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Cell Transplantation 2020Ovarian insufficiency is described as a multifaceted issue typically encountered in the field of assisted reproduction. The three main identified diagnoses of ovarian... (Review)
Review
Ovarian insufficiency is described as a multifaceted issue typically encountered in the field of assisted reproduction. The three main identified diagnoses of ovarian insufficiency include premature ovarian failure (POF), poor ovarian response (POR), and advanced maternal age (AMA). Patient heterogeneity in the era of individualized medicine drives research forward leading to the emergence of novel approaches. This plethora of innovative treatments in the service of adequately managing ovarian insufficiency is called to undertake the challenge of addressing infertile patients exploring their reproductive options. This review provides an all-inclusive presentation and critical analysis on novel treatments that have not achieved routine clinical practice status yet, but have recently emerged as promising. In light of the lack of randomized controlled trials conveying safety and efficiency, clinicians are left puzzled in addressing the "how" and "for whom" these approaches may be beneficial. From ovarian injection employing platelet-rich plasma (PRP) or stem cells to artificial gametes and ovaries, ovarian transplantation, and mitochondrial replacement therapy, this descriptive review provides insight toward assisting the practitioner in decision making regarding these cutting-edge treatments. Biological mechanisms, invasiveness levels, efficiency, as well as possible complications, the current status along with bioethical concerns are discussed in the context of identifying future optimal treatment.
Topics: Animals; Female; Humans; Primary Ovarian Insufficiency; Randomized Controlled Trials as Topic; Stem Cell Transplantation
PubMed: 32686983
DOI: 10.1177/0963689720926154 -
Frontiers in Endocrinology 2023Ovarian dysfunction is one of the most common features of women with Turner syndrome. In these women, oocyte apoptosis is markedly accelerated from the early stage of... (Review)
Review
Ovarian dysfunction is one of the most common features of women with Turner syndrome. In these women, oocyte apoptosis is markedly accelerated from the early stage of fetal life. Reduction in the number of germ cells disturbs primordial follicle development and thereby leads to the formation of streak gonads. There are three possible causes of accelerated germ cell loss in 45,X ovaries. First, chromosomal pairing failure due to X chromosomal aneuploidy is believed to induce meiotic arrest. Indeed, it has been suggested that the dosage of the X chromosome is more critical for the survival of the oocytes than for other cells in the ovary. Second, impaired coupling between oocytes and granulosa cells may also contribute to germ cell apoptosis. Previous studies have shown that 45,X ovaries may tend to lose tight junctions which are essential for intercellular interactions. Lastly, ovarian dysfunction in women with Turner syndrome is partly attributable to the reduced dosage of several genes on the X chromosome. Specifically, , , and some other genes on the X chromosome have been implicated in ovarian function. Further studies on the mechanisms of ovarian dysfunction are necessary to improve the reproductive outcomes of women with Turner syndrome.
Topics: Humans; Female; Turner Syndrome; Ovarian Follicle; Oocytes; Granulosa Cells; Ovarian Diseases; Membrane Proteins; Receptors, Progesterone
PubMed: 37033245
DOI: 10.3389/fendo.2023.1160258 -
Gynecological Endocrinology : the... Dec 2023Premature ovarian failure (POF), also known as primary ovarian insufficiency, is a major cause of infertility in female worldwide. Excessive apoptosis and impaired...
OBJECTIVE
Premature ovarian failure (POF), also known as primary ovarian insufficiency, is a major cause of infertility in female worldwide. Excessive apoptosis and impaired autophagy in ovarian granulosa cells are the main pathological mechanisms of POF. The total flavonoids from (TFSC) are often used in the treatment of gynecological endocrine disorders. In addition, low intensity pulsed ultrasound (LIPUS) is report as an effective method to improve ovarian function. This study aims to investigate the protective effect of POF by the combined use of TFSC and LIPUS.
METHODS
POF rats model and granulosa cell model were successfully induced by tripterygium glycosides and cyclophosphamide, respectively. After that, model rats and cells received TFSC plus LIPUS administration. Then ovarian histomorphology, senescence, estrus cycle, and serum sex hormone levels were detected in rats. Ovarian tissue and granulosa cells autophagy and apoptosis levels were also assessed.
RESULTS
Disturbed sex hormone levels, atrophied and senescent ovaries, and abnormal estrous cycle were found in POF rats. Meanwhile, cell autophagy was inhibited and cell apoptosis was activated in POF ovarian tissue and granulosa cells. However, TFSC combined with LIPUS improved these changes, and this combination treatment exhibited synergistic effects. The abnormal expression of the cell apoptosis-, autophagy-, and PI3K/AKT/mTOR signaling pathway-related proteins were also improved by combination treatment.
CONCLUSION
The study found that the combination of TFSC and LIPUS can alleviate POF by modulating cell autophagy and apoptosis. The findings may provide a viable scientific basis for POF treatment.
Topics: Animals; Female; Humans; Rats; Apoptosis; Flavonoids; Gonadal Steroid Hormones; Granulosa Cells; Phosphatidylinositol 3-Kinases; Primary Ovarian Insufficiency; Semen; Ultrasonic Waves; Drugs, Chinese Herbal
PubMed: 37855244
DOI: 10.1080/09513590.2023.2258422 -
Brain Communications 2022To date, potential mechanisms of menopause-related memory and cognitive deficits have not been elucidated. Therefore, we studied brain oscillations, their...
To date, potential mechanisms of menopause-related memory and cognitive deficits have not been elucidated. Therefore, we studied brain oscillations, their phase-amplitude coupling, sleep and vigilance state patterns, running wheel use and other behavioural measures in a translationally valid mouse model of menopause, the 4-vinylcyclohexene-diepoxide-induced accelerated ovarian failure. After accelerated ovarian failure, female mice show significant alterations in brain rhythms, including changes in the frequencies of θ (5-12 Hz) and γ (30-120 Hz) oscillations, a reversed phase-amplitude coupling, altered coupling of hippocampal sharp-wave ripples to medial prefrontal cortical sleep spindles and reduced δ oscillation (0.5-4 Hz) synchrony between the two regions during non-rapid eye movement sleep. In addition, we report on significant circadian variations in the frequencies of θ and γ oscillations, and massive synchronous δ oscillations during wheel running. Our results reveal novel and specific network alterations and feasible signs for diminished brain connectivity in the accelerated ovarian failure mouse model of menopause. Taken together, our results may have identified changes possibly responsible for some of the memory and cognitive deficits previously described in this model. Corresponding future studies in menopausal women could shed light on fundamental mechanisms underlying the neurological and psychiatric comorbidities present during this important transitional phase in women's lives.
PubMed: 35794872
DOI: 10.1093/braincomms/fcac166 -
Journal of Traditional and... Jul 2023Recent studies show that combination of apoptosis and oxidative stress forms a "vicious circle" in the process of premature ovarian failure (POF). Pearl extract has a...
BACKGROUND AND AIM
Recent studies show that combination of apoptosis and oxidative stress forms a "vicious circle" in the process of premature ovarian failure (POF). Pearl extract has a good effect for anti-oxidation and anti-aging in vitro and vivo and can be used to treat various aging diseases. However, reports about effect and mechanism of pearl on ovarian function of premature ovarian failure (POF)are limited.
EXPERIMENTAL PROCEDURE
The effect and mechanism of pearl on ovarian function of rats with POF were evaluated using rats with premature ovarian failure induced by tripterygium glycosides. The estrous cycle, contents of serum reproductive hormones, tissue structure, oxidative stress level, autophagy and apoptotic protein expression, and MAPK signaling pathway of ovary were assessed to characterise pearl.
RESULT AND CONCLUSION
Low, medium and high-dose pearl improved the estrous cycle in POF rats, and high-dose pearl was the best in terms of recovery effect; high-dose pearl significantly increased ( < 0.05) contents of E2, AMH and GSH, activities of SOD, CAT and GSH-PX and follicular development, while significantly decreased ( < 0.05)contents of FSH, LH and ROS and MDA in POF rats; low, medium and high-dose pearl notably reduced ( < 0.05) the apoptotic protein cleaved-caspase 3 and Bax expression, and MAPK signaling pathway of ERK1/2, p38 and JNK in POF rats, among which high-dose pearl behaved best. Medium and high-dose pearl apparently raised ( < 0.05)expressions of autophagy protein LC3II, Beclin-1 and p62 in POF rats. Therefore, pearl can effectively enhance ovarian function of POF rats. The optimal concentration was found to be 740 mg kg at a high dose. The mechanism may be related with the enhanced follicular development through improving granulosa cell autophagy and inhibiting granulosa cell apoptosis by inhibition of MAPK signaling pathway after scavenging excessive ROS.
SECTION
1. Natural Products.
TAXONOMY CLASSIFICATION BY EVISE
Ovarian Cancer, Chinese Herbal Medicine, Traditional Medicine, Oxidative Stress, Antioxidant Studies, Rat, Autophagy.
PubMed: 37396156
DOI: 10.1016/j.jtcme.2023.02.004 -
Cancers Dec 2022Metastatic ovarian cancer is the main reason for treatment failures and consequent deaths. Ovarian cancer is predisposed to intraperitoneal dissemination. In comparison... (Review)
Review
Metastatic ovarian cancer is the main reason for treatment failures and consequent deaths. Ovarian cancer is predisposed to intraperitoneal dissemination. In comparison to the transcoelomic route, distant metastasis via lymph vessels and blood is less common. The mechanisms related to these two modes of cancer spread are poorly understood. Nevertheless, the presence of tumor cells circulating in the blood of OC patients is a well-established phenomenon confirming the significant role of lymphatic and hematogenous metastasis. Thus, the detection of CTCs may provide a minimally invasive tool for the identification of ovarian cancer, monitoring disease progression, and treatment effectiveness. This review focuses on the biology of ovarian CTCs and the role they may play in cancer diagnosis and therapy.
PubMed: 36551515
DOI: 10.3390/cancers14246030 -
Journal of Reproduction & Infertility 2017Premature ovarian failure (POF) is an ovarian defect characterized by the premature depletion of ovarian follicles before the age of 40, representing one major cause of...
BACKGROUND
Premature ovarian failure (POF) is an ovarian defect characterized by the premature depletion of ovarian follicles before the age of 40, representing one major cause of female infertility. Mutations in bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) have been shown to be associated with POF.
METHODS
Genomic DNA was isolated from 52 idiopathic premature ovarian failure patients and 100 normal control individuals. Exons of BMP15 and GDF9 gene were amplified using PCR method and subjected to directed sequencing. Variants were identified by comparing the sequences obtained with normal sequences from NCBI database.
RESULTS
Four BMP15 gene variants were identified in 6 patients in heterozygous condition. Out of these 4 variants, 3 variants namely, c.165A>T (p.Glu55Asp), c.538 G>T (p.Aln180 Ser) and c. 510_512 delT were novel variants. In silico analysis using SIFT, Provean and Polyphen 2 score predicted the non-deleterious effect of c.165A>T and c.538 G>T variant. 788insTCT variant was identified in 3 patients. No variant was identified in GDF9 gene in any patients and controls.
CONCLUSION
Although the variant has been identified in BMP15 gene but it may not be associated with the premature ovarian failure.
PubMed: 28377898
DOI: No ID Found -
Frontiers in Cell and Developmental... 2021Tet enzymes participate in DNA demethylation and play critical roles in stem cell pluripotency and differentiation. DNA methylation alters with age. We find that...
Tet enzymes participate in DNA demethylation and play critical roles in stem cell pluripotency and differentiation. DNA methylation alters with age. We find that deficiency reduces fertility and leads to accelerated reproductive failure with age. Noticeably, -deficient mice at young age exhibit dramatically reduced follicle reserve and the follicle reserve further decreases with age, phenomenon consistent with premature ovarian failure (POF) syndrome. Consequently, deficient mice become infertile by reproductive middle age, while age matched wild-type mice still robustly reproduce. Moreover, by single cell transcriptome analysis of oocytes, deficiency elevates organelle fission, associated with defects in ubiquitination and declined autophagy, and also upregulates signaling pathways for Alzheimer's diseases, but down-regulates X-chromosome linked genes, such as , which is known to be implicated in POF. Additionally, is aberrantly upregulated and endogenous retroviruses also are altered in deficient oocytes. These molecular changes are consistent with oocyte senescence and follicle atresia and depletion found in premature ovarian failure or insufficiency. Our data suggest that enzyme plays roles in maintaining oocyte quality as well as oocyte number and follicle reserve and its deficiency can lead to POF.
PubMed: 33834024
DOI: 10.3389/fcell.2021.644135 -
Frontiers in Endocrinology 2022As per the theory of traditional Chinese medicine (TCM), the liver and kidney dysfunction are important pathogenies for premature ovarian failure (POF). POF is a common...
As per the theory of traditional Chinese medicine (TCM), the liver and kidney dysfunction are important pathogenies for premature ovarian failure (POF). POF is a common gynecological disease that reduced the pregnancy rate. Electro-acupuncture (EA) is a useful non-pharmaceutical therapy that supposedly regulates the function of the liver and kidney in the treatment of POF with TCM. However, the underlying mechanism of EA in the treatment of POF has not been adequately studied through metabonomics with reference to the theory of TCM. Accordingly, we investigated the effect of EA on the liver and kidney metabolites in POF mice through metabolomics. POF mice were established intraperitoneal injection of cisplatin. Both Sanyinjiao (SP6) and Guanyuan (CV4) were stimulated by EA for 3 weeks. The biological samples (including the serum and the ovary, liver, and kidney tissues) were evaluated by histopathology, molecular biology, and hydrogen-1 nuclear magnetic resonance (HNMR)-based metabolomics to assess the efficacy of EA. HNMR data were analyzed by the orthogonal partial least squares discriminant analysis (OPLS-DA). The results revealed that EA was beneficial to ovarian function and the menstrual cycle of POF. Both the energy metabolism and neurotransmitter metabolism in the liver and kidney were regulated by EA. Notably, EA played an important role in regulating energy-related metabolism in the kidney, and the better effect of neurotransmitter-related metabolism in the liver was regulated by EA. These findings indicated that the ovarian functions could be improved and the metabolic disorder of the liver and kidney caused by POF could be regulated by EA. Our study results thus suggested that the EA therapy, based on the results for the liver and kidney, were related to POF in TCM, as preliminarily confirmed through metabolomics.
Topics: Acupuncture Therapy; Animals; Female; Humans; Kidney; Liver; Metabolic Diseases; Mice; Neurotransmitter Agents; Primary Ovarian Insufficiency
PubMed: 35957829
DOI: 10.3389/fendo.2022.882214 -
Current Molecular Medicine 2021Premature ovarian failure (POF) refers to ovarian dysfunction in women under 40 years old. It is characterized by low estrogen, high gonadotropin, amenorrhea, and... (Review)
Review
Premature ovarian failure (POF) refers to ovarian dysfunction in women under 40 years old. It is characterized by low estrogen, high gonadotropin, amenorrhea, and infertility, which seriously affect physical and mental health of women. The pathogenic factors of POF include iatrogenic factors, autoimmune factors, genetic factors, oxidative stress, infection, thyroid dysfunction, and adrenal diseases. Chemotherapy is a common cause of POF and is gaining increasing attention. With the development of modern medicine and advances in understanding cancer, women's cancer survival rates have been significantly increased. Currently, the main treatment options for POF are hormone supplement and in vitro activation (IVA), but there is still no specific treatment for POF. Stem cells, known as undifferentiated cells of multicellular organisms, exhibit characteristics of self-renewal, directional differentiation into different cells, and low immunogenicity. Thus, they have potential in regenerative medicine and provide a promising direction for POF treatment. In this review, we summarize the latest research progress of various stem cells in chemotherapy-induced POF models to provide a theoretical basis for further research and treatment.
Topics: Animals; Antineoplastic Agents; Cell Differentiation; Female; Humans; Ovarian Follicle; Primary Ovarian Insufficiency; Regenerative Medicine; Stem Cells
PubMed: 32888266
DOI: 10.2174/1566524020666200905113907