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1.
Sheng Li Xue Bao ; 72(1): 125-132, 2020 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-32099990

RESUMO

In recent years, it has been found that kisspeptin plays some key roles in the physiological processes of the brain, such as gender differentiation, positive and negative feedback of sex hormones, onset of puberty, and transduction of energy signals in the body, which suggests that kisspeptin may be a key molecule for the maturation and regulation of female reproductive function. In addition to the systemic roles of the kisspeptin, its local roles in reproductive organs are constantly being discovered. With the discovery that kisspeptin is involved in the pathological process of reproductive endocrine diseases such as isolated hypogonadotropic hypogonadism (IHH), polycystic ovary syndrome (PCOS), premature ovarian failure (POF) and pathological hyperprolactinemia, exogenous application of kisspeptin to solve reproductive problems has become a new hot topic. The review focuses on the research progress of kisspeptin in the female reproductive system, especially on its application in assisted reproduction.


Assuntos
Kisspeptinas/fisiologia , Técnicas de Reprodução Assistida , Feminino , Hormônios Esteroides Gonadais/fisiologia , Humanos , Hiperprolactinemia/fisiopatologia , Hipogonadismo/fisiopatologia , Kisspeptinas/farmacologia , Síndrome do Ovário Policístico/fisiopatologia , Gravidez , Insuficiência Ovariana Primária/fisiopatologia
2.
Mayo Clin Proc ; 94(12): 2455-2466, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31806099

RESUMO

OBJECTIVE: To investigate the factors that are associated with the effect of metformin on endothelial dysfunction in polycystic ovary syndrome (PCOS). PATIENTS AND METHODS: From March 24, 2014, to November 18, 2016, 48 women with PCOS were randomly assigned to 1500 mg/d of metformin (N=29) or no treatment (N=13) for 3 months; 42 patients (29 in the initial treatment group and 13 in the no treatment group) completed the study. Study variables were measured at baseline and after 3 months. Participants who did not receive metformin initially were then treated with metformin for another 3 months, and study variables were measured again. Endothelial function was measured as reactive hyperemia-peripheral arterial tonometry (RH-PAT) from the index finger. RESULTS: The age and baseline endothelial function (mean ± SD) of the participants were 32.7±6.9 years and 1.8±0.5, respectively. No notable change was observed in endothelial function after 3 months with metformin compared with no treatment. However, after stratifying participants who received metformin based on baseline endothelial function, there was a significant improvement following metformin treatment in participants with abnormal baseline endothelial function (1.3±0.3 vs 1.7±0.3; P<.001) but not in those with normal baseline endothelial function (2.1±0.4 vs 2.0±0.5; P=.11). CONCLUSION: Metformin improves endothelial function in women with PCOS and endothelial dysfunction independent of changes in glucose metabolism, dyslipidemia, or presence of prediabetes. Metformin has a direct effect on endothelial function in PCOS, and measurement of endothelial function can stratify and follow response to metformin treatment in PCOS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02086526.


Assuntos
Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Adulto , Feminino , Humanos , Manometria , Síndrome do Ovário Policístico/fisiopatologia , Vasodilatação/efeitos dos fármacos , Vasodilatação/fisiologia
3.
Nat Med ; 25(12): 1894-1904, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31792459

RESUMO

How obesity and elevated androgen levels in women with polycystic ovary syndrome (PCOS) affect their offspring is unclear. In a Swedish nationwide register-based cohort and a clinical case-control study from Chile, we found that daughters of mothers with PCOS were more likely to be diagnosed with PCOS. Furthermore, female mice (F0) with PCOS-like traits induced by late-gestation injection of dihydrotestosterone, with and without obesity, produced female F1-F3 offspring with PCOS-like reproductive and metabolic phenotypes. Sequencing of single metaphase II oocytes from F1-F3 offspring revealed common and unique altered gene expression across all generations. Notably, four genes were also differentially expressed in serum samples from daughters in the case-control study and unrelated women with PCOS. Our findings provide evidence of transgenerational effects in female offspring of mothers with PCOS and identify possible candidate genes for the prediction of a PCOS phenotype in future generations.


Assuntos
Androgênios/metabolismo , Oócitos/metabolismo , Síndrome do Ovário Policístico/genética , Efeitos Tardios da Exposição Pré-Natal/genética , Animais , Estudos de Coortes , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Camundongos , Núcleo Familiar , /metabolismo , Oócitos/imunologia , Fenótipo , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/fisiopatologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Análise de Célula Única
4.
Horm Metab Res ; 51(10): 639-648, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31578050

RESUMO

The aim of the study is to determine the impact of different anthropometric measurements of fat distribution on baseline sex-steroid concentrations and corticosteroidogenic enzyme activity in women with polycystic ovary syndrome compared to those with regular menstrual cycles. The current cross-sectional study included 106 normal cycling controls and 268 polycystic ovary syndrome patients. Patients with polycystic ovary syndrome, diagnosed by Rotterdam criteria, were divided in normoandrogenemic (n=91) and hyperandrogenemic (n=177). Anthropometric, biochemical, and hormone parameters were assessed and correlated with corticosteroidogenic enzyme activities in all three groups. Corticosteroidogenic enzyme activities were calculated using product-to-precursor ratios. Regarding sex-steroids individually, anthropometric parameters correlated with the concentrations of several androgens in polycystic ovary syndrome patients, most of them in patients with biochemical hyperandrogenism. The androgen precursors androstenedione, 17-hydroxyprogesterone, and dehydroepiandrosterone were less correlated with anthropometric parameters. The 17,20 lyase activity, in both Δ4 and Δ5 pathways, correlated with several anthropometric measurements in normo- and hyperandrogenemic polycystic ovary syndrome patients. The 17,20 lyase enzyme activity (Δ4 pathway) also correlated with conicity index, visceral adiposity index, and lipid accumulation product in the control group. 17-Hydroxylase activity positively correlated with waist-height ratio in both polycystic ovary syndrome groups. In contrast, 17-hydroxilase negatively correlated with the conicity index. Anthropometric markers of adiposity are associated with androgen levels and their precursors in blood. Body fat distribution correlates with the activities of some steroidogenic enzyme in both normo-and hyperandrogenemic polycystic ovary syndrome phenotypes. The molecular mechanisms involved in these associations are largely unclear and more investigations are required.


Assuntos
Androgênios/sangue , Biomarcadores/análise , Distribuição da Gordura Corporal , Hiperandrogenismo/fisiopatologia , Síndrome do Ovário Policístico/fisiopatologia , Esteroide 17-alfa-Hidroxilase/metabolismo , Adulto , Idoso , Antropometria , Estudos de Casos e Controles , Estudos Transversais , Feminino , Seguimentos , Humanos , Hiperandrogenismo/metabolismo , Pessoa de Meia-Idade , Síndrome do Ovário Policístico/metabolismo , Prognóstico
5.
Eur J Endocrinol ; 181(5): 473-480, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31491743

RESUMO

Objective: To evaluate whether brown adipose tissue (BAT) activity is altered in women with polycystic ovary syndrome (PCOS), and whether BAT activity correlates with plasma levels of irisin, a myokine that can induce BAT formation. Design: We performed a cross-sectional study including women with PCOS (n = 45) and a healthy control group (n = 25) matched by age and body mass index (BMI). Methods: BAT activity was measured using 18F-FDG positron emission tomography-computed tomography (PET-CT) and plasma irisin levels were measured by a validated enzyme immunoassay. Results: Total BAT activity was significantly reduced in women with PCOS (maximal standardized uptake value (SUVmax): median 7.4 g/mL, interquartile range 0.9-15.4) compared to controls (median 13.0 g/mL, interquartile range 4.7-18.4, P = 0.047). However, this difference was no longer significant after adjustment for waist circumference, a surrogate marker of central adiposity. In the PCOS group, BAT activity correlated negatively with BMI (Spearman's r = -0.630, P = 0.000) and waist circumference (r = -0.592, P = 0.000) but not with plasma irisin levels. Conclusions: BAT activity was reduced in women with PCOS possibly due to increased central adiposity. In PCOS women, BAT activity did not correlate with plasma irisin levels.


Assuntos
Tecido Adiposo Marrom/fisiopatologia , Síndrome do Ovário Policístico/fisiopatologia , Tecido Adiposo Marrom/diagnóstico por imagem , Adiposidade , Adolescente , Adulto , Índice de Massa Corporal , Estudos Transversais , Feminino , Fibronectinas/sangue , Fluordesoxiglucose F18 , Humanos , Estilo de Vida , Pessoa de Meia-Idade , Síndrome do Ovário Policístico/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Resultado do Tratamento , Circunferência da Cintura , Adulto Jovem
6.
Endocrinology ; 160(11): 2529-2542, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31415088

RESUMO

Prenatal testosterone (T)-treated female sheep display reproductive deficits similar to women with polycystic ovarian syndrome (PCOS), including an increase in LH pulse frequency due to actions of the central GnRH pulse generator. In this study, we used multiple-label immunocytochemistry to investigate the possibility of changes in the γ-aminobutyric acid (GABA) neurotransmitter system at two key components of the GnRH pulse generator in prenatal T-treated sheep: kisspeptin/neurokinin B/dynorphin (KNDy) neurons of the arcuate nucleus, and GnRH neurons in the preoptic area (POA) and mediobasal hypothalamus (MBH). We observed a significant decrease and increase, respectively, in the number of GABAergic synapses onto POA and MBH GnRH neurons in prenatal T-treated ewes; additionally, there was a significant increase in the number of GABAergic inputs onto KNDy neurons. To determine the actions of GABA on GnRH and KNDy neurons, we examined colocalization with the chloride transporters NKCC1 and KCC2, which indicate stimulatory or inhibitory activation of neurons by GABA, respectively. Most GnRH neurons in both POA and MBH colocalized NKCC1 cotransporter whereas none contained the KCC2 cotransporter. Most KNDy neurons colocalized either NKCC1 or KCC2, and 28% of the KNDy population contained NKCC1 alone. Therefore, we suggest that, as in the mouse, GABA in the sheep is stimulatory to GnRH neurons, as well as to a subset of KNDy neurons. Increased numbers of stimulatory GABAergic inputs to both MBH GnRH and KNDy neurons in prenatal T-treated animals may contribute to alterations in steroid feedback control and increased GnRH/LH pulse frequency seen in this animal model of PCOS.


Assuntos
Núcleo Arqueado do Hipotálamo/fisiopatologia , Neurônios GABAérgicos/fisiologia , Hormônio Liberador de Gonadotropina/metabolismo , Síndrome do Ovário Policístico/fisiopatologia , Área Pré-Óptica/fisiopatologia , Animais , Núcleo Arqueado do Hipotálamo/metabolismo , Modelos Animais de Doenças , Dinorfinas/metabolismo , Feminino , Kisspeptinas/metabolismo , Neurocinina B/metabolismo , Síndrome do Ovário Policístico/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Área Pré-Óptica/metabolismo , Ovinos , Membro 2 da Família 12 de Carreador de Soluto/metabolismo , Simportadores/metabolismo , Testosterona
7.
Diabetes Metab Syndr ; 13(4): 2747-2753, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31405703

RESUMO

INTRODUCTION: Polycystic ovary syndrome (PCOS) is an endocrinopathy with unknown pathophysiology among women of reproductive age. Several studies have been conducted to determine the prevalence of metabolic syndrome (MetS) among PCOS patients. However, the results were contradictory. The present study was conducted to evaluate the prevalence of MetS in PCOS patients using the related published data. METHOD: The present systematic review was perfumed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search was done using MeSH keywords in databases of PubMed, Scopus, Embase, CINAHL, Web of Science, Cochrane Library, EBSCO, and Google scholar search engine as well as the reference list of the retrieved papers without time limit until October 2018. We used Cochran's Q test and I2 Index to evaluate the heterogeneity among the studies and the random effects model was used to combine the results. Data analysis was performed using Stata ver. 11.1. RESULTS: Forty six studies including 8946 patients with PCOS were included in the final analysis. Total heterogeneity was high (I2: 91.43%, P < 0.001). The prevalence of MetS in PCOS patients was estimated to be 30% (95%CI: 27-33). Subgroup analysis based on MetS diagnostic criteria showed an estimated prevalence of 0.27% (95%CI: 0.18-0.37), 0.30% (95%CI: 0.27-0.34), 0.32 (95%CI: 0.25-0.39), 0.32 (95%CI: 0.27-0.37) and 0.24 (95%CI: 0.14-0.34) for IDF, NECP-ATPIII, AHA NHLBI, CDS, and unknown criteria, respectively. CONCLUSION: Considering the prevalence of MetS in PCOS patients, diagnosis of MetS in PCOS patients is necessary to reduce the mortality and morbidity rates.


Assuntos
Síndrome Metabólica/epidemiologia , Síndrome do Ovário Policístico/fisiopatologia , Feminino , Humanos , Irã (Geográfico)/epidemiologia , Prevalência
8.
Reprod Biol Endocrinol ; 17(1): 67, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31420039

RESUMO

Polycystic ovary syndrome (PCOS) is a prevalent hormonal disorder of premenopausal women worldwide and is characterized by reproductive, endocrine, and metabolic abnormalities. The clinical manifestations of PCOS include oligomenorrhea or amenorrhea, hyperandrogenism, ovarian polycystic changes, and infertility. Women with PCOS are at an increased risk of suffering from type 2 diabetes; me\tabolic syndrome; cardiovascular events, such as hypertension, dyslipidemia; gynecological diseases, including infertility, endometrial dysplasia, endometrial cancer, and ovarian malignant tumors; pregnancy complications, such as premature birth, low birthweight, and eclampsia; and emotional and mental disorders in the future. Although numerous studies have focused on PCOS, the underlying pathophysiological mechanisms of this disease remain unclear. Mitochondria play a key role in energy production, and mitochondrial dysfunction at the cellular level can affect systemic metabolic balance. The recent wide acceptance of functional mitochondrial disorders as a correlated factor of numerous diseases has led to the presupposition that abnormal mitochondrial metabolic markers are associated with PCOS. Studies conducted in the past few years have confirmed that increased oxidative stress is associated with the progression and related complications of PCOS and have proven the relationship between other mitochondrial dysfunctions and PCOS. Thus, this review aims to summarize and discuss previous and recent findings concerning the relationship between mitochondrial dysfunction and PCOS.


Assuntos
Mitocôndrias/fisiologia , Ovário/fisiopatologia , Síndrome do Ovário Policístico/fisiopatologia , Pré-Menopausa/fisiologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Humanos , Infertilidade/metabolismo , Infertilidade/fisiopatologia , Mitocôndrias/metabolismo , Ovário/metabolismo , Ovário/patologia , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/metabolismo , Pré-Menopausa/metabolismo , Fatores de Risco
9.
Acta Clin Croat ; 58(1): 103-106, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31363331

RESUMO

The aim of the study was to investigate knee cartilage thickness in polycystic ovary syndrome (PCOS) patients using ultrasonography and to assess the effects of sex steroids on osteoarthritis development. A total of 90 female patients were enrolled in the study, including 47 patients diagnosed with PCOS as study group and 43 patients admitted to our hospital for any other complaints as control group. Ultrasonographic evaluation of both knees was performed in all patients. The knee cartilage thickness was measured at lateral condyle, intercondylar area and medial condyle. The measurements were averaged for each region. The mean femoral cartilage thickness was greater in the study group compared with control group in all regions, with a statistically significant difference (p<0.005). In conclusion, we found PCOS patients to have greater mean cartilage thickness, supporting the possible effects of sex steroids on osteoarthritis development.


Assuntos
Doenças das Cartilagens/diagnóstico por imagem , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/patologia , Síndrome do Ovário Policístico/fisiopatologia , Adulto , Doenças das Cartilagens/etiologia , Estudos Transversais , Feminino , Fêmur/diagnóstico por imagem , Humanos , Articulação do Joelho/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/diagnóstico por imagem , Tomografia Computadorizada por Raios X
10.
Diabetes Metab Syndr ; 13(5): 2907-2915, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31425955

RESUMO

BACKGROUND: Polycystic Ovary Syndrome (PCOS) is the most common female endocrinopathy among premenopausal women associated with hyperandrogenism, obesity, dyslipidemia, insulin resistance and inflammation. Oxidative stress is an important component of cardio-metabolic risk seen in PCOS. MATERIAL AND METHODS: A total of 95 women with PCOS and 95 healthy controls were included in this observational study. Serum PON1 activity and stress markers were measured by spectrophotometric methods. Circulating TF level was measured by ELISA. RESULTS: We found decreased PON1 activity and increased TF levels in women with PCOS compared to healthy controls. Fasting insulin, HOMA-IR, testosterone, LDL-C, MDA, PC and SOD activity were significantly increased whereas FGIR, QUICKI, HDLC, CAT and TAC were significantly decreased in PCOS women than controls. We observed a positive association of PON1 activity with FGIR, QUICKI, HDL-C and TAC, and its negative association was observed with LH, testosterone, fasting insulin and HOMA-IR in PCOS women. We further observed a positive association of TF with waist, waist to hip ratio, BMI, glucose 1hr, cholesterol, LDL-C, SGPT, uric acid and SOD activity in PCOS women. CONCLUSIONS: Decreased PON1 activity and raised circulating TF levels are respective indicators of pro-inflammatory and procoagulant status in PCOS women. The imbalanced oxidant/antioxidant status further supports the evidences that PCOS is an oxidant state. Further, the association of PON1 activity and TF levels with the clinical, laboratory findings and stress marker levels suggest that these factors taken together are involved in aggravating the pro-inflammatory status in PCOS women.


Assuntos
Arildialquilfosfatase/sangue , Biomarcadores/sangue , Índice de Massa Corporal , Resistência à Insulina , Estresse Oxidativo , Síndrome do Ovário Policístico/fisiopatologia , Tromboplastina/análise , Adulto , Antioxidantes/metabolismo , Estudos de Casos e Controles , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Seguimentos , Humanos , Síndrome do Ovário Policístico/sangue , Prognóstico , Superóxido Dismutase/sangue , Testosterona/sangue , Adulto Jovem
11.
Endocrinology ; 160(11): 2663-2672, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31436841

RESUMO

Polycystic ovary syndrome (PCOS) is a common condition of reproductive-aged women. In a well-validated sheep model of PCOS, testosterone (T) treatment of pregnant ewes culminated in placental insufficiency and intrauterine growth restriction of offspring. The purpose of this study was to explore specific mechanisms by which T excess compromises placental function in early, mid, and late gestation. Pregnant Suffolk sheep received T propionate 100 mg intramuscularly or control vehicle twice weekly from gestational days (GD) 30 to 90 (term = 147 days). Placental harvest occurred at GD 65, 90, and 140. Real-time RT-PCR was used to assess transcript levels of proinflammatory (TNF, IL1B, IL6, IL8, monocyte chemoattractant protein-1/chemokine ligand 2, cluster of differentiation 68), antioxidant (glutathione reductase and superoxide dismutase 1 and 2), and angiogenic [vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1α (HIF1A)] genes. Lipid accumulation was assessed using triglyceride assays and Oil Red O staining. Placental measures of oxidative and nitrative stress included the thiobarbituric acid reactive substance assay and high-pressure liquid chromatography. Tissue fibrosis was assessed with Picrosirius Red staining. Student t tests and Cohen effect-size analyses were used for statistical analysis. At GD 65, T-treated placentomes showed increased lipid accumulation and collagen deposition. Notable findings at GD 90 were a significant increase in HIF1A expression and a large effect increase in VEGF expression. At GD 140, T-treated placentomes displayed large effect increases in expression of hypoxia and inflammatory markers. In summary, T treatment during early pregnancy induces distinct gestational age-specific effects on the placental milieu, which may underlie the previously observed phenotype of placental insufficiency.


Assuntos
Placenta/fisiopatologia , Síndrome do Ovário Policístico/fisiopatologia , Animais , Modelos Animais de Doenças , Feminino , Placenta/metabolismo , Síndrome do Ovário Policístico/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Ovinos , Testosterona
12.
Int J Mol Sci ; 20(15)2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31382403

RESUMO

Adipokines are a potential link between reproduction and energy metabolism and could partly explain some infertilities related to some pathophysiology, such as polycystic ovary syndrome (PCOS). However, adipokines were predominantly assessed in blood samples, while very little is known concerning their variations in follicular fluid (FF) and ovarian granulosa cells (GCs) of PCOS women. Thus, the objectives of our study were to investigate adiponectin, chemerin, resistin, visfatin, omentin, and apelin ovarian expression in PCOS women in comparison with controls and women with only a polycystic ovary morphology. In total, 78 women undergoing an in vitro fertilization procedure were divided into three groups: 23 PCOS women, 28 women presenting only ≥12 follicles per ovary (ECHO group), and 27 control women. Each group almost equally included normal weight and obese women. Follicular fluid (FF) concentration and granulosa cells (GCs) mRNA expression of adipokines and their receptors were assessed by ELISA and RT-qPCR, respectively. Omentin levels in FF and GC were higher in PCOS than in ECHO and control women, while apelin expression was increased in both PCOS and ECHO groups. FF chemerin concentration was predominant in normal-weight PCOS women compared to BMI (Body Mass Index)-matched ECHO and control women, while GC mRNA levels were higher in the obese PCOS group than in the ECHO one. Compared to PCOS, ECHO women had increased FF adiponectin concentrations and lower plasma AMH levels. The FF concentration of all adipokines was higher in obese subjects except for adiponectin, predominant in normal-weight women. In conclusion, women with PCOS expressed higher GC chemerin and omentin, whereas the ECHO group presented higher levels of FF adiponectin and apelin and lower plasma AMH and LH concentrations. Chemerin, omentin, and apelin expression was differently regulated in women with PCOS, suggesting their possible role in follicular growth arrest and ovulatory dysfunction characterizing PCOS pathogenesis.


Assuntos
Adipocinas/genética , Apelina/genética , Quimiocinas/genética , Citocinas/genética , Lectinas/genética , Síndrome do Ovário Policístico/genética , Feminino , Proteínas Ligadas por GPI/genética , Regulação da Expressão Gênica , Humanos , Ovário/metabolismo , Ovário/patologia , Ovulação , Síndrome do Ovário Policístico/patologia , Síndrome do Ovário Policístico/fisiopatologia
13.
Life Sci ; 232: 116640, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31295470

RESUMO

INTRODUCTION AND AIM: Polycystic ovary syndrome is one of the most common causes of female infertility, affecting 5-10% of the population. Women with PCOS manifest hyperandrogenism, hyperinsulinemia, low-grade systemic inflammation, and polycystic ovaries. Unfortunately, current available medications are only symptomatic without relevant reported treatment. Therefore, a pressing need for alternative safe approaches is necessitated. To this end, the present study is designed to investigate therapeutic merits of the edible plant: Ocimum kilimandscharicum (Ok), in a letrozole PCOS rat model, and compare it to metformin. MATERIAL AND METHODS: PCOS rats were treated with Ok total extract and its different fractions at 100 mg/kg orally for 10 consecutive days. Moreover, phytochemical characterization was applied using HPLC/PDA/ESI-MS to identify different secondary metabolites in the bioactive fractions. KEY FINDINGS: Results revealed that the total extract (Ok) and ethyl acetate (EA) fraction improved insulin sensitivity and restored normal hormonal and lipid profiles as well as normal morphological structure of the reproductive system. Furthermore, elevation of SOD and reduction of VEGF levels in comparison with metformin were recorded. SIGNIFICANCE: These results suggest that Ok extract and EA fraction halt letrozole-induced reproductive dysfunctions and restore normal morphological and physiological functions in PCOS rats, even superior to metformin.


Assuntos
Inibidores da Aromatase/farmacologia , Hipoglicemiantes/farmacologia , Letrozol/farmacologia , Metformina/farmacologia , Ocimum/química , Ovário/efeitos dos fármacos , Ovário/fisiopatologia , Extratos Vegetais/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Idoso , Animais , Antioxidantes/metabolismo , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Citocinas/metabolismo , Modelos Animais de Doenças , Estrogênios/sangue , Estro , Feminino , Glicosídeos/metabolismo , Humanos , Hidroxibenzoatos/metabolismo , Insulina/sangue , Tamanho do Órgão/efeitos dos fármacos , Ovário/patologia , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/patologia , Síndrome do Ovário Policístico/fisiopatologia , Progesterona/sangue , Ratos , Ratos Wistar , Espectrometria de Massas por Ionização por Electrospray , Testosterona/sangue , Triglicerídeos/sangue , Útero/efeitos dos fármacos
14.
Endocrinology ; 160(10): 2230-2242, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31265059

RESUMO

Polycystic ovary syndrome (PCOS) is a prevalent and distressing disorder of largely unknown etiology. Although PCOS defined by ovarian dysfunction, accumulating evidence supports a critical role for the brain in the ontogeny and pathophysiology of PCOS. A critical pathological feature of PCOS is impaired gonadal steroid hormone negative feedback to the GnRH neuronal network in the brain that regulates fertility. This impairment is associated with androgen excess, a cardinal feature of PCOS. Impaired steroid hormone feedback to GnRH neurons is thought to drive hyperactivity of the neuroendocrine axis controlling fertility, leading to a vicious cycle of androgen excess and reproductive dysfunction. Decades of clinical research have been unable to uncover the mechanisms underlying this impairment, because of the extreme difficulty in studying the brain in humans. It is only recently, with the development of preclinical models of PCOS, that we have begun to unravel the role of the brain in the development and progression of PCOS. Here, we provide a succinct overview of what is known about alterations in the steroid hormone-sensitive GnRH neuronal network that may underlie the neuroendocrine defects in clinical PCOS, with a particular focus on those that may contribute to impaired progesterone negative feedback, and the likely role of androgens in driving this impairment.


Assuntos
Hormônios Esteroides Gonadais/metabolismo , Sistemas Neurossecretores/fisiopatologia , Neurotransmissores/metabolismo , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/fisiopatologia , Animais , Feminino , Humanos
15.
Turk J Med Sci ; 49(4): 1117-1125, 2019 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-31286756

RESUMO

Background/aim: This study aims to investigate the association between polycystic ovary syndrome (PCOS) and obesity and insulin resistance (IR) with respect to anti-Müllerian hormone (AMH), inhibin A (INH-A), inhibin B (INH-B), and insulin-like peptide 3 (INSL3) levels, all factors which may have an impact on IR. Materials and methods: In this cross sectional study, 52 adolescent girls diagnosed with PCOS[groups:nonobese (NO), n = 23; overweight/obese (OW/O), n = 29] were included. Blood samples were obtained to measure AMH, INH-B, INH-A, and INSL3 levels, together with hormonal and biochemical assessments. Oral glucose tolerance test (OGTT) was performed and the indexes of IR [homeostasis model assessment: insulin resistance (HOMA-IR) and Matsuda index] were calculated. Results: Insulin resistance was 56.5% with OGTT and 30.4% with HOMA-IR in nonobese-PCOS girls. There was a correlation between INH-A and HOMA-IR even when controlled for body mass index (BMI). INH-B and FAI also had correlations with HOMA-IR which disappeared when controlled for BMI. In regression analyses, AMH (odds ratio = [0.903, P = 0.015) and FAI (odds ratio = 1.353, P = 0.023) are found to be contributors to IR. Their effect was BMI-independent. In ROC analysis, the cutoff value for FAI was 5.93 (sensitivity 71%) to define IR in PCOS girls. Conclusion: AMH and FAI may contribute to IR (defined by OGTT) in PCOS. FAI might be used as a supporting IR marker (defined by OGTT) in adolescent girls with PCOS.


Assuntos
Androgênios/sangue , Hormônio Antimülleriano/sangue , Inibinas/sangue , Resistência à Insulina/fisiologia , Insulina/sangue , Síndrome do Ovário Policístico , Adolescente , Adulto , Glicemia/análise , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Obesidade , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/epidemiologia , Síndrome do Ovário Policístico/fisiopatologia , Proteínas , Curva ROC , Adulto Jovem
16.
Nat Med ; 25(8): 1225-1233, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31332392

RESUMO

Polycystic ovary syndrome (PCOS) is characterized by androgen excess, ovulatory dysfunction and polycystic ovaries1, and is often accompanied by insulin resistance2. The mechanism of ovulatory dysfunction and insulin resistance in PCOS remains elusive, thus limiting the development of therapeutics. Improved metabolic health is associated with a relatively high microbiota gene content and increased microbial diversity3,4. This study aimed to investigate the impact of the gut microbiota and its metabolites on the regulation of PCOS-associated ovarian dysfunction and insulin resistance. Here, we report that Bacteroides vulgatus was markedly elevated in the gut microbiota of individuals with PCOS, accompanied by reduced glycodeoxycholic acid and tauroursodeoxycholic acid levels. Transplantation of fecal microbiota from women with PCOS or B. vulgatus-colonized recipient mice resulted in increased disruption of ovarian functions, insulin resistance, altered bile acid metabolism, reduced interleukin-22 secretion and infertility. Mechanistically, glycodeoxycholic acid induced intestinal group 3 innate lymphoid cell IL-22 secretion through GATA binding protein 3, and IL-22 in turn improved the PCOS phenotype. This finding is consistent with the reduced levels of IL-22 in individuals with PCOS. This study suggests that modifying the gut microbiota, altering bile acid metabolism and/or increasing IL-22 levels may be of value for the treatment of PCOS.


Assuntos
Ácidos e Sais Biliares/metabolismo , Fator de Transcrição GATA3/fisiologia , Microbioma Gastrointestinal , Interleucinas/fisiologia , Síndrome do Ovário Policístico/etiologia , Animais , Feminino , Humanos , Inflamação/complicações , Resistência à Insulina , Camundongos , Camundongos Endogâmicos C57BL , Ovário/fisiopatologia , Síndrome do Ovário Policístico/fisiopatologia
17.
Med Hypotheses ; 128: 58-63, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31203910

RESUMO

We were interested whether fluorine, at the concentrations regarded as normal, can play a role in PCOS pathogenesis. The effect was not described in PCOS. Women with PCOS were diagnosed according to Rotterdam's criteria. The average age of 40 examined women with PCOS was 26.3 ±â€¯5.5 years, BMI-29.16 ±â€¯0.8, WHR-0.91 ±â€¯0.08. Main Outcome Measures: ECLIA was used to analyse testosterone, FSH, LH, oestradiol, TSH, prolactin, insulin and SHBG. Fluorine content was analysed by potentiometry using ion selective electrode. Fluorine content in serum of women with PCOS did not statistically significantly differ from that of the control group and amounted to 0.224 ±â€¯0.043 and 0.228 ±â€¯0.023 ppm, respectively. There were significant differences in the levels of TSH and HOMA-IR between the groups. Based on the correlation matrix, a negative correlation with the level of SHBG protein and the level of glucose on fasting was showed for the group with a lower of fluorine, and a positive correlation with HDL level was observed in the group with higher concentration of fluorine. In the phenotype with a higher level of androgens, there was a negative correlation with triglycerides level and a positive correlation with HDL. Fluorine, even in concentrations regarded as proper, takes part in PCOS pathogenesis. It increases the synthesis of TSH and increases insulin resistance. Higher insulin resistance leads to the reduced synthesis of SHBG transport protein. Therefore, the key factor in PCOS pathogenesis is testosterone, but fluorine facilitates disruptions in carbohydrates and lipids metabolism leading to increased levels of androgens in blood.


Assuntos
Flúor/farmacologia , Resistência à Insulina , Síndrome do Ovário Policístico/fisiopatologia , Tireotropina/metabolismo , Adolescente , Adulto , Glicemia/análise , Índice de Massa Corporal , Feminino , Humanos , Hiperinsulinismo/metabolismo , Insulina/sangue , Hormônio Luteinizante/metabolismo , Síndrome do Ovário Policístico/etiologia , Valores de Referência , Adulto Jovem
18.
Curr Med Sci ; 39(3): 431-436, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31209815

RESUMO

Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in women. Progestin-primed ovarian stimulation (PPOS) protocol, which used oral progestin to prevent premature luteinizing hormone (LH) surges in ovarian stimulation, has been proved to be effective and safe in patients with PCOS. The aim of the present study was to compare the efficacy of PPOS protocol with that of the traditional gonadotropin-releasing hormone (GnRH) antagonist protocol in patients with PCOS. A total of 157 patients undergoing in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) were recruited into this study. The patients were divided into two groups by the stimulation protocols: the GnRH antagonist protocol group and the PPOS protocol group. There was no significant difference in the clinical characteristics between the two groups. Dose and duration of gonadotropin were higher in the PPOS protocol group. Estradiol levels on the day of human chorionic gonadotropin (hCG) administration were significantly lower in the PPOS protocol group. Fertilization rates and the number of good quality embryos were similar between the two groups. Remarkably, we found 6 patients with moderate ovarian hyperstimulation syndrome (OHSS) in the GnRH antagonist protocol group but 0 in the PPOS protocol group. A total of 127 women completed their frozen embryo transfer (FET) cycles. There were no significant differences between the two groups in terms of clinical pregnancy rate per transfer, implantation rate, first-trimester miscarriage rate and on-going pregnancy rate per transfer. To conclude, PPOS protocol decreased the incidence of OHSS without adversely affecting clinical outcomes in patients with PCOS.


Assuntos
Fármacos para a Fertilidade Feminina/uso terapêutico , Hormônio Liberador de Gonadotropina/análogos & derivados , Antagonistas de Hormônios/uso terapêutico , Infertilidade Feminina/terapia , Indução da Ovulação/métodos , Síndrome do Ovário Policístico/fisiopatologia , Progestinas/administração & dosagem , Adulto , Gonadotropina Coriônica/administração & dosagem , Transferência Embrionária/métodos , Estradiol/sangue , Feminino , Fertilização In Vitro/métodos , Expressão Gênica , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Hormônio Liberador de Gonadotropina/genética , Hormônio Liberador de Gonadotropina/metabolismo , Hormônio Liberador de Gonadotropina/uso terapêutico , Humanos , Infertilidade Feminina/complicações , Infertilidade Feminina/diagnóstico , Infertilidade Feminina/fisiopatologia , Masculino , Síndrome de Hiperestimulação Ovariana/induzido quimicamente , Síndrome de Hiperestimulação Ovariana/diagnóstico , Síndrome de Hiperestimulação Ovariana/prevenção & controle , Ovário/efeitos dos fármacos , Ovário/metabolismo , Ovário/fisiopatologia , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/diagnóstico , Gravidez , Taxa de Gravidez , Progestinas/efeitos adversos , Estudos Prospectivos , Injeções de Esperma Intracitoplásmicas/métodos , Resultado do Tratamento
19.
Arch Endocrinol Metab ; 63(3): 288-292, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31166365

RESUMO

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. The renal resistive index (RRI) is a measure of renal arterial resistance to blood flow. The aim of this study was to investigate the renal resistive index levels of patients with PCOS. SUBJECTS AND METHODS: A total of 216 women were included in this cross-sectional study. The study group consisted of 109 patients with PCOS, and the control group consisted of 107 healthy subjects. The RRI of all subjects was measured using renal Doppler ultrasonography. RESULTS: The patients with PCOS had higher RRI levels in comparison to the healthy subjects (0.64 ± 0.06 vs. 0.57 ± 0.06, p < 0.001). The RRI levels of the patients with PCOS were correlated with systolic blood pressure (p = 0.004, r = 0.268) and with homeostasis model assessment of insulin resistance (HOMA-IR) (p = 0.02, r = 0.216). CONCLUSION: In this study, we observed higher RRI levels in patients with PCOS. High RRI levels may be an indicator of cardiovascular and/or cardiovascular-associated diseases in patients with PCOS.


Assuntos
Rim/fisiopatologia , Síndrome do Ovário Policístico/fisiopatologia , Adulto , Pressão Sanguínea , Estudos Transversais , Feminino , Humanos , Resistência à Insulina , Rim/diagnóstico por imagem , Masculino , Ultrassonografia Doppler em Cores
20.
EBioMedicine ; 44: 582-596, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31178425

RESUMO

BACKGROUND: Enhanced GABA activity in the brain and a hyperactive hypothalamic-pituitary-gonadal axis are associated with polycystic ovary syndrome (PCOS), the most common form of anovulatory infertility. Women with PCOS exhibit elevated cerebrospinal fluid GABA levels and preclinical models of PCOS exhibit increased GABAergic input to GnRH neurons, the central regulators of reproduction. The arcuate nucleus (ARN) is postulated as the anatomical origin of elevated GABAergic innervation; however, the functional role of this circuit is undefined. METHODS: We employed a combination of targeted optogenetic and chemogenetic approaches to assess the impact of acute and chronic ARN GABA neuron activation. Selective acute activation of ARN GABA neurons and their fiber projections was coupled with serial blood sampling for luteinizing hormone secretion in anesthetized male, female and prenatally androgenised (PNA) mice modelling PCOS. In addition, GnRH neuron responses to ARN GABA fiber stimulation were recorded in ex vivo brain slices. Chronic activation of ARN GABA neurons in healthy female mice was coupled with reproductive phenotyping for PCOS-like features. FINDINGS: Acute stimulation of ARN GABA fibers adjacent to GnRH neurons resulted in a significant and long-lasting increase in LH secretion in male and female mice. The amplitude of this response was blunted in PNA mice, which also exhibited a blunted LH response to GnRH administration. Infrequent and variable GABAA-dependent changes in GnRH neuron firing were observed in brain slices. Chronic activation of ARN GABA neurons in healthy females impaired estrous cyclicity, decreased corpora lutea number and increased circulating testosterone levels. INTERPRETATION: ARN GABA neurons can stimulate the hypothalamic-pituitary axis and chronic activation of ARN GABA neurons can mimic the reproductive deficits of PCOS in healthy females. Unexpectedly blunted HPG axis responses in PNA mice may reflect a history of high frequency GnRH/LH secretion and reduced LH stores, but also raise questions about impaired function within the ARN GABA population and the involvement of other circuits.


Assuntos
Núcleo Arqueado do Hipotálamo/metabolismo , Neurônios GABAérgicos/metabolismo , Hormônio Luteinizante/biossíntese , Ovário/metabolismo , Síndrome do Ovário Policístico/etiologia , Síndrome do Ovário Policístico/metabolismo , Androgênios/metabolismo , Animais , Núcleo Arqueado do Hipotálamo/fisiopatologia , Encéfalo/metabolismo , Encéfalo/patologia , Modelos Animais de Doenças , Feminino , Hormônio Liberador de Gonadotropina/metabolismo , Imuno-Histoquímica , Camundongos , Camundongos Transgênicos , Ovário/patologia , Ovário/fisiopatologia , Síndrome do Ovário Policístico/fisiopatologia , Ácido gama-Aminobutírico/metabolismo
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