Analysis of secreted peptidome from omental adipose tissue in polycystic ovarian syndrome patients.

Polycystic ovarian syndrome (PCOS) is a common endocrinopathy associated with increased risk of metabolic disorders. Prevalence of adiposity and obesity is greater in women suffering from PCOS. Moreover, adipose tissue dysfunction has been demonstrated in PCOS patients, particularly in abdominal adipose tissue. This dysfunction likely aggravates the metabolic and reproductive abnormalities. We used liquid chromatography-mass spectrometry to compare the peptides secreted from PCOS and non-PCOS abdominal adipose tissue. We detected 298 upregulated peptides and 31 downregulated peptides (absolute fold change ≥ 2 and p < 0.05). Twenty-nine peptides were only detected in the PCOS group, while 18 were only detected in the control group. In addition, we demonstrate that these cleavage products are not degradation products of the proteasome based on previous studies reported. Gene Ontology enrichment and pathway analysis were performed to study differentially secreted peptides through their precursor proteins. We identified 12 peptides from 10 precursor proteins associated with PCOS, and 6 peptide sequences were located in the functional domains of their corresponding precursor proteins. These results provide a deeper understanding of adipose tissue-derived peptides in PCOS for future functional studies.

Identification of microRNAs and genes associated with hyperandrogenism in the follicular fluid of women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease, which is characterized by hyperandrogenism (HA), chronic anovulation, polycystic ovaries, insulin resistance, and obesity. At present, the mechanism by which PCOS/HA occurs has not been fully elucidated, thus, the mechanisms behind and interventions for HA in PCOS are current hot topics in research. MiRNAs have recently been shown to serve as diagnostic or prognostic biomarkers in patients with cancer. Thus, we are currently focused on studying the altered expression of miRNAs in follicular fluid and their correlation with HA in PCOS. Illumina deep sequencing technology was used to explore different miRNAs in the follicular fluid of women with PCOS/HA and in the follicular fluid of women in a control group. Target prediction databases were then used to analyse the target genes of different expressed miRNAs, and GO analysis and the KEGG pathway database were used to identify the functions and the main biochemical and signalling pathways of differentially expressed target genes. The expression levels of 263 miRNAs were significantly different (>2-fold up-regulated or <0.5-fold down-regulated, P < 0.05) between the two groups of women. For example, the expression levels of miRNA (200a-3p, 10b-3p, 200b-3p, 29c-3p, 99a-3p, and 125a-5p) were significantly increased, while there was a decreased expression of miR-105-3p in PCOS patients with respect to the control. Literature has shown that the above seven miRNAs were associated with HA in PCOS. Furthermore, 31 770 genes were predicted to be targets of the 263 differentially expressed microRNAs. GO analysis and the KEGG pathway database showed involvement of these target genes in HA in PCOS. These results suggest the presence of differentially expressed miRNAs in the follicular fluid of women with PCOS/HA versus women in the control group. The potential role of these microRNAs was elucidated using bioinformatics tools and was found to be involved in the regulation of different pathways, biological functions, and cellular components underlying PCOS. The results of this research may reveal new mechanisms of PCOS/HA and suggest potential treatment targets.

Peptidomic Analysis of Endometrial Tissue from Patients with Ovarian Endometriosis.

BACKGROUND/AIMS: Ovarian endometriosis (OvE) is ovarian cyst that is lined with endometrial tissue. They are found in 17-44% of women with endometriosis. Their clinical manifestations include pelvic pain, dysmenorrhea, dyspareunia, and infertility. Although the incidence of OvE has increased yearly, the exact pathogenesis of OvE is still unclear. We used peptidomics, an emerging branch of proteomics, to identify differentially expressed peptides in order to determine the possible roles of these peptides in the pathogenesis of OvE. METHODS: The ectopic and eutopic endometria of OvE were used to extract peptides with 10-kDa molecular weight cutoff filters, and the peptide precursor proteins were then identified with PEAKS software, followed by quantification with the TMT labeling method and subsequent analysis by liquid chromatography-tandem mass spectrometry. Gene ontology (GO) analysis, pathway analysis, SMART, and SABLE were used to study the possible functions of these peptide according to their precursor proteins' function. The effects of peptides derived from VCAM-1 (PDFV) on endometrial stromal cell (ESC) migration and invasion were examined with wound healing assays and Transwell assays and the expression of E-cadherin was detected by western blotting. RESULTS: A total of 491 peptides were identified with abundant differences between the two groups of samples (p < 0.05, and absolute fold change ≥ 2). SMART and SABLE database showed that 42 of the 491 peptides were located in the conserved structural domains of their protein precursors and contained secondary structure and, among them, 2 peptides' precursor proteins were associated with the cell proliferation. Additionally, 5 peptides' precursor proteins were associated with endometriosis. Our study confirmed that PDFV promoted ESC migration and invasion and reduced E-cadherin expression (p < 0.05). CONCLUSION: PDFV and its precursor protein VCAM-1 may be involved in the process of OvE formation by reducing the expression of E-cadherin. The peptidomics analysis provides new insight for future studies of the mechanisms of OvE development.

Comparison of three treatment strategies for cesarean scar pregnancy.

PURPOSE: To explore the optimal treatment for cesarean scar pregnancy. METHOD: In total, 86 women diagnosed with a cesarean scar pregnancy were divided into three groups according to treatment. The human chorionic gonadotrophin (hCG) decline percentage, intraoperative blood loss and success rate were analyzed in Group A [combination of uterine arterial embolization (UAE), local methotrexate (MTX) injection and dilation & curettage (D&C)], Group B (combination of UAE and local MTX injection) and Group C (D&C). Then, the best treatment was carefully analyzed, and recommendations were provided. RESULTS: The success rate was highest in Group A (97.5%) compared with Group B (76%) and Group C (63.15%). The reduction in hCG was greatest in Group A (86.62%, 44.0-99.97%) compared with group B (67.83%, 18.0-98.03%) and Group C (68.21%, 27.0-93.24%). The intraoperative blood loss was lowest in Group A (44.881, 5-200 ml) compared with Group C (224.737, 10-1000 ml). Additionally, we found that the best time to perform D&C in group A depended on the hCG reduction percentage, and a 35% reduction after UAE and local MTX injection could be used as the indicator to perform D&C. CONCLUSIONS: The combination of UAE, local MTX injection and D&C for CSP patients is the optimal treatment strategy. A 35% reduction in hCG after UAE and local MTX injection can be recommended as the indicator to perform D&C.

Effect of vitamin D on biochemical parameters in polycystic ovary syndrome women: a meta-analysis.

AIM: To investigate the therapeutical effect of vitamin D supplementation on the metabolism and endocrine parameters of PCOS patients. MATERIALS AND METHODS: Clinical studies investigating the therapeutic effect of vitamin D supplementation on PCOS patients were selected by searching PubMed, Embase, The Cochrane library and Web of Science until April 2016. The included articles were selected according to the inclusion criteria. Serum HOMA-IR, QUICKI, LDL, DHEAS, free testosterone (FT), total testosterone (TT), PTH, 25-hydroxy-vitamin D, and triglyceride of PCOS patients were enrolled for evaluating the therapeutic effects of vitamin D. RESULTS: 16 studies were included in this study. There was no significant difference between the placebo group and vitamin D group in the concentration of serum 25-hydroxy-vitamin D in patients with PCOS (P = 0.06). After treated with vitamin D, the serum 25-hydroxy-vitamin D in PCOS patients was increased (P < 0.00001), while the serum PTH (P = 0.003) and triglyceride (P = 0.006) were decreased. In addition, the serum HOMA-IR, QUICKI, LDL, DHEAS, FT, and TT in PCOS patients did not change. Subgroup analysis showed that the serum triglyceride of PCOS patients was decreased by low dose of vitamin D supplementation (<50,000 IU) (P = 0.03), but no significantly changed by high-dose vitamin D supplementation (≥50,000 IU) (P = 0.17). CONCLUSION: Vitamin D supplementation significantly attenuates serum PTH and triglyceride in PCOS patients except for serum HOMA-IR, QUICKI, LDL, DHEAS, FT, and TT. Furthermore, less than 50,000 IU vitamin D supplementation is sufficient for decreasing serum triglyceride.

Androgen-induced exosomal miR-379-5p release determines granulosa cell fate: cellular mechanism involved in polycystic ovaries.

Polycystic ovarian syndrome (PCOS) is a complex multi-factorial syndrome associated with androgen excess and anovulatory infertility. In the current study, we investigated the role of dihydrotestosterone-induced exosomal miR-379-5p release in determining the destiny of the developing follicles. Our hypothesis was that androgen regulates granulosa cell miR-379-5p content by facilitating its exosomal release in a follicular-stage dependent manner, a process which determines granulosa cell fate. Compared to human non-PCOS subjects, individuals with PCOS exhibit higher follicular fluid free testosterone levels, lower exosomal miR-379-5p content and granulosa cell proliferation. Androgenized rats exhibited lower granulosa cell miR-379-5p but higher phosphoinositide-dependent kinase-1 (PDK1; a miR-379-5p target) content and proliferation. Androgen reduced granulosa cell miR-379-5p content by increasing its exosomal release in preantral follicles, but not in antral follicles in vitro. Studies with an exosomal release inhibitor confirmed that androgen-induced exosomal miR-379-5p release decreased granulosa cell miR-379-5p content and proliferation. Ovarian overexpression of miR-379-5p suppressed granulosa cell proliferation, and basal and androgen-induced preantral follicle growth in vivo. These findings suggest that increased exosomal miR-379-5p release in granulosa cells is a proliferative response to androgenic stimulation specific for the preantral stage of follicle development and that dysregulation of this response at the antral stage is associated with follicular growth arrest, as observed in human PCOS.