ovarian insufficiency (POI) is the loss of normal ovarian function before the age of 40 years, a condition that affects approximately 1% of women under 40 years old and 0.1% of women under 30 years old. It is biochemically characterized by amenorrhea with hypoestrogenic and hypergonadotropic conditions, in some cases, causing loss of fertility. Heterogeneity of POI is registered by genetic and non-genetic causes, such as autoimmunity, environmental toxins, and chemicals. The identification of possible causative genes and selection of candidate genes for POI confirmation remain to be elucidated in cases of idiopathic POI. This review discusses the current understanding and future prospects of heterogeneous POI. We focus on the genetic basis of POI and the recent studies on non-coding RNA in POI pathogenesis as well as on animal models of POI pathogenesis, which help unravel POI mechanisms and potential targets. Despite the latest discoveries, the crosstalk among gene regulatory networks and the possible therapies targeting the same needs to explore in near future.
PubMed: 34041247
DOI: 10.3389/fcell.2021.672890 -
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 -
International Journal of Environmental... Apr 2022Regenerative medicine combines elements of tissue engineering and molecular biology aiming to support the regeneration and repair processes of damaged tissues, cells and... (Review)
Review
Regenerative medicine combines elements of tissue engineering and molecular biology aiming to support the regeneration and repair processes of damaged tissues, cells and organs. The most commonly used preparation in regenerative medicine is platelet rich plasma (PRP) containing numerous growth factors present in platelet granularities. This therapy is increasingly used in various fields of medicine. This article is a review of literature on the use of PRP in gynecology and obstetrics. There is no doubt that the released growth factors and proteins have a beneficial effect on wound healing and regeneration processes. So far, its widest application is in reproductive medicine, especially in cases of thin endometrium, Asherman's syndrome, or premature ovarian failure (POF) but also in wound healing and lower urinary tract symptoms (LUTS), such as urinary incontinence or recurrent genitourinary fistula auxiliary treatment. Further research is, however, needed to confirm the effectiveness and the possibility of its application in many other disorders.
Topics: Endometrium; Female; Gynecology; Humans; Platelet-Rich Plasma; Pregnancy; Regenerative Medicine; Tissue Engineering
PubMed: 35564681
DOI: 10.3390/ijerph19095284 -
Annales D'endocrinologie Aug 2022Turner syndrome (TS) is tightly associated with hypergonadotropic hypogonadism and ovarian dysgenesis, typically resulting in infertility in the great majority of...
Turner syndrome (TS) is tightly associated with hypergonadotropic hypogonadism and ovarian dysgenesis, typically resulting in infertility in the great majority of patients. Therefore females with TS are usually treated with female sex steroids from 11-12years of age until the normal age of natural menopause of around 53-54years of age. Infertility is rated among females with TS as a distressing concern and a detractor from a good quality of life. Options for motherhood for females with TS has expanded during recent years. Originally, only adoption was an option, unless of course for the small minority of TS females that still has ovarian function and are capable of achieving pregnancy through normal means. Oocyte donation has become the mainstream option in many countries and seems to work well, especially if patients have been treated with optimal estrogen and gestagen for a prolonged time before the intervention. It comes with an increased risk of cardiovascular complications and TS oocyte donation pregnancies are viewed as high risk pregnancies necessitating increased vigilance. Oocyte cryopreservation of own oocytes is also becoming an option in a select group of TS and has special challenges. Ovarian tissue cryopreservation is a promising new techniques that has been applied successfully in children with cancer. Currently, several trials are running around the world evaluating this techniques in TS. The genetics and genomics behind the ovarian dysgenesis seen in TS is not understood, but new studies have elucidated global changes in DNA methylation and RNA expression in blood from persons with TS and it is likely that similar changes are present in the ovaries. We still, however, need more thorough research to fully uncover the genetic background of ovarian failure in TS. Gene expression studies and methylation analysis from ovarian TS tissues still needs to be performed.
Topics: Cryopreservation; Female; Fertility; Fertility Preservation; Humans; Infertility; Pregnancy; Primary Ovarian Insufficiency; Quality of Life; Turner Syndrome
PubMed: 35728697
DOI: 10.1016/j.ando.2022.06.001 -
Frontiers in Medicine 2022Premature ovarian failure (POF) is a multifactorial disease that refers to the occurrence of secondary amenorrhea, estrogen decrease, and gonadotropin increase in women... (Review)
Review
Premature ovarian failure (POF) is a multifactorial disease that refers to the occurrence of secondary amenorrhea, estrogen decrease, and gonadotropin increase in women under the age of 40. The prevalence of POF is increasing year by year, and the existing instances can be categorized as primary or secondary cases. This disease has adverse effects on both the physiology and psychology of women. Hormone replacement therapy is the recommended treatment for POF, and a multidisciplinary strategy is required to enhance the quality of life of patients. According to recent studies, the primary mechanism of POF is the depletion of ovarian reserve function as a result of increased primordial follicular activation or primordial follicular insufficiency. Therefore, understanding the processes of primordial follicle activation and associated pathways and exploring effective interventions are important for the treatment of POF.
PubMed: 36507521
DOI: 10.3389/fmed.2022.999440 -
Nature Communications Feb 2022Premature ovarian failure (POF) is a leading cause of women's infertility without effective treatment. Here we show that intravenous injection of Ab4B19, an agonistic... (Observational Study)
Observational Study
Premature ovarian failure (POF) is a leading cause of women's infertility without effective treatment. Here we show that intravenous injection of Ab4B19, an agonistic antibody for the BDNF receptor TrkB, penetrates into ovarian follicles, activates TrkB signaling, and promotes ovary development. In both natural aging and cyclophosphamide-induced POF models, treatment with Ab4B19 completely reverses the reduction of pre-antral and antral follicles, and normalizes gonadal hormone. Ab4B19 also attenuates gonadotoxicity and inhibits apoptosis in cyclophosphamide-induced POF ovaries. Further, treatment with Ab4B19, but not BDNF, restores the number and quality of oocytes and enhances fertility. In human, BDNF levels are high in granulosa cells and TrkB levels increase in oocytes as they mature. Moreover, BDNF expression is down-regulated in follicles of aged women, and Ab4B19 activates TrkB signaling in human ovary tissue ex vivo. These results identify TrkB as a potential target for POF with differentiated mechanisms, and confirms superiority of TrkB activating antibody over BDNF as therapeutic agents.
Topics: Adult; Aging; Animals; Apoptosis; Brain-Derived Neurotrophic Factor; Cell Line, Tumor; Cyclophosphamide; Disease Models, Animal; Female; Fertility; Fertility Agents, Female; Humans; Male; Membrane Glycoproteins; Mice; Middle Aged; Organ Culture Techniques; Ovary; Primary Ovarian Insufficiency; Receptor, trkB; Young Adult
PubMed: 35177657
DOI: 10.1038/s41467-022-28611-2 -
Journal of Assisted Reproduction and... May 2021Platelet-rich plasma (PRP) has become a novel treatment in various aspects of medicine including orthopedics, cardiothoracic surgery, plastic surgery, dermatology,... (Review)
Review
PURPOSE
Platelet-rich plasma (PRP) has become a novel treatment in various aspects of medicine including orthopedics, cardiothoracic surgery, plastic surgery, dermatology, dentistry, and diabetic wound healing. PRP is now starting to become an area of interest in reproductive medicine more specifically focusing on infertility. Poor ovarian reserve, menopause, premature ovarian failure, and thin endometrium have been the main areas of research. The aim of this article is to review the existing literature on the effects of autologous PRP in reproductive medicine providing a summation of the current studies and assessing the need for additional research.
METHODS
A literature search is performed using PubMed, MEDLINE, and CINAHL Plus to identify studies focusing on the use of PRP therapy in reproductive medicine. Articles were divided into 3 categories: PRP in thin lining, PRP in poor ovarian reserve, and PRP in recurrent implantation failure.
RESULTS
In women with thin endometrium, the literature shows an increase in endometrial thickness and increase in chemical and clinical pregnancy rates following autologous PRP therapy. In women with poor ovarian reserve, autologous intraovarian PRP therapy increased anti-Mullerian hormone (AMH) levels and decreased follicle-stimulating hormone (FSH), with a trend toward increasing clinical and live birth rates. This trend was also noted in women with recurrent implantation failure.
CONCLUSIONS
Limited literature shows promise in increasing endometrial thickness, increasing AMH, and decreasing FSH levels, as well as increasing chemical and clinical pregnancy rates. The lack of standardization of PRP preparation along with the lack of large randomized controlled trials needs to be addressed in future studies. Until definitive large RCTs are available, PRP use should be considered experimental.
Topics: Anti-Mullerian Hormone; Female; Fertilization in Vitro; Humans; Infertility, Female; Ovarian Reserve; Ovulation Induction; Platelet-Rich Plasma; Pregnancy; Reproductive Medicine
PubMed: 33723748
DOI: 10.1007/s10815-021-02146-9 -
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 -
Stem Cell Research & Therapy Aug 2021As one of the problems and diseases for women before 40 years, premature ovarian failure (POF) could be characterized by amenorrhea, low estrogen levels, infertility,... (Review)
Review
As one of the problems and diseases for women before 40 years, premature ovarian failure (POF) could be characterized by amenorrhea, low estrogen levels, infertility, high gonadotropin levels, and lack of mature follicles. Causes of the disease involve some genetic disorders, autoimmunity diseases, and environmental factors. Various approaches have been employed to treat POF, however with limited success. Today, stem cells are used to treat POF, since they have the potential to self-repair and regenerate, and are effective in treating ovarian failure and infertility. As mesenchymal stem cell (MSC) could simultaneously activate several mechanisms, many researchers consider MSC transplantation to be the best and most effective approach in cell therapy. A good source for mesenchymal stem cells is human umbilical cord (HUCMSC). Animal models with cyclophosphamide are required for stem cell treatment and performance of HUCMSC transplantation. Stem cell therapy could indicate the levels of ovarian markers and follicle-stimulating hormone receptor. It also increases ovarian weight, plasma E2 levels, and the amount of standard follicles. Herein, the causes of POF, effective treatment strategies, and the effect of HUCMSC transplantation for the treatment of premature ovarian failure are reviewed. Many studies have been conducted in this field, and the results have shown that stem cell treatment is an effective approach to treat infertility.
Topics: Animals; Female; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Primary Ovarian Insufficiency; Umbilical Cord
PubMed: 34380572
DOI: 10.1186/s13287-021-02529-w -
Journal of Ovarian Research Sep 2022Ovarian aging refers to the process by which ovarian function declines until eventual failure. The pathogenesis of ovarian aging is complex and diverse; oxidative stress... (Review)
Review
Ovarian aging refers to the process by which ovarian function declines until eventual failure. The pathogenesis of ovarian aging is complex and diverse; oxidative stress (OS) is considered to be a key factor. This review focuses on the fact that OS status accelerates the ovarian aging process by promoting apoptosis, inflammation, mitochondrial damage, telomere shortening and biomacromolecular damage. Current evidence suggests that aging, smoking, high-sugar diets, pressure, superovulation, chemotherapeutic agents and industrial pollutants can be factors that accelerate ovarian aging by exacerbating OS status. In addition, we review the role of nuclear factor E2-related factor 2 (Nrf2), Sirtuin (Sirt), mitogen-activated protein kinase (MAPK), protein kinase B (AKT), Forkhead box O (FoxO) and Klotho signaling pathways during the process of ovarian aging. We also explore the role of antioxidant therapies such as melatonin, vitamins, stem cell therapies, antioxidant monomers and Traditional Chinese Medicine (TCM), and investigate the roles of these supplements with respect to the reduction of OS and the improvement of ovarian function. This review provides a rationale for antioxidant therapy to improve ovarian aging.
Topics: Antioxidants; Female; Humans; NF-E2-Related Factor 2; Ovary; Oxidative Stress
PubMed: 36050696
DOI: 10.1186/s13048-022-01032-x