Effect of High Fat Diet on Disease Development of Polycystic Ovary Syndrome and Lifestyle Intervention Strategies.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder that affects premenopausal women. The etiology of PCOS is multifaceted, involving various genetic and epigenetic factors, hypothalamic-pituitary-ovarian dysfunction, androgen excess, insulin resistance, and adipose-related mechanisms. High-fat diets (HFDs) has been linked to the development of metabolic disorders and weight gain, exacerbating obesity and impairing the function of the hypothalamic-pituitary-ovarian axis. This results in increased insulin resistance, hyperinsulinemia, and the release of inflammatory adipokines, leading to heightened fat synthesis and reduced fat breakdown, thereby worsening the metabolic and reproductive consequences of PCOS. Effective management of PCOS requires lifestyle interventions such as dietary modifications, weight loss, physical activity, and psychological well-being, as well as medical or surgical interventions in some cases. This article systematically examines the pathological basis of PCOS and the influence of HFDs on its development, with the aim of raising awareness of the connection between diet and reproductive health, providing a robust approach to lifestyle interventions, and serving as a reference for the development of targeted drug treatments.

Effects of gut microbiota on omega-3-mediated ovary and metabolic benefits in polycystic ovary syndrome mice.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder that frequently exhibits low-grade inflammation, pro-oxidant activity, and gut dysbiosis. PCOS has become one of the leading causes of female infertility worldwide. Recently, omega-3 polyunsaturated fatty acids (PUFAs) have been proven to benefit metabolic disorders in PCOS patients. However, its roles in the regulation of metabolic and endocrinal balances in PCOS pathophysiology are not clear. In the present study, we aimed to explore how omega-3 PUFAs alleviate ovarian dysfunction and insulin resistance in mice with dehydroepiandrosterone (DHEA)-induced PCOS by modulating the gut microbiota. METHODS: We induced PCOS in female mice by injecting them with DHEA and then treated them with omega-3 PUFAs. 16S ribosomal DNA (rDNA) amplicon sequencing, fecal microbiota transplantation (FMT) and antibiotic treatment were used to evaluate the role of microbiota in the regulation of ovarian functions and insulin resistance (IR) by omega-3 PUFAs. To further investigate the mechanism of gut microbiota on omega-3-mediated ovarian and metabolic protective effects, inflammatory and oxidative stress markers in ovaries and thermogenic markers in subcutaneous and brown adipose tissues were investigated. RESULTS: We found that oral supplementation with omega-3 PUFAs ameliorates the PCOS phenotype. 16S rDNA analysis revealed that omega-3 PUFA treatment increased the abundance of beneficial bacteria in the gut, thereby alleviating DHEA-induced gut dysbiosis. Antibiotic treatment and FMT experiments further demonstrated that the mechanisms underlying omega-3 benefits likely involve direct effects on the ovary to inhibit inflammatory cytokines such as IL-1ß, TNF-α and IL-18. In addition, the gut microbiota played a key role in the improvement of adipose tissue morphology and function by decreasing multilocular cells and thermogenic markers such as Ucp1, Pgc1a, Cited and Cox8b within the subcutaneous adipose tissues. CONCLUSION: These findings indicate that omega-3 PUFAs ameliorate androgen-induced gut microbiota dysbiosis. The gut microbiota plays a key role in the regulation of omega-3-mediated IR protective effects in polycystic ovary syndrome mice. Moreover, omega-3 PUFA-regulated improvements in the ovarian dysfunction associated with PCOS likely involve direct effects on the ovary to inhibit inflammation. Our findings suggest that omega-3 supplementation may be a promising therapeutic approach for the treatment of PCOS by modulating gut microbiota and alleviating ovarian dysfunction and insulin resistance.

Síndrome de ovario poliquístico y calidad de vida

Introducción: El síndrome de ovario poliquístico es la endocrinopatía más frecuente que afecta la mujer en la etapa reproductiva. Se ha investigado mucho en lo que concierne a su fisiopatología y criterios diagnósticos. Sin embargo, existen evidencias de que las mujeres que padecen el síndrome tienen mayor afectación en su calidad de vida. El tema ha sido poco abordado en general y en Cuba no existen estudios al respecto. Objetivo: Identificar las evidencias científicas que amplíen el conocimiento acerca del efecto del síndrome de ovario poliquístico en la calidad de vida. Métodos: Se realizó una revisión bibliográfica sobre la calidad de vida en mujeres con diagnóstico de síndrome de ovario poliquístico. La búsqueda se realizó en las bases de datos electrónicas Google Scholar, Pubmed Central y SCIELO Regional, a las cuales se accedió por medio del buscador web de Google. Se revisaron artículos completos, relacionados con estudios observacionales, prospectivos, artículos de revisión, revisiones sistemáticas y metaanálisis publicados fundamentalmente entre 2000 y 2020. Conclusiones: La presente revisión pone en evidencia que el síndrome de ovario poliquístico es una condición que por la variedad de manifestaciones clínicas que lo caracterizan conlleva a un deterioro de la calidad de vida de las mujeres que la padecen. Una intervención terapéutica en cada una de ellas resulta beneficiosa para elevar el bienestar físico y psicológico y como resultado de la calidad de vida(AU)

Introduction: Polycystic ovary syndrome is the most common endocrinopathy affecting women in the reproductive stage. Much research has been done regarding its pathophysiology and diagnostic criteria. However, there is evidence that women who suffer from the syndrome have greater negative effects in their quality of life. The subject has not been amply approached in general and there are no studies on the subject in Cuba. Objective: To identify the scientific evidence that broadens knowledge about the effect of polycystic ovary syndrome on quality of life. Methods: A bibliographic review was carried out on the quality of life in women diagnosed with polycystic ovary syndrome. The search was performed in the electronic databases Google Scholar, Pubmed central and SCIELO Regional, which were accessed through the Google web search engine. Full articles related to observational studies, prospective studies, review articles, systematic reviews and meta-analyses, published mainly between 2000 and 2020, were reviewed. Conclusions: The present review highlights that PCOS is a condition that, due to the variety of clinical manifestations that characterize it, leads to a deterioration in the quality of life of women who suffer from it. A therapeutic intervention in each of them is beneficial to improve physical and psychological well-being and as a result, quality of life(AU)

La función sexual y su relación con los factores psicológicos en las mujeres con el síndrome de ovario poliquístico / Sexual function and its relationship to psychological factors in women with polycystic ovary syndrome

Introducción: El síndrome de ovario poliquístico tiene un notable impacto en la vida de las personas que lo padecen, siendo las áreas psicológica y sexual frecuentemente afectadas. Objetivos: Realizar una revisión bibliográfica sobre la función sexual y su relación con factores psicológicos en mujeres con síndrome de ovario poliquístico. Métodos: Se revisaron las bases de datos Google Scholar, Pubmed Central y SciELO Regional por intermedio del buscador web de Google. Algunos de los aspectos tratados en el artículo fueron los factores psicológicos, las hormonas sexuales y la función sexual, la imagen corporal y el síndrome de ovario poliquístico, y la función sexual y el síndrome de ovario poliquístico. Conclusiones: Los aspectos más estudiados del síndrome de ovario poliquístico han estado relacionados con la conceptualización y fisiopatología de la enfermedad, y las manifestaciones reproductivas y metabólicas. Otros aspectos igualmente importantes como los psicosociales y sexuales han sido muy escasamente abordados y los datos disponibles son contradictorios. Se requieren investigaciones de corte psicosocial para profundizar en las particularidades de la vida psicoemocional y sexual de esta población. Aún existe un campo novedoso poco explorado y permanecen vacíos de información en torno a la sexualidad que por su impacto influyen en el bienestar psicológico y la calidad de vida(AU)

Introduction: Polycystic ovary syndrome has a notable impact on the lives of those who suffer from it, with the psychological and sexual areas frequently affected. Objective: To carry out a literature review on sexual function and its relationship with psychological factors in women with polycystic ovary syndrome. Methods: Google Scholar, Pubmed Central and SciELO Regional databases were reviewed through the Google web search engine. Some of the aspects covered in the article were psychological factors, sex hormones and sexual function, body image and polycystic ovary syndrome, and sexual function and polycystic ovary syndrome. Conclusions: The reviewed literature allows affirming that in the Cuban and international context the most studied aspects of polycystic ovary syndrome have been related to the conceptualization and physiopathology of the disease, and its reproductive and metabolic manifestations. Other equally important aspects such as psychosocial and sexual aspects have been very scarcely broached and the available information is contradictory. Psychosocial research is needed to delve deeper into the particularities of the psychoemotional and sexual life of this population. There is still a novel field that has not been sufficiently explored and there are still gaps in the information on sexuality that, due to their impact, influence the psychological well-being and the patients' quality of life(AU)

Fisiopatología del síndrome de ovario poliquístico / Pathophysiology of polycystic ovary syndrome

Introducción: En la génesis del síndrome de ovario poliquístico intervienen múltiples factores sistémicos y locales que tienen una relación multidireccional sobre los que persisten muchas cuestiones aún sin dilucidar y cierta confusión e incertidumbre. Objetivo: Describir el enfoque actual sobre las causas y los mecanismos involucrados en el origen y desarrollo del síndrome de ovario poliquístico. Métodos: Se realizó una revisión bibliográfica tipo estado del arte. Se revisaron alrededor de 250 artículos, que se obtuvieron de las bases PubMed, Medline, SciELO y Google Académico. Se describen los factores y las vías que se proponen para explicar la etiopatogenia y fisiopatología de alteraciones genéticas, ambientales, endocrinas y metabólicas asociadas al síndrome y su expresión clínica. Conclusiones: La fisiopatología del síndrome de ovario poliquístico es compleja. Muchos aspectos permanecen sin esclarecerse, pero se tiene cada vez más conocimiento que aporta luz a los enigmas que aún persisten y a la comprensión de fenómenos previamente desconocidos. Existe el convencimiento creciente de que la alteración central es a nivel ovárico, que el síndrome es heterogéneo en todos sus elementos y que conocer la gran diversidad de factores y mecanismos que intervienen en su etiología y patogenia es fundamental no sólo desde lo científico, sino también por su utilidad práctica(AU)

Introduction: Multiple systemic and local factors are involved in the genesis of polycystic ovary syndrome that have a multidirectional relationship about which many there are questions yet to be clarified and some confusion and uncertainty persist. Objective: To describe the current approach to the causes and mechanisms involved in the origin and development of polycystic ovary syndrome. Methods: A state-of-the-art literature review was performed. The factors and pathways proposed to explain the etiopathogenesis and pathophysiology of genetic, environmental, endocrine and metabolic alterations associated with the syndrome and its clinical expression are described. Conclusions: The pathophysiology of polycystic ovary syndrome is complex. Many aspects remain unclear, but there is increasing knowledge that sheds light on the enigmas that still persist and on the understanding of previously unknown phenomena. There is a growing conviction that the central alteration is at the ovarian level, that the syndrome is heterogeneous in all its elements and that knowledge of the great diversity of factors and mechanisms involved is fundamental, not only from the scientific point of view but also for its practical utility(AU)

Female sexual behavior is disrupted in a preclinical mouse model of PCOS via an attenuated hypothalamic nitric oxide pathway.

Women with polycystic ovary syndrome (PCOS) frequently experience decreased sexual arousal, desire, and sexual satisfaction. While the hypothalamus is known to regulate sexual behavior, the specific neuronal pathways affected in patients with PCOS are not known. To dissect the underlying neural circuitry, we capitalized on a robust preclinical animal model that reliably recapitulates all cardinal PCOS features. We discovered that female mice prenatally treated with anti-Müllerian hormone (PAMH) display impaired sexual behavior and sexual partner preference over the reproductive age. Blunted female sexual behavior was associated with increased sexual rejection and independent of sex steroid hormone status. Structurally, sexual dysfunction was associated with a substantial loss of neuronal nitric oxide synthase (nNOS)-expressing neurons in the ventromedial nucleus of the hypothalamus (VMH) and other areas of hypothalamic nuclei involved in social behaviors. Using in vivo chemogenetic manipulation, we show that nNOSVMH neurons are required for the display of normal sexual behavior in female mice and that pharmacological replenishment of nitric oxide restores normal sexual performance in PAMH mice. Our data provide a framework to investigate facets of hypothalamic nNOS neuron biology with implications for sexual disturbances in PCOS.

Effects of Different Ovulation Induction Regimens on Sex Hormone Levels and Serum CTRP3 and CTRP15 Levels in Patients with Polycystic Ovary Syndrome (PCOS).

Objective: A retrospective cohort study aimed to explore the effects of different ovulation induction regimens on the levels of sex hormones and serum C1q/TNF-related protein-3 (CTRP3) and C1q/TNF-related protein-15 (CTRP15) in patients with PCOS. Methods: A total of 100 patients with PCOS treated in the department of gynecology and obstetrics from February 2019 to April 2021 in our hospital were enrolled. The patients were arbitrarily assigned into control group and study group. The treatment effect, pregnancy rate, ovulation rate, follicle size, thickness of endometrium, number of mature follicles and ovulation, serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), testosterone (T), serum CTRP3, CTRP15 and menstrual score were compared. Results: There exhibited no statistical difference in baseline clinical data between the two kinds of patients. The therapeutic effects were compared, the effective rate was 98.00% in the study group, 13 cases in the control group, 20 cases in the effective group and 7 cases in the control group, and the effective rate was 86.00%. The effective rate in the study group was higher (P <0.05). The size of follicles and the thickness of endometrium in the two groups were compared before and after intervention. There exhibited no significant difference in the size of follicles and the thickness of endometrium before and after intervention (P >0.05). The size of follicles and the thickness of endometrium in the study group were significantly higher (P <0.05). The size of follicles and the thickness of endometrium in the study group were significantly higher (P <0.05). There exhibited no significant difference in the number of mature follicles and ovulation before and after intervention (P >0.05). After intervention, the number of mature follicles and ovulation in the two groups increased. The number of mature follicles and ovulation in the study group were (4.76 ± 0.90) and (4.48 ± 0.73), respectively, which were higher compared to the control group (2.45 ± 0.86) and (2.82 ± 0.84), respectively (P <0.05). The levels of serum LH, FSH, E2 and T were not significantly different before and after intervention. After the intervention of different ways of ovulation induction, the levels of serum LH, FSH, E2 and T in the two groups continued to decrease, and the levels of the above sex hormones in the study group were significantly lower (P <0.05). The menstrual score and the levels of serum CTRP3 and CTRP15 were compared before and after intervention. After intervention, the menstrual score of patients in both groups decreased, and the menstrual score of the study group was lower. In addition, the levels of serum CTRP3 and CTRP15 in the two groups decreased after intervention. Compared with the control group, the levels of CTRP3 and CTRP15 in the study group were lower after intervention (P <0.05). The ovulation rate and pregnancy rate of the two groups were compared. In the study group, there were 45 ovulation cases, the ovulation rate was 90.00% (45/50), the pregnancy rate was 33 cases, the pregnancy rate was 66.00% (33/50), and the ovulation rate in the control group was 31 cases, the ovulation rate was 62.00% (31/50), the pregnancy rate was 20 cases, and the pregnancy rate was 40.00% (20/50). The ovulation rate and pregnancy rate in the study group were higher (P <0.05). Conclusion: Different ovulation induction regimens have different effects on the levels of sex hormones and serum CTRP3 and CTRP15 in patients with PCOS. Long-acting follicular phase regimens can effectively promote the therapeutic effect of patients and increase the ovulation rate and pregnancy rate. In addition, it can also reduce the levels of serum LH, follicle stimulating FSH, E2 and testosterone T, and help to promote the levels of serum CTRP3 and CTRP15, which is worth popularizing and applying in clinic.

A personalized medicine approach to ovulation induction/ovarian stimulation: development of a predictive model and online calculator from level-I evidence.

OBJECTIVE: To estimate the probability of clinical or multiple pregnancy during ovulation induction (OI)/ovarian stimulation (OS). DESIGN: Secondary analysis of two multicenter randomized clinical trials (combined). SETTING: Multicenter. PATIENTS: A total of 750 women with polycystic ovary syndrome and 900 women with unexplained infertility. INTERVENTIONS: Ovulation induction/OS with either timed intercourse (polycystic ovary syndrome) or intrauterine insemination. MAIN OUTCOME MEASURES: Clinical and multiple pregnancy rates/cycle, cumulative pregnancy rates. Age, body mass index, parity, diagnosis, medication, markers of ovarian reserve, and ovarian response were considered in multivariable regression models for clinical, multiple, and cumulative pregnancy rates. Receiver operating characteristic curves were created for clinical and multiple pregnancy rates. RESULTS: Younger patient and partner age, treatment type, lower body mass index, and medication dose were all associated with clinical pregnancy. Variables associated with multiple pregnancy included the abovementioned variables (except age), in addition to diagnosis, parity, higher antral follicle count, antimüllerian hormone levels, and ovarian response. Gonadotropin use was associated with multiple pregnancy, with progressively increasing odds ratios (cycles 1-4). Receiver operating characteristic curves indicated the model's predictive power to be fair for clinical pregnancy (areas under the curve [95% confidence interval {CI}]: 0.78 [0.75-0.81] for cycle 1 and 0.70 [0.64-0.75] for cycle 4) and good-to-excellent for multiple pregnancy (areas under the curve [95% CI]: 0.78 [0.72-0.84] for cycle 1 and 0.86 [0.78-0.93] for cycle 4). Partner age, lower medication dose, parity, antimüllerian hormone levels, and diagnosis were associated with cumulative pregnancy rates. CONCLUSIONS: Using the majority of the factors known to predict the outcome of OI/OS cycles, we constructed an easy-to-use formula that may predict individualized chances of clinical and multiple pregnancy for commonly used fertility treatments (https://pregnancyprediction.medicine.yale.edu/CalDirect.html). CLINICAL TRIAL REGISTRATION NUMBERS: Assessing Multiple Intrauterine Gestations after Ovulation Stimulation NCT01044862; PPCOSII NCT00719186.

Basic aspects of endometrial receptivity in PCOS patients.

Polycystic Ovarian Syndrome (PCOS) is an endocrine disorder commonly affecting the reproductive capacity of women leading to infertility. PCOS-related infertility is majorly due to anovulation; however, it is not the only cause. The defective endometrium causing recurrent miscarriage and implantation failure can also be accountable for infertility in PCOS women. The unusual levels of hormones and their receptors in the PCOS endometrium have a hostile effect during WOI, making the microenvironment unfavorable for embryo implantation. To date, many studies have been performed to determine the role of candidate genes in endometrial receptivity but very limited data is available using whole genome approach. This review aims at summarizing the existing studies on the basic aspects of endometrial receptivity in PCOS. The review focuses on aberrant levels of hormones and their receptors in the endometrium, affecting the receptivity. Additionally, it explores the novel approach reviewing the effect on treatment options administered for ovulation induction in PCOS on their endometrial receptivity. Overall, this review will help us to understand the molecular milieu in PCOS endometrium and its effect on the receptivity potential. However, to have a thorough understanding of the mechanistic approach of hormonal imbalance in PCOS on endometrial receptivity, there is a need to give more weightage to genome-wide studies in the future. The current review will further guide us to formulate future studies using whole genome technologies for the assessment of endometrial receptivity in different cohorts of PCOS women, which may have future diagnostic implementations.

High-Intensity Interval Training in Polycystic Ovary Syndrome: A Two-Center, Three-Armed Randomized Controlled Trial.

PURPOSE: Exercise training is recommended to improve cardiometabolic health and fertility in women with polycystic ovary syndrome (PCOS), yet there are few randomized controlled trials on the effects of different exercise protocols on clinical reproductive outcomes. Our aim was to determine the effect of high-intensity interval training (HIT) on menstrual frequency, as a proxy of reproductive function, in women with PCOS. METHODS: The IMPROV-IT study was a two-center randomized controlled trial undertaken in Norway and Australia. Women with PCOS were eligible for inclusion. After stratification for body mass index <27 or ≥27 kg·m-2 and study center, participants were randomly allocated (1:1:1) to high-volume HIT (HV-HIT), low-volume HIT (LV-HIT), or a control group. Measurements were assessed at baseline, after the 16-wk exercise intervention, and at 12-month follow-up. The primary outcome was menstrual frequency after 12 months. Secondary outcomes included markers of cardiometabolic and reproductive health, quality of life, and adherence to and enjoyment of HIT. RESULTS: We randomly allocated 64 participants to the HV-HIT (n = 20), LV-HIT (n = 21), or control group (n = 23). There were no differences in menstrual frequency at 12 months between the LV-HIT and control groups (frequency ratio, 1.02; 95% confidence interval [CI], 0.73-1.42), the HV-HIT and control groups (frequency ratio, 0.93; 95% CI, 0.67-1.29), or the LV-HIT and HV-HIT groups (frequency ratio, 1.09; 95% CI, 0.77-1.56). Menstrual frequency increased in all groups from baseline to 12 months. More participants became pregnant in the LV-HIT group (n = 5) than in the control group (n = 0, P = 0.02). CONCLUSIONS: A semisupervised HIT intervention did not increase menstrual frequency in women with PCOS.Clinical Trial Registration Number:ClinicalTrials.gov (NCT02419482).

Diacerein ameliorates induced polycystic ovary in female rats via modulation of inflammasome/caspase1/IL1ß and Bax/Bcl2 pathways.

Polycystic ovary syndrome (PCOS) is a very common gynecological disease during childbearing period and markedly affects female fertility. Until now, there are no studies evaluating the possible curative effect of diacerein (DIA) in induced PCOS. For the first time, we aimed in current model to study the effect of DIA (50 mg/kg/day) orally for 3 weeks on experimentally induced PCOS by letrozole (1 mg/kg/day) for 3 weeks. We measured rats' body weight changes, levels of serum insulin, anti-Müllerian hormone (AMH), testosterone, inflammasome, caspase1, and total anti-oxidant capacity (TAC). Moreover, we measured ovarian tissue parameters as malondialdehyde (MDA), interleukin 1ß (IL1ß), real-time polymerase chain reaction (rt-PCR) of Bcl2-associated X protein (Bax), and interleukin 10 (IL10) gene expression changes. Furthermore, histopathological features and anti-apoptotic marker B cell lymphoma 2 (Bcl2) immunoexpression changes were evaluated. Our results showed that letrozole markedly induced PCOS as manifested by significant increase in serum testosterone, insulin, AMH, rats' body weights, ovarian tissue MDA, IL1ß, inflammasome, and caspase1 but decrease of serum TAC. In addition, gene expression of Bax increased but IL10 gene expression decreased. Ovaries showed the typical histopathological changes of PCOS with no immunoexpression of Bcl2. DIA was greatly able to ameliorate letrozole-induced PCOS changes in rats mainly via prevention of IL1ß, and improving metabolic disturbances, and its anti-apoptotic, anti-oxidant, and anti-inflammatory effects with further regulation of inflammasome/caspase1/IL1ß and Bax/Bcl2 pathways.

Metformin exposure, maternal PCOS status and fetal venous liver circulation: A randomized, placebo-controlled study.

BACKGROUND: Metformin is prescribed to women with polycystic ovary syndrome (PCOS) to prevent pregnancy complications. Children exposed to metformin vs. placebo in utero, have increased head circumference at birth and are more overweight and obese at 8 years of age. Also, maternal PCOS-status seems to alter the long-term cardio-metabolic health of offspring. We hypothesized that the long-term effects of metformin-exposure and/or maternal PCOS may be mediated by circulatory adaptations during fetal life. MATERIAL AND METHODS: This is a sub-study of a larger double-blinded, placebo-controlled trial, where women with PCOS were randomized to metformin (2g/day) or placebo in pregnancy, a total of 487 women. A sub-group of participants (N = 58) took part in this sub-study and had an extended ultrasound examination at gestational week 32, including blood flow velocity and diameter measurements of the umbilical vein (UV), the ductus venosus (DV) and the portal vein (PV). Blood flow volume was calculated and adjusted for estimated fetal weight (EFW) (normalized flow). Metformin exposed fetuses were compared to placebo exposed fetuses. Fetuses of mothers with PCOS (metformin [n = 30] and placebo [n = 28]) were compared to a low-risk reference population (N = 160) by z-score statistics. RESULTS: There was no difference in fetal liver flow between metformin vs. placebo-exposed fetuses. Fetuses of mothers with PCOS had higher EFW (0.63 [95% CI 0.44-0.83] p<0.001), lower normalized UV, DV, PV, and lower total venous liver blood flows than the reference population. CONCLUSION: Metformin during pregnancy did not affect fetal liver blood-flow. In our population, maternal PCOS-status was associated with reduced total venous liver blood-flow, which may explain altered growth and metabolism later in life.

Evidence-based hormonal, mutational, and endocrine-disrupting chemical-induced zebrafish as an alternative model to study PCOS condition similar to mammalian PCOS model.

Polycystic ovarian syndrome (PCOS) causes swollen ovaries in women at reproductive age due to hormonal disorder with small cysts on the outer edges. The cause of the disorder is still yet to be found. Multiple factors have increased PCOS prevalence, hyperandrogenism, oxidative stress, inflammation, and insulin resistance. Various animal PCOS models have been developed to imitate the pathophysiology of PCOS in humans. Zebrafish is one of the most versatile animal experimental models because of the transparency of the embryos, small size, and rapid growth. The zebrafish similarity to higher vertebrates made it a useful non-mammalian model for PCOS drug testing and screening. This review provides an insight into the usage of zebrafish, a non-mammalian model for PCOS, as an opportunity for evaluating future initiatives in such a research domain.

The effect of Myo-Inositol supplement on molecular regulation of folliculogenesis, steroidogenesis, and assisted reproductive technique outcomes in patients with polycystic ovarian syndrome.

RESEARCH QUESTION: The mechanism of Myo-Inositol, as an adjuvant, on key signaling pathways related to oocyte maturation, fertilization rate, and embryo quality as well as ovarian steroidogenesis in cumulus cells of PCOS patients, is still unclear. DESIGN: Infertile patients who were candidates for ART cycles were divided into three groups (n = 30 in each group), including group 1: PCOS patients only receiving folic acid, group 2: PCOS patients receiving daily Myo-Inositol combined with folic acid, and a control group (group 3): normal ovulatory women without PCOS receiving only folic acid from 1 month prior to IVF cycle until the day of ovum pick up. During the ART procedure, oocytes maturation, fertilization rate, and embryo quality were assessed. The gene expressions of FSHR, LHR, CYP11A1, CYP19A1, 3ß-HSD2, and StAR were also analyzed using qRT-PCR. Western blot analysis was performed for the evaluation of AKT, ERK, CREB, and AMPK phosphorylation. RESULT: Despite equal number of retrieved oocytes, the percentages of MII oocytes, fertilization rate, and embryo quality were found to be significantly higher in group 2 due to the administration of inofolic. The expressions of all the studied genes were significantly higher in the cumulus cells of group 1 compared to the group 2. Higher phosphorylation of ERK1/2 was found in the groups 2 and 3 compared to the group 1. On the other hand, p-Akt has significantly decreased in the group 2 compared to the group 1. CONCLUSION: Our study provides new insight into the molecular mechanism underlying the positive effect of Myo-Inositol on intrinsic ovarian defects in PCOS, steroidogenesis, oocyte maturation, fertilization rate, and embryo quality.

Insulin resistance, autophagy and apoptosis in patients with polycystic ovary syndrome: Association with PI3K signaling pathway.

Polycystic ovary syndrome (PCOS) is a disease in which endocrine metabolic abnormalities coexist with reproductive system abnormalities, with the main clinical manifestations including abnormal menstruation, hirsutism, acne, infertility, and obesity, and it is also a high risk for the development of many pregnancy complications, gynecological malignancies and other diseases. Therefore, timely intervention to prevent the progression of PCOS is of great significance for improving the quality of life of most female patients. Insulin resistance (IR) is one of the most common endocrine disorders in PCOS patients, with approximately 75% of PCOS patients experiencing varying degrees of IR. It is now believed that it is mainly related to the PI3K signaling pathway. The role of autophagy and apoptosis of ovarian granulosa cells (GCs) in the pathogenesis of PCOS has also been gradually verified in recent years. Coincidentally, it also seems to be associated with the PI3K signaling pathway. Our aim is to review these relevant studies, to explore the association between the IR, cellular autophagy and apoptosis in PCOS patients and the PI3K pathway. We summarize some of the drug studies that have improved PCOS as well. We have also found that proteomics holds great promise in exploring the pathogenesis of PCOS, and we have published our views on this.

Shared postulations between bipolar disorder and polycystic ovary syndrome pathologies.

INTRODUCTION: Women with bipolar disorder (BD) present a high prevalence of polycystic ovary syndrome (PCOS) and other reproductive disorders even before diagnosis or treatment of the disease. Postulations on the potential molecular mechanisms of comorbid PCOS in women with BD remain limited to influence of medications and need further extension. OBJECTIVES: This review focuses on evidence suggesting that common metabolic and immune disorders may play an important role in the development of BD and PCOS. RESULTS: The literature covered in this review suggests that metabolic and immune disorders, including the dysfunction of the hypothalamic-pituitary-adrenal axis, chronic inflammatory state, gut microbial alterations, adipokine alterations and circadian rhythm disturbance, are observed in patients with BD and PCOS. Such disorders may be responsible for the increased prevalence of PCOS in the BD population and indicate a susceptibility gene overlap between the two diseases. Current evidence supports postulations of common metabolic and immune disorders as endophenotype in BD as well as in PCOS. CONCLUSIONS: Metabolic and immune disorders may be responsible for the comorbid PCOS in the BD population. The identification of hallmark metabolic and immune features common to these two diseases will contribute to the clarification of the effect of BD on the reproductive endocrine function and development of symptomatic treatments targeting the biomarkers of the two diseases.

The effects of coenzyme Q10 supplementation on metabolic profiles and parameters of mental health in women with polycystic ovary syndrome.

OBJECTIVE: Evaluating the impact of coenzyme Q10 (CoQ10) supplementation on hormonal indices, mental health, and biomarkers of inflammatory responses and oxidative stress among female patients suffering from polycystic ovary syndrome (PCOS). METHODS: The present double-blinded, placebo-controlled randomized clinical trial consisted of 55 PCOS women (aged 18-40 years old), who were randomized into groups receiving 100 mg/day of CoQ10 (28 cases) or placebo (27 cases) for 12 weeks. RESULTS: The supplementation of CoQ10 decreased significantly the scores of Beck Depression Inventory (BDI) (p = .03) and Beck Anxiety Inventory (BAI) (p = .01) and high-sensitivity C-reactive protein (hs-CRP) level (p = .005) when comparing with the placebo group. Moreover, CoQ10 group exhibited a significant drop in total testosterone (p = .004), dehydroepiandrosterone sulfate (DHEAS) (p < .001), hirsutism (p = .002) and malondialdehyde (MDA) (p = .001) levels in the serum, and a significant rise in sex hormone-binding globulin (SHBG) (p < .001) and total antioxidant capacity (TAC) (p < .001) levels in the serum than the placebo group. CONCLUSIONS: 12-week supplementation of CoQ10 to PCOS women showed beneficial impact on BDI, BAI, hs-CRP, total testosterone, DHEAS, hirsutism, SHBG, TAC and MDA levels.

Polycystic ovarian syndrome: signs and feedback effects of hyperandrogenism and insulin resistance.

Polycystic ovary syndrome (PCOS) is a disease whose diagnosis is based on the detection of hyperandrogenism (HA) and ovulatory dysfunction. Women with PCOS frequently develop insulin resistance (IR), which generates a metabolic condition that involves a decrease in the action of insulin at the cellular level and is linked to compensatory hyperinsulinemia (HI). In PCOS, the ovary remains sensitive to the action of insulin. Additionally, it has been observed that the main effect of insulin in the ovary is the stimulation of androgen synthesis, resulting in HA, one of the fundamental characteristics of the PCOS. In this sense, the excess of androgens favors the development of IR, thus perpetuating the cycle of IR-HI-HA, and therefore PCOS. Moreover, mitochondrial dysfunction is present in PCOS patients and is a common feature in both IR and HA. This review places electron transfer as a key element in HA and IR development, with emphasis on the relationship between androgen biosynthesis and mitochondrial function. Indeed, metformin has been involved in repair mitochondrial dysfunction, decrease of oxidative stress, reduction of androgens levels and the enhancing of insulin sensitivity. Therefore, we propose that treatment with metformin could decrease HI and consequently HA, restoring, at least in part, the metabolic and hormonal disorders of PCOS.

Analysis of the proportion and clinical characteristics of obstructive sleep apnea in women with polycystic ovary syndrome.

PURPOSE: To investigate the proportion and clinical characteristics of obstructive sleep apnea (OSA) in Chinese patients with polycystic ovarian syndrome (PCOS) through home sleep apnea test (HSAT) and to evaluate the reproductive endocrine and metabolic characteristics in these patients. METHODS: The study was a cross-sectional analysis of infertile PCOS patients who underwent sleep respiratory monitoring between January and December 2019 at Peking University Third Hospital Reproductive Medical Center and respiratory and critical care medicine department. The prevalence of OSA, body mass index (BMI), menstruation, reproductive endocrine, and metabolic characteristics were collected in patients with PCOS. Logistic regression was performed to identify significant relationships among these factors and OSA. RESULTS: Amont 328 patients with PCOS, the prevalence of OSA was 40% (131/328), and six cases (5%) were severe. Univariate analysis showed that BMI and blood pressure were significantly higher in patients with OSA than in those without OSA (P < 0.05), whereas the anti-Mullerian hormone was lower than that in patients without OSA. In terms of glucose and lipid metabolism, the glycosylated hemoglobin (HbA1c), fasting plasma glucose, and fasting insulin levels were significantly higher in patients with PCOS and comorbid OSA than in those without OSA (all P < 0.05). Patients with OSA also had higher triglyceride, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein levels and lower high-density lipoprotein cholesterol levels (P < 0.05). Logistic regression analysis revealed that higher BMI, elevated serum testosterone, and decreased high-density lipoprotein cholesterol (HDL-C) are correlated with occurrence of OSA (P < 0.05). CONCLUSION: OSA in patients with PCOS was associated with multiple alterations in indexes of reproductive endocrine and metabolic disorders.

HOMA-IR for predicting clinical pregnancy rate during IVF.

OBJECTIVE: To determine the cutoff values of HOMA-IR for predicting clinical pregnancy rate in normal weight patients during their first IVF. MATERIALS AND METHODS: The data was retrospectively analyzed from 329 normal-weight women aged 21-40 years with BMI <25 kg/m2 who received first IVF-ET during the period from December 2018 to June 2019.We assessed the associations between HOMA-IR and clinical pregnancy rates during IVF in the women with or without PCOS according to different BMI ranges. RESULTS: In non PCOS,clinical pregnancy rate was significantly decreased at the HOMA-IR values ranging from 2.2 to 3.15 (OR, 0.188, 95% CI, 0.084-0.42; p < .05) and at those >3.15 (OR, 0.018, 95% CI, 0.004-0.081; p < .05).In PCOS, clinical pregnancy rate significantly decreased at the HOMA-IR >3.15 (OR, 0.15, 95% CI, 0.044-0.507; p < .05). In non PCOS with BMI <21.45 kg/m2, clinical pregnancy rate was decreased with HOMA-IR >2.2, and a significant cutoff point at HOMA-IR >3.15; with 21.45 ≤ BMI <25 kg/m2, clinical pregnancy rate was declined significantly at the HOMA-IR >1.56 (OR, 0.196, 95% CI, 0.055-0.704).In PCOS with BMI <21.45 kg/m2, clinical pregnancy rate was decreased as the HOMA-IR increased, but there was no significant cutoff point; with 21.45 ≤ BMI < 25 kg/m2, clinical pregnancy rate was declined significantly at the HOMA-IR > 3.15 (OR, 0.186; 95% CI, 0.04-0.872). CONCLUSION: HOMA-IR and BMI had adverse effects on the IVF outcome of infertility women. Moreover, obesity can increase the degree of insulin resistance in infertility women. These findings suggested that only better HOMA-IR and BMI will lead to better IVF results.