Pathogenesis Of Polycystic Ovary Syndrome Research Articles

Polycystic Ovary Syndrome: Challenges and Possible Solutions

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. This syndrome not only impairs female fertility but also increases the risk of obesity, diabetes, dyslipidemia, cardiovascular diseases, psychological diseases, and other health problems. Additionality, because of the high clinical heterogeneity, the current pathogenesis of PCOS is still unclear. There is still a large gap in precise diagnosis and individualized treatment. We summarize the present findings concerning the genetics, epigenetics, gut microbiota, corticolimbic brain responses, and metabolomics of the PCOS pathogenesis mechanism, highlight the remaining challenges in PCOS phenotyping and potential treatment approaches, and explain the vicious circle of intergenerational transmission of PCOS, which might provide more thoughts for better PCOS management in the future.

Hyperhomocysteinemia and pregnancy outcomes in women with polycystic ovary syndrome: A case-control study.

One of the reproductive medicine challenges is to determine the role of hyperhomocysteinemia in the pathogenesis of polycystic ovary syndrome (PCOS), especially in women with recurrent pregnancy loss (RPL). Determine the correlation between hyperhomocysteinemia and pregnancy outcome in women with PCOS. This case-control study involved 245 women (20-30 yr) and was conducted in Georgia, Tbilisi from 2019-2022. Of these, 175 were women with PCOS (study group) and 70 were healthy women (control group). Women with PCOS were divided into group I with RPL (n = 90), and group II with live births (n = 85). Group I was divided into subgroups A and B with and without insulin resistance. The investigation measured homocysteine (Hcy), follicle-stimulating, luteinizing, anti-Mullerian hormones, total and free testosterone were determined. To determine the ovarian volume and antral follicle count, participants also underwent an ultrasound examination. In women with PCOS, the average Hcy level was significantly higher than in the controls, p 0.05. In group I, the average Hcy level was significantly higher than in group II and controls, p 0.05. There was no significant difference in average Hcy level between group II and controls. The average Hcy level in group I, subgroup A was significantly higher than in subgroup B, p 0.05. The average total, free testosterone levels, and homeostatic model assessment-insulin resistance levels (HOMA-IR) in group I was significantly higher than in group II and controls. HOMA-IR in group II and controls did not differ significantly. The average anti-Mullerian hormone levels in women with PCOS were significantly higher than controls, p 0.05. No significant difference was observed in average anti-Mullerian hormone level, ovarian volume, antral follicle count, and body mass index between the comparison groups of PCOS. In group I, a positive correlation between Hcy with HOMA-IR was detected. Serum Hcy levels are elevated in women with PCOS and RPL, which correlates with their insulin resistance status.

The Association Between Increment of Interleukin-1 and Interleukin-6 in Women with Polycystic Ovary Syndrome and Body Mass Index.

There is an association between inflammatory factors and polycystic ovary syndrome (PCOS) and most of women with PCOS experience the symptoms of hirsutism. The purpose of this study was to evaluate the role of obesity in PCOS occurrence, which is linked with inflammation and hirsutism. This study was designed as a case-control research. It was performed on 102 women with PCOS and 102 healthy women as controls who were age-matched. Serum concentrations of testosterone, estradiol (E2), IL-1, IL-6, high-sensitivity c-reactive protein (hs-CRP), and aromatase activity were measured in blood samples. Statistical tests including unpaired t-tests, Mann-Whitney U test, Kruskal-Wallis, Spearman's correlation, and Chi-square tests were used for data analysis. Statistical significance was set at p<0.05. A significant difference was found between hs-CRP, IL-1, and IL-6 in PCOS patients and healthy individuals (p<0.001). Aromatase activity was markedly lower in PCOS cases. The serum level of IL-1 (p=0.392) and IL-6 (p=0.764) was not different between overweight and normal weight women. In both studied groups (case and control), hirsutism frequency was markedly higher in individuals with BMI ≥25 kg/m 2 (p<0.05). Inflammatory factors significantly affected the PCOS group (p<0.05). However, logistic regression showed that hs-CRP increment is more effective on increasing the risk of PCOS (OR: 6.324, p<0.001). In this study, hs-CRP, IL-1, and IL-6 levels increased in all PCOS women. Although the incidence of hirsutism in PCOS is associated with obesity, in PCOS pathogenesis, only IL-1 and IL-6 were independent of BMI.

Insulin Metabolism in Polycystic Ovary Syndrome: Secretion, Signaling, and Clearance.

Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in women of reproductive age. Its heterogeneous clinical presentation is characterized by hyperandrogenemia, reproductive changes, polycystic ovary morphology, and insulin resistance (IR). The primary pathophysiological process in its multifactorial etiology has not yet been identified. However, the two most proposed core etiologies are the disruption of insulin metabolism and hyperandrogenemia, both of which begin to intertwine and propagate each other in the later stages of the disease. Insulin metabolism can be viewed as the interconnectedness of beta cell function, IR or insulin sensitivity, and insulin clearance. Previous studies of insulin metabolism in PCOS patients have yielded conflicting results, and literature reviews have focused mainly on the molecular mechanisms and clinical implications of IR. In this narrative review, we comprehensively explored the role of insulin secretion, clearance, and decreased sensitivity in target cells as a potential primary insult in PCOS pathogenesis, along with the molecular mechanism behind IR in PCOS.

PCOS in Adolescents-Ongoing Riddles in Diagnosis and Treatment.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. A diagnosis of PCOS is established when a patient exhibits two of three Rotterdam criteria: oligoovulation or anovulation, excess androgen activity, and polycystic ovarian morphology. The pathogenesis of PCOS, as it affects adolescents, is often discussed in terms of a "two-hit" theory. This refers to a stepwise process in which the first "hit" is an inborn congenitally programmed predisposition, while the second "hit" arises from a provocative factor such as insulin resistance. The dynamic physiological and anatomical changes which occur in puberty make for a challenging diagnosis in this group of patients. It is important to be mindful of the physiological particularities in adolescence which often mimic the symptoms of PCOS. In their first-year post-menarche, approximately 75% of menstruating adolescents report their cycle to last between 21-45 days. Recent studies have shown that regular menstrual cyclicity is only achieved within 2-3 years post-menarche. Anovulation, as a crucial diagnostic element for PCOS, features in about half of early-post-menarchal adolescents. Hirsutism and acne are the most common clinical manifestations of hyperandrogenism, and mild features are developed by most adolescents as a result of elevated androgen levels. Distinguishing between a pathological sign and normal features of maturation is often difficult. A polycystic ovarian morphology (PCOM) through ultrasound has been found in up to 40%, 35%, and 33.3% of patients when assessed at 2, 3, and 4 years, respectively, after menarche. PCOM in adolescence is not associated with future abnormalities in ovulatory rate or menstrual cycle duration. For this reason, international guidelines recommend against the use of pelvic ultrasound until 8 years post-menarche. The primary aim of management is focused mainly on improving hormonal and metabolic status, the prevention of future comorbid complications, and generally improving the overall quality of life in young women with PCOS. Considerable controversy surrounds the choice of optimal pharmacological treatment to address PCOS in adolescents. Reliable studies, which include this sub-section of the population, are very limited. There is a lack of robust and reliable trials in the literature addressing the use of combined oral contraceptives. Further work needs to be undertaken in order to provide safe and effective care to the adolescent population in this regard.

Elevated Insulin-Like Growth Factor-1-Induced Female Rats Perpetuate the Polycystic Ovary Syndrome Phenotype: Pathological Mechanism of Insulin-Like Growth Factor-1 in Polycystic Ovary Syndrome

Objectives: This study was designated to establish a polycystic ovary syndrome (PCOS) rat model with recombinant human insulin-like growth factor-1 (RH-IGF-1). We made assessment on the characteristics of hyperinsulinemia and hyperandrogenism in the rat model. Design: This study performed the characteristics of PCOS upon RH-IGF-1 injection and evaluated the disease process of PCOS syndrome caused by the insulin-resistant pathological condition of IGF-1 based on the comparative study of in vivo test. Setting: The experiment was conducted in the experimental research center of Yinzhou NO.2 hospital, Ningbo, Zhejiang Province, China. Materials and Methods: Thirty-four female Sprague Dawley immature rats aged 21 days were randomly divided into two groups. Those treated with RH-IGF-1 2 mg/100 g daily were in RH-IGF-1 group (n = 20), and those with 0.9% sodium chloride 0.2 mL/100 g daily were in the saline group (n = 14). The experiment was carried out in two stages. In stage I, rats were anesthetized upon the first estrous cycle in the saline group with tissue and blood samples collected (n = 7), and rats in the RH-IGF-1-treated group were anesthetized on the 5th day after vaginal opening (VO) (n = 10). In stage II, rats in the saline group were anesthetized after three complete cycles (n = 7), meanwhile, while on the 15th day after VO (n = 10) for those in the RH-IGF-1 group. Results: We have found that compared with the control group, rats injected with RH-IGF-1 expressed an early VO, disordered estrous cycle, polycystic ovaries, and significantly increased ovarian weight/body weight ratio. And from the perspective of hormone secretion, their androgen increased significantly and the insulin resistance index also elevated distinctly, possessing main characteristics similar to PCOS. Limitations: In this study, we were limited by the inability to examine IGF-1 in hypothalamus. IGF-1 in hypothalamus and in vitro experiments would be taken into consideration for further study in the future. Conclusions: These findings suggest that IGF-1 may be a key factor in the pathogenesis of PCOS, and the increase of androgen may be the pathological result, not the cause of PCOS.

Improvement in Polycystic Ovarian Syndrome using Pharmacological and Non- Pharmacological Approaches: Current Perspectives and Principles

Abstract: Polycystic ovarian syndrome (PCOS) is characterized by a wide range of metabolic and endocrine abnormalities, which can be quite complex in the diagnosis and treatment. The pathogenesis of PCOS is unclear. Therefore, symptoms of this condition differ from person to person, and it becomes difficult to treat PCOS. So far, many pharmacological interventions such as antilipidemic, ovulatory stimulants, and oral contraceptives have been used alone or in combination for the treatment of PCOS and have not been significantly effective. Precision medicine could be of importance in the treatment of PCOS, and the use of artificial intelligence could be beneficial in understanding the pathogenesis and management of this condition. Biotechnological interventions using small mRNA have been explored for this condition. Moreover, it is also hypothesized that the gut microbiota has a key role in regulating hormones through the gut-brain axis. Herbal remedies have also been used, but it is limited due to improper standardization. The treatment of PCOS is based on providing symptomatic relief and limiting the perpetuation of this condition. Understanding the use of different interventions is important to bring out better clinical outcomes.

Transcriptome-wide association analyses identify an association between ARL14EP and polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder, which is accompanied by a variety of comorbidities including metabolic, reproductive, and psychiatric disorders. Genome-wide association studies have identified several genetic variants that are associated with PCOS. However, these variants often occur outside of coding regions and require further investigation to understand their contribution to PCOS. A transcriptome-wide association study (TWAS) was performed to uncover heritable gene expression profiles that are associated with PCOS in two independent cohorts. Causal gene prioritization was subsequently performed and expression of genes prioritized through these analyses was examined in 49 PCOS patients and 30 controls. TWAS analyses revealed that increased expression of ARL14EP was significantly associated with PCOS risk in the discovery (P = 1.6 × 10-6) and replication cohorts (P = 2.0 × 10-13). Gene prioritization pipelines provided further evidence that ARL14EP is the most likely causal gene at this locus. ARL14EP gene expression was shown to be significantly different between PCOS cases and controls, after adjusting for body mass index, age and testosterone levels (P = 1.2 × 10-13). This study has provided evidence for the role of ARL14EP in PCOS. Given that ARL14EP has been reported to play an important role in chromatin remodeling, variants affecting the expression of ARL14EP may also affect the expression of other genes that contribute to PCOS pathogenesis.

The Nutritional Intervention Improves the Metabolic Profile of Overweight and Obese PCOS Along with the Differences in Gut Microbiota.

Previous studies had shown that the gut microbiota of polycystic ovary syndrome (PCOS) patients had significant differences from those of healthy individuals, which may play an important role in the pathogenesis of PCOS. Lifestyle intervention, such as nutritional intervention, could improve the metabolic profiles and PCOS-like phenotypes of PCOS patients. Meanwhile, nutritional intervention could rapidly alter and reshape the distribution of gut microbiota in individuals. Therefore, we sought to investigate the differences in gut microbiota in overweight and obese PCOS patients with or without nutritional intervention. Thirty-six overweight and obese PCOS patients were finally enrolled in the study. Eighteen individuals who refused nutritional intervention (RNI) were collected as the RNI group. Eighteen individuals who received the nutritional intervention were collected as the pre-NI group before the nutritional intervention. And they were also collected as the NI group after the nutritional intervention for 4-12weeks. Significant decreases in BMI, FBG, TC, TG, APO A1, and APO B were observed when comparing the NI group with the pre-NI and RNI groups after the nutritional intervention for 4-12weeks. Meanwhile, the differences in the phylum Firmicutes, Bacteroidetes, and the species Eubacterium rectale, Flavonifractor plautii, and Bacteroides vulgatus between the NI and the RNI groups were observed, which may be potentially linked to the improved inflammatory state and PCOS-like phenotypes of overweight and obese PCOS individuals.

Transcriptomic survey of key reproductive and metabolic tissues in mouse models of polycystic ovary syndrome

Excessive androgen production and obesity are key to polycystic ovary syndrome (PCOS) pathogenesis. Prenatal androgenized (PNA), peripubertal androgenized, and overexpression of nerve growth factor in theca cells (17NF) are commonly used PCOS-like mouse models and diet-induced maternal obesity model is often included for comparsion. To reveal the molecular features of these models, we have performed transcriptome survey of the hypothalamus, adipose tissue, ovary and metaphase II (MII) oocytes. The largest number of differentially expressed genes (DEGs) is found in the ovaries of 17NF and in the adipose tissues of peripubertal androgenized models. In contrast, hypothalamus is most affected in PNA and maternal obesity models suggesting fetal programming effects. The Ms4a6e gene, membrane-spanning 4-domains subfamily A member 6E, a DEG identified in the adipose tissue in all mouse models is also differently expressed in adipose tissue of women with PCOS, highlighting a conserved disease function. Our comprehensive transcriptomic profiling of key target tissues involved in PCOS pathology highlights the effects of developmental windows for androgen exposure and maternal obesity, and provides unique resource to investigate molecular mechanisms underlying PCOS pathogenesis.

The Role of Heat Shock Proteins in the Pathogenesis of Polycystic Ovarian Syndrome: A Review of the Literature.

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women of reproductive age and post-menopausal women. PCOS is a multifactorial heterogeneous disorder associated with a variety of etiologies, outcomes, and clinical manifestations. However, the pathophysiology of PCOS is still unclear. Heat shock proteins (HSPs) have recently been investigated for their role in the pathogenesis of PCOS. HSPs are a class of proteins that act as molecular chaperones and maintain cellular proteostasis. More recently, their actions beyond that of molecular chaperones have highlighted their pathogenic role in several diseases. In PCOS, different HSP family members show abnormal expression that affects the proliferation and apoptotic rates of ovarian cells as well as immunological processes. HSP dysregulation in the ovaries of PCOS subjects leads to a proliferation/apoptosis imbalance that mechanistically impacts follicle stage development, resulting in polycystic ovaries. Moreover, HSPs may play a role in the pathogenesis of PCOS-associated conditions. Recent studies on HSP activity during therapeutic interventions for PCOS suggest that modulating HSP activity may lead to novel treatment strategies. In this review, we summarize what is currently known regarding the role of HSPs in the pathogenesis of PCOS and their potential role in the treatment of PCOS, and we outline areas for future research.

Genetic variations in OLR1 gene associated with PCOS and atherosclerotic risk factors.

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. The aim of this study was to investigate the association of oxidized low-density lipoprotein receptor 1 (OLR1) gene variations with the susceptibility of PCOS and to examine the relationship between the frequencies of OLR1 gene variations and atherosclerotic risk factors. Genomic DNA was extracted from blood samples collected from 49 patients with PCOS and 43 healthy controls. The variants in the OLR1 gene were identified using next-generation sequencing (NGS). Heterozygous rs11053646 (K167N), rs11611438, rs11611453, and rs35688880 genotype frequencies were significantly higher in the PCOS group than that of control group. Single nucleotide polymorphism (SNP) rs34163097 minor A allele increased the PCOS risk by ∼10-fold (p = 0.03). SNPs rs11053646, rs11611438, rs11611453, rs34163097, and rs35688880 were positively correlated with body mass index (BMI). The logistic regression model (area under the curve: 0.770, p = 0.000) further revealed a combination of 2-h plasma glucose (PG-2 h), dehydroepiandrosterone sulfate (DHEAS), and rs11053646 as predictors of PCOS phenotype. This is the first study reporting the NGS data of OLR1 gene variants which might be associated with the pathogenesis of PCOS and several atherosclerotic risk factors, particularly higher BMI and DHEAS. To fully understand the genetic basis of PCOS and the contribution of OLR1 gene variants to PCOS pathogenesis, additional large-scale studies are warranted.

Advancements in lead therapeutic phytochemicals polycystic ovary syndrome: A review.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases in women of reproductive age and features complex pathological symptoms and mechanisms. Existing medical treatments have, to some extent, alleviated the deterioration of PCOS. However, these strategies only temporarily control symptoms, with a few side effects and no preventive effect. Phytochemicals extracted from medicinal herbs and plants are vital for discovering novel drugs. In recent years, many kinds of research have proven that phytochemicals isolated from traditional Chinese medicine (TCM) and medicinal plants show significant potential in preventing, alleviating, and treating PCOS. Nevertheless, compared to the abundance of experimental literature and minimal specific-topic reviews related to PCOS, there is a lack of systematic reviews to summarize these advancements in this promising field. Under this background, we systematically document the progress of bioactive phytochemicals from TCM and medicinal plants in treating PCOS, including flavonoids, polyphenols, and alkaloids. According to the literature, these valuable phytochemicals demonstrated therapeutic effects on PCOS supported by in vivo and in vitro experiments, mainly depending on anti-inflammatory, antioxidation, improvement of hormone disorder and insulin resistance (IR), and alleviation of hyperinsulinemia. Based on the current progress, future research directions should emphasize 1) exploring bioactive phytochemicals that potentially mediate bone metabolism for the treatment of PCOS; 2) improving unsatisfactory bioavailability by using advanced drug delivery systems such as nanoparticles and antibody-conjugated drugs, as well as a chemical modification; 3) conducting in-depth research on the pathogenesis of PCOS to potentially impact the gut microbiota and its metabolites in the evolution of PCOS; 4) revealing the pharmacological effects of these bioactive phytochemicals on PCOS at the genetic level; and 5) exploring the hypothetical and unprecedented functions in regulating PCOS by serving as proteolysis-targeting chimeras and molecular glues compared with traditional small molecule drugs. In brief, this review aims to provide detailed mechanisms of these bioactive phytochemicals and hopefully practical and reliable insight into clinical applications concerning PCOS.

ANGPTL4 inhibits granulosa cell proliferation in polycystic ovary syndrome by EGFR/JAK1/STAT3-mediated induction of p21.

Polycystic ovary syndrome (PCOS) is one of the most common, heterogenous endocrine disorders and is the leading cause of ovulatory obstacle associated with abnormal folliculogenesis. Dysfunction of ovarian granulosa cells (GCs) is recognized as a major factor that underlies abnormal follicle maturation. Angiopoietin-like 4 (ANGPTL4) expression in GCs differs between patients with and without PCOS. However, the role and mechanism of ANGPTL4 in impaired follicular development are still poorly understood. Here, the case-control study was designed to investigate the predictive value of ANGPTL4 in PCOS while cell experiments in vitro were set for mechanism research. Results found that ANGPTL4 levels in serum and in follicular fluid, and its expression in GCs, were upregulated in patients with PCOS. In KGN and SVOG cells, upregulation of ANGPTL4 inhibited the proliferation of GCs by blocking G1/S cell cycle progression, as well as the molecular activation of the EGFR/JAK1/STAT3 cascade. Moreover, the STAT3-dependent CDKN1A(p21) promoter increased CDKN1A transcription, resulting in remarkable suppression effect on GCs. Together, our results demonstrated that overexpression of ANGPTL4 inhibited the proliferation of GCs through EGFR/JAK1/STAT3-mediated induction of p21, thus providing a novel epigenetic mechanism for the pathogenesis of PCOS.

Melatonin effective to reduce the microscopic symptoms of polycystic ovary syndrome-related infertility: An experimental study

Polycystic ovary syndrome (PCOS) is an endocrine disorder seen in women of reproductive age and has been gradually increasing over the years. The mechanism of the syndrome has still not been clearly understood. In this study, the possible effects of exogenously administrated melatonin on melatonin (MT1) receptor, Growth Differentiation Factor-9 (GDF9), and Bone Morphogenetic Protein-15 (BMP15) in experimental PCOS were investigated. Thirty-two 6–8-week-old Sprague-Dawley rats were randomly divided into four groups (n = 8 in each) as Sham control (Group 1), Melatonin (Group 2), PCOS (Group 3), and PCOS + Melatonin (Group 4) groups. At the end of the 21st day, the experiment was terminated, the ovary tissues were taken, and Hematoxylin-Eosin staining, MT1, GDF9, BMP15 immunohistochemical labeling, western blot, and quantitative real-time polymerase chain reaction (qPCR) analyses were performed. Serum Luteinizing Hormone (LH)/Follicle Stimulating Hormone (FSH) levels and colpo-cytological examinations were also carried out. The results revealed that melatonin administration increased the expression levels of the MT1 receptor, GDF9, and BMP15 in PCOS at protein and mRNA levels. It was determined that melatonin administration reduced the microscopic symptoms of PCOS. Melatonin was found to be effective via the MT1 receptor in the pathogenesis of PCOS, and it suppressed the transport pathways of GDF9 to granulosa cells in antral follicles.

Endometrial Pathology and Reproductive Outcomes in Polycystic Ovary Syndrome (PCOS)

Introduction: The common and key in the pathogenesis of PCOS and chronic endometritis (CE) is the chronic course of inflammation. Persistent damage to the endometrium leads to impaired endometrial receptivity and creates conditions for the development of infertility. The purpose of the study was to identify the most common endometrial pathology in women with PCOS and infertility and to analyze the effectiveness of infertility treatment in women with this pathology, to evaluate reproductive outcomes. Materials and methods: Analyzed 240 case histories of patients of LLC “Clinic of Professor Pasman”, Novosibirsk Clinical Oncological Dispancery for the period 2012-2022, diagnosed with PCOS, Infertility. Patients were included in the study group by random sequential selection. The frequency of occurrence of each of the PCOS phenotypes was analyzed, as well as the prevalence of endometrial pathology. The most common pathology is chronic endometritis, therefore, in addition to the standard methods of treating infertility in PCOS, CE was additionally treated by the following methods: photodynamic therapy (PDT) and the introduction of a macrophage medium into the uterine cavity. Results and discussion: In 61% of cases, hysteroscopy was performed and endometrial pathology was detected, which indicates the need to diagnose the endometrium in women with PCOS, especially before using ART. The most common endometrial pathology is chronic endometritis (61.6%). PDT and the introduction of macrophage medium increase the effectiveness of the treatment of CE and infertility in PCOS. The results obtained indicate a high incidence of PCOS without hyperandrogenism and obesity.

Exploring Spleen-Based Treatment Based on the Correlation between Intestinal Flora and Spleen Polycystic Ovary Syndrome

Modern medicine believes that intestinal flora affects the development of polycystic ovary syndrome through five pathways: brain-gut axis, chronic inflammatory state, intestinal mucosal permeability, short-chain fatty acid metabolism, and bile metabolism. According to TCM, the key pathogenesis of polycystic ovary syndrome is spleen deficiency and phlegm obstruction, and it is mostly treated from the spleen. The intestinal flora and the spleen have many physiopathological correlations, and prescriptions for strengthening the spleen have a regulatory effect on the number and structure of intestinal flora, which provides a basis for treating polycystic ovary syndrome from the spleen and broadens the thinking of clinical treatment of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) – role of chronic inflammation in the expression of dysmetabolic phenotype

Polycystic ovary syndrome (PCOS) is a complex disorder that affects both reproductive and metabolic functions. In­su­lin resistance (IR) and compensatory hyperinsulinemia (HI) are considered major factors in the pathophysiology of PCOS and are involved in the development of hyper­an­dro­ge­nism and reproductive dysfunction. Excess androgens are a distinctive sign of PCOS, which determines many of the phenotypic features. Chronic low-grade inflammation is associated with PCOS characteristics, including insulin re­sis­tance and cardiovascular risk factors. Adipose tissue can be considered a proinflammatory organ, involved in the PCOS pathogenesis. Mediators released from immune cells and adipocytes have been identified as being involved in the development of IR. In conclusion, PCOS is a complex dis­order with multiple contributing factors, including in­su­lin resistance, hyperinsulinism, hyperandrogenism, and chro­nic inflammation. Understanding these mechanisms is es­sen­tial for the development of more effective diagnostic and therapeutic approaches to this multifactorial con­di­tion.

EXPRESSION PROFILES OF MIR-155-5P AND MIR-518B MICRORNAS IN CIRCULATING LEUKOCYTES OF THE PREGNANT PATIENTS WITH PREECLAMPSIA AND POLYCYSTIC OVARY SYNDROME.

Polycystic ovary syndrome (PCOS) is associated with increased prevalence of preeclampsia (PE); microRNAs (miRs) could play an important role in the pathogenesis of PE and PCOS. To investigate the expression levels of miRs 155-5p and 518b in blood leukocytes of patients with PE and PCOS. Using real-time quantitative PCR method, miR-155-5p and miR-518b were examined from PE, PCOS, PE+PCOS, and controls. The relative expression of the target miRs in patient samples was compared to control samples. The results were calculated as relative quantification values. Confounding variables were controlled using analyses for covariance. Significant differences were observed in miR-155-5p (p=0.008) and miRNA-518 (p=0.016) expression levels among the groups. miR-155-5p (p=0.014) and miR-518b (p=0.036) were upregulated in PCOS patients and miR-518b (p=0.028) were increased in cases with PCOS+PE. Near significant difference was found (p=0.06) in miR-518b expression levels in cases with PE, compared to controls. miR-518b was observed to be positively correlated with alanine transaminase in cases with PE (r=0.80; P=0.017) and PE+PCOS (r=0.80, p=0.017). Our preliminary findings suggested that expression profiling of miR-155-5p and miR-518b in blood leukocytes were upregulated in pregnant women with PCOS. Moreover, miR-518b was found to be related to PE in cases with PCOS.

Evaluation of renal disturbance in animal models of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is an endocrine disease characterized by hyperandrogenism and hyperinsulinemia, followed by luteinizing hormone and follicle-stimulating hormone deficiency. PCOS conditions cause metabolic disorders that increase uric acid levels and malondialdehyde (MDA) levels. Animal models of PCOS have been used extensively in research to study the pathogenesis, clinical characteristics, and treatment of PCOS. This study aimed to identify the pathological mechanisms underlying renal dysfunction in PCOS by observing several parameters, including blood urea nitrogen (BUN), creatinine, uric acid, and renal MDA levels. This research was an experimentally designed study using a Wistar rat (Rattus norvegicus) as an animal model of PCOS which were divided into three groups: negative control group (n = 6), Testosterone propionate (TP) induction group (n = 6), and estradiol valerate (EV) induction group (n = 6). According to statistical analysis it indicated that induction of TP and EV can increase blood uric acid levels in PCOS model rats (p < 0.05), TP induction can increase kidney BUN and MDA levels significantly (p < 0.05), However, the observation of creatinine levels did not show significant differences in all treatment groups (p > 0.05). Based on the results of this study, it can be concluded that the induction of animal models with TP can trigger significant renal damage compared to EV.