Risk Of Polycystic Ovary Syndrome Research Articles

Meta-Analysis of Determinants of the Incidence of Polycystic Ovarian Syndrome (PCOS) in Indonesia

In 2013 the infertility rate in Indonesia has increased to 15-25% of all married couples or 4 to 6 million couples require infertility treatment to get offspring. Infertility in women is generally caused by ovulation disorders, one of the causes of ovulation disorders is Polycystic Ovary Syndrome (PCOS). PCOS is caused by various factors or determinants. The purpose of this study was to analyze the influence of determinants of obesity, stress and employment status factors on the incidence of PCOS in women in Indonesia. This study was conducted with systematic review and meta-analysis. Research data is searched from: PubMed and google scholar. By using the search keywords "determinant AND PCOS", " risk factor AND PCOS", " Factor associated AND PCOS AND adjusted odds ratio", and "Risk Factors AND PCOS AND adjusted odds ratio", "obesity AND PCOS", "stress AND PCOS", "Occupation AND PCOS". Indonesian women who are obese will increase the risk of PCOS incidence by 34 times and statistically significant Odds Ratio (OR 34.32; 95% CI: 10.45 – 112.67; p value < 0.001). Severe stress increases the risk of PCOS by 75 times (OR 75.84; 95% CI: 6.91 – 832.00; p value = 0.0004). and women who have jobs will increase the risk of PCOS events up to 35 times (OR 35.41; 95% CI: 2.81 – 446.69; p value = 0.006). In Indonesian women factors Obesity, stress and employment status can increase the risk of PCOS.

Cardiovascular disease risk in women with hyperandrogenism, oligomenorrhea/menstrual irregularity or polycystic ovaries (components of polycystic ovary syndrome): a systematic review and meta-analysis.

Prior meta-analyses indicate polycystic ovary syndrome (PCOS) is associated with cardiovascular diseases (CVDs), but have high statistical heterogeneity, likely because PCOS is a heterogenous syndrome diagnosed by having any two of the three components: hyperandrogenism, oligomenorrhea/menstrual irregularity or polycystic ovaries. Several studies report higher risk of CVDs from individual PCOS components, but a comprehensive assessment of how each component contributes to CVD risk is lacking. This study aims to assess CVD risk for women with one of the PCOS components. A systematic review and meta-analysis of observational studies was conducted. PubMed, Scopus, and Web of Science were searched without restrictions in July 2022. Studies meeting inclusion criteria examined the association between PCOS components and risk of a CVD. Two reviewers independently assessed abstracts and full-text articles, and extracted data from eligible studies. Where appropriate, relative risk (RR) and 95% confidence interval (CI) were estimated by random-effects meta-analysis. Statistical heterogeneity was assessed using the I2 statistic. Twenty-three studies, including 346 486 women, were identified. Oligo-amenorrhea/menstrual irregularity was associated with overall CVD (RR = 1.29, 95%CI = 1.09-1.53), coronary heart disease (CHD) (RR = 1.22, 95%CI = 1.06-1.41), and myocardial infarction (MI) (RR = 1.37, 95%CI = 1.01-1.88) but not cerebrovascular disease. These results were broadly consistent even after further adjustment for obesity. There was mixed evidence for the role of hyperandrogenism in CVDs. No studies examined polycystic ovaries as an independent exposure for CVD risk. Oligo-amenorrhea/menstrual irregularity is associated with greater risk of overall CVD, CHD, and MI. More research is needed to assess the risks associated with hyperandrogenism or polycystic ovaries.

Fetal genome predicted birth weight and polycystic ovary syndrome in later life: a Mendelian randomization study.

Associations between lower birth weight and higher polycystic ovary syndrome (PCOS) risk have been reported in previous observational studies, however, the causal relationship is still unknown. Based on decomposed fetal and maternal genetic effects on birth weight (n = 406,063), we conducted a two-sample Mendelian randomization (MR) analysis to assess potential causal relationships between fetal genome predicted birth weight and PCOS risk using a large-scale genome-wide association study (GWAS) including 4,138 PCOS cases and 20,129 controls. To further eliminate the maternally transmitted or non-transmitted effects on fetal growth, we performed a secondary MR analysis by utilizing genetic instruments after excluding maternally transmitted or non-transmitted variants, which were identified in another birth weight GWAS (n = 63,365 parent-offspring trios from Icelandic birth register). Linkage disequilibrium score regression (LDSR) analysis was conducted to estimate the genetic correlation. We found little evidence to support a causal effect of fetal genome determined birth weight on the risk of developing PCOS (primary MR analysis, OR: 0.86, 95% CI: 0.52 to 1.43; secondary MR analysis, OR: 0.86, 95% CI: 0.54 to 1.39). In addition, a marginally significant genetic correlation (rg = -0.14, se = 0.07) between birth weight and PCOS was revealed via LDSR analysis. Our findings indicated that observed associations between birth weight and future PCOS risk are more likely to be attributable to genetic pleiotropy driven by the fetal genome rather than a causal mechanism.

Plasma-free metanephrines, nerve growth factor, and renalase significance in patients with PCOS.

Polycystic ovarian syndrome (PCOS) is a common heterogeneous condition with probably multifactorial genesis. Animal studies have proven the essential role of the sympathetic nervous system in the syndrome development, while human studies are still contradictory. The present study aims to investigate the possible influence of plasma-free metanephrine (MN), and normetanephrine (NMN), nerve growth factor (NGF), and renalase (RNL) on the hormonal and metabolic parameters in women with PCOS and healthy controls. Fifty patients with PCOS and 30 healthy women participated in the study. The plasma-free MN and NMN, NGF, RNL, anti-Mullerian hormone (AMH), gonadotropin, androgen levels, and metabolic parameters were investigated. Plasma-free NMN and NGF concentrations were increased in PCOS individuals, while RNL levels were decreased compared to healthy volunteers. Increased plasma-free NMN (OR = 1.0213 [95%CI 1.0064-1.0364], p = 0.005) and NGF (OR = 1.0078 [95%CI 1.0001-1.0155], p = 0.046) but not MN or RNL levels were associated with a higher risk of PCOS after adjustment for age. Plasma-free NMN levels were positively associated with the LH (r = +0.253; p = 0.039). androstenedione (r = +0.265; p = 0.029), 17-OH progesterone (r = +0.285; p = 0.024), NGF (r = +0.320; p = 0.008), and AMH (r = +0.417; p < 0.001) concentrations of the investigated women. RNL levels were inversely related to the BMI (r = -0.245; p = 0.029), HOMA-IR (r = -0.250; p = 0.030), free testosterone (r = -0.303; p = 0.006) levels. systolic (r = -0.294; p = 0.008) and diastolic (r = -0.342; p = 0.002) blood pressure. Increased sympathetic noradrenergic activity and NGF synthesis might be related to the increased AMH and delta-4 androgen levels in a subgroup of PCOS patients. RNL levels might influence the metabolic status of PCOS patients. Further studies are needed to explore the significance of adrenal medullar and autonomic dysfunction for developing different PCOS phenotypes and their subsequent cardiovascular complications.

Relation of resistin gene variants to resistin plasma levels and altered susceptibility to polycystic ovary syndrome: A case control study.

A role for resistin in the pathogenesis of polycystic ovarian syndrome (PCOS) and related features were described for various ethnicities. As its expression is partly inherited, a role for RETN polymorphisms in regulating resistin levels and PCOS risk was shown, but with varied results. To investigate the association of rs34124816 (-537A>C), rs1862513 (-420C>G), rs3219175 (-358G>A), rs3745367 (+299G>A), rs3745369 (+1263G>C), and rs1423096 (+4965C>T) RETN SNPs with PCOS. Study subjects included 583 women with PCOS, and 713 eumenorrheic women serving as controls. Genotyping was done by real-time PCR. Higher minor allele frequency (MAF) of rs34124816, rs3219175, and rs3745369, and lower MAF of rs1862513 and rs1423096 were seen in PCOS cases. Reduced PCOS risk was found with rs3745367 minor-allele homozygotes and rs1423096 minor-allele homozygotes, while increased risk was linked with rs3745367 heterozygotes, and with rs3745369 heterozygotes and minor-allele homozygotes. While it did not reach statistical significance, serum resistin levels were elevated in PCOS cases than in control women and major-allele homozygotes of rs34124816 and rs1862513, and in rs1423096 minor-allele-containing carriers. Carriage of rs34124816 correlated positively with age and LH, whereas rs1862513 positively and rs3745367 negatively correlated with fasting glucose. Six-locus (rs34124816-rs1862513-rs3219175-rs3745367-rs3745369-rs1423096) haplotype analysis demonstrated a significant reduction in AGGGGG and a marked increase in AGGGCG haplotypes between cases and controls, thus assigning PCOS protective and susceptible nature to these haplotypes, respectively. This study is the first to document the contribution of rs34124816 and rs1423096 RETN variants to the risk of PCOS. The varied association of RETN gene variants with PCOS suggests an ethnic contribution of RETN association with PCOS.

Association between pediatric asthma and adult polycystic ovarian syndrome (PCOS): a cross-sectional analysis of the UAE healthy future Study (UAEHFS).

Asthma and polycystic ovarian syndrome (PCOS) are linked in several possible ways. To date, there has been no study evaluating whether pediatric asthma is an independent risk factor for adult PCOS. Our study aimed to examine the association between pediatric asthma (diagnosed at 0-19 years) and adult PCOS (diagnosed at ≥20 years). We further assessed whether the aforementioned association differed in two phenotypes of adult PCOS which were diagnosed at 20-25 years (young adult PCOS), and at >25 years (older adult PCOS). We also evaluated whether the age of asthma diagnosis (0-10 vs 11-19 years) modified the association between pediatric asthma and adult PCOS. This is a retrospective cross-sectional analysis using the United Arab Emirates Healthy Future Study (UAEHFS) collected from February 2016 to April 2022 involving 1334 Emirati females aged 18-49 years. We fitted a Poisson regression model to estimate the risk ratio (RR) and its 95% confidence interval (95% CI) to assess the association between pediatric asthma and adult PCOS adjusting for age, urbanicity at birth, and parental smoking at birth. After adjusting for confounding factors and comparing to non-asthmatic counterparts, we found that females with pediatric asthma had a statistically significant association with adult PCOS diagnosed at ≥20 years (RR=1.56, 95% CI: 1.02-2.41), with a stronger magnitude of the association found in the older adult PCOS phenotype diagnosed at >25 years (RR=2.06, 95% CI: 1.16-3.65). Further, we also found females reported thinner childhood body size had a two-fold to three-fold increased risk of adult PCOS diagnosed at ≥20 years in main analysis and stratified analyses by age of asthma and PCOS diagnoses (RR=2.06, 95% CI: 1.08-3.93 in main analysis; RR=2.74, 95% CI: 1.22-6.15 among those diagnosed with PCOS > 25 years; and RR=3.50, 95% CI: 1.38-8.43 among those diagnosed with asthma at 11-19 years). Pediatric asthma was found to be an independent risk factor for adult PCOS. More targeted surveillance for those at risk of adult PCOS among pediatric asthmatics may prevent or delay PCOS in this at-risk group. Future studies with robust longitudinal designs aimed to elucidate the exact mechanism between pediatric asthma and PCOS are warranted.

Age at menarche and polycystic ovary syndrome: A Mendelian randomization study.

The authors aimed to use a large two-sample Mendelian randomization (MR) study to reveal the causality between age at menarche (AAM) and polycystic ovary syndrome (PCOS) incidence. The authors collected summary statistics from the hitherto largest genome-wide association studies conducted in AAM and PCOS in the same ancestry. MR with inverse variance weighting was conducted as the main analysis method, while weighted median and MR-Egger regression were used for comprehensive analysis. As for pleiotropy detection, inverse variance weighting, MR-Egger regression, Mendelian Randomization Pleiotropy Residual Sum and Outlier, as well as leave-one-out analysis were used to detect pleiotropy. Risk factor analysis was conducted to investigate the underlying mechanisms linking AAM to PCOS. Each standard deviation increment in AAM was associated with a significantly lower incidence of PCOS (odds ratio, 0.86 [95% confidence interval, 0.75-0.98]). After adjustment in horizontal pleiotropy by eliminating four outliers, this pathogenic association was still statistically detected. All pleiotropy indexes were without statistical differences, which suggested the conclusions were robust. It showed the causal association between later AAM and lower body mass index, lower fasting insulin level and insulin resistance. Our MR analysis verified that a slightly later onset age (15 to 18 years) at menarche could reduce the risk of PCOS. A more comprehensive investigation in a prospective setting is strongly advised.

Invited Perspective: Challenges in Evaluating the Effect of Per- and Polyfluoroalkyl Substance Mixtures on Polycystic Ovarian Syndrome

Invited Perspective: Challenges in Evaluating the Effect of Per- and Polyfluoroalkyl Substance Mixtures on Polycystic Ovarian Syndrome

Practical considerations for diagnosis and treatment of polycystic ovary syndrome in adolescence - distilling guidelines into clinical practice.

The diagnostic criteria for polycystic ovary syndrome (PCOS) in adults may overdiagnose PCOS in adolescents. Since 2015, three guidelines have developed adolescent-specific diagnostic criteria and treatment recommendations. In this review, we compare and contrast the recommendations to assist in the practical application to clinical practice. The guidelines agree that hyperandrogenism with menstrual irregularity be diagnostic criteria for PCOS in adolescents yet have slight differences in how to diagnose hyperandrogenism and in the definition of menstrual irregularity. The diagnostic option of 'at risk for PCOS' is recommended for those girls presenting with criteria within 3 years of menarche or with hyperandrogenism without menstrual irregularity, with re-assessment later in adolescence. Lifestyle changes is first line treatment. Treatment with combined oral contraceptives or metformin is suggested, using patient characteristics and preferences to guide decision-making. PCOS is associated with long term reproductive and metabolic complications and will present during adolescence. Yet, diagnostic features may overlap with normal adolescent physiology. The recent guidelines strove to develop criteria to accurately identify girls with PCOS allowing early surveillance and treatment yet avoid overdiagnosis of normal adolescents.

Target therapy of polycystic ovary syndrome

Due to the complexity of the diagnosis and treatment of polycystic ovary syndrome (PCOS) in adolescents, studies are currently underway to select targeted therapy to normalize the metabolic and reproductive status of girls, including those at risk for PCOS. There are a lot of researches, that evaluate the effectiveness of inositol therapy in PCOS, ovarian dysfunction, insulin resistance (IR), ovarian hyperandrogenism in both adolescents and adult women, including those in IVF cycles. Currently, the choice of determining the ratio of myo-inositol (MI) and d-chiro-inositol (DCI) for the treatment of PCOS often leads to the physiological proportion of inositols in plasma (40:1), since research results are insufficient to unambiguously confirm it. In this connection, there is a large number of pharmaceuticals without or with a low dosage of DCI, that can’t bypass the defective epimerase activity and achieve an adequate level of DCI in the ovaries. Determination of a fair assessment and dosage of MI/DCI is required for long-term correction of metabolic, endocrinological and clinical manifestations of various PCOS phenotypes. Inositols are promising and safe treatment of hyperandrogenism, obesity, insulin resistance in women of various age groups and can also effectively complement a therapeutic effect of metformin and combined oral contraceptives.

Investigation of the Association of Serum Trace Elements Concentrations and Serum Biochemical Parameters with the Risk of Polycystic Ovary Syndrome: a Case-Control Study.

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrinological syndrome characterized by hyperandrogenism of ovarian origin and is often considered a predisposing factor for metabolic disorders. The objective of the study was to investigate serum levels of (a) trace elements (copper (Cu), zinc (Zn), magnesium (Mg), selenium (Se), iron (Fe), chromium (Cr), and manganese (Mn)); and (b) biochemical parameters (glucose, cholesterol, triglycerides, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), albumin, total protein, creatinine, and C-reactive protein (CRP) with risk of PCOS. Another objective was to explore the relationship between serum trace elements and biochemical variables. Serum trace elements were estimated by inductively coupled plasma mass spectrometry (ICP-MS) and biochemical parameters were estimated by colorimetric methods in 99 PCOS cases and 82 controls. Linear and non-linear associations of serum variables with PCOS risk were studied under logistic, probit, GAM, and BKMR model. Statistical analyses were performed using IBM SPSS 22.0 and R package version 4.2.1. All studied serum trace elements (except Zn) are significantly associated with PCOS. Combined effect analysis revealed Mg-Se and Fe-Cu association with PCOS risk. A significant association of cholesterol, HDL-C, LDL-C, CRP, and albumin was observed. Furthermore, linear regression analysis suggests an association between Mg-Cu and Mg-Fe-Mn with HDL-C; Fe and Cr-Cu with albumin; and Cu-Se with cholesterol and LDL-C both.

Androgen-Induced Cardiovascular Risk in Polycystic Ovary Syndrome: The Role of T Lymphocytes.

An estimated 15-20% of reproductive-age women are affected by polycystic ovary syndrome (PCOS). PCOS is associated with substantial metabolic and cardiovascular long-term consequences. In young women with PCOS, several cardiovascular risk factors may be found, including chronic inflammation, high blood pressure, and elevated leukocytes. These women are at an increased risk of cardiovascular diseases (CVD), not only during the reproductive years, but also with aging and menopause; therefore, the early prevention and treatment of future cardiovascular adverse effects are necessary. The fundamental characteristic of PCOS is hyperandrogenemia, which is associated with increased pro-inflammatory cytokines and T lymphocytes. Whether these factors play a role in the pathophysiology of hypertension, a risk factor of CVD, due to PCOS is not well established. This review will briefly discuss how a modest increase in androgens in females is linked to the development of hypertension through pro-inflammatory cytokines and T lymphocyte subsets and the promotion of renal injury. Moreover, it reveals a few existing research gaps in this area, including the lack of specific therapy directed at androgen-induced inflammation and immune activation, thus emphasizing the necessity to explore the systemic inflammation in women with PCOS to halt the inevitable inflammatory process targeting the underlying abnormalities of CVD.

N6-methyladenosine regulator-mediated methylation modification patterns and immune infiltration characterization in Polycystic Ovary Syndrome (PCOS)

BackgroundPolycystic ovary syndrome (PCOS) is a multisystem-related disease whose pathophysiology is still unclear. Several regulators of N6-methyladenosine (m6A) modification were confirmed to play a regulatory role in PCOS. Nonetheless, the roles of m6A regulators in PCOS are not fully demonstrated.Materials and methodsFour mRNA expression profiling microarrays were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed m6A regulators between PCOS and normal patients were identified by R software. A random forest modal and nomogram were developed to assess the relationship between m6A regulators and the occurrence risk of PCOS. A consensus clustering method was utilized to distinctly divide PCOS patients into two m6A subtypes (m6A cluster A/B). The patterns of differential expression and immune infiltration were explored between the two m6A clusters.ResultsIn this study, 22 significant m6A regulators were identified between healthy controls and PCOS patients. The random forest model determined three optimal m6A regulators which are related to the occurrence risk of PCOS, including YTHDF1, RBM15 and METTL14. A nomogram was established based on these genes, and its predictive reliability was validated by decision curve analysis. The consensus clustering algorithm distinctly divided PCOS cases into two m6A subtypes. The ssGSEA algorithm found that the immune infiltration was markedly enriched in m6A cluster B than in cluster A. The m6A-pattern related differentially expressed genes (DEGs) of the two m6A subtypes were demonstrated by differential expression analysis. We found that they were enriched in immune-related genes and various infection pathways. Based on the m6A-pattern related DEGs, the PCOS patients were classified into two m6A-pattern related genomic subtypes (gene clusters A and B).ConclusionsThe present study provided evidence concerning the different modification patterns of m6A regulators in PCOS compared with normal patients. This study will help clarify the overall impact of m6A modification patterns and related immune infiltration on PCOS.

Evaluation of Adiponectin and Hepcidin with some Biochemical Parameters in Sera of Women with Polycystic Ovary Syndrome

Polycystic ovarian syndrome (PCOS) is the most recorded endocrinological condition that impacts women throughout their fertile years and causes a variety of clinical symptoms. The study included 60 women with PCOS and 60 women who were matched for age and body mass index (BMI) and excluded the participants refrain from vigorous exercise and drink anything with alcohol or caffeine. were tested levels for IR, insulin, Hepcidin, Adiponectin, lipids profile in control and PCOS. and found Reduced levels (non sig.) of adiponectin have been documented in Iraqi patients with Polycystic Ovary Syndrome. There was an inverse relationship between IR and hepcidin levels in both groups meaning increase in IR (0.001) and decrease in hepcidin (0.001) levels may increase the risk of PCOS. well found that lipid profile (HDL, LDL, TG) that is non-significant but cholesterol high significant 0.001 in patients.

Awareness of Lifestyle Modifications in the Management of Polycystic Ovarian Syndrome: A Hospital-Based Descriptive Cross-Sectional Study.

Polycystic ovarian syndrome (PCOS) is a prevalent endocrinological disorder in reproductive-age women. Due to varied presentations, it's often difficult to diagnose and manage women with PCOS. Management usually focuses on treating the symptoms and preventing long-term sequelae of the disease. This study was planned to assess the knowledge among reproductive-age women (15-44 years) regarding the risk factors, symptoms, complications, and management of PCOS. This is ahospital-based descriptive cross-sectional study. A pre-validated well-structured questionnaire which included basic demographic data, menstrual history, knowledge about PCOS symptoms, risk factors, complications, prevention, and treatment, was administered. Completed questionnaires were analyzed to calculate the knowledge score of the participants and its association with their education level and occupation was seen. A total of 350 women participated but only 334 completed questionnaires were included for final evaluation. The mean age of the study population was 28.70±6.29 years. Around 9.3% of the participants were already diagnosed with PCOS. Most of the women (43.4%) had heard about PCOS. The source of information was doctors (26.6%), the internet (6.28%), teachers (5.6%), and friends (4.7%). Obesity (33.5%), unhealthy dietary habits (35%), and genetic predisposition (40.7%) were thought as risk factors for PCOS.Most of the participants were aware that subfertility (40.1%), abortions (34.4%), diabetes (28.7%), hypertension (31.7%), cardiovascular disease (33.5%), endometrial carcinoma (35.9%), and psychological disturbances (37.1%) are among the known PCOS related complications. Eating a healthy diet (37.1%) and weight reduction (41%) can help in the management of PCOS. Around 60.5% of women showed poor knowledge, 14.7% fair knowledge, and 24.9% good knowledge regarding PCOS. Education level and occupation status were found to be significantly related to the knowledge score (P≤0.001). PCOS is a prevalent condition with varied presentations which significantly affects one's quality of life. Since there is no definitive treatment for PCOS the management generally aims at managing symptoms and reducing the risk of long-term complications. To reduce the burden of PCOS-related long-term complications behavioral changes in terms of regular exercise and healthy dietary habits need to be incorporated from childhood.

Angiotensin Converting Enzyme (ACE) Gene I/D Polymorphism Is Significantly Associated with Insulin Resistance and Polycystic Ovary Syndrome: A Meta-Analysis

Introduction: This study was performed to clarify the effects of angiotensin converting enzyme (ACE) I/D polymorphism on the risk of insulin resistance and polycystic ovary syndrome (PCOS). Methods: Six genotype models and the mean difference (MD)/standardized mean difference (SMD) were applied to evaluate the effects of ACE I/D polymorphism on insulin resistance and PCOS risk. Results: Thirteen studies with 3,212 PCOS patients and 2,314 controls were collected. In the pooled analysis and Caucasian subgroup, the ACE I/D polymorphism was significantly associated with PCOS risk, even after removing the non-Hardy-Weinberg equilibrium (HWE) studies. Moreover, the positive effect of ACE I/D polymorphism in PCOS was mainly presented in Caucasians (removing non-HWE, DD + DI vs. II: odds ratio [OR] = 2.15, p = 0.017; DD vs. DI + II: OR = 2.64, p = 0.007; DD vs. DI: OR = 2.48, p = 0.014; DD vs. II: OR = 3.31, p = 0.005; D vs. I: OR = 2.02, p = 0.005) compared to Asians. Interestingly, only in Asians was the ACE I/D polymorphism significantly correlated to insulin levels (DI vs. II: SMD = 0.19, 95% CI = (0.03, 0.35), p = 0.023) and HOMA-IR (DI vs. II: MD = 0.50, 95% CI = (0.05, 0.95), p = 0.031). Conclusions: The D allele of the ACE I/D polymorphism promotes PCOS development. Moreover, the ACE I/D polymorphism was also associated with insulin-resistant PCOS, especially among Asians.

Effects of Mindfulness-Based Therapy on Clinical Symptoms and DNA Methylation in Patients with Polycystic Ovary Syndrome and High Metabolic Risk

Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder affecting women of reproductive age. Research has shown that epigenetic alterations such as DNA methylation may play a role in the development and progression of abnormal ovarian function and metabolic disorders in PCOS. Studies have identified specific genes (related with insulin signaling and steroid hormone metabolism) that are methylated in women with PCOS. DNA methylation appears to respond to various interventions aimed at altering health and lifestyle factors. We tested the efficacy of a mindfulness-based stress reduction program (MBSR) in PCOS patients. We examined its effects on anthropometric measurements, mental health and wellbeing, and alterations in DNA methylation in peripheral blood. MBSR was associated with a reduction in body mass index, waist circumference and blood glucose level, an improvement in subjectively perceived general health, emotional role limitation, and levels of pain, as well as mindfulness-like traits. MBSR reduced the expression of anxious symptomatology and subjectively perceived stress. Methylation changes were observed in four genes: COMT, FST, FKBP51, and MAOA. We conclude that MBSR may be a useful supplementary therapy to mitigate the deleterious effects of PCOS on mental health.

Utilizing Contrast-Enhanced Ultrasonography with Phosphatidylserine Microbubbles to Detect Placental Inflammation in Rhesus Macaques.

The ability to comprehensively monitor physiological and detect pathophysiologic processes early during pregnancy can reduce maternal and fetal morbidity and mortality. Contrast-enhanced ultrasound (CEUS) is a non-invasive imaging technology that utilizes the acoustic detection of microbubbles to examine vascular spaces. Furthermore, microbubbles conjugated to specific compounds can focus studies on precise physiological pathways. We hypothesized that CEUS with phosphatidylserine microbubbles (MB-PS) could be employed to monitor placental inflammation. We tested this hypothesis in rhesus macaques (Macaca mulatta), a translational and relevant animal model of human placental health. As placental inflammation impacts many at-risk pregnancies, we performed CEUS with MB-PS in pregnant macaques fed a high-fat diet (e.g., a western-style diet, WSD) in the presence or absence of testosterone (T) to mimic the increased risk of polycystic ovary syndrome and subfertility. We have previously demonstrated a placental inflammation phenotype in this model, and, thus, we related the MB-PS CEUS signal intensity to placental inflammation markers: selectin p and angiopoietins. Testosterone exposure increased the MB-PS signal in the placental microcirculation on the maternal side compared to control animals. We found that T increased placental weight and decreased angiopoietin 2 (ANGPT2) immunoreactivity. Furthermore, a significant inverse correlation was found between MB-PS signal and ANGPT2. This indicated that CEUS with MB-PS can be used to monitor placental parameters. We propose that CEUS with MB-PS could aid in the identification of pregnancies at risk of placental vascular compromise.

High dietary copper intake induces perturbations in the gut microbiota and affects host ovarian follicle development

Increasing evidence has shown that gut microbes play an important role in the reproductive endocrine system and the development of polycystic ovary syndrome (PCOS). However, whether environmental factors are involved in these gut microbiota alterations has seldom been studied. In this study, we aimed to explore the crucial role of an imbalanced gut microbiota on abnormal ovarian follicle development induced by Cu. A 1:1 matched case-control study with 181 PCOS patients and 181 controls was conducted using a propensity score matching protocol. Information regarding dietary Cu intake was obtained from a face-to-face dietary intake interview. Alterations in the gut microbiota were detected by high-throughput 16 S rDNA sequencing. The results showed that dietary Cu intake was positively correlated with the risk of PCOS, and the risk threshold was approximately 1.992 mg/d. Compared with those with dietary Cu intakes lower than 1.992 mg/d, those who had a higher dietary Cu intake had a 1.813-fold increased risk of PCOS (OR=1.813, 95% CI: 1.150–2.857). PCOS patients had a lower relative abundance of Bacteroides than controls (P = 0.003), and Bacteroides played a partial mediating role between dietary Cu exposure and PCOS (Pindirect effect=0.026, 95% CI: 0.002–0.072). In addition, an animal model of Cu exposure through the diet showed that Cu can induce gut microbiota disorder; increase serum levels of LPS, MDA, and IL-6; and alter host ovarian steroidogenesis to affect ovarian follicle development. Staphylococcus played a partial mediating role between Cu exposure and CYP17A1 (Pg_Staphylococcus=0.083, 95% CI: 0.001–0.228). Overall, this study shows that long-term exposure to high dietary Cu levels can affect the composition of the gut microbiota, cause inflammation and oxidative stress, and then interfere with hormone signaling, ultimately affecting ovarian follicle development.

Polycystic ovary syndrome and 25-hydroxyvitamin D: A bidirectional two-sample Mendelian randomization study.

Accumulating observational studies have indicated that vitamin D deficiency (serum 25-hydroxyvitamin D (25OHD) < 50 nmol/L) is common in women with polycystic ovary syndrome (PCOS). However, the direction and causal nature remain unclear. In this study, we aimed to investigate the causal association between PCOS and 25OHD. A bidirectional two-sample Mendelian randomization (MR) study was used to evaluate the causal association between PCOS and 25OHD. From the publicly available European-lineage genome-wide association studies (GWAS) summary statistics for PCOS (4,890 cases of PCOS and 20,405 controls) and 25OHD (n = 417,580), we selected 11 and 102 single nucleotide polymorphisms (SNPs) as instrumental variables (IVs), respectively. In univariate MR (uvMR) analysis, inverse-variance weighted (IVW) method was employed in the primary MR analysis and multiple sensitivity analyses were implemented. Additionally, a multivariable MR (mvMR) design was carried to adjust for obesity and insulin resistance (IR) as well. UvMR demonstrated that genetically determined PCOS was negatively associated with 25OHD level (IVW Beta: -0.02, P = 0.008). However, mvMR found the causal effect disappeared when adjusting the influence of obesity and IR. Both uvMR and mvMR analysis didn't support the causal effect of 25OHD deficiency on risk of PCOS (IVW OR: 0.86, 95% CI: 0.66 ~ 1.12, P = 0.280). Our findings highlighted that the casual effect of PCOS on 25OHD deficiency might be mediated by obesity and IR, and failed to find substantial causal effect of 25OHD deficiency on risk of PCOS. Further observational studies and clinical trials are necessary.