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Reproductive Biology Jun 2024Mitophagy, the cellular process that removes damaged mitochondria, plays a crucial role in maintaining normal cell functions. It is deeply involved in the entire process... (Review)
Review
Mitophagy, the cellular process that removes damaged mitochondria, plays a crucial role in maintaining normal cell functions. It is deeply involved in the entire process of follicle development and is associated with various ovarian diseases. This review aims to provide a comprehensive overview of mitophagy regulation, emphasizing its role at different stages of follicular development. Additionally, the study illuminates the relationship between mitophagy and ovarian diseases, including ovary aging (OA), primary ovarian insufficiency (POI), and polycystic ovary syndrome (PCOS). A detailed understanding of mitophagy could reveal valuable insights and novel strategies for managing female ovarian reproductive health.
Topics: Mitophagy; Female; Ovarian Follicle; Humans; Animals; Mitochondria; Primary Ovarian Insufficiency
PubMed: 38733657
DOI: 10.1016/j.repbio.2024.100889 -
Biology of Reproduction May 2022Benign disorders of the human female reproductive system, such primary ovarian insufficiency and polycystic ovary syndrome are associated with infertility and recurrent... (Review)
Review
Benign disorders of the human female reproductive system, such primary ovarian insufficiency and polycystic ovary syndrome are associated with infertility and recurrent miscarriage, as well as increased risk of adverse health outcomes, including cardiovascular disease and type 2 diabetes. For many of these conditions, the contributing molecular and cellular processes are poorly understood. The overarching similarities between mice and humans have rendered mouse models irreplaceable in understanding normal physiology and elucidating pathological processes that underlie disorders of the female reproductive system. The utilization of Cre-LoxP recombination technology, which allows for spatial and temporal control of gene expression, has identified the role of numerous genes in development of the female reproductive system and in processes, such as ovulation and endometrial decidualization, that are required for the establishment and maintenance of pregnancy in mammals. In this comprehensive review, we provide a detailed overview of Cre drivers with activity in the neuroendocrine-reproductive axis that have been used to study disruptions in key intracellular signaling pathways. We first summarize normal development of the hypothalamus, pituitary, ovary, and uterus, highlighting similarities and differences between mice and humans. We then describe human conditions resulting from abnormal development and/or function of the organ. Finally, we describe loss-of-function models for each Cre driver that elegantly recapitulate some key features of the human condition and are associated with impaired fertility. The examples we provide illustrate use of each Cre driver as a tool for elucidating genetic and molecular underpinnings of reproductive dysfunction.
Topics: Animals; Diabetes Mellitus, Type 2; Female; Humans; Integrases; Mice; Polycystic Ovary Syndrome; Pregnancy; Reproduction
PubMed: 35084017
DOI: 10.1093/biolre/ioac012 -
Journal of Ovarian Research Nov 2023Clinical prediction models play an important role in the field of medicine. These can help predict the probability of an individual suffering from disease,... (Review)
Review
Clinical prediction models play an important role in the field of medicine. These can help predict the probability of an individual suffering from disease, complications, and treatment outcomes by applying specific methodologies. Polycystic ovary syndrome (PCOS) is a common disease with a high incidence rate, huge heterogeneity, short- and long-term complications, and complex treatments. In this systematic review study, we reviewed the progress of clinical prediction models in PCOS patients, including diagnosis and prediction models for PCOS complications and treatment outcomes. We aimed to provide ideas for medical researchers and clues for the management of PCOS. In the future, models with poor accuracy can be greatly improved by adding well-known parameters and validations, which will further expand our understanding of PCOS in terms of precision medicine. By developing a series of predictive models, we can make the definition of PCOS more accurate, which can improve the diagnosis of PCOS and reduce the likelihood of false positives and false negatives. It will also help discover complications earlier and treatment outcomes being known earlier, which can result in better outcomes for women with PCOS.
Topics: Female; Humans; Polycystic Ovary Syndrome; Models, Statistical; Prognosis
PubMed: 38007488
DOI: 10.1186/s13048-023-01310-2 -
Radiologia 2022The main objective in the imaging differential diagnosis of an ovarian mass is to establish whether it is cystic or solid; solid lesions are less common. Ovarian...
The main objective in the imaging differential diagnosis of an ovarian mass is to establish whether it is cystic or solid; solid lesions are less common. Ovarian fibromatosis is a benign disease of the ovary that is rarely included in the differential diagnosis of solid ovarian lesions. Characteristic features of masses that have a fibrous component are low signal in T1-weighted MRI sequences and especially in T2-weighted MRI sequences. The presence of peripheral fibrotic tissue around the residual ovarian tissue is specific to ovarian fibromatosis; on MRI, this results in marked hypointensity on T2-weighted images that has been dubbed the "black garland sign". This sign, together with slight peripheral enhancement after the administration of contrast material and the preservation of the ovarian architecture, facilitates the diagnosis, making it possible to avoid unnecessary surgical interventions.
Topics: Contrast Media; Female; Fibroma; Humans; Ovarian Cysts; Ovarian Neoplasms
PubMed: 35504682
DOI: 10.1016/j.rxeng.2020.11.009 -
Fertility and Sterility May 2022Polycystic ovary syndrome (PCOS), first described over 80 years ago, is a chronic condition with gynecologic, metabolic, and psychologic manifestations. Both... (Review)
Review
Polycystic ovary syndrome (PCOS), first described over 80 years ago, is a chronic condition with gynecologic, metabolic, and psychologic manifestations. Both hyperandrogenism and insulin resistance are associated with the high prevalence of cardiometabolic risk factors described in this population. Although robust data in reproductive-age women demonstrate a high rate of obesity, impaired glucose tolerance, hypertension, dyslipidemia, and metabolic syndrome, studies show mixed results in the adolescent and menopausal age groups. There is emerging evidence to support an association between PCOS and nonalcoholic fatty liver disease and obstructive sleep apnea, conditions known to influence cardiovascular disease (CVD) outcomes. Studies from different world regions show an increased risk of subclinical atherosclerosis, measured by a variety of modalities, especially in reproductive-age women. Similarly, there is increasing evidence for a higher prevalence of CVD events, such as stroke, myocardial infarction, and ischemic heart disease. Over the past decade, a number of medical society guidelines have recommended screening women with PCOS for cardiometabolic risk factors for the primary prevention of CVD. This series of Views and Reviews highlights the urgency to implement these guidelines and invest in identifying newer therapies for comprehensively managing the symptoms of PCOS while lowering long-term cardiometabolic risk.
Topics: Adolescent; Cardiovascular Diseases; Female; Humans; Hyperandrogenism; Insulin Resistance; Metabolic Syndrome; Polycystic Ovary Syndrome; Risk Factors
PubMed: 35512972
DOI: 10.1016/j.fertnstert.2022.03.014 -
Expert Opinion on Biological Therapy Nov 2022High-grade serous ovarian carcinoma (HGSC) is an aggressive subtype of epithelial ovarian carcinoma (EOC) and remains the most lethal gynecologic cancer. A lack of...
INTRODUCTION
High-grade serous ovarian carcinoma (HGSC) is an aggressive subtype of epithelial ovarian carcinoma (EOC) and remains the most lethal gynecologic cancer. A lack of effective and tolerable therapeutic options and nonspecific symptoms at presentation with advanced stage of disease are among the challenges in the management of the disease.
AREAS COVERED
An overview of ovarian cancer, followed by a discussion of the current therapeutic regimes and challenges that arise during and after the treatment of EOC. We discuss different formats of antibody therapeutics and their usage in targeting validated targets implicated in ovarian cancer, as well as three emerging novel proteins as examples recently implicated in their contribution to adaptive resistance in ovarian cancer.
EXPERT OPINION
Antibody therapeutics allow for a unique and effective way to target proteins implicated in cancer and other diseases, and have the potential to radically change the outcomes of patients suffering from ovarian cancer. The vast array of targets that have been implicated in ovarian cancer and yet the lack of effective therapeutic options for patients further stresses the importance of discovering novel proteins that can be targeted, as well as predictive biomarkers that can inform the stratification of patients into treatment-specific populations.
Topics: Humans; Female; Carcinoma, Ovarian Epithelial; Ovarian Neoplasms; Neoplasms, Glandular and Epithelial
PubMed: 36302510
DOI: 10.1080/14712598.2022.2141565 -
Cancer Treatment Reviews Jan 2023High-grade serous ovarian cancers (HGSOCs) most commonly arise from the fimbrial end of the fallopian tube and harbor TP53 gene mutations. In contrast, low-grade serous... (Review)
Review
High-grade serous ovarian cancers (HGSOCs) most commonly arise from the fimbrial end of the fallopian tube and harbor TP53 gene mutations. In contrast, low-grade serous ovarian cancers (LGSOCs) appear to have different pathological, epidemiological, and clinical features and should be seen as a distinct serous epithelial ovarian cancer subtype. Our current understanding of LGSOC is limited, and treatment has generally been derived from the more common HGSOCs due to a lack of separate trial data. LGSOCs are characterized by slow tumor growth and are assumed to develop from serous borderline ovarian tumors as precursors. These cancers are often estrogen-receptor positive and show an activated mitogen-activated protein kinase pathway together with KRAS and BRAF mutations and, rarely, TP53 mutations. These characteristics are now commonly used to guide therapeutical decision making and, consequently, a substantial part of treatment consists of maintenance with endocrine treatment, thus balancing disease stabilization and mild toxicity. Additionally, new trials are ongoing that examine the role of targeted therapies such as MEK inhibitors in combination with endocrine treatments. The purpose of this work is to summarize current knowledge and present ongoing trial efforts for LGSOCs.
Topics: Humans; Female; Rare Diseases; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Cystadenocarcinoma, Serous; Mutation
PubMed: 36525716
DOI: 10.1016/j.ctrv.2022.102497 -
Journal of Cellular and Molecular... Feb 2022Polycystic ovary syndrome (PCOS) is known as the most common metabolic/endocrine disorder among women of reproductive age. Its complicated causality assessment and... (Review)
Review
Polycystic ovary syndrome (PCOS) is known as the most common metabolic/endocrine disorder among women of reproductive age. Its complicated causality assessment and diagnostic emphasized the role of non-coding regulatory RNAs as molecular biomarkers in studying, diagnosing and even as therapeutics of PCOS. This review discusses a comparative summary of research into microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) that are molecularly or statistically related to PCOS. We categorize the literature in terms of centering on either miRNAs or lncRNAs and discuss the combinatory studies and promising ideas as well. Additionally, we compare the pros and cons of the prominent research methodologies used for each of the abovementioned research themes and discuss how errors can be stopped from propagation by selecting correct methodologies for future research. Finally, it can be concluded that research into miRNAs and lncRNAs has the potential for identifying functional networks of regulation with multiple mRNAs (and hence, functional proteins). This new understanding may eventually afford clinicians to control the molecular course of the pathogenesis better. With further research, RNA (with statistical significance and present in the blood) may be used as biomarkers for the disease, and more possibilities for RNA therapy agents can be identified.
Topics: Biomarkers; Female; Humans; MicroRNAs; Polycystic Ovary Syndrome; RNA, Long Noncoding; RNA, Messenger
PubMed: 34989136
DOI: 10.1111/jcmm.17139 -
Frontiers in Endocrinology 2023A typical condition of the female reproductive system is polycystic ovary syndrome (PCOS). Hyperinsulinemia, insulin resistance, obesity, and hyperandrogenism are just a... (Review)
Review
A typical condition of the female reproductive system is polycystic ovary syndrome (PCOS). Hyperinsulinemia, insulin resistance, obesity, and hyperandrogenism are just a few of the metabolic abnormalities linked to this disease. Type 2 diabetes, hypertension, and cardiovascular disease are further issues related to PCOS. One consequence of this syndrome for which numerous treatment procedures have been developed is infertility. Metformin and clomiphene, two common allopathic medications used to treat PCOS, both have drawbacks and are ineffective. It is vital to seek novel therapeutic modalities to address these constraints. Exosomes (EXOs) are a particular class of extracellular vesicles that cells release, and they are known to play a significant role in mediating intercellular communication. A wide range of cargo, including lipids, proteins, mRNA, miRNAs, and numerous other noncoding RNAs, are contained in the nanoscale lipid bilayer exosomes. The cytokine effects of stem cells and EXOs derived from them enable the defense against metabolic diseases like PCOS. Moreover, EXO microRNAs can potentially be employed as biomarkers in the detection and management of PCOS. In this study, the potential of stem cells and exosomes are specifically investigated in the diagnosis and treatment of PCOS as one of the diseases of the female reproductive system.
Topics: Humans; Female; Polycystic Ovary Syndrome; Diabetes Mellitus, Type 2; Biological Factors; Exosomes; MicroRNAs; Stem Cells
PubMed: 37964963
DOI: 10.3389/fendo.2023.1269266 -
Journal of Ovarian Research Jul 2023Premature ovarian insufficiency (POI) is a clinically heterogeneous disease that may seriously affect the physical and mental health of women of reproductive age. POI... (Review)
Review
Premature ovarian insufficiency (POI) is a clinically heterogeneous disease that may seriously affect the physical and mental health of women of reproductive age. POI primarily manifests as ovarian function decline and endocrine disorders in women prior to age 40 and is an established cause of female infertility. It is crucial to elucidate the causative factors of POI, not only to expand the understanding of ovarian physiology, but also to provide genetic counselling and fertility guidance to affected patients. Factors leading to POI are multifaceted with genetic factors accounting for 7% to 30%. In recent years, an increasing number of DNA damage-repair-related genes have been linked with the occurrence of POI. Among them, DNA double-strand breaks (DSBs), one of the most damaging to DNA, and its main repair methods including homologous recombination (HR) and non-homologous end joining (NHEJ) are of particular interest. Numerous genes are known to be involved in the regulation of programmed DSB formation and damage repair. The abnormal expression of several genes have been shown to trigger defects in the overall repair pathway and induce POI and other diseases. This review summarises the DSB-related genes that may contribute to the development of POI and their potential regulatory mechanisms, which will help to further establish role of DSB in the pathogenesis of POI and provide theoretical guidance for the study of the pathogenesis and clinical treatment of this disease.
Topics: Humans; Female; Adult; DNA Breaks, Double-Stranded; Menopause, Premature; Primary Ovarian Insufficiency; Fertility; Infertility, Female
PubMed: 37430352
DOI: 10.1186/s13048-023-01221-2