OBJECTIVEOvarian fibrosis is characterized by excessive proliferation of ovarian fibroblasts and deposition of extracellular matrix (ECM) and it is one of the principal reasons for ovarian dysfunction. This review aimed to investigate the pathogenetic mechanism of ovarian fibrosis and to clarify the relationship between ovarian diseases and fibrosis.

DATA SOURCESWe searched PubMed for English language articles published up to November 2016. The search terms included ovarian fibrosis OR fibrosis, ovarian chocolate cyst OR ovarian endometrioma, polycystic ovarian syndrome (PCOS), premature ovarian failure, ECM, matrix metalloproteinases (MMPs), tissue inhibitors of matrix metalloproteinases (TIMPs), transforming growth factor-beta 1 (TGF-β1), connective tissue growth factor (CTGF), peroxisome proliferator-activated receptor gamma (PPAR-γ), vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), and combinations of these terms.

STUDY SELECTIONArticles were obtained and reviewed to analyze the pathogenic mechanism of ovarian fibrosis and related ovarian diseases.

RESULTSMany cytokines, such as MMPs, TIMPs, TGF-β1, CTGF, PPAR-γ, VEGF, and ET-1, are involved in ovarian fibrogenesis. Ovarian fibrogenesis is associated with various ovarian diseases, including ovarian chocolate cyst, PCOS, and premature ovarian failure. One finding of particular interest is that fibrogenesis in peripheral tissues around an ovarian chocolate cyst commonly causes ovarian function diminution, and therefore, this medical problem should arouse widespread concern in clinicians worldwide.

CONCLUSIONSPatients with ovarian fibrosis are susceptible to infertility and tend to have decreased responses to assisted fertility treatment. Thus, protection of ovarian function should be a priority for women who wish to reproduce when making therapeutic decisions about ovarian fibrosis-related diseases.

Animals ; Cytokines ; metabolism ; Female ; Fibrosis ; complications ; diagnosis ; etiology ; metabolism ; Humans ; Infertility, Female ; etiology ; Ovary ; pathology

The endoplasmic reticulum (ER) is the principal organelle responsible for several specific cellular functions including synthesis and folding of secretory or membrane proteins, lipid metabolism, and Ca storage. Different physiological as well as pathological stress conditions can, however, perturb ER homeostasis, giving rise to an accumulation of unfolded or misfolded proteins in the ER lumen, a condition termed ER stress. To deal with an increased folding demand, cells activate the unfolded protein response (UPR), which is initially protective but can become detrimental if ER stress is severe and prolonged. Accumulating evidence demonstrates a link between the UPR and ovarian development and function, including follicular growth and maturation, follicular atresia, and corpus luteum biogenesis. Additionally, ER stress and the UPR may also play an important role in the ovary under pathological conditions. Understanding the molecular mechanisms related to the dual role of unfolded protein response in the ovarian physiology and pathology may reveal the pathogenesis of some reproductive endocrine diseases and provide a new guidance to improve the assisted reproductive technology. Here we review the current literature and discuss concepts and progress in understanding the UPR, and we also analyze the role of ER stress and the UPR in the ovary.
Animals ; Apoptosis ; Calcium ; metabolism ; Endoplasmic Reticulum ; metabolism ; pathology ; Female ; Humans ; Lipid Metabolism ; Ovarian Diseases ; metabolism ; pathology ; therapy ; Ovary ; metabolism ; pathology ; Unfolded Protein Response

OBJECTIVETo investigate the effect of Shouwu Jiangqi Decoction (SJD) on polycystic ovary syndrome (PCOS) with insulin resistance (IR) in rats and to explore the underlining molecular mechanisms.

METHODSA total of 51 female Sprague-Dawley rats were randomly divided into 6 groups: control group (n=7), model group (n=8), SJD high-dose group (n=9), SJD medium-dose group (n=9), SJD low-dose group (n=9) and DMBG group (n=9). Radioimmunoassay was used to measure serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone concentrations and qRT-PCR and western blot were used to examine the expression levels of mRNA and protein respectively of insulin receptor substrate 1 (IRS-1) and phosphatidylinositide 3-kinases (PI3K) p85α in different groups.

RESULTSFSH level significantly decreased in the model group compared with the normal control (P<0.01), and high-dose SJD and DMBG can significantly increase FSH level (P<0.01). LH level showed a mild increase without statistic significance in the model group compared with the control and different dosages of SJD had no significance effect on LH level, while DMBG can significantly decrease LH level (P<0.01). Testosterone level significantly increased in the model group compared with the control group (P<0.01), and high-dose SJD and DMBG can significantly decrease testosterone level (P<0.01). The expression of IRS-1 as well as PI3Kp85α were significantly decreased in the model group compared with the normal control group at both mRNA (P<0.001) and protein (P<0.01) level, and both high-dose SJD and DMBG can enhance IRS-1 and PI3K expression (P<0.05).

CONCLUSIONSSJD has potent therapeutic effects on PCOS with IR in rats. The therapeutic effects of SJD on IR and ovulatory dysfunction are probably achieved through correcting the defective insulin signaling transduction.

Animals ; Blood Glucose ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Fasting ; blood ; Female ; Follicle Stimulating Hormone ; blood ; Insulin ; blood ; Insulin Receptor Substrate Proteins ; metabolism ; Insulin Resistance ; Liver ; pathology ; Luteinizing Hormone ; blood ; Ovary ; pathology ; Phosphatidylinositol 3-Kinases ; metabolism ; Polycystic Ovary Syndrome ; blood ; drug therapy ; Rats, Sprague-Dawley ; Testosterone ; blood

INTRODUCTIONThe aim of this study was to determine the effect of a high-fat diet (HFD) on oocyte maturation and quality in a mouse model.

METHODSFemale BALB/c mice were allocated to one of the following groups: (a) control group (n = 40), which received a controlled diet; or (b) HFD group (n = 40), which received an HFD for 12 weeks. Sections of the ovary were examined histologically. The number of follicles and corpora lutea were counted. In vitro maturation and in vitro fertilisation (IVF) were assessed in germinal vesicle (GV) and metaphase II (MII) oocytes, respectively. The expression of bone morphogenetic protein 15 (BMP15) and leptin receptor genes in GV and MII oocytes was evaluated using reverse transcription real-time polymerase chain reactions.

RESULTSIn the HFD group, there was a decreased number of primordial and Graafian follicles, as well as corpora lutea (p < 0.05). The rate of oocyte development to the MII stage was also reduced (p < 0.001). Cumulus expansion was observed more frequently in the control group than the HFD group (p < 0.05). The IVF rate in the HFD group was lower than that in the control group (p < 0.05). In the HFD group, BMP15 and leptin receptor genes were upregulated in the GV stage (p > 0.05) and MII stage (p < 0.05), compared to the control group.

CONCLUSIONAn HFD reduces folliculogenesis in the primordial and Graafian stages, in vitro maturation and in vitro fertilisation rates, as well as oocyte quality in mice.

Animals ; Body Weight ; Bone Morphogenetic Protein 15 ; metabolism ; Corpus Luteum ; pathology ; Diet, High-Fat ; Female ; Fertility ; Fertilization in Vitro ; methods ; Gene Expression Regulation ; Metaphase ; Mice ; Mice, Inbred BALB C ; Obesity ; complications ; Oocytes ; cytology ; pathology ; Ovarian Follicle ; pathology ; Ovary ; metabolism ; pathology ; Photography ; Polymerase Chain Reaction ; Receptors, Leptin ; metabolism

Epithelial ovarian cancers (EOCs) are highly lethal gynecological malignancies with a high recurrence rate. Therefore, developing prognostic markers for recurrence after chemotherapy is crucial for the treatment of ovarian cancers. As ovarian cancers frequently respond to DNA-damaging agents, we assessed the clinicopathological significance of key double-strand DNA break (DSB) repair genes, including BRCA1, BRCA2, BARD1, ATM, RAD51 and NBS1 in EOC cell lines and paraffin-embedded tissue sections from 140 EOC patients treated with cytoreductive surgery, followed by platinum-based chemotherapy. These samples were analyzed for the clinicopathological impact of DSB genes by western blot analysis, immunohistochemistry and quantitative real-time PCR. Of the DSB repair genes, BRCA1, ATM and NBS1, which are involved in the homologous recombination-mediated repair pathway, were related to aggressive parameters in EOC. When survival analysis was performed, NBS1 expression exhibited an association with EOC recurrence. Specifically, increased NBS1 expression was found in 107 out of 140 cases (76.0%) and correlated with advanced stage (P=0.001), high grade (P=0.001) and serous histology (P=0.008). The median recurrence-free survival in patients with positive and negative expression of NBS1 was 30 and 78 months, respectively (P=0.0068). In multivariate analysis, NBS1 was an independent prognostic factor for the recurrence of EOC. Together, these results suggest that NBS1 is a marker of poor prognosis for the recurrence of EOC and is associated with aggressive clinicopathological parameters.
Adolescent ; Adult ; Aged ; Biomarkers, Tumor/analysis/genetics ; Cell Cycle Proteins/analysis/*genetics ; Cell Line, Tumor ; *DNA Breaks, Double-Stranded ; *DNA Repair ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasms, Glandular and Epithelial/diagnosis/*genetics/*pathology ; Nuclear Proteins/analysis/*genetics ; Ovarian Neoplasms/diagnosis/*genetics/*pathology ; Ovary/metabolism/*pathology ; Prognosis ; Real-Time Polymerase Chain Reaction ; Young Adult

OBJECTIVE: To examine the expression of G protein-coupled estrogen receptor (GPER) and Gankyrin in ovarian endometriosis (OEM) and to evaluate its clinicopathological significance.
 METHODS: Immunohistochemistry was conducted to determine the expression and distribution of GPER and Gankyrin in matched ectopic and eutopic endometrium of OEM and the normal endometrium. The association of these two proteins with the stages of OEM was also investigated.
 RESULTS: The positive rate for GPER protein in paired ectopic and eutopic endometrium of OEM and the normal endometrium were 63.6%, 51.5% and 21.2%, respectively. There was significant difference in matched ectopic and eutopic endometrium from OEM compared with the control endometrium (P<0.0125). No statistical significance was found between ectopic and eutopic endometrium from OEM (P>0.0125). The positive rate for Gankyrin protein were 69.7%, 36.4% and 9.1%, respectively. Significant difference in Gankyrin protein was found between ectopic and eutopic endometrium of OEM, ectopic and normal endometrium or eutopic and normal endometrium (P<0.0125). Higher positive expression rate for GPER was also observed in eutopic endometrium from OEM during proliferative phase in comparison to secretory phase (P<0.05). There was no significant difference in Gankyrin between proliferative and secretory phase (P>0.05). These two proteins were positively correlated with the revised American Society for Reproductive Medicine (rASRM) stages of OEM. Both of them were found to be significantly higher in advanced stages (III-IV) compared with those in early stages (I-II, P<0.05). Moreover, a significant positive correlation was found between GPER and Gankyrin proteins in ectopic endometrium of OEM (rs=0.640, P<0.01). 
 CONCLUSION GPER and Gankyrin might be involved in the pathogenesis of OEM, which could possibly facilitate the formation of ectopic lesions.
Case-Control Studies ; Endometriosis ; metabolism ; Endometrium ; pathology ; Female ; Humans ; Immunohistochemistry ; Ovary ; pathology ; Proteasome Endopeptidase Complex ; metabolism ; Proto-Oncogene Proteins ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, G-Protein-Coupled ; metabolism

AIM: To evaluate the effect of Cocus nucifera L. flowers in reducing the major multiple symptoms of letrozole-induced polycystic ovarian disease (PCOD) in female rats. METHOD: Female, virgin Wistar rats were treated with letrozole (1 mg/kg body wt) to induce PCOD, and after 21 days of induction rats were administered orally with 100 and 200 mg·kg(-1) of Cocus nucifera flower aqueous extract, respectively. Estrus cycle and blood sugar were monitored once a week throughout the study. After scarification, various biochemical parameters, such as antioxidant status (superoxide dismutase (SOD) and glutathione reductase (GSH)) of the uterus homogenate, lipid profile (total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL), and triglycerides (TG)) of the serum were determined. Weights of the uterus and ovaries were separately monitored. The characteristics of changes in the ovary were evaluated by histopathological studies. RESULTS: GC-MS analysis of the aqueous extract showed the presence of volatile and pharmacologically active phytoconstituents. C. nucifera flower extract-treated groups showed estrus cyclicity and increased uterus weight which indicates the estrogenic effect. The improved blood sugar level, ideal lipid profile, good antioxidant status, and histopathology results revealed the recovery from poly cystic ovaries. CONCLUSION The results indicate that C. nucifera flower is a potential medicine for the treatment of PCOD and this study supports the traditional uses of C. nucifera flower.
Animals ; Antioxidants ; metabolism ; Blood Glucose ; metabolism ; Cocos ; chemistry ; Estrus ; drug effects ; Female ; Flowers ; chemistry ; Gas Chromatography-Mass Spectrometry ; Hypoglycemic Agents ; pharmacology ; therapeutic use ; Letrozole ; Lipids ; blood ; Nitriles ; Oils, Volatile ; analysis ; pharmacology ; therapeutic use ; Ovary ; drug effects ; pathology ; Phytoestrogens ; pharmacology ; therapeutic use ; Phytotherapy ; Plant Extracts ; chemistry ; pharmacology ; therapeutic use ; Polycystic Ovary Syndrome ; blood ; chemically induced ; drug therapy ; pathology ; Rats, Wistar ; Triazoles ; Uterus ; drug effects

Carcinoma in Situ ; metabolism ; pathology ; Cystadenocarcinoma, Serous ; metabolism ; pathology ; Fallopian Tube Neoplasms ; metabolism ; pathology ; Fallopian Tubes ; metabolism ; pathology ; Female ; Humans ; Neoplasm Invasiveness ; Ovary ; pathology ; Tumor Suppressor Protein p53 ; metabolism

OBJECTIVETo explore the Intervention effect of Rosiglitozone in ovarian fibrosis of PCOS rats.

METHODS60 female SD rats were randomly divided into 3 groups: control group, model group and treatment group. The model and treatment groups were established by subcutaneous injection of DHEA, while the treatment group was given RGZ. The serum hormone values, pathohistology of ovarian structure of rats, ovarian ultrastructure and the expressions of TGF-β(1) and CTGF were detected.

RESULTSThe PCOS model was established successfully. The expression intensity of TGF-β(1) and CTGF in Oocytes of the PCOS groups was 9.545±2.954 and 9.665±2.400, respectively and was significantly higher than that of the control group 6.636±2.264 and 7.036±2.133; after treatment with rosiglitazone, the expression was significantly decreased 6.980±2.421 and 6.642±2.721 as compared with that of the model group (P<0.05, P<0.001). The values in serum of the PCOS groups were 3.749±2.054 and 0.265±0.129, and 1.914±1.801 and 0.096±0.088 in the control group which had statistically significant difference (P<0.05, P<0.001). After treatment with rosiglitazone, the values were 2.3100±1.825 and 0.112±0.187 and were significantly different with those of the model group (P<0.05, P<0.001).

CONCLUSIONTGF-β(1) and CTGF play an important role in the development of ovary fibrosis in PCOS. However, RGZ may postpone the development of fibrosis by decreasing the levels of TGF-β(1) and CTGF.

Animals ; Connective Tissue Growth Factor ; blood ; Female ; Fibrosis ; Hypoglycemic Agents ; therapeutic use ; Ovary ; metabolism ; ultrastructure ; Polycystic Ovary Syndrome ; blood ; drug therapy ; pathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Thiazolidinediones ; therapeutic use ; Transforming Growth Factor beta ; blood

OBJECTIVETo study the characteristics of the metabolic syndrome (MS) in patients with polycystic ovary syndrome (PCOS).

METHODSOral glucose tolerance test (OGTT) was performed in 336 patients with PCOS, and the serum levels triglycerides (TG), total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and testosterone were measured.

RESULTSThe total incidence of MS was 18.8% in these 336 patients with PCOS. The incidence of MS increased with percent body fat (%BF) and lipid accumulation product (LAP) in patients with PCOS. The patients at child-bearing age appeared to have a higher incidence of MS than those in puberty. The muscle distribution coefficient, age, body mass index, and the metabolic parameters were all higher in patients with MS than in those without MS. The bilateral lower limb muscle strength were lower in patients with MS than in those without, but the level of testosterone showed no significant difference between them.

CONCLUSIONThe risk of MS increases with BF%, age and LAP in patients with PCOS.

Adolescent ; Adult ; Body Composition ; Body Mass Index ; Female ; Humans ; Metabolic Syndrome ; metabolism ; pathology ; Obesity ; metabolism ; Polycystic Ovary Syndrome ; metabolism ; pathology ; Risk Factors ; Young Adult