多囊卵巢综合征患者血清VitD水平及与炎症因子之间的相关性研究

目的 了解多囊卵巢综合征（PCOS）患者血清中25-羟维生素D（25-OH-VitD3）水平情况,并探讨其与白细胞介素-6（IL-6）、肿瘤坏死因子（TNF-α）、转化生长因子（TGF-β）、单核细胞趋化蛋白-1（MCP-1）及C-反应蛋白（CRP）之间的相关性。方法 选择2017年8月—2018年12月来医院妇科门诊就诊并确诊为PCOS的患者共135例作为PCOS组,选择同期来医院体检的健康妇女共120例作为对照组,采用化学发光法检测血清中25-OH-VitD3水平,免疫比浊法检测CRP水平及采用酶联免疫吸附法（ELISA）检测IL-6、TNF-α及TGF-β水平,并对检测结果进行统计学分析。结果 PCOS组患者血清中25-OH-VitD3水平为31.87±6.29 nmol/L,明显低于对照组的65.08±13.76 nmol/L,差异有统计学意义（t=3.190,P<0.05）。PCOS组患者血清IL-6、TNF-α、TGF-β、MCP-1及CRP水平分别为23.71±11.23 ng/L、20.54±3.16 ng/L、76.54±8.03 ng/L、375.92±40.15 ng/L及13.48±3.10 mg/L,均明显高于对照组,差异均有统计学意义（t=9.065,8.091,10.178,13.052,7.059,Ps<0.05）。通过Pearson相关性分析,25-OH-VitD3水平与IL-6、TNF-α、TGF-β、MCP-1及CRP水平均呈明显的负相关（r= -0.562,-0.628,-0.780,-0.850,-0.505,Ps<0.05）。结论 25-OH-VitD3低表达水平可能通过其免疫调节及抑制炎症因子生成能力下降,引起各种炎症因子水平升高,导致PCOS的发病。因此,维生素D可能与PCOS病的发生和发展有密切关系。     

多囊卵巢综合征患者与健康人群肠道菌群差异性分析

目的 比较多囊卵巢综合征(PCOS)患者与健康人群间肠道菌群的差异,为后续研究提供参考.方法 采用16SrDNA扩增子测序法对30例PCOS患者(PCOS组)和20例健康人(健康组)粪便标本中菌群结构进行分析,并比较两组之间的区别.结果 与健康组相比,PCOS组患者肠道菌群α多样性降低.PCOS组患者肠道厚壁菌门(Fi...     

多囊卵巢综合征患者阴道微生态变化及其与性激素水平的关系

目的探讨多囊卵巢综合征(PCOS)患者阴道微生态变化及其与性激素水平的关系。方法将2018年7月-2019年7月我院生殖健康与不孕症科收治的132例PCOS患者作为研究组,选择同期在我院进行妇科体检的86例健康女性作为对照组。16S rRNA法和定量PCR反应检测阴道分泌物微生态情况,放射免疫法测定血清中睾酮(T)、卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇(E2)、孕酮(P)、催乳素(PRL)水平,分析微生态变化与性激素水平的关系。结果研究组患者阴道分泌物清洁度Ⅳ度检出率,滴虫、假丝酵母菌及线索细胞阳性检出率,阴道微生态失调率,血清T、LH、E2及PRL水平均高于对照组(P0.05),研究组患者血清FSH、P水平低于对照组(P0.05)。阴道微生态失调患者血清中E2水平高于阴道微生态正常患者,P水平低于阴道微生态正常患者(P0.05)。结论 PCOS患者存在阴道微生态失衡,阴道微生态的变化与血清性激素水平存在相关性,考虑激素水平的变化可能参与阴道微生态失调的发生。     

Modelling the control of ovulation and polycystic ovary syndrome

 The control of ovulation in mammalian species appears to be a highly robust process. The primary mechanism is believed to be competition amongst a group of developing follicles, mediated by a hormonal feedback loop involving in the first instance the pituitary. Successful follicles reach maturity and ovulate, the remainder atrophy and die. A model of this control process has been derived by Lacker and his group. Based on simple qualitative assumptions about the hormonal feedback loop, this is able to reflect many of the basic physiological features of ovulation in mammals. However, a fundamental hypothesis of Lacker’s work is that all follicles are identical and respond to hormonal signals in precisely the same way. Not only is this improbable, but it also leads to several aspects of the model which are qualitatively unrealistic, most notable of these is its inability to accurately model the condition known as Polycystic Ovary Syndrome. This common malfunction of the ovulatory control mechanism accounts for up to three-quarters of cases of anovulatory infertility in humans and its understanding is therefore of considerable medical significance. In this paper we extend the analysis of Lacker’s model to the case of non-identical follicles; this allows us to obtain behaviour much closer to that observed in PCOS patients and to draw some tentative conclusions about the mechanisms underlying this condition. Received 19 August 1996; received in revised form 14 February 1997     

2型糖尿病并发多囊卵巢综合征与肠道菌群相关性的研究进展

2型糖尿病并发多囊卵巢综合征（PCOS）的患病率逐年上升,但在临床中并未引起足够重视,二者并发增加了临床治疗难度,对患者的生活带来严重的不良影响。在药物治疗方面,虽然双胍类药物和SGLT-2抑制剂等治疗2型糖尿病并发PCOS具有一定的治疗效果,但受限于疾病发病机制不清及药物相关的不良反应,目前临床治疗此病的治疗效果欠佳,预后一般。研究发现,microRNA的异常表达、线粒体功能障碍、脂联素水平的下降与2型糖尿病并发PCOS密切相关。通过调节肠道菌群,可以调节microRNA的异常表达,改善线粒体功能障碍及升高血浆脂联素水平,提示肠道菌群失调可能是2型糖尿病并发PCOS的关键因素。因此,调节肠道菌群紊乱对治疗2型糖尿病并发PCOS具有重要意义。

     

多囊卵巢综合征和肠道菌群的关系及中药防治研究现状

多囊卵巢综合征是育龄期女性最常见的疾病之一,以多种内分泌代谢紊乱为特征。近年来的研究发现肠道菌群和多囊卵巢综合征的发生发展相关,肠道菌群和中医的关系已成为研究热点。本文分析了肠道菌群及其代谢产物和肠道屏障在多囊卵巢综合征发生发展中的作用,总结了单味中药和复方中药通过影响肠道菌群改善多囊卵巢综合征的研究进展。今后研究中应进一步探索与多囊卵巢综合征相关的特异菌属,探索中药有效成分及作用靶点,为中医治疗多囊卵巢综合征提供新思路。     

粪菌移植对多囊卵巢综合征的影响

多囊卵巢综合征是无排卵不孕女性常见的内分泌紊乱疾病,临床表现为月经不调、高雄激素血症和卵巢多囊样改变等,并伴有糖代谢和脂代谢异常。肠道菌群不仅作用于肠道,还调节营养摄取、脂肪储存和胰岛素敏感性,与多囊卵巢综合征有着密切关系。肠道菌群失调可能导致慢性低度炎症状态,免疫系统的激活会干扰胰岛素受体,提高胰岛素水平,促进卵巢睾酮的产生,导致多囊卵巢综合征。粪菌移植可以恢复肠道菌群失调和重建黏膜屏障,从而调节性类固醇的浓度、改善发情周期、恢复卵巢正常形态、降低空腹胰岛素水平、改善胰岛素抵抗、增加胰岛素敏感性和减轻慢性炎症等,对多囊卵巢综合征具有一定的治疗效果。     

阴道微生物与多囊卵巢综合征相关性的研究进展

多囊卵巢综合征（PCOS）是育龄期女性最常见的内分泌失调性疾病,具有高度的异质性和复杂性,是女性不孕的常见因素之一,且PCOS会显著增加2型糖尿病、肥胖、心血管疾病、高血压和心理疾病的风险,严重危害患者健康。阴道微生物群是每个女性特有的,正常的阴道微生物群在维持女性生殖健康方面起着至关重要的作用,而异常的阴道微生物定植与不良生殖结局密切相关。结合PCOS患者不孕症、高流产率、高早产率和胚胎停育等不良妊娠事件的发生,阴道乃至整个生殖道的不良微生物群可能通过免疫和炎症反应等途径影响着PCOS的发生发展,但其机制仍不清楚。因此,本文综述了阴道微生物群和PCOS患者相关性的研究概况,包括PCOS患者阴道微生物群的组成、阴道微生物群与PCOS的发生机制以及PCOS患者阴道微生物对生殖结局的影响,以期为PCOS的诊疗提供新思路。

     

Proteomics and polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder of heterogeneous etiology. Proteomics techniques have been used for elucidating the physiopathology of PCOS, yet the proteins identified so far were rarely the same across tissues and studies. The present review discusses the current challenges in the application of proteomics to the study of PCOS. A well-defined research design and an appropriate selection of study populations, samples and proteomic platforms are essential in clinical proteomics. Furthermore, the findings derived from proteomic approaches should be validated by complementary techniques, and the reproducibility of the results has ideally to be confirmed by different studies. Only when meeting these requirements, the proteins identified by proteomic techniques should be considered as candidates for future studies aiming to define specific molecular phenotypes of PCOS and their possible role in the metabolic and hormonal abnormalities characteristic of this syndrome.     

补充维生素D联合益生菌对多囊卵巢综合征患者肠道菌群多样性、代谢和激素水平的影响

目的探究补充维生素D联合益生菌治疗多囊卵巢综合征(PCOS)对患者菌群多样性、代谢和激素水平的影响。方法选取2019年1月至2019年3月在东南大学附属中大医院诊断并治疗的PCOS患者60例,采用随机数表法分为联合补充组(30例)和维生素D组(30例),联合补充组同时使用维生素D和益生菌,维生素D组只补充维生素D。对治疗前后患者肠道菌群进行检测,并比较代谢因子和激素水平,使用Pearson相关性分析探究指标间的相关性。结果治疗后两组菌群丰富度、Shannon-Wiener指数及最大Shannon-Wiener指数均较治疗前显著升高(均P<0.05),且联合补充组丰富度、Shannon-Wiener指数显著高于维生素D组(t=4.496,2.896,均P<0.05);治疗后两组GSH、TAC水平均显著升高,其中联合补充组TAC显著高于维生素D组(t=2.505,P=0.002);治疗后两组MDA、TT显著降低,其中联合补充组MDA、TT显著低于维生素D组(t=2.371,2.177,P=0.021,0.034)。副拟杆菌属与MDA呈显著正相关(r=0.339,P=0.040),肠杆菌科与TT呈显著正相关(r=0.330,P=0.046),粪杆菌属与TAC呈显著正相关(r=0.437,P=0.007),乳杆菌属与TAC呈显著正相关(r=0.350,P=0.033),与TT呈显著负相关(r=-0.371,P=0.024)。结论补充维生素D联合益生菌可有效改善PCOS患者代谢因子及激素水平,且其肠道微生物与PCOS代谢及激素指标存在一定相关性。     

CircRNA circ_0043533 facilitates cell growth in polycystic ovary syndrome by targeting miR-1179

Increasing evidence indicates that circular RNAs (CircRNAs) have an important role in human diseases, including polycystic ovary syndrome (PCOS). Recently, circ_0043533, a novel circRNA, was proposed to be involved in the progression of PCOS. However, its role in PCOS has not been explored. In this study, the expression levels of circ_0043533 and miR-1179 in ovarian granulosa cells (OGCs) were examined by qRT-PCR analysis. Moreover, knockdown of circ_0043533 in OGC lines COV434 and KGN, respectively, the cell viability, proliferation, apoptosis, and cycle-related markers of insulin-triggered OGCs were examined by CCK-8, EdU staining, flow cytometry, and western blot assays, respectively. The interaction between circ_0043533 and miR-1179 was examined by bioinformatics, dual-luciferase assay, and RNA immunoprecipitation. Besides, effects of the miR-1179 inhibitor on cell viability and apoptosis in OGC lines with circ_0043533 knockdown were also evaluated. OGCs and insulin-treated OGCs exhibited higher circ_0043533 levels in comparison to the IOSE80 cells. Additionally, knockdown of circ_0043533 remarkably inhibited the cell viability and proliferation and promoted the apoptosis of insulin-treated COV434 and KGN cells, respectively. Meanwhile, circ_0043533 knockdown could down-regulate the Bcl-2, CDK2, and Cyclin D1 expressions, and up-regulate the Bax levels. Furthermore, we demonstrated that circ_0043533 acted as a sponge to absorb miR-1179. Interestingly, miR-1179 inhibition remarkably attenuated the effect of circ_0043533 silence on cell proliferation and apoptosis in insulin-treated COV434 and KGN cells. Taken together, this study revealed that circ_0043533 knockdown restrained the malignant progression of PCOS via targeting miR-1179. Our data suggested that circ_0043533 would serve as a novel therapeutic target for PCOS.     

Oncostatin M and its receptor in women with polycystic ovary syndrome and association with assisted reproductive technology outcomes

The role of adipokines in ovarian-related disorders such as polycystic ovary syndrome (PCOS) has been reported. However, the involvement of Oncostatin M (OSM), a recently identified adipokine, in ovarian function is unknown. Therefore, we investigated the association of the OSM signaling pathway with ovarian functions and PCOS pathogenesis. This case-control study enrolled 30 PCOS and 30 healthy women who underwent the intracytoplasmic sperm injection procedure. OSM and OSM receptor (OSMR) levels were evaluated in the follicular fluid (FF). Moreover, the expression of insulin receptor substrates (IRS1 and IRS2), OSM, OSMR, suppressor of cytokine signaling 3 (SOCS3), and androgen receptor (AR) genes were analyzed in the isolated cumulus cells (CCs). For the in-vitro experiment, the effect of recombinant OSM on the expression of related genes in isolated CCs was analyzed. Follicular concentrations of OSM and OSMR were significantly lower in PCOS (123.91±48.58 pg/ml and 0.93±0.35 ng/ml, respectively) compared to control women (283.53 ± 96.62 pg/ml and 1.45 ± 0.18 ng/ml, respectively; p < 0.001) and were positively correlated with the oocyte maturation (r = 0.611 and r = 0.611, respectively) and fertilization (r = 0.592 and r = 0.627, respectively) rates in the PCOS group. Furthermore, the SOCS3 expression was upregulated about eight times in PCOS patients compared to the controls (p < 0.05). The treatment of cells with recombinant OSM significantly increased SOCS3, OSMR, IRS-1, and -2 expression and decreased AR expression. The decreased levels of OSM and its receptor in PCOS patients, possibly mediated by SOCS3, could negatively affect oocyte maturation and fertilization rates.     

Circulating levels of apoptotic markers and oxidative stress parameters in women with polycystic ovary syndrome: a case-controlled descriptive study

Context: Apoptotic dysregulation plays a role in the pathogenesis of polycystic ovary syndrome (PCOS).

Objective: To evaluate circulatory apoptotic markers and oxidative stress in patients with PCOS.

Materials and methods: Forty-four women with PCOS, and 44 healthy women as controls were enrolled in the study. Oxidative stress parameters and caspases levels were measured in serum.

Results: The caspase 9 level was significantly lower and related with oxidant status in patients with PCOS, while the circulating levels of caspases 3 and 7 were statistically similar in both groups.

Discussion: This study is the first report demonstrating the circulating levels of apoptotic markers and their relationship with oxidant status in PCOS.

Conclusion: The circulating caspase 9 and oxidant status might contribute to apoptotic dysregulation in PCOS.     

Evaluation of the Rho A/Rho-kinase pathway in the uterus of the rat model of polycystic ovary syndrome

The aim of this study was to investigate the expression of RhoA/Rho-kinase in the uterus and the effect of Rho-kinase inhibitors on uterine contractions of dehydroepiandrosterone (DHEA) induced polycystic ovary syndrome (PCOS) rats. Forty-four female Sprague-Dawley (21 days old) rats divided into three groups: The control group (n?=?14, any procedure was not performed), vehicle group (n?=?14, 0.2?ml of sesame oil, subcutaneous injection, 20 days) and PCOS group (n?=?16, DHEA 6?mg/100?g in 0.2?ml of sesame oil, subcutaneous injection, 20 days). The myometrium thickness and uterine wet weight were assessed. The mRNA and protein expressions of Rho A, the effect of Rho-kinase inhibitors (fasudil and Y-27632) on KCl, carbachol, and PGF2α induced contractions were evaluated in the uterus. In the PCOS group, the myometrium thickness and uterine wet weight significantly increased compared to the control group and vehicle group. The mRNA expression level and the immunoreactive score of Rho A, ROCK 1, ROCK 2 were similar in all groups. In the PCOS group, KCl, carbachol, and PGF2α induced uterine contractions significantly increased compared to the control group and vehicle group. Fasudil and Y-27632 significantly inhibited KCl, carbachol, and PGF2α induced uterine contractions in all groups. In conclusion, the expression of Rho A, ROCK 1, ROCK 2 not changed although myometrium thickness, uterine wet weight and the contractile responses of uterus increased in the PCOS group. The results suggest that the Rho-kinase inhibitors effectively suppressed increased contractions in the PCOS group they might be potential therapeutic agents.     

Correlations of selenium and selenoprotein P with asymmetric dimethylarginine and lipid profile in patients with polycystic ovary syndrome

BackgroundPolycystic ovary syndrome (PCOS) is associated with an increased risk of cardiovascular diseases (CVD). Accumulating evidence has suggested that selenium (Se) is of importance for optimal function of the cardiovascular system. This study aimed to investigate the associations of selenium and selenoprotein P (SePP) with asymmetric dimethylarginine (ADMA) and lipid profile in women with PCOS.MethodsIn this cross-sectional study, 125 females aged 18–45 years diagnosed with PCOS were recruited. An interviewer-administered questionnaire was applied to gather the relevant demographic characteristics, detailed clinical information, and lifestyle habits of participants. Fasting blood samples were obtained to measure biochemical parameters. Serum concentrations of total testosterone, sex hormone-binding globulin (SHBG), ADMA, and lipid profiles as well as anthropometric measurements were assessed across tertiles of serum Se and SePP concentrations.ResultsThere was a positive correlation between serum Se and SePP concentrations (r = 0.434, p < 0.001). Serum Se level was inversely correlated with ADMA (r = −0.21, p = 0.025) and TG (r = −0.17, p = 0.041) concentrations. There were also inverse correlations between SePP and ADMA (r = −0.34, p < 0.001), TG (r = −0.21, p = 0.019), and oxidized low density lipoprotein (ox-LDL) (r = −0.25, p = 0.007) levels. No significant relationship was found between serum Se and SePP concentrations with total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), apolipoprotein-A1 (Apo-A1), apolipoprotein-B (Apo-B100), total testosterone, SHBG, and free androgen index as well as anthropometric parameters (All p > 0.05).ConclusionThe present study found that Se and SePP levels were inversely correlated with ADMA and TG concentrations as well as ox-LDL levels.     

Melatonin alleviates insulin resistance through the PI3K/AKT signaling pathway in ovary granulosa cells of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a common endocrine gynecological disorder. Insulin resistance (IR) is a major cause of PCOS. Melatonin, a critical endogenous hormone, has beneficial effects on the female reproductive system. This study aims to investigate the molecular effect of melatonin on IR in human ovarian granulosa cells (GCs). Hormone levels of the subjects were determined through clinical examination. The expression levels of insulin receptor substrate (IRS)-1 and glucose transporter (GLUT4) in GCs from PCOS patients and a human granulosa cell line (SVOG) were examined using qRT-PCR and western blot. The IR cell model was established by inducing SVOG cells with palmitic acid (PA). IR was detected in GCs of PCOS patients and SVOG by measuring glucose content and glucose uptake. Cell viability and apoptosis levels were detected by CCK-8 assay and flow cytometry. PI3K/Akt pathway expression in SVOG was assessed by western blot. PCOS patients had higher levels of luteinizing hormone (LH), testosterone, and LH/follicle-stimulating hormone. PA decreased cell viability, promoted apoptosis, and reduced glucose uptake in SVOG cells. IRS-1 and GLUT4 mRNA and protein expression was downregulated, and glucose uptake capacity was reduced in PCOS GCs and SVOG cells. Melatonin significantly upregulated IRS-1 and GLUT4 expression, downregulated p-IRS-1 (Ser307), and improved glucose uptake in PCOS patients' GCs and SVOG cells. PA decreased PI3K and Akt phosphorylation, whereas melatonin increased p-PI3K and p-Akt levels. Melatonin can reduce IR in GCs and PA-induced SVOG cells via the PI3K/Akt signaling pathway, providing more evidence for treating polycystic ovary syndrome.     

Testosterone levels and cognitive functioning in women with polycystic ovary syndrome and in healthy young women

We investigated the possible influence of testosterone (T) on cognitive functioning in women with polycystic ovary syndrome (PCOS), an endocrine disorder associated with elevated levels of free testosterone (free T). Performance on a battery of neuropsychological tests in 29 women with elevated free T levels due to PCOS was compared to the performance of 22 age- and education-matched, healthy control women with free T levels in the normal female range. Women with PCOS had significantly higher levels of free T (estimated by the free androgen index) and demonstrated significantly worse performance on tests of verbal fluency, verbal memory, manual dexterity, and visuospatial working memory than the healthy control women. No differences between the groups were found on tests of mental rotation, spatial visualization, spatial perception, or perceptual speed. These results suggest that, in women, elevations in free T may be associated with poorer performance on cognitive tasks that tend to show a female advantage.     

Contrasting association of Leptin receptor polymorphisms and haplotypes with polycystic ovary syndrome in Bahraini and Tunisian women: a case–control study

Background: The present study examined the contribution of ethnicity to the association of leptin receptor gene (LEPR) gene variants with polycystic ovary syndrome (PCOS) in Tunisian and Bahraini Arabic-speaking women.Methods: Subjects consisted of 320 women with PCOS, and 446 eumenorrhic women from Tunisia, and 242 women with PCOS and 238 controls from Bahrain. Genotyping of (exonic) rs1137100 and rs1137101 and (intronic) rs2025804 LEPR variants was done by allelic exclusion.Results: The minor allele frequencies (MAFs) of rs1137100 and rs1137101 were significantly different between PCOS cases and control women from Bahrain but not Tunisia, and LEPR rs1137101 was associated with increased PCOS susceptibility only in Bahraini subjects. Furthermore, rs1137100 was associated with decreased PCOS risk among Bahrainis under codominant and recessive models; rs1137100 was negatively associated with PCOS in Tunisians after controlling for testosterone. In addition, rs2025804 was associated with increased PCOS risk among Tunisian but not Bahraini women, after adjusting for key covariates. Negative correlation was seen between rs1137101 and triglycerides in Tunisians, while homeostasis model assessment of insulin resistance (HOMA-IR) and insulin correlated with rs2025804 and rs1137101 among Bahraini subjects, and rs1137101 correlated with estradiol and prolactin. Taking TAG haplotype as common, positive association of TAA and negative association of TGG haplotype with PCOS was seen among Bahraini women; no three-locus PCOS-associated haplotypes were found in Tunisians.Conclusions: The present study is the first to demonstrate the contribution of ethnicity to the association of LEPR gene variants with PCOS, thereby highlighting the significance of controlling for ethnicity in gene association investigations.     

Effects of the pharmacologic manipulation of testosterone on cognitive functioning in women with polycystic ovary syndrome: a randomized, placebo-controlled treatment study

In a previous study, we found that women with polycystic ovary syndrome (PCOS), an endocrine disorder characterized by chronic hyperandrogenism, performed more poorly than healthy, matched controls on a number of neuropsychological tests, in particular tests of verbal fluency, verbal memory, manual dexterity, and visuospatial working memory. This randomized, placebo-controlled trial was undertaken to investigate whether pharmacologic manipulation of free testosterone (free T) levels in women with PCOS might affect their performance on cognitive tests. Nineteen women with PCOS completed a battery of neuropsychological tests before and after 3 months of treatment with either an anti-androgen (cyproterone acetate) plus estrogen or with a placebo. Hormone treatment of women with PCOS caused a significant reduction in their free T levels but did not affect performance on tests visuospatial ability, verbal memory, manual dexterity, or perceptual speed. Women treated with hormone therapy did, however, demonstrate an improvement in their performance on a test of verbal fluency compared to their pre-treatment scores. These findings suggest that changes in free T levels do not have a significant impact on cognitive performance in women with PCOS, although reductions in free T may be beneficial for verbal fluency.