scholarly journals Profile of Bile Acid Metabolomics in the Follicular Fluid of PCOS Patients

Metabolites ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 845
Author(s):  
Xiao Yang ◽  
Richao Wu ◽  
Dan Qi ◽  
Linlin Fu ◽  
Tian Song ◽  
...  

Polycystic ovary syndrome (PCOS) is a complex heterogeneous endocrine disease affected by genetic and environmental factors. In this manuscript, we aimed to describe the composition of bile acid metabolomics in the follicular fluid (FF) of PCOS. The FF was collected from 31 control patients and 35 PCOS patients diagnosed according to the Rotterdam diagnostic criteria. The Bile Acid Assay Kit and ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) were used in this study to detect the total bile acid and 24 bile acid metabolites. Glycocholic acid (GC3A), taurocholic acid (TCA), glycochenodeoxycholic acid (GCDCA), and chenodeoxycholic acid-3-β-D-glucuronide (CDCA-3Gln) were elevated in the PCOS group. GCDCA was positively correlated with the serum follicle-stimulating hormone (FSH) (r = 0.3787, p = 0.0017) and luteinizing hormone (LH) (r = 0.2670, p = 0.0302). The level of CDCA-3Gln also rose with the increase in antral follicle counts (AFC) (r = 0.3247, p = 0.0078). Compared with the control group, the primary bile acids (p = 0.0207) and conjugated bile acids (p = 0.0283) were elevated in PCOS. For the first time, our study described the changes in bile acid metabolomics in the FF of PCOS patients, suggesting that bile acids may play an important role in the pathogenesis of PCOS.

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yanna Ban ◽  
Haiying Ran ◽  
Ying Chen ◽  
Li Ma

Abstract Background The polycystic ovary syndrome (PCOS) is the most common endocrine associated with insulin resistance, even in the absence of overweight. The global lipid profile of the follicular fluid in PCOS with normal weight as yet has not been investigated. The objection of this pilot study was to explore the changes of lipids in the follicular fluid of PCOS with normal weight. Methods Follicular fluid samples were collected from patients who underwent IVF, including normal-weight women without PCOS (control group, n = 10) and normal-weight women with PCOS (PCOS group, n = 8). A lipidomic analysis was performed by high performance liquid chromatography/ mass spectrometry (HPLC-MS). Multidimensional statistical analysis was performed to disclose the global differences between the two groups. Further, differential lipid analysis between the two groups was performed by Fold Change Analysis (FC Analysis) and T-test to screen potential markers. Results All 812 species of 32 subclasses of lipids were identified by lipidomics analysis. 108 kinds of lipids were considered as the potential candidate differential metabolites with the score of variable importance in the project (VIP) more than 1 by the orthogonal partial least squares discriminant analysis. 32 lipids were significantly different between the PCOS group and the control group simultaneously with FC > 1.5 or FC < 0.67, p-value < 0.05 and VIP value > 1. These differential species of lipid belong to lipid subclasses including triglycerides (TG), phosphatidylethanolamines (PE) and phosphatidylinositols (PI). Conclusion The identified differential lipids in the follicular fluid may be considered as candidate biomarkers as well as therapeutic targets of PCOS with normal-weight.


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8640 ◽  
Author(s):  
Junhe Hu ◽  
Tao Tang ◽  
Zhi Zeng ◽  
Juan Wu ◽  
Xiansheng Tan ◽  
...  

Polycystic ovary syndrome (PCOS) can cause reproductive disorders that may affect oocyte quality from punctured follicles in human follicular fluid (HFF). The non-coding RNA family includes micro RNA (miRNA), piwi-interacting RNA (piRNA) and transfer RNA (tRNA); these non-coding RNA transcripts play diverse functions and are implicated in a variety of diseases and health conditions, including infertility. In this study, to explore the role of HFF exosomes in PCOS, we extracted and sequenced RNA from HFF exosomes of PCOS patients and compared the analysis results with those of non-PCOS control group. The HFF exosomes were successfully isolated and characterized in a variety of ways. The sequencing results of the HFF exosomal RNA showed that about 6.6% of valid reads in the PCOS group and 8.6% in the non-PCOS group were successfully mapped to the human RNA database. Using a hierarchical clustering method, we found there were ten small RNA sequences whose expression was significantly different between the PCOS and non-PCOS groups. We chose six of them to predict target genes of interest for further GO analysis, and pathway analysis showed that the target genes are mainly involved in biosynthesis of amino acids, glycine, serine and glycosaminoglycan, as well as threonine metabolism. Therefore, the small RNA sequences contained in HFF EXs may play a key role in the mechanism that drives PCOS pathogenesis, and thereby can act as molecular biomarkers for PCOS diagnosis in the future.


2021 ◽  
Author(s):  
Yaping Jiang ◽  
Rui Jiang ◽  
Peng Zhang ◽  
qiong Yu ◽  
Hongping Ba ◽  
...  

Abstract Purpose To investigate the changes of human granulosa cell, TNFR1, TNFR2 and their downstream molecules in patients with polycystic ovary syndrome (PCOS) and the control group. Methods We recruited infertile women with polycystic ovary syndrome (n = 30) and compared them with infertility due to fallopian tube obstruction(n = 30, control group). The ovaries were stimulated with GnRH agonists and gonadotropins. Follicular fluid from large follicles ([14 mm]) was pooled and granulosa cells (GCs) were separated by a cellular filter. The TNF-α level of follicular fluid was measured by ELISA. TUNEL assay were used to detect the apoptosis of purified GCs. Real-time PCR and Western blotting were used to detect the expression of TNF-related signaling molecules in GCs. Results The rate of high quality embryos in the PCOS group was lower than that in the control group. There were higher percentages of apoptosis in GCs of PCOS patients than in the control group. TNF-α is upregulated in follicular fluid of PCOS patients. TNFR1 and caspase-3 mRNA level were signifificantly higher in PCOS group than in the control group. TNF-α-mediated apoptosis of PCOS granulosa cells was mainly dependent on TNFR1.The TNF-α/TNFR1 signaling pathway mediates apoptosis rather than survival in cumulus cells of PCOS patients. Conclusions TNF-α expression was upregulated in follicular fluid of PCOS patients, and TNFR1 overexpression in female granulosa cells of PCOS was associated with higher levels of apoptosis in these cells, suggesting that the TNF-α/TNFR1 signaling pathway may be a candidate for higher apoptosis in female granulosa cells of PCOS.


2021 ◽  
pp. 1779-1786
Author(s):  
Banan Salam Kadhum ◽  
Shatha Abdul Wadood AL- Shammaree

Iron status may influence the outcome of infertile women under the intracytoplasmic sperm injection (ICSI) technique of in vitro fertilization (IVF). The aim of this study is to evaluate iron status and ceruloplasmin ferroxidase activity in the follicular fluid (FF) and their association with IVF outcomes. The study enrolled fertile women with male cause infertility (n=25), infertile women with polycystic ovary syndrome (PCOS; n=21), infertile women with low AMH level (n=26), and women with unexplained infertility (UI; n=27), all undergoing IVF/ICSI. On the day of oocyte suction, the selection of FF samples was accomplished. Iron, ferritin, and transferrin levels, as well as ceruloplasmin (CP) ferroxidase activity, were measured in the FF. In the PCOS group, iron showed significantly higher level (P<0.05) as compared to the control and UI groups. In the PCOS group, ferritin showed significantly higher level (P<0.05) compared with the control group. In the PCOS group, transferrin showed significantly higher level (P<0.05) when compared with the UI group. Also, Cp. ferroxidase activity in the PCOS group showed a lower level, but non-significant difference, compared with the other groups. In conclusion, the increased iron level in the follicular fluid of women with PCOS may lead to decrease pregnancy success after applying IVF protocol.


2018 ◽  
Vol 50 (3) ◽  
pp. 236-242
Author(s):  
Xinyan Shi ◽  
Duo Peng ◽  
Yanfei Liu ◽  
Xiaofen Miao ◽  
Hui Ye ◽  
...  

Abstract Objective To evaluate the advantages of using anti-Müllerian hormone (AMH) in the diagnosis of polycystic ovary syndrome (PCOS). Methods We compared data from 56 Han Chinese patients with PCOS and 52 female control Han Chinese individuals in terms of biochemical markers and the antral follicle count (AFC). Then, the correlation between serum AMH levels and various endocrine and metabolic factors was analyzed. We generated receiver operating characteristic (ROC) curves to assess the usefulness of AMH, AFC, the luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio, and testosterone (T), to discriminate between the PCOS and control groups. Results The LH/FSH ratio, homeostatis model assessment of insulin resistance (HOMA-IR), testosterone (T), blood glucose (Glu), triglyceride (TG), body mass index (BMI), AFC and, in particular, serum AMH level were significantly higher in the PCOS group than in the control group (P <.05; P <.001). The serum AMH level had a significant positive effect on the likelihood of AFC changes in patients with PCOS and control-group women. The areas under the ROC curve (AUC) of AMH, AFC, LH/FSH ratio, and T were 0.952, 0.778, 0.760, and 0.665, respectively. The best cutoff point for AMH was 6.09 ng per mL, with sensitivity of 88% and specificity of 88%.


2021 ◽  
Author(s):  
Yanna Ban ◽  
Haiying Ran ◽  
Ying Chen ◽  
Li Ma

Abstract Background The polycystic ovary syndrome (PCOS) is the most common endocrine associated with insulin resistance, even in the absence of overweight. The global lipid profile of the follicular fluid in PCOS with normal weight as yet has not been investigated. The objection of this study was to explore the changes of lipids in the follicular fluid of PCOS with normal weight.MethodsFollicular fluid samples were collected from patients who underwent IVF, including normal women (control group, n=10) and normal weight women with PCOS (PCOS group, n=8). A lipidomic analysis was performed by high performance liquid chromatography/ mass spectrometry (HPLC-MS). Multidimensional statistical analysis was performed to disclose the global differences between the two groups. Further, differential lipid analysis between the two groups was performed by Fold Change Analysis (FC Analysis) and T-test to screen potential markers. ResultsAll 812 species of 32 subclasses of lipids were identified by lipidomics analysis. 108 kinds of lipids were considered as the potential candidate differential metabolites with the score of variable importance in the project (VIP) more than 1 by the orthogonal partial least squares discriminant analysis. 32 lipids were significantly different between the PCOS group and the control group simultaneously with FC > 1.5 or FC<0.67, p-value <0.05 and VIP value > 1. These differential metabolites were the lipid subclasses including triglycerides (TG), phosphatidylethanolamines (PE) and phosphatidylinositols (PI).ConclusionThe identified differential lipids in the follicular fluid may be considered as candidate biomarkers as well as therapeutic targets of PCOS with normal weight.


Author(s):  
Aysegul Altunkeser ◽  
Zeynep Ozturk Inal ◽  
Nahide Baran

Background: Shear wave electrography (SWE) is a novel non-invasive imaging technique which demonstrate tissue elasticity. Recent research evaluating the elasticity properties of normal and pathological tissues emphasize the diagnostic importance of this technique. Aims: Polycystic ovarian syndrome (PCOS), which is characterized by menstrual irregularity, hyperandrogenism, and polycystic overgrowth, may cause infertility. The aim of this study was to evaluate the elasticity of ovaries in patients with PCOS using SWE. Methods: 66 patients diagnosed with PCOS according to the Rotterdam criteria (PCOS = group I) and 72 patients with non-PCOS (Control = group II), were included in the study. Demographic and clinical characteristics of the participants were recorded. Ovarian elasticity was assessed in all patients with SWE, and speed values were obtained from the ovaries. The elasticity of the ovaries was compared between the two groups. Results: While there were statistically significant differences between the groups in body mass index (BMI), right and left ovarian volumes, luteinizing hormone and testosterone levels (p<0.05), no significant differences were found between groups I and II in the velocity (for the right ovary 3.89±1.81 vs. 2.93±0.72, p=0.301; for the left ovary 2.88±0.65 vs. 2.95±0.80, p=0.577) and elastography (for the right ovary 36.62±17.78 vs. 36.79±14.32, p=0.3952; for the left ovary 36.56±14.15 vs. 36.26±15.10, p=0.903) values, respectively. Conclusion: We could not obtain different velocity and elastography values from the ovaries of the patients with PCOS using SWE. Therefore, further large-scale studies are needed to elucidate this issue.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Fahimeh Ramezani Tehrani ◽  
Maryam Rahmati ◽  
Fatemeh Mahboobifard ◽  
Faezeh Firouzi ◽  
Nazanin Hashemi ◽  
...  

Abstract Background The majority of available studies on the AMH thresholds were not age-specific and performed the receiver operating characteristic curve (ROC) analysis, based on variations in sensitivity and specificity rather than positive and negative predictive values (PPV and NPV, respectively), which are more clinically applicable. Moreover, all of these studies used a pre-specified age categorization to report the age-specific cut-off values of AMH. Methods A total of 803 women, including 303 PCOS patients and 500 eumenorrheic non-hirsute control women, were enrolled in the present study. The PCOS group included PCOS women, aged 20–40 years, who were referred to the Reproductive Endocrinology Research Center, Tehran, Iran. The Rotterdam consensus criteria were used for diagnosis of PCOS. The control group was selected among women, aged 20–40 years, who participated in Tehran Lipid and Glucose cohort Study (TLGS). Generalized additive models (GAMs) were used to identify the optimal cut-off points for various age categories. The cut-off levels of AMH in different age categories were estimated, using the Bayesian method. Main results and the role of chance Two optimal cut-off levels of AMH (ng/ml) were identified at the age of 27 and 35 years, based on GAMs. The cut-off levels for the prediction of PCOS in the age categories of 20–27, 27–35, and 35–40 years were 5.7 (95 % CI: 5.48–6.19), 4.55 (95 % CI: 4.52–4.64), and 3.72 (95 % CI: 3.55–3.80), respectively. Based on the Bayesian method, the PPV and NPV of these cut-off levels were as follows: PPV = 0.98 (95 % CI: 0.96–0.99) and NPV = 0.40 (95 % CI: 0.30–0.51) for the age group of 20–27 years; PPV = 0.96 (95 % CI: 0.91–0.99) and NPV = 0.82 (95 % CI: 0.78–0.86) for the age group of 27–35 years; and PPV = 0.86 (95 % CI: 0.80–0.94) and NPV = 0.96 (95 % CI: 0.93–0.98) for the age group of 35–40 years. Conclusions Application of age-specific cut-off levels of AMH, according to the GAMs and Bayesian method, could elegantly assess the value of AMH in discriminating PCOS patients in all age categories.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Li Yu ◽  
Miao Liu ◽  
Zhenxin Wang ◽  
Te Liu ◽  
Suying Liu ◽  
...  

Abstract Background Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder with various manifestations and complex etiology. Follicular fluid (FF) serves as the complex microenvironment for follicular development. However, the correlation between the concentration of steroid in FF and the pathogenesis of PCOS is still unclear. Methods Twenty steroid levels in FF from ten patients with PCOS and ten women with male-factor infertility undergoing in vitro fertilization were tested by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in order to explore their possibly correlation with PCOS. Meanwhile, the mRNA levels of core enzymes in steroid synthesis pathway from exosomes of FF were also detected by qPCR. Results The estriol (p < 0.01), estradiol (p < 0.05) and prenenolone (p < 0.01) levels in FF of PCOS group were significantly increased, compared to the normal group, and the progesterone levels (p < 0.05) were decreased in PCOS group. Increased mRNA levels of CYP11A, CYP19A and HSD17B2 of exosomes were accompanied by the hormonal changes in FF. Correlation analysis showed that mRNA levels of CYP11A and HSD17B2 were negatively correlated with percent of top-quality embryos and rate of embryos develop to blastocyst. Conclusion Our results suggest that increased levels of estrogen and pregnenolone in follicular fluid may affect follicle development in PCOS patients, and the mechanism is partially related to HSD17B1, CYP19A1 and CYP11A1 expression change in FF exosomes.


2021 ◽  
Author(s):  
Xiaoxuan Zhao ◽  
Xiaoling Feng ◽  
Xinjie Zhao ◽  
Yuepeng Jiang ◽  
Xianna Li ◽  
...  

Abstract Background: Polycystic ovary syndrome (PCOS) is a complex reproductive endocrine disorder,with an increased risk of type 2 diabetes mellitus and cardiovascular disease, of which metabolic syndrome (MS) is an indispensable springboard to communicate PCOS and various comlications. Our aim was to study the potential metabolic characteristics of PCOS-MS, and identify sensitive biomarkers so as to provide targets for clinical screening, diagnosis and treatment.Methods: 44 PCOS patients with MS, 34 PCOS patients without MS and 32 healthy controls were studied. Plasma samples of subjects were tested by ultra performance liquid chromatography (UPLC) system combined with LTQ-orbi-trap mass spectrometry. The changes of metabolic characteristics from PCOS to PCOS-MS were systematically analyzed. Correlations between differential metabolites and clinical characteristics of PCOS-MS were assessed. Differential metabolites with high correlation were further evaluated by the receiver operating characteristic (ROC) curve to identify their sensitivity as screening indicators.Results: There were significant difference in general characteristics, reproductive hormone and metabolic parameters in PCOS-MS group when compared with PCOS group and healthy controls. We found 30 differential metabolites which were involved in 23 pathways when compared with PCOS group. The metabolic network further reflects the metabolic environment, including the interaction between metabolic pathways, modules, enzymes, reactions and metabolites.In the correlation analysis, 17 pairs of correlation coefficient between differential metabolites and clincal parameters were greater than 0.4, involving 11 metabolites that has the potential to be a marker for clinical diagnosis. They were assessed by ROC whose area under curve (AUC) were all greater than 0.7, with a good sensitivity. Furthermore, combinational metabolic biomarkers, such as glutamic acid+leucine+phenylalanine and carnitine C 4: 0+carnitine C18:1+carnitine C5:0 are expected to be sensitive combinational biomarkers in clinical practice.Conclusion: Our study provides a new insight to understand the pathogenesis mechanism, and the discriminating metabolites may help screen high-risk of MS in patients with PCOS and provide sensitive biomarkers for clinical diagnosis.


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