Pathogenesis Of PCOS Research Articles

Bisphenol-A and polycystic ovary syndrome: a review of the literature.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age with reproductive, metabolic and endocrine implications. While the exact pathophysiological mechanisms of the syndrome are unknown, its heterogeneity suggests a multifactorial causal background. In the last two decades, numerous environmental chemicals, including Bisphenol-A (BPA) that is used in the synthesis of polycarbonate plastics, have been proposed as potential contributors to the aetiology of PCOS. This review provides a holistic overview of the available data regarding the possible relation of PCOS with BPA exposure. We have included a total number of 24 studies. Eleven human case-control and 13 animal studies provided data regarding this potential relation. Accumulating evidence suggests that a correlation between high levels of BPA and the presence of PCOS may exist. Contradicting results from human and animal studies, however, render it difficult to conclude on the exact role of BPA in the pathogenesis of PCOS. BPA may constitute a consequence of the syndrome rather than a cause, but further research is still needed to clarify this. Continued efforts to study the early origins of PCOS, using prospective-designed studies, are required to identify the exact effect of BPA on women with PCOS.

Serum Adiponectin in women with polycystic ovary syndrome of different body mass index

Background: Polycystic ovary syndrome is an extremely common disorder in women of the reproductive age that is associated with a disturbance of reproductive, endocrine, and metabolic functions. The pathophysiology of PCOS appears to be multifactorial and polygenic. Adiponectin seems to play an important role in the pathogenesis of PCOS, especially in obese women. Objectives: To (1) measure serum adiponectin levels in women with PCOS of different body mass index; and (2) assess possible relation between adiponectin level and the hormonal changes of the disease. Setting: Baghdad Teaching Hospital. Duration of study one year from 2018 to 2019.Methods: 80 women were included in this study, 40 women were suffering from PCOS (study group), and the remainder 40 were healthy women served as a control group. BMI is calculated, then each group subdivided into 2 groups: overweight with BMI≥25Kg/m2 and the normal weight with BMI

SAT-018 Androgen Actions in Adipose Tissue and the Brain Are Key Mediators in the Development of Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is a complex disorder characterised by endocrine, reproductive and metabolic abnormalities. Despite PCOS being the most common endocrinopathy affecting women of reproductive age, its etiology is poorly understood so there is no cure and symptom-oriented treatment is suboptimal. Elucidation of the underlying mechanisms involved in the pathogenesis of PCOS would pave the way for the development of new interventions for PCOS. Hyperandrogenism is the most consistent feature observed in PCOS patients, and recently aberrant neuroendocrine signalling and adipose tissue function have been proposed as playing a pathogenic role in the development of experimental PCOS. To investigate the role of adipose tissue and the brain as potential key sites for androgen receptor (AR)-mediated development of PCOS, we combined an adipocyte and brain-specific ARKO knockout (AdBARKO) mouse model with a dihydrotestosterone (DHT)-induced mouse model of PCOS. Wildtype (WT) and AdBARKO prepubertal mice were implanted with a blank or DHT implant and examined after 12 weeks. In WT control females, DHT exposure induced the PCOS reproductive traits of cycle irregularity, ovulatory dysfunction and reduced follicle health. In contrast, these reproductive features of PCOS were absent in DHT-treated AdBARKO females. The PCOS metabolic characteristics of increased adiposity, adipocyte hypertrophy and hepatic steatosis were induced by DHT in WT females. Despite DHT treatment, AdBARKO females displayed normal white adipose tissue weight, and adipocyte hypertrophy and hepatic steatosis were not evident. However, as with WT mice, DHT treatment induced increased fasting glucose levels in AdBARKO females. These results demonstrate that adipose tissue and the brain are key loci for androgen-mediated actions involved in the developmental origins of PCOS. These findings support targeting adipocyte and neuroendocrine AR-driven pathways in the future development of novel therapeutic strategies for PCOS.

SAT-029 AMH Is Higher Across the Menstrual Cycle in Early Post-Menarchal Girls Than in Ovulatory Women

Ovaries of young girls contain healthy and degenerating follicles from the primordial to antral stage, suggesting coordination of growth and atresia. At age 6 yrs, antral follicle (AF) number and size increase; by late puberty, AF count is higher than at any other life stage. The discovery of AMH, a biomarker of AFs, has facilitated the study of the immature ovary. AMH, a granulosa cell product of pre-antral and small AFs, inhibits primordial follicle growth and AF selection. As a marker of AF count, AMH should be highest during puberty, yet cross-sectional studies suggest that AMH peaks in the mid-20’s. In the current studies we compared AMH levels in early post-menarchal girls and regularly cycling adults. The rich phenotypic data available for this adolescent cohort (Sun 2019) was used to investigate further the relationship between AMH, LH, FSH, and sex steroids, and the propensity for anovulatory cycles (ANOV) in girls. 23 healthy girls (12.8–17.6 yrs;1.7±0.2 yrs post-menarche; 56% overweight/obese [OB]) underwent hormone measurements and pelvic ultrasounds during 2 consecutive menstrual cycles. Cycles were classified as ovulatory (OV) based on an LH and E2 peak and P4 >1.65 ng/mL (Sun 2019). AMH was measured in a random subset of samples (5x/subject) with the Ansh ultrasensitive ELISA. Maximum average ovarian volume (VOL) was calculated in the absence of a dominant follicle. Hormones were compared with data from 32 historic adult controls (18–34 yrs; 44% OB) with regular cycles (Lambert-Messerlian 2016). In adults, AMH was measured during the follicular and luteal phase of an OV (5x/subject) using the Ansh assay. AMH was compared among groups using a mixed model. AMH (in adults), LH (in both) and androgens (in girls) were natural log-transformed (ln) before analysis. 11 girls had 2 OV, 5 girls had 1 OV, and 5 girls had no OV; 2 could not be classified due to loss to follow-up. Girls had higher AMH than women (5.2 ± 0.3 vs. 3.3 ± 0.4 ng/mL; p<0.01) and girls with more OV tended to have lower AMH than those with ANOV (2 OV 4.5 ± 0.2, 1 OV 5.7 ± 1.1, 0 OV 6.8 ± 1.1 ng/mL; p=0.1). In girls, AMH correlated with ln_LH (r=0.4, p=0.02), ln_a’dione (r=0.4, p=0.04), ln_testosterone (r=0.5, p=0.02) and VOL (r=0.6, p=0.01) but not with FSH, E2, or BMI. In women, AMH correlated with E2 (r=-0.4, p=0.03) and not with ln_LH or BMI. Within-person variability in AMH was similar in girls and adults (CV 18%). During the early post-menarchal years, AMH levels exceed those of adults with OV, particularly among girls with ANOV, and correlate with LH and androgens. The finding of higher AMH in adolescents is consistent with previous studies demonstrating a peak in AF count during this stage of development. Investigation into how the normal ovary matures and is pruned of excess AFs, either by increased recruitment and growth or by atresia, may provide insights into the pathogenesis of PCOS, wherein follicles are arrested at the pre-antral and antral stage.

OR11-02 Distinctive Neuroendocrine Changes and Menstrual Dysfunction in Early Postmenarchal Daughters of Women With PCOS

PCOS is a complex genetic disease with strong familial aggregation - ~40% of reproductive-age sisters have elevated testosterone (T) levels and other features of the syndrome. Beginning in infancy, daughters of affected women (PCOS-d) have elevated anti-Müllerian hormone (AMH) levels and evidence for global increases in 5α-reductase activity. Peripubertally, PCOS-d have increased T levels. Peripubertal overweight and obesity (OB) girls also have elevated T but not AMH levels.We initiated a prospective study of PCOS-d and OB to test the hypothesis that only PCOS-d are at increased risk to develop PCOS. Herein, we present the baseline assessments in 14 PCOS-d, 14 OB, and 18 lean control girls (LC) aged 11-16 yrs who were enrolled within 2-yrs of menarche. PCOS-d mothers fulfilled NIH criteria, OB and LC mothers had no history of irregular menses or clinical hyperandrogenism. Morning blood sampling was performed for hormone levels. Free T was calculated from total T and SHBG. Ovarian MRI was performed to assess morphology. Data are mean ± SD, α=0.05.By design, age did not differ between the groups, but BMI z-score was higher in OB compared with PCOS-d and LC (1.3±1.1 PCOS-d v 2.0±0.6 OB v 0.1±0.7 LC, P<0.0001). The prevalence of irregular menses (cycles ≤ 21d or ≥ 45d apart) was significantly increased only in PCOS-d (61% PCOS-d, 23% OB, 19% LC, Χ 2 P=0.03). Total T levels did not differ between the groups. SHBG levels were decreased in PCOS-d and OB (23±16 PCOS-d v 30±16 OB v 56±15 LC, nmol/L, P<0.0001), resulting in a trend toward increased free T levels in these groups (0.6±0.3 PCOS-d v 0.6±0.5 OB v 0.4±0.2 LC, ng/dL, P=0.06). DHEAS levels were higher in PCOS-d and OB compared with LC (135±35 PCOS-d v 150±68 OB v 88±46 LC, ug/dL, P=0.05). AMH levels, follicle counts and ovarian volume did not differ.GnRH analog (GnRHa,10 µg/kg SC) stimulation was performed in 9 PCOS-d and 13 OB. Both baseline LH levels (7.6±4.4 PCOS-d v 3.7±2.1 OB, mIU/mL, P=0.01) and LH responses to GnRHa were significantly increased in PCOS-d (LH AUC: 2110±1132 PCOS-d v 1047±808 OB, P=0.01). Baseline FSH and FSH AUC did not differ. Post-GnRHa 17-OHP levels did not differ.Early postmenarchal PCOS-d but not OB have evidence for increased GnRH-mediated LH release, a cardinal feature of PCOS disordered gonadotropin secretion. The increased prevalence of irregular menses in PCOS-d is consistent with this change. In contrast, androgen levels are similarly increased in both groups. These findings align with genomewide association studies implicating gonadotropin secretion and action in PCOS pathogenesis and suggest that neuroendocrine alternations in gonadotropin release are a core causal pathway in PCOS. Moreover, these findings provide further support for our hypothesis that PCOS-d but not OB are at increased risk for PCOS. Longitudinal studies are ongoing to test this hypothesis at 2-yrs postmenarche when the diagnosis of PCOS can be established.

Mini Review: Update on Polycystic Ovarian syndrome

Polycystic ovarian Syndrome is one of the most common disorders among the women of reproductive age. Women suffering from PCOS present with menstrual disturbances and excess of androgens which may affect their reproductive life and quality of life at the same time. women with PCOS may be at increased risk of having multiple morbidities, which include obesity, type II Diabetes mellitus, cancer, cardiovascular disease, infertility and psychological disorders. The pathogenesis of PCOS still remains unclear. More and more supplementary studies needed to make a correlation between several factors that might play an active role in the pathogenesis of PCOS.

Downregulation of Lnc-OC1 attenuates the pathogenesis of polycystic ovary syndrome

Long non-coding RNAs (lncRNAs) play a vital role in the progression of many human diseases. The aim of this study is to explore the relationship between lncRNA-ovarian cancer associated 1 (Lnc-OC1) and PCOS. In this study, we found that Lnc-OC1 was significantly higher in PCOS granulosa cells (GCs) compared to non-PCOS GCs. Lnc-OC1 knockdown inhibited cell viability and promoted cell apoptosis, expression of aromatase mRNA and production of estradiol in KGN cells. In PCOS mice, Lnc-OC1 promoted the serum insulin release, production of angiogenesis-related factors and IκBα phosphorylation, which could be partially restored by Lnc-OC1 shRNA. These results suggest that Lnc-OC1 plays an important part in the pathogenesis of PCOS.

Elucidating the role of pigment epithelium-derived factor (PEDF) in metabolic PCOS models.

PCOS is the most common endocrinopathy in women; associated with obesity and insulin resistance (IR). IR leads to accumulation of advanced-glycation-end-products (AGEs) and their receptor, RAGE. PCOS patients have increased levels of vascular endothelial growth factor (VEGF), interleukin 6/8 (IL-6/8) and anti-Mϋllerian-hormone (AMH). PEDF is a secreted-glycoprotein known for its anti-angiogenic and anti-inflammatory properties. We aimed to elucidate the role of PEDF in the pathogenesis and treatment of PCOS. We used a prenatal PCOS mouse model and fed the female offspring a high-fat diet, inducing metabolic PCOS (met.PCOS) characteristics. Female offspring were divided into three groups: control; met.PCOS; met.PCOS + recombinant PEDF (rPEDF). Met.PCOS mice gained more weight, had elevated serum IL-6 and higher mRNA levels of AMH, PEDF and RAGE in their granulosa cells (GCs) than met.PCOS + rPEDF mice. An in vitro Met.PCOS model in human GCs (KGN) line was induced by prolonged incubation with insulin/AGEs, causing development of IR. Under the same conditions, we observed an elevation of VEGF, IL-6/8 mRNAs, concomitantly with an increase in PEDF mRNA, intracellular protein levels, and an elevation of PEDF receptors (PEDF-Rs) mRNA and protein. Simultaneously, a reduction in the secretion of PEDF from GCs, was measured in the medium. The addition of rPEDF (5 nM) activated P38 signaling, implying that PEDF-Rs maintained functionality, and negated AGE-induced elevation of IL-6/8 and VEGF mRNAs. Decreased PEDF secretion may be a major contributor to hyperangiogenesis and chronic inflammation, which lie at the core of PCOS pathogenesis. rPEDF treatment may restore physiological angiogenesis inflammatory balance, thus suggesting a potential therapeutic role in PCOS.

Adipose Insulin Resistance and Circulating Betatrophin Levels in Women with PCOS.

The role of IR and metabolic disorders has become a crucial topic of study in the pathogenesis of PCOS. Adipose tissue is an important target organ of insulin, and adipose IR plays an important role in the occurrence and development of PCOS. This study seeks to investigate the role of adipose IR in the development of PCOS and to examine its relationship with circulating betatrophin levels in women with PCOS. A cross-sectional analysis of a cohort of women with PCOS and healthy women was performed in this study. Serum betatrophin concentrations were measured by ELISA. Adipose IR was calculated using the product of fasting insulin and FFA concentrations, and the relationship between adipose IR, circulating betatrophin, and other parameters was analyzed. Adipose IR in women with PCOS was significantly higher than that in controls. We found that women with PCOS who have adipose IR (adipose IR ≥ 55) have a higher BMI and higher blood glucose, insulin, PRL, FFA, TG, HOMA-IR, AUCglucose, AUCinsulin, VAIfemale, and BAI levels than PCOS-afflicted women without adipose IR, while M-values, and SHBG and LH levels were lower. In women with PCOS, serum betatrophin levels were significantly increased compared with controls. Adipose IR negatively correlated with M values and positively with circulating betatrophin levels in the study population. After metformin treatment, circulating betatrophin levels and adipose IR in women with PCOS were significantly decreased compared with pretreatment. Adipose IR is associated with betatrophin levels in women with PCOS. The combination of adipose IR and circulating betatrophin measurements may be significant for screening patients with PCOS.

PCOS without hyperandrogenism is associated with higher plasma Trimethylamine N-oxide levels

BackgroundPolycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder, and its pathogenesis is still under debate. Trimethylamine-N-oxide (TMAO) is a small, organic compound generated by the gut microbiome with a hypothesized relation to insulin resistance (IR) and low-grade inflammation in PCOS. By comparing plasma TMAO levels in non-PCOS participants and PCOS patients without hyperandrogenism (HA), we aimed to determine whether plasma TMAO levels correlate with PCOS without HA and to analyze their relationship with low-grade inflammation and IR.MethodsA total of 27 PCOS patients without HA and 23 non-PCOS participants were enrolled in this study and subdivided into “nonobese” and “obese” arms for each group. Levels of plasma TMAO were quantified, and basic clinical characteristics and plasma biomarkers of inflammation were assessed.ResultsFirst, plasma TMAO levels, insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) values were higher in PCOS patients without HA, especially in the obese subgroup. Second, the levels of the inflammatory factors interleukin (IL)-17A, IL-18 and interferon gamma (IFN-γ) were significantly increased in obese PCOS patients without HA. Third, plasma TMAO levels were associated with body mass index (BMI) in the normal-weight groups, and the obese groups had higher fasting plasma insulin (FINS) and HOMA-IR values. Finally, logistic regression showed that the plasma levels of TMAO and luteinizing hormone/follicle-stimulating hormone (LH/FSH) were independent predictors of PCOS and indicated an increased risk of PCOS.ConclusionsElevated plasma TMAO levels may be associated with the pathogenesis of PCOS without HA and correlated with increased systemic inflammation. Further studies are needed to determine the suitability of TMAO as a predictive biomarker and to identify possible therapies for PCOS.

Serum levels of zinc, copper and magnesium in polycystic ovarian syndrome: A cross Sectional study

Introduction: Polycystic ovarian syndrome is the most common endocrinopathy affecting approximately 5 to 21% of reproductive age women. Although the exact aetiology of PCOS is unknown, recent reports have indicated the association between PCOS and disturbance in trace elements (e.g. zinc, copper and magnesium) levels and oxidative stress. Aim and Objective: To compare serum levels of essential trace elements Zinc (Zn), Copper (Cu) and Magnesium (Mg) among patients with PCOS and healthy controls of age group (15-35 years) from same socio economic status. Material and Methods: Present study was carried out in 240 patients (120 cases and 120 healthy controls) of age group (15-35 years) and serum levels of Zinc, Copper and magnesium were compared in PCOS women and healthy controls by using colorimetric method Results: High baseline serum concentration of zinc, copper and magnesium were found in both i.e. women with PCOS and the healthy controls and it may be attributed to the socio-cultural and environmental characteristics of this population. Serum zinc and magnesium levels were found to be significantly higher while serum copper levels were significantly lower in women with PCOS in comparison to healthy controls in present study. Conclusion: The results of the present study provide clues to explore the role of trace elements in pathogenesis of PCOS and provide an area of interest for further clinical trials in PCOS.

The Relationship Between The AMHR2 SNP (–482 A andgt;G) With The Level of The Hormone, Oxidative Stress Status and IL-18 in PCOS Iraqi Woman

The polycystic ovarian syndrome is a heterogeneous endocrine disorder that affected young women in child-bearing age and has severe consequences on women’s health. Many studies on the PCOS found that genetic variation is an essential factor that leads to the development of PCOS. The genetic variation in the AMHR2 and their association with PCOS gives inconstant results. The current study revealed an increment in concentration of AMH among the PCOS, and this elevation may reflect a disturbance in the normal signaling of AMH and thereby, the genetic polymorphism of Anti-mullerian hormone type 2 receptor and their potential association with the pathogenesis and phenotype of PCOS. This is the first study in Iraq concerning AMH receptor-related- PCOS. IL-18 and oxidative stress have a great impact on the severity of PCOS.

Intercellular adhesion molecule-1 expression and serum levels as markers of pre-clinical atherosclerosis in polycystic ovary syndrome

BackgroundPolycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder characterized by obesity, hyperandrogenism, and insulin resistance. Intercellular adhesion molecule-1 (ICAM-1) is a proinflammatory and proatherogenic cytokine which is associated with atherosclerosis, insulin resistance, and cardiovascular disease (CVD). The pathogenesis of PCOS is not precisely known. Thus, the purpose of this study was to investigate the potential role of ICAM-1 expression and serum ICAM-1 concentrations in pathogenesis of PCOS. Moreover, we aimed to evaluate the possible relationship between ICAM-1 gene expression with carotid intima-media thickness as well as clinic-morphological features of PCOS.MethodsThis case control study enrolled 180 patients with PCOS and 120 controls groups and they were stratified according to their fasting plasma glucose (FPG) into three subgroups; normal glucose tolerance (NGT) [n = 75], those with impaired glucose tolerance (IGT) [n = 65], and 40 patients with type 2 diabetes mellitus (T2DM). Circulating ICAM-1 expression levels were determined by real time polymerase chain reaction (RT-PCR). Serum ICAM-1 concentrations were measured using enzyme-linked immunosorbent assay (ELISA).ResultsOur results revealed that PCOS patients had higher values of ICAM-1expression and serum levels. Among PCOS patients, T2DM patients had the highest values of ICAM-1 expression and serum levels compared to IGT and NGT subgroups. The ICAM-1 expression and serum levels were significantly positive correlated with cardiovascular risk and PCOS phenotypes. Linear regression test showed that HOMA-IR was the main predictors of serum ICAM-1 levels in PCOS. Receiver operating characteristic curve (ROC) analysis revealed that, the power of ICAM-1 expression levels was higher than serum ICAM-1 in diagnosis of PCOS and in differentiating T2DM from IGT and NGT subgroups. Interestingly, combination of both ICAM-1 expression and serum levels improved the diagnostic role of serum ICAM-1.ConclusionICAM-1 expression and serum levels were higher in women with PCOS compared to control group also, there was a strong independent association between higher ICAM-1 expression and serum levels with cardiovascular risks in PCOS group.

Identification of potential metabolic biomarkers of polycystic ovary syndrome in follicular fluid by SWATH mass spectrometry

BackgroundPolycystic ovary syndrome (PCOS) is a complex disorder associated with multiple metabolic disturbance, including defective glucose metabolism and insulin resistance. The altered metabolites caused by the related metabolic disturbance may affect ovarian follicles, which can be reflected in follicular fluid composition. The aim of this study is to investigate follicular fluid metabolic profiles in women with PCOS using an advanced sequential window acquisition of all theoretical fragment-ion spectra (SWATH) mass spectrometry.Materials and methodsNineteen women with PCOS and twenty-one healthy controls undergoing IVF/ET were recruited, and their follicular fluid samples were collected for metabolomic study. Follicular fluid metabolic profiles, including steroid hormones, free fatty acids, bioactive lipids, and amino acids were analyzed using the principal component analysis (PCA) and partial least squares to latent structure-discriminant analysis (PLS-DA) model.ResultsLevels of free fatty acids, 3-hydroxynonanoyl carnitine and eicosapentaenoic acid were significantly increased (P < 0.05), whereas those of bioactive lipids, lysophosphatidylcholines (LysoPC) (16:0), phytosphingosine, LysoPC (14:0) and LysoPC (18:0) were significantly decreased in women with PCOS (P < 0.05). Additionally, levels of steroid hormone deoxycorticosterone and two amino acids, phenylalanine and leucine were higher in the PCOS patients (P < 0.05).ConclusionWomen with PCOS display unique metabolic profiles in their follicular fluid, and this data may provide us with important biochemical information and metabolic signatures that enable a better understanding of the pathogenesis of PCOS.

The CYP17 MSP AI (T-34C) and CYP19A1 (Trp39Arg) variants in polycystic ovary syndrome: A case-control study.

BackgroundPolycystic ovary syndrome (PCOS) is a common and chronic disorder of endocrine glands where genetic factors play a major role in the susceptibility to the disease. The cytochrome (CYP) 17 enzyme is essential for androgens biosynthesis. Also, the CYP19 enzyme converts the androgens to the aromatic estrogens.ObjectiveWe aimed to investigate the association of CYP 17 MSP AI (T-34C) and CYP 19A1 (Trp39Arg) variants with the pathogenesis of PCOS in a population from Western Iran with Kurdish ethnic background.Materials and MethodsThe present case-control study consisted of 50 patients with PCOS and 109 controls. The CYP17 T-34C and CYP19A1 (Trp39Arg) polymorphisms were identified by polymerase chain reaction-restriction fragment length polymorphism. The serum lipid and lipoprotein profile were detected by the Bionic Diagnostic Kits. Estradiol, dehydroepiandrosterone (DHEA), and sex hormone-binding globulin (SHBG) levels were measured using the chemiluminescent method.ResultsThe serum levels of estradiol and SHBG in PCOS patients were lower than controls (p 0.001 and p = 0.06, respectively). However, the level of DHEA was higher (p = 0.01) in patients compared to controls. The higher frequency of CYP17 TC genotype in patients (30%) compared to controls (15.6%) was associated with 2.31-fold susceptibility to PCOS (p = 0.038). The frequency of CYP19 TC genotype was 6.4% in controls and 10% in patients (p = 0.42). Conclusion The present study suggests that CYP17 TC genotype could be associated with the risk of PCOS. Also, the study indicated the sex steroid hormones level alteration and the lower level of SHBG in PCOS patients compared to healthy individuals.

Role of Cystic Fluid Growth Factors and Inflammatory Mediators in Pathogenesis of Polycystic Ovary Syndrome

Objective: Present study was carried out to investigate whether there is any localized growth factor/s involved and mediated by inflammatory cytokines through measuring their level in fluid aspirated from ovarian cyst. Study Design: Data was collected from 62 infertile female patients having PCOS and without PCOS. The cystic and follicular fluid obtained from consented patients was used in estimating inflammatory and growth factors. Further, these values were analyzed and interpreted with respect to number, size, length and depth of cysts. Results: Indicates that there is a low level of inflammatory reaction centralized to IL-18 triggering the release of MMP-2 to degrade the extracellular matrix followed by release of ANG-1, VEGF, IGF-1 and EGF to maintain the growth of ovarian cysts. Our findings support the prominent role of IL-18, MMP-2 and ANG-1 in pathogenesis of severe PCOS. Conclusion: In conclusion, the levels of inflammatory mediators in follicular fluid are significantly higher in women having PCOS than compared to cystic fluid of Non-PCOS patients. Despite the promising results of present study we recommend the readers to consider these results as preliminary. Further larger cohort studies are recommended by including more number of heterogeneous population, for extended period of time and more number of cytokines and growth factors with higher accuracy to understand how local inflammatory and growth factors are inter-related in development of ovarian cysts in PCOS patients.

Decreased Serum Level of Gamma-amino Butyric Acid in Egyptian Infertile Females with Polycystic Ovary Syndrome is Correlated with Dyslipidemia, Total Testosterone and 25(OH) Vitamin D Levels.

SummaryBackgroundPolycystic ovary syndrome (PCOS) is one of the most common female endocrine disorders around the world. Increasing evidence suggests that neurotransmitter Gamma-aminobutyric acid (GABA) is involved in the pathogenesis of PCOS through its central role in the hypothalamus. However, the peripheral role of GABA in PCOS has not been sufficiently investigated in spite of its existence in peripheral organs. First, the aim of this study is to, investigate serum GABA level in Egyptian PCOS patients. Second, to explore the correlation between serum GABA level with Body Mass Index (BMI), dyslipidemia, totaltestosterone and 25 (OH) vitamin D.MethodsEighty PCOS patients and eighty age-matched healthy females were included in this study. All parameters were assessed colourimetrically or with ELISA.ResultsPCOS patients exhibited significantly decreased serum GABA level compared to controls (p < 0.001). There was a significant positive correlation between serum GABA and 25(OH) vitamin D levels (r = 0.26, p = 0.018), and a significant negative correlation with total testosterone (r = - 0.3, p = 0.02), total cholesterol (TC) (r = - 0.31, p = 0.01) and LDL-Cholesterol (LDL-C) (r = - 0.23, p = 0.045), respectively.ConclusionsThe findings of this study suggest that disrupted GABA level in the peripheral circulation is an additional contributing factor to PCOS manifestations. GABA deficiency was correlated with 25 (OH) vitamin D deficiency, dyslipidemia, and total testosterone. Further investigations for GABA adjustment might provide a promising means for better management of PCOS symptoms.

Comprehensive assessment the expression of core elements related to IGFIR/PI3K pathway in granulosa cells of women with polycystic ovary syndrome

ObjectivePolycystic ovary syndrome (PCOS) is the most common multisystem endocrinopathy in women, characterized by chronic hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. But its etiology remains elusive. A plethora of information suggests phosphatidylinositol-3-kinase (PI3K) pathway is key to the pathogenesis of PCOS but little is known about the expression pattern and possible role of insulin like growth factor 1 receptor (IGFIR)/PI3K pathway in PCOS. The goal of this study was to determine whether the core elements of the IGF1R/PI3K pathway were differentially expressed in GCs isolated from PCOS. Study designWestern blot (WB) and reverse transcription-polymerase chain reaction (RT-PCR) for IGF1R, insulin receptor substrate 1 (IRS1), insulin receptor substrate 2 (IRS2) and phosphatase and tensin homolog (PTEN) related to IGFIR/PI3K pathway were performed in GCs isolated from 60 PCOS patients and 60 controls. ResultsCompared to controls, body mass index (BMI), the levels of fasting plasma glucose (FPG), fasting insulin (FINS), anti-Mullerian hormone (AMH), testosterone (T), luteotropic hormone (LH), homeostasis model assessment of insulin resistance (HOMA-IR), antral follicle count (AFC) were markedly elevated while follicle stimulating hormone (FSH) decreased (p < 0.05). Furthermore, at both mRNA and protein levels, the expression of IGF1R, IRS1, IRS2 were significantly increased whereas PTEN was dramatically decreased in PCOS patients (p < 0.05). ConclusionOur findings indicate that IGFIR/PI3K pathway is differently expressed in PCOS GCs compared with controls, with IGFIR, IRS1, IRS2 significantly increased while PTEN decreased. Thus, our study probably provides new evidences about the pathogenesis of PCOS in term of molecular mechanism.

Identification of mRNAs related to endometrium function regulated by lncRNA CD36\u2013005 in rat endometrial stromal cells

BackgroundPolycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder in women of reproductive age and is commonly complicated by adverse endometrial outcomes. Long non-coding RNAs (lncRNAs) are a class of non-protein-coding transcripts that are more than 200 nucleotides in length. Accumulating evidence indicates that lncRNAs are involved in the development of various human diseases. Among these lncRNAs, lncRNA CD36–005 (CD36–005) is indicated to be associated with the pathogenesis of PCOS. However, the mechanisms of action of CD36–005 have not yet been elucidated.MethodsThis study determined the CD36–005 expression level in the uteri of PCOS rat model and its effect on the proliferation activity of rat primary endometrial stromal cells. RNA sequencing (RNA-seq) and bioinformatics analysis were performed to detect the mRNA expression profiles and the biological pathways in which these differentially expressed mRNAs involved, after CD36–005 overexpression in the primary endometrial stromal cells. The differential expression of Hmgn5, Nr5a2, Dll4, Entpd1, Fam50a, and Brms1 were further validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR).ResultsCD36–005 is highly expressed in the uteri of PCOS rat model and promotes the proliferation of rat primary endometrial stromal cells. A total of fifty-five mRNAs differentially expressed were identified in CD36–005 overexpressed stromal cells. Further analyses identified that these differentially expressed mRNAs participate in many biological processes and are associated with various human diseases. The results of qRT-PCR validation were consistent with the RNA-seq data.ConclusionsThese data provide a list of potential target mRNA genes of CD36–005 in endometrial stromal cells and laid a foundation for further studies on the molecular function and mechanism of CD36–005 in the endometrium.

Crosstalk between advanced glycation end products and vitamin D: A compelling paradigm for the treatment of ovarian dysfunction in PCOS.

Women with PCOS have elevated levels of the harmful advanced glycation end products (AGEs) and low serum levels of vitamin D. AGEs and their receptors may contribute to the pathogenesis of PCOS and its metabolic and reproductive consequences. On the other hand, vitamin D might improve PCOS phenotype and could alleviate the detrimental effects of AGEs. A literature review using PubMed was performed. Critical analysis was carried out for articles pertaining to: 1) the role of AGEs and their receptors in the pathophysiology of PCOS, in particular ovarian dysfunction, and 2) the action of vitamin D in attenuating the adverse effects of AGEs in women with PCOS at both the serum and the cellular levels. Data from in vitro experiments, animal models, and human studies provide compelling evidence that AGEs and their receptors may contribute to the pathogenesis of ovarian dysfunction in PCOS. The actions of AGEs in PCOS might be attenuated and/or reversed by the presence or supplementation of vitamin D. Once a mechanistic understanding of the relationship between AGEs and vitamin D is established, this knowledge might contribute to the subsequent development of new-targeted pharmacological therapies for improving ovarian health in women with PCOS.