Animal Models to Understand the Etiology and Pathophysiology of Polycystic Ovary Syndrome.
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ABSTRACT:
SUBMITTER: Stener-Victorin E
PROVIDER: S-EPMC7279705 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Polycystic ovary syndrome (PCOS) is a fertility disorder affecting 5-7% of reproductive-aged women. Women with PCOS manifest both reproductive and metabolic defects. Several animal models have evolved, which implicate excess steroid exposure during fetal life in the development of the PCOS phenotype. This review addresses the fetal and adult reproductive and metabolic consequences of prenatal steroid excess in sheep and the translational relevance of these findings to PCOS. By comparing findings in various breeds of sheep, the review targets the role of genetic susceptibility to fetal insults. Disruptions induced by prenatal testosterone excess are evident at both the reproductive and metabolic level with each influencing the other thus creating a self-perpetuating vicious cycle. The review highlights the need for identifying a common mediator of the dysfunctions at the reproductive and metabolic levels and developing prevention and treatment interventions targeting all sites of disruption in unison for achieving optimal success.
| S-EPMC3568226 | biostudies-literature
Project description:Polycystic ovary syndrome (PCOS) is one of the most common gynecological endocrinopathies. Evidence suggest that flavonoids have beneficial effects on endocrine and metabolic diseases, including PCOS. However, high-quality clinical trials are lacking. We aimed to conduct a systematic review and meta-analysis of experimental studies to determine the flavonoids' effects in animal models of PCOS. Three electronic databases including PubMed, Scopus, and Web of Science were systematically searched from their inception to March 2022. The Systematic Review Center for Laboratory Animal Experimentation's risk of bias tool was used to assess methodological quality. The standardized mean difference was calculated with 95% confidence intervals as the overall effects. R was used for all statistical analyses. This study was registered in PROSPERO (registration number: CRD42022328355). A total of eighteen studies, including 300 animals, met the inclusion criteria. Our analyses demonstrated that, compared to control groups, flavonoid groups showed a significantly lower count of atretic follicles and cystic follicles and the count of corpus luteum was higher. A significant reduction in the luteinizing hormone (LH), LH/follicle-stimulating hormone (FSH), and free testosterone were observed in intervention groups. Nevertheless, there was no significant difference in the effects of flavonoids on the level of FSH, estradiol, and progesterone. Subgroup analyses indicated that the type of flavonoid, dose, duration of administration, and PCOS induction drug were relevant factors that influenced the effects of intervention. Current evidence supports the positive properties of flavonoids on ovarian histomorphology and hormonal status in animal models of PCOS. These data call for more randomized controlled trials and further experimental studies investigating the mechanism in more depth.
| S-EPMC9571610 | biostudies-literature
Project description:Polycystic ovary syndrome (PCOS) is the most common endocrine-metabolic disorder affecting females across the lifespan. Eating disorders (EDs) are psychiatric conditions that may impact the development of PCOS and comorbidities including obesity, metabolic syndrome, and type 2 diabetes. The aim of this scoping review was to determine the prevalence of EDs and disordered eating, and to review the etiology of EDs in PCOS. The review was conducted using search terms addressing PCOS, EDs, and disordered eating in databases, including PubMed, Scopus, PsycINFO, and CINAHL. Structured interviews, self-administered questionnaires, chart review, or self-reported diagnosis were used to identify EDs in 38 studies included in the review. The prevalence of any ED in those with PCOS ranged from 0% to 62%. Those with PCOS were 3-6-fold more likely to have an ED and higher odds ratios (ORs) of an elevated ED score compared with controls. In those with PCOS, 30% had a higher OR of bulimia nervosa and binge ED was 3-fold higher compared with controls. Studies were limited on anorexia nervosa and other specified feeding or ED (such as night eating syndrome) and these were not reported to be higher in PCOS. To our knowledge, no studies reported on avoidant/restrictive food intake disorder, rumination disorder, or pica in PCOS. Studies showed strong associations between overweight, body dissatisfaction, and disordered eating in PCOS. The etiologic development of EDs in PCOS remains unclear; however, psychological, metabolic, hypothalamic, and genetic factors are implicated. The prevalence of any ED in PCOS varied because of the use of different diagnostic and screening tools. Screening of all individuals with PCOS for EDs is recommended and high-quality studies on the prevalence, pathogenesis of specific EDs, relationship to comorbidities, and effective interventions to treat ED in those with PCOS are needed.
| S-EPMC10973592 | biostudies-literature
Project description:Objective This study aimed to evaluate the efficacy of Chinese herbal medicine (CHM) on ovarian mass, weight, sex hormone disorders, and insulin resistance in animal models of polycystic ovary syndrome (PCOS). Methods This systematic review and meta-analysis was conducted through a comprehensive search in three databases to find studies testing CHM in animal models of PCOS. Two researchers independently reviewed the retrieval, extraction, and quality assessment of the dataset. The pooled effects were calculated using random-effect models; heterogeneity was explored through subgroup analysis; and stability was assessed through sensitivity analysis. In addition, publication bias was assessed using the Egger's bias test. Results Fifteen studies with twelve mice and 463 rats published from 2016 to 2021 met the inclusion criteria. The results of primary outcomes revealed that CHM therapy was significantly different with control animals in ovarian mass and testosterone (SMD, −1.01 (95% CI, −1.58, −1.45); SMD, −1.62 (95% CI, −2.07, −1.16), respectively). The secondary outcomes as well showed an overall positive effect of CHM compared with control animals in weight (SMD, −1.02 (95% CI, −1.39, −0.65)), follicle-stimulating hormone (FSH) (SMD, 0.58 (95% CI, 0.19, 0.97)), luteinizing hormone (LH) (SMD, −0.94 [95% CI, −1.25, −0.64)), homeostasis model assessment-insulin resistance (HOMA-IR) (SMD, −1.24 (95% CI, −1.57, −0.92)). Subgroup analyses indicated that PCOS induction drug, formula composition, random allocation, and assessment of model establishment were relevant factors that influenced the effects of interventions. The stability of the meta-analysis was showed robust through sensitivity analysis. The publication bias was substantial. Conclusions Administration with CHM revealed a statistically positive effect on ovarian mass, weight, sex hormone disorders, and insulin resistance. Moreover, these data call for further high-quality studies investigating the underlying mechanism in more depth.
| S-EPMC9392647 | biostudies-literature
Project description:Objectives:One of the common heterogeneous reproductive disorders in women of childbearing age is polycystic ovary syndrome (PCOS). It is characterized by lack of fertility due to anovulatory cycles, hyperandrogenemia, polycystic ovaries, hyperinsulinemia, and obesity. Both reproductive anomalies and metabolic disorders are involved in PCOS pathology. Although the role of increased levels of androgens in initiation of PCOS is almost proven, mechanisms of PCOS pathophysiology are not clear. Here we discuss roles of altered metabolic conditions, obesity, and chronic inflammation in PCOS pathophysiology. Materials and Methods:In this review, we attempted to identify genes related to obesity and chronic inflammation aspects of PCOS and their physiological functions to explain the pathways that are regulated by these genes and can be a prominent function in PCOS predisposition. For this purpose, published articles and reviews dealing with genetic evaluation of PCOS in women in peer-reviewed journals in PubMed and Google Scholar databases were included in this review. Results:Obesity and chronic inflammation are not prominent diagnostic features of PCOS, but they play an important role in exacerbating metabolic and hyperandrogenic states. ADIPOQ, FTO TGF?, and DENND1A as the main obesity- and chronic inflammation-related genes have roles in PCOS pathophysiology. Conclusion:It seems that genes related to obesity pathology in genomic research association, are related to metabolic aspects and body mass index in PCOS patients. Genomes have roles in chronic inflammation, followed by obesity, in the pathogenesis of PCOS.
| S-EPMC7043875 | biostudies-literature
Project description:Objectives:Polycystic ovary syndrome (PCOS) is an endocrinopathy in women, which, unlike its impact on fertility and health of women, there is no clear understanding about the causal mechanisms of this pathogenesis. The aim of this review paper is to investigate the pathophysiological pathways affecting the PCOS etiology, based on functions of gonadotropins- and steroid hormones-related genes. Materials and Methods:Due to different hormonal and metabolic signs of this complex disorder, different hypotheses are mentioned about etiology of this syndrome. Because of the heterogeneity of the reasons given for this syndrome and the spread of the effective genes in its pathophysiology, most of genes affected by sex-related hormonal imbalances are examined for discriminative diagnosis. For this purpose, published articles and reviews dealing with genetic evaluation of PCOS in women in peer-reviewed journals in PubMed and Google Scholar databases were included in this review. Results:In previous studies, it has been well demonstrated that PCOS in some individuals have a genetic origin. Pathophysiological functions of genes are primarily responsible for the synthesis of proteins that have role in PCOS before hyperandrogenism including GnRHR, FSH?, FSHR, LHCGR, CYP19A1, HSD17B, AR and SHBG, and their effects in PCOS of human have been confirmed. Conclusion:Hormonal imbalances are the first reason mentioned in PCOS etiology, and usually characterized with menstrual irregularities in PCOS women. Hyperandrogenism and gonadotropin secretion disorders are shown in PCOS condition, which are related to steroidogenesis pathways and hypothalamic-pituitary-ovarian axis disturbances, respectively.
| S-EPMC6437453 | biostudies-literature
Project description:Polycystic ovary syndrome (PCOS) is a common endocrinopathy in women. PCOS is characterized by anovulation, hyperandrogenism, polycystic ovaries, insulin resistance, and obesity. Despite the finding that the genetic origin of PCOS is well demonstrated in previous twin and familial clustering studies, genes and factors that can exactly explain the PCOS pathophysiology are not known. Objective(s). In this review, we attempted to identify genes related to secretion and signaling of insulin aspects of PCOS and their physiological functions in order to explain the pathways that are regulated by these genes which can be a prominent function in PCOS predisposition. Materials and Methods. For this purpose, published articles and reviews dealing with genetic evaluation of PCOS in women from peer-reviewed journals in PubMed and Google Scholar databases were included in this review. Results. The genomic investigations in women of different populations identified many candidate genes and loci that are associated with PCOS. The most important of them are INSR, IRS1-2, MTNR1A, MTNR1B, THADA, PPAR-γ2, ADIPOQ, and CAPN10. These are mainly associated with metabolic aspects of PCOS. Conclusions. In this review, we proposed that each of these genes may interrupt specific physiological pathways by affecting them and contribute to PCOS initiation. It is clear that the role of genes involved in insulin secretion and signaling is more critical than other pathways.
| S-EPMC8668318 | biostudies-literature
Project description:Polycystic ovary syndrome (PCOS) is a heterogeneous and complex disorder that has both adverse reproductive and metabolic implications for affected women. However, there is generally poor understanding of its etiology. Varying expert-based diagnostic criteria utilize some combination of oligo-ovulation, hyperandrogenism, and the presence of polycystic ovaries. Criteria that require hyperandrogenism tend to identify a more severe reproductive and metabolic phenotype. The phenotype can vary by race and ethnicity, is difficult to define in the perimenarchal and perimenopausal period, and is exacerbated by obesity. The pathophysiology involves abnormal gonadotropin secretion from a reduced hypothalamic feedback response to circulating sex steroids, altered ovarian morphology and functional changes, and disordered insulin action in a variety of target tissues. PCOS clusters in families and both female and male relatives can show stigmata of the syndrome, including metabolic abnormalities. Genome-wide association studies have identified a number of candidate regions, although their role in contributing to PCOS is still largely unknown.
| S-EPMC4591526 | biostudies-literature
Project description:PurposeThis study aimed to identify differentially methylated genes (DMGs) and differentially expressed genes (DEGs) to investigate new biomarkers for the diagnosis and treatment of polycystic ovary syndrome (PCOS).MethodsTo explore the potential biomarkers of PCOS diagnosis and treatment, we performed methyl-binding domain sequencing (MBD-seq) and RNA sequencing (RNA-seq) on ovarian granulosa cells (GCs) from PCOS patients and healthy controls. MBD-seq was also performed on the ovarian tissue of constructed prenatally androgenized (PNA) mice. Differential methylation and expression analysis were implemented to identify DMGs and DEGs, respectively. The identified gene was further verified by real-time quantitative PCR (RT-qPCR) and methylation-specific PCR (MSP) in clinical samples. Furthermore, ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) was carried out on PCOS patients and healthy controls to identify differential lipid metabolites.ResultsCompared to the control group, 13,526 DMGs related to the promoter region and 2429 DEGs were found. The function analysis of DMGs and DEGs showed that they were mainly enriched in glycerophospholipid, ovarian steroidogenesis, and other lipid metabolic pathways. Moreover, 5753 genes in DMGs related to the promoter region were screened in the constructed PNA mice. Integrating the DMGs data from PCOS patients and PNA mice, we identified the following 8 genes: CDC42EP4, ERMN, EZR, PIK3R1, ARHGEF18, NECTIN2, TSC2, and TACSTD2. RT-qPCR and MSP verification results showed that the methylation and expression of TACSTD2 were consistent with sequencing data. Additionally, 15 differential lipid metabolites were shown in the serum of PCOS patients. The differential lipids were involved in glycerophospholipid and glycerolipid metabolism.ConclusionUsing integration of methylome and lipid metabolites profiling we identified 8 potential epigenetic markers and 15 potential lipid metabolite markers for PCOS. Our results suggest that aberrant DNA methylation and lipid metabolite disorders may provide novel insights into the diagnosis and etiology of PCOS.
| S-EPMC10503565 | biostudies-literature
Project description:Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in women of fertile age. Obesity is encountered in 30-70% of PCOS-affected women, and its presence significantly modifies both clinical and laboratory expression of the syndrome. Obesity increases the risk of co-morbidities associated with PCOS, such as impaired glucose tolerance and type 2 diabetes mellitus, hyperlipidemia and arterial hypertension. The etiopathogenesis of obesity in PCOS has not yet been exactly clarified. There clearly is a vicious circle of abdominal obesity, insulin resistance, and hyperadrogenemia. Differences in ghrelin and neuropeptide Y levels between PCOS patients and those with simple obesity were also described. Weight loss is the first choice recommendation for the treatment of clinical manifestations of PCOS, such as menstrual cycle irregularities, infertility or hirsutism. However, the best treatment approach in obese PCOS patients remains to be defined. Studies concerning different weight loss regimens, antiobesity drugs, bariatric surgery, insulin sensitizers, and hormonal therapy are reviewed.
| S-EPMC6444522 | biostudies-literature