Dataset Information

Influence of Sleep Stage on LH Pulse Initiation in the Normal Late Follicular Phase and in Polycystic Ovary Syndrome.

ABSTRACT: OBJECTIVE:During the early follicular phase, sleep-related luteinizing hormone (LH) pulse initiation is positively associated with brief awakenings but negatively associated with rapid eye movement (REM) sleep. The relationship between sleep architecture and LH pulse initiation has not been assessed in other cycle stages or in women with polycystic ovary syndrome (PCOS). DESIGN AND METHODS:We performed concomitant frequent blood sampling (LH pulse analysis) and polysomnography on 8 normal women (cycle day 7-11) and 7 women with PCOS (at least cycle day 7). RESULTS:In the normal women, the 5 min preceding LH pulses contained more wake epochs and fewer REM epochs than the 5 min preceding randomly determined time points (wake: 22.3 vs. 9.1%, p = 0.0111; REM: 4.4 vs. 18.8%, p = 0.0162). However, LH pulse initiation was not related to wake or REM epochs in PCOS; instead, the 5 min preceding LH pulses contained more slow-wave sleep (SWS) than the 5 min before random time points (20.9 vs. 6.7%, p = 0.0089). Compared to the normal subjects, the women with PCOS exhibited a higher REM-associated LH pulse frequency (p = 0.0443) and a lower proportion of wake epochs 0-5 min before LH pulses (p = 0.0205). CONCLUSIONS:Sleep-related inhibition of LH pulse generation during the later follicular phase is normally weakened by brief awakenings and strengthened by REM sleep. In women with PCOS, LH pulse initiation is not appropriately discouraged by REM sleep and may be encouraged by SWS; these abnormalities may contribute to a high sleep-related LH pulse frequency in PCOS.

SUBMITTER: Lu C

PROVIDER: S-EPMC7053660 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Influence of Sleep Stage on LH Pulse Initiation in the Normal Late Follicular Phase and in Polycystic Ovary Syndrome.

Lu Christine C Hutchens Eleanor G EG Farhy Leon S LS Bonner Heather G HG Suratt Paul M PM McCartney Christopher R CR

Neuroendocrinology 20180305 1

<h4>Objective</h4>During the early follicular phase, sleep-related luteinizing hormone (LH) pulse initiation is positively associated with brief awakenings but negatively associated with rapid eye movement (REM) sleep. The relationship between sleep architecture and LH pulse initiation has not been assessed in other cycle stages or in women with polycystic ovary syndrome (PCOS).<h4>Design and methods</h4>We performed concomitant frequent blood sampling (LH pulse analysis) and polysomnography on ...[more]

PMID: 29506013

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Project description:Background: Polycystic ovary syndrome (PCOS) is a major endocrine and metabolic disorder with heterogeneous manifestations and complex etiology. As a leading cause of anovulatory infertility, the molecular diversity of the follicular microenvironment has not been fully elucidated. The aim of the present study was to investigate the follicular fluid proteomic profiles of overweight/obese and normal-weight women with PCOS, to identify novel molecular mechanisms underlying PCOS and to determine the effect of obesity on the follicular fluid protein profiles. Methods: Follicular fluid samples were collected from 3 different groups: overweight/obese PCOS patients (n = 29), normal-weight PCOS patients (n = 29), and normo-ovulatory controls (n = 29). We used a quantitative approach with tandem mass tag labeling and liquid chromatography tandem mass spectrometry to identify the differentially expressed proteins. Differential abundance of four selected proteins was confirmed by ELISA. Gene Set Enrichment Analysis was also conducted to further explore our findings. Furthermore, we compared the clinical, hormonal, and biochemical characteristics of overweight/obese and normal-weight patients with PCOS to determine the effects of obesity. Results: A total of 1,153 proteins were identified, of which 41 and 19 proteins were differentially expressed in the overweight/obese PCOS group vs. the control group, and in the normal-weight PCOS group vs. the control group, respectively. Bioinformatics analyses showed that the inflammatory, immunological, and metabolic-related biological processes were co-enriched in both subgroups of PCOS. Apolipoprotein A-II, complement C5, fetuin-B, and stromal cell-derived factor 1 were found to be involved in various processes and were validated using the ELISA analysis. From clinical features and proteomic data, obesity was found to worsen follicular development disturbances in PCOS. Conclusion: In this proteomic study, a panel of proteins were found differentially expressed in the follicular fluid of PCOS. Inflammatory, immunological, and metabolic abnormalities were identified inside the intra-follicular environment, which could be aggravated by obesity. The identified proteins were correlated with follicular growth and may be considered as candidate biomarkers as well as therapeutic targets of PCOS.

Project description:Objectives: Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder with heterogeneous manifestations and complex etiology. We used quantitative proteomics analysis based on mass spectrometry to identify the differences in proteomics profiles for follicular fluid obtained from patients with or without PCOS and explore possible mechanisms underlying PCOS. Methods: Follicular fluid samples were collected from infertile patients with (n = 9) or without (n = 9) PCOS. Total protein was extracted, quantitatively labeled with a tandem mass tag (TMT), and analyzed using liquid chromatography-mass spectrometry (LC-MS). TMT-based proteomics and bioinformatics analysis were used to determine the differentially expressed proteins (DEPs) and understand the protein networks. The analysis included protein annotation, unsupervised hierarchical clustering, functional classification, functional enrichment and clustering, and protein-protein interaction analysis. Selected DEPs were confirmed by ELISA, and correlation analysis was performed between these DEPs and the clinical characteristics. Results: In this study, we have identified 1,216 proteins, including 70 DEPs (32 upregulated proteins, 38 downregulated proteins). Bioinformatics analysis revealed that the inflammatory response, complement and coagulation cascades, activation of the immune response, lipid transport, and regulation of protein metabolic processes were co-enriched in patients with PCOS. Based on ELISA results, insulin-like growth factor binding protein 1 (IGFBP1) and apolipoprotein C2 (APOC2) were differentially expressed between patients with and without PCOS. Follicular IGFBP1 showed a positive correlation with the serum levels of high-density lipoprotein cholesterol (HDL-C) (r = 0.3046, p = 0.0419), but negatively correlated with the serum levels of anti-Müllerian hormone (AMH) (r = -0.2924, p = 0.0354) and triglycerides (r = -0.3177, p = 0.0246). Follicular APOC2 was negatively correlated with the serum apolipoprotein A1 (APOA1) levels (r = 0.4509, p = 0.0002). Conclusion: Our study identified DEPs in the follicular fluid of patients with PCOS. Inflammatory response, complement and coagulation cascades, activation of the immune response, lipid transport, and regulation of protein metabolic process were deregulated in PCOS, which may play essential roles in the pathogenesis of PCOS.

Project description:Polycystic ovary syndrome (PCOS) has a largely unknown etiology and presents with a clinical heterogeneous patient group. Small noncoding microRNA (miRNA) might prove promising as biomarker candidates for PCOS patient stratification. Altered miRNA expression profiles have been observed in few studies.The aim was to assess the miRNA expression profile in follicular fluid from PCOS patients and healthy, regularly cycling, matched controls.Experimental case-control study including 49 PCOS women (19 of which were hyperandrogenic and 30 normo-androgenic) and 21 healthy matched women all undergoing in vitro fertilization treatment.Anthropometric and relevant clinical baseline measurements were obtained. Relative expression of miRNA levels were estimated using miRNA quantitative PCR arrays and validated by quantitative RT-PCR. Correlation between miRNAs and clinical relevant measurements was estimated.PCOS women, both normo-androgenic and hyperandrogenic, had decreased levels of miR-24-3p, -29a, -151-3p, and -574-3p compared with controls. Furthermore, miR-518f-3p was differentially expressed within the PCOS group with high levels observed in the hyperandrogenic group compared with the normo-androgenic PCOS patients. Serum levels of total and free T were positively correlated with miR-518f-3p in PCOS subjects (P = .001). Distinction between PCOS and controls could be made using miR-151-3p alone with an area under the curve of 0.91 or a combination of four selected miRNAs (area under the curve, 0.93). Bioinformatic target analysis points to an involvement of these miRNAs in biological pathways involving regulation of cell proliferation, extracellular matrix, and processes in intermediary metabolism.Our study provides evidence that the miRNA expression profile in follicular fluid is altered in PCOS and indicates that specific follicular fluid miRNAs are associated with phenotypical traits of PCOS. An altered miRNA profile holds potentials for new methods of PCOS patient stratification and may contribute to and in part explain the heterogeneous nature found within PCOS women.

Dataset Information

Influence of Sleep Stage on LH Pulse Initiation in the Normal Late Follicular Phase and in Polycystic Ovary Syndrome.

Publications

Influence of Sleep Stage on LH Pulse Initiation in the Normal Late Follicular Phase and in Polycystic Ovary Syndrome.

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