Android subcutaneous adipose tissue topography in lean and obese women suffering from PCOS: comparison with type 2 diabetic women

The new optical device, the lipometer, enables the noninvasive, quick, safe, and precise determination of the thickness of subcutaneous adipose tissue (SAT) layers at any given site of the human body. Fifteen anatomically well-defined body sites from neck to calf describe a SAT topography (SAT-Top) like an individual "fingerprint" of a subject. This SAT-Top was examined in 16 women with polycystic ovary syndrome (PCOS) and compared to the body fat distribution of 87 age-matched healthy controls and 20 type-2 diabetic women. SAT-Top differences of these three groups were described and, to render the possibility of visual comparison, the 15-dimensional body fat information was condensed to a two-dimensional factor plot by factor analysis. All PCOS patients had an android body fat distribution with significantly thinner SAT layers on the legs as compared to healthy controls. Moreover, a hierarchical cluster analysis resulted in two distinctly different groups of PCOS women, a lean (PCOSL) and an obese (PCOSO) cluster: compared to healthy women, lean PCOS patients had significantly lower total SAT development, even though height, weight, and body mass index did not deviate significantly. Especially on the legs, their SAT layers were significantly lowered, indicating a more "apple-like" fat distribution type. Obese PCOS women showed a SAT-Top pattern very similar to that of women with type-2 diabetes, although the mean age difference between these groups was more than 30 years. Compared to healthy controls, the SAT-Top of these obese PCOS patients was strongly shifted into the android direction, appearing as "super-apples" with a significantly increased upper trunk obesity to 237.8% and a significantly decreased leg SAT development to 79.8%.     

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     

The role of xanthine oxidoreductase and uric acid in metabolic syndrome

Xanthine oxidoreductase (XOR) could contribute to the pathogenesis of metabolic syndrome through the oxidative stress and the inflammatory response induced by XOR-derived reactive oxygen species and uric acid. Hyperuricemia is strongly linked to hypertension, insulin resistance, obesity and hypertriglyceridemia. The serum level of XOR is correlated to triglyceride/high density lipoprotein cholesterol ratio, fasting glycemia, fasting insulinemia and insulin resistance index. Increased activity of endothelium-linked XOR may promote hypertension. In addition, XOR is implicated in pre-adipocyte differentiation and adipogenesis. XOR and uric acid play a role in cell transformation and proliferation as well as in the progression and metastatic process. Collected evidences confirm the contribution of XOR and uric acid in metabolic syndrome. However, in some circumstances XOR and uric acid may have anti-oxidant protective outcomes. The dual-face role of both XOR and uric acid explains the contradictory results obtained with XOR inhibitors and suggests caution in their therapeutic use.     

Chamomile flower extract ameliorates biochemical and histological kidney dysfunction associated with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder in females of childbearing age and research findings have revealed a potential association between PCOS and renal dysfunction. This study aimed to investigate renal dysfunction that might be associated with PCOS in rats and to evaluate the potential protective effect of chamomile against PCOS complicated by kidney damage. A rat model of PCOS was induced by injecting estradiol valerate (0.2 mg/rat × 2) into adult virgin female rats. Rats were treated with either ethyl alcohol extract of chamomile flower (75 mg/kg/day) or metformin (Met) (500 mg/kg/day). Induction of PCOS was associated with increased relative right kidney weight percentage and increased serum levels of urea, lipid peroxide product, and testosterone. PCOS was also associated with increased p53 expression in kidney glomeruli and medullary tubules with decreased Bcl2 expression in kidney glomeruli. Administration of chamomile extract significantly decreased levels of serum urea, testosterone, and lipid peroxide product, and p53 expression in kidney glomeruli and tubules. The extract significantly increased levels of antioxidant markers levels (reduced glutathione, catalase, and superoxide dismutase) and the expression of the anti-apoptotic gene Bcl2. Conversely, administration of Met did not improve serum levels of urea. Met also exerted no pronounced effect on p53 gene expression. The results of this study highlight the importance of monitoring kidney function in patients with PCOS and investigating the associated underlying mechanism. Chamomile extract was found to ameliorate kidney damage associated with PCOS through antioxidant, testosterone-lowering, and anti-apoptotic mechanisms.     

Polymorphisms in the IRS-1 and PPAR-γ genes and their association with polycystic ovary syndrome among South Indian women

Polycystic ovary syndrome is known to be characterized by metabolic abnormalities such as hyperinsulinemia, adiposity and dyslipidemia. Both insulin receptor substrate-1 and peroxisome proliferator-activated receptor-γ have emerged as significant candidate genes in the pathogenesis of PCOS. In this study, we report for the first time, the association pattern of these genes with PCOS among South Indian women. Two hundred fifty PCOS cases and 299 controls were sequenced for IRS-1 exon1 and PPAR-γ exon 2 and exon 6 to study the already reported SNPs in other ethnic groups and to identify any novel SNP in these exonic regions specific to the Indian population. We did not find any novel SNP in our population except for those already reported- two IRS-1 polymorphisms (Gly972Arg and G2323A) and two PPAR-γ polymorphisms (Pro12Ala and His447His). While the IRS-1 polymorphic alleles had a similar distribution between cases and controls, the PPAR-γ exon 2 Ala allele and exon 6 His447His T allele were significantly more in the controls than in the cases (p≤0.05). Haplotype association analysis also suggests that both IRS-1 and PPAR-γ haplotypes with mutations depicted reduced frequency of hyperandrogenic and metabolic traits in PCOS compared to the haplotype with only wild type alleles. Our study on Indian women suggests that while IRS-1, contrary to the earlier findings in other ethnic groups, seems to have a probable protective role against development of specific PCOS sub-phenotypes, the evidence for a probable protective role of PPAR-γ is reaffirmed in our study.     

Androgen levels and metabolic parameters are associated with a genetic variant of F13A1 in women with polycystic ovary syndrome

The polycystic ovary syndrome (PCOS), characterized by hyperandrogenism, is one of the most common hormonal disorders among premenopausal women and is associated with infertility, obesity, and insulin resistance. Accumulating evidence suggests a role of the blood coagulation factor gene F13A1 in obesity (GeneBank ID: NM_000129.3). The aim of this study was to investigate the association of intronic allelic variants of the F13A1 gene with PCOS susceptibility and metabolic parameters in lean and obese PCOS women. In a case-control study, we determined an intronic F13A1 single nucleotide polymorphism (SNP) (dbSNP ID: rs7766109) in 585 PCOS and 171 control women and tested for PCOS susceptibility and associations with anthropometric, metabolic and hormonal parameters. Genotype frequencies of the F13A1 SNP rs7766109 were equivalent in PCOS and control women. In PCOS women, F13A1 gene variants were significantly associated with body mass index (BMI) (p=0.013), systolic blood pressure (p=0.042), insulin response (AUCins) (p=0.015), triglycerides (TG) (p=0.001), and high density lipoprotein cholesterol (HDL) (p=0.012). In the subgroup of obese PCOS women free androgen index (FAI), free testosterone and sex hormone binding globulin (SHBG) as well as glucose measurements showed a significantly different pattern across F13A1 gene variants (p=0.043; p=0.039 and p=0.013, respectively). We report for the first time an association of the F13A1 SNP rs7766109 with BMI, androgens, and insulin resistance in PCOS women. Further studies are needed to confirm our findings and to evaluate whether F13A1 is causally involved in the pathogenesis of PCOS related metabolic and hormonal disturbances.     

多囊卵巢综合征患者胰岛素受体基因外显子 17 的多态性研究

摘要 目的： 探索胰岛素受体基因 外显子 17 的基因多态性与多囊巢综合症 （PCOS ） 的关系, 为多囊巢综合症的治疗寻找新的 途径。方法： 利用 PCR-SSCP 技术检测 45 例多囊巢综合症患者 （实验组） 与 40 例健康妇女 （对照组）全血中胰岛素受体基因外 显子 17 位点 1058 的基因多态性, 同时测定 PCOS 患者的一般指标及血清学指标。按照体重指数、 胰岛素抵抗、有无高雄激素血 症比较胰岛素受体基因外显子 17 位点 1058C、 T 等位基因出现的频率。 结果： 实验组患者 T 等位基因出现的频率为 71.2%, 明显 高于对照组的 25%(P>0.05); 实验组非肥胖组患者中 T 等位基因出现的频率为 69.2%, 明显高于肥胖组患者的 25%(P<0.01), 亦高 于对照组, 差异具有统计学意义(P<0.05)。根据胰岛素受体基因外显子 17 出现 T、 C 基因的频率, 将其分为 1、 2 两组, 1 组出现 T 基因的频率的 BMI(20.34± 2.47)明显低于 2 组出现 C 基因的频率的 BMI(26.68± 5.52); PCOS 患者胰岛素抵抗组与非胰岛素抵 抗组中 INSR 基因外显子 17 出现 T、 C 等位基因的频率无明显差别(P>0.05); PCOS 患者高雄激素组组与无高雄激素组中胰岛素 受体基因外显子 17 出现 T、 C 等位基因的频率无明显差别(P>0.05)。结论： 胰岛素受体基因外显子 17 中 T/C 单核酸多态性表现 与 PCOS 患者的发病密切相关, T 等位基因的高发频率与非肥胖因型 PCOS 患者的发病密切相关; 瘦型 PCOS 患者与肥胖型患 者胰岛素抵抗的发病机制或许不同; T 等位基的高发频率与 PCOS 的主要临床表现如： 胰岛素抵抗、 高雄激素血症并无明显相关 关系。     

APPL1 as an important regulator of insulin and adiponectin‐signaling pathways in the PCOS: A narrative review

Adaptor protein containing a PH domain, PTB domain and leucine zipper motif 1 (APPL1) plays a central role as the main contributing factor in the adiponectin and insulin signaling. This review aims to discuss previous and recent findings concerning the role of APPL1 in the polycystic ovary syndrome (PCOS) patients with conclusions regarding more efficient therapeutic approaches. A literature review was performed in PubMed, Web of Science, ScienceDirect, Scopus, and Google Scholar from August 1999 to May 2020. This study reveals that APPL1 has a key role in adiponectin, insulin, and follicle‐stimulating hormone signaling pathways occurring within the ovaries. Recent studies in mouse model systems have indicated that APPL1 can prevent diabetes, endothelial disorders, and insulin resistance. In contrast, APPL1 deficiency can lead to the metabolic and vascular disorders. APPL1 due to its potential roles in different signaling pathways might be suggested as a novel diagnostic and therapeutic option for prediction of ovarian dysfunctions and treatment of reproductive disorders, especially PCOS.     

来曲唑联合GnRH-a对多囊卵巢综合征患者雌激素水平及对排卵质量的影响

目的:研究来曲唑(Letrozole,LE)联合醋酸曲普瑞林(GnRH-a)治疗多囊卵巢综合征(PCOS)的临床疗效及对排卵质量的影响。方法:选取我院2014年8月到2016年1月收治的PCOS患者112例,随机将其分为对照组(50例)和观察组(62例)。在月经周期第3~7天时,观察组患者口服LE,2.5 mg/d;对照组患者肌肉注射人绝经期促性腺素(HMG),75 IU/d。当最大卵泡直径(MFD)≥18mm时,观察组患者皮下注射0.1 mg醋酸曲普瑞林诱发排卵,对照组患者肌肉注射6000~10000 IU人绒毛膜促性腺激素(HCG)诱发排卵。比较两组患者诱发排卵日的排卵效果和血清各激素水平,并统计妊娠结局。结果:诱发排卵日,两组患者的子宫内膜厚度、成熟卵泡数目、血清黄体生成激素(LH)和孕酮(P)水平、排卵率、妊娠率及黄体功能不全发生率比较差异均无统计学意义(P0.05),观察组的优势卵泡数目、血清E2和T水平、多胎率、OHSS发生率及卵巢囊肿发生率均明显低于对照组(P0.05)。结论:LE联合GnRH-a可有效提高PCOS患者的排卵质量,降低血清雌激素水平,并能预防OHSS发生,改善妊娠结局。     

A study on the immunological vitality of an inflammatory biomarker explored with rs5743708 polymorphism in TLR2 gene among Saudi women confirmed with polycystic ovarian syndrome

IntroductionPolycystic ovary syndrome (PCOS) is an ovarian health condition as well as a long-term endocrine dysfunction that affects reproductive-aged women. Toll-like receptor 2 (TLR2) gene was linked to PCOS and chronic inflammation, and the prevalence of obesity was rising in Saudi women. Previous studies on rs5743708 polymorphism were documented in the obesity as well as in PCOS women.AimIn this study, we investigated the molecular role of rs5743708 polymorphism in TLR2 gene among Saudi women diagnosed with PCOS using the Rotterdam criteria.MethodsBlood samples were collected from 220 Saudi women in this hospital-based case-control study; 110 were PCOS women and remaining 110 were non-PCOS (control women). Biochemical analysis was performed on serum samples, and molecular analysis was performed on EDTA blood. Genotyping for rs5743708 polymorphism was performed with polymerase chain reaction-restriction fragment length polymorphism analysis.ResultsIn both groups, clinical data was calculated using t-test, which revealed both positive (p < 0.05) and negative (p > 0.05) associations. HWE analysis supported the rs5743708 polymorphism (p < 0.05). In the rs5743708 polymorphism, none of the genotypes, genetic models, or allele frequencies were found to be associated with PCOS and non-PCOS women. However, both ANOVA and regression analyses revealed a positive relationship in PCOS with weight and BMI (p < 0.0001).ConclusionThe rs5743708 polymorphism was not associated to PCOS in Saudi women. One of the predictions could be that 42.7% of PCOS and 73.6% of non-PCOS women were obese, and the rs5743708 polymorphism has been linked to both obesity and PCOS in the previous studies. This study suggests screening for additional polymorphisms with a large sample size.