Effects of IL-18 on the proliferation and steroidogenesis of bovine theca cells: Possible roles in the pathogenesis of polycystic ovary syndrome.

Interleukin 18 (IL-18) is a pleiotropic pro-inflammatory cytokine and is associated with arrested follicle development and anovulation which are the typical pathological changes of PCOS. Theca cells (TCs) have a key role in follicular growth and atresia. But whether IL-18 can directly affect ovarian TCs function is unknown. Therefore, the objective of this study was to determine the effect of IL-18 on proliferation and steroidogenesis of bovine TCs and to explore the biological effect of IL-18 on folliculogenesis. This work revealed that at 300-1000 pg/mL, IL-18 led to a time- and dose-dependently increase in cell proliferation (P < .05). IL-18 increased 17-hydroxyprogesterone (17OHP4) and androstenedione (A2) secretion with up-regulation of key steroidogenesis-related genes CYP11A1 and CYP17A1 (P < .05). Furthermore, our data demonstrated that the IL-18R protein is predominantly expressed in small-follicle (3-6 mm) TCs than large follicles (8-22 mm) by immunohistochemistry. We also found that the stimulation effects of IL-18 on TCs can be reversed with the addition of IL-18BP as early as at 4 hours of culture and reached the peak at 16 hours. We conclude that IL-18 appears to target TCs in bovine, and suggest an important role for this cytokine in ovarian function. Present findings further validate potential effects of IL-18 in the conditions associated with follicular dysplasia and excessive growth of ovarian TCs (such as PCOS). But additional research is needed to further understand the mechanism of action of IL-18 in theca cells as well as its precise role in folliculogenesis.

Identification of Potential Biomarkers for Urine Metabolomics of Polycystic Ovary Syndrome Based on Gas Chromatography-Mass Spectrometry.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder, and it's diagnosis is difficult. The aim of this study was to investigate the metabolic profiles of PCOS patients by analyzing urine samples and identify useful biomarkers for diagnosis of PCOS. METHODS: This study was carried out in the Department of Obstetrics and Gynecology of the Maternal and Child Health Hospital of Hunan Province from December 2014 to July 2016. In this study, the urine samples of 21 women with PCOS and 16 healthy controls were assessed through gas chromatography-mass spectrometry to investigate the urine metabolite characteristics of PCOS and identify useful biomarkers for the diagnosis of this disorder. The Student's t-test and rank sum test were applied to validate the statistical significance of the between the two groups. RESULTS: In total, 35 urine metabolites were found to be significantly different between the PCOS patients and the controls. In particular, a significant increase in the levels of lactose (10.01 [0,13.99] mmol/mol creatinine vs. 2.35 [0.16, 3.26] mmol/mol creatinine, P = 0.042), stearic acid (2.35 [1.47, 3.14] mmol/mol creatinine vs. 0.05 [0, 0.14] mmol/mol creatinine, P < 0.001), and palmitic acid (2.13 [1.07, 2.79] mmol/mol creatinine vs. 0 [0, 0] mmol/mol creatinine, P < 0.001) and a decrease in the levels of succinic acid (0 [0, 0] mmol/mol creatinine vs. 38.94 [4.16, 51.30] mmol/mol creatinine, P < 0.001) were found in the PCOS patients compared with the controls. It was possible to cluster the PCOS patients and the healthy controls into two distinct regions based on a principal component analysis model. Of the differentially expressed metabolites, four compounds, including stearic acid, palmitic acid, benzoylglycine, and threonine, were selected as potential biomarkers. CONCLUSIONS: This study offers new insight into the pathogenesis of PCOS, and the discriminating urine metabolites may provide a prospect for the diagnosis of PCOS.

Characterization of the microRNA expression profile of cervical squamous cell carcinoma metastases.

OBJECTIVES: MicroRNAs (miRNAs) are important regulators of many physiological and pathological processes, including tumorigenesis and metastasis. In this study, we sought to determine the underlying molecular mechanisms of metastatic cervical carcinoma by performing miRNA profiling. METHODS: Tissue samples were collected from ten cervical squamous cancer patients who underwent hysterectomy and pelvic lymph node (PLN) dissection in our hospital, including four PLN-positive (metastatic) cases and six PLN-negative (non-metastatic) cases. A miRNA microarray platform with 1223 probes was used to determine the miRNA expression profiles of these two tissue types and case groups. MiRNAs having at least 4-fold differential expression between PLN-positive and PLN-negative cervical cancer tissues were bioinformatically analyzed for target gene prediction. MiRNAs with tumor-associated target genes were validated by quantitative reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Thirty-nine miRNAs were differentially expressed (>4-fold) between the PLN-positive and PLN-negative groups, of which, 22 were up-regulated and 17 were down-regulated. Sixty-nine percent of the miRNAs (27/39) had tumor-associated target genes, and the expression levels of six of those (miR-126, miR-96, miR-144, miR-657, miR-490-5p, and miR-323-3p) were confirmed by quantitative (q)RT-PCR. CONCLUSIONS: Six MiRNAs with predicted tumor-associated target genes encoding proteins that are known to be involved in cell adhesion, cytoskeletal remodeling, cell proliferation, cell migration, and apoptosis were identified. These findings suggest that a panel of miRNAs may regulate multiple and various steps of the metastasis cascade by targeting metastasis-associated genes. Since these six miRNAs are predicted to target tumor-associated genes, it is likely that they contribute to the metastatic potential of cervical cancer and may aid in prognosis or molecular therapy.

Low expression of mixed lineage kinase domain-like protein is associated with poor prognosis in ovarian cancer patients.

BACKGROUND: Mixed lineage kinase domain-like protein (MLKL) was initially identified as a key receptor interacting protein 3 downstream component of tumor-necrosis-factor-induced necrosis. In this study, we characterized the expression of MLKL in ovarian carcinomas and evaluated the prognostic value of MLKL in patients with ovarian cancer. MATERIALS AND METHODS: The ovarian cancer tissue specimens were collected from 153 patients diagnosed as primary ovarian cancer after operation at The Second Xiangya Hospital from January 2005 to December 2008. Immunohistochemistry was performed for MLKL and the protein expression score was quantified using an established scoring system. Kaplan-Meier survival curves were generated for disease-free survival (DFS) and overall survival (OS) for all patients. MLKL expression levels were correlated with DFS and OS using univariate and multivariate Cox regression analysis. RESULTS: Seventy-five patients (49%) were defined as having high MLKL expression and 67 patients (43.7%) had >80% of cells staining for MLKL. Remarkably, low MLKL expression was significantly associated with decreased DFS (median 40 months versus 25 months, P=0.0282) and OS (median 43 months versus 28 months, P=0.0032). In multivariate analysis, retained significance was also observed. CONCLUSION: Low MLKL expression was significantly associated with both decreased DFS and OS in patients with primary ovarian cancer. MLKL expression may serve as a potential prognostic marker in patients with ovarian cancer.

Clinical characteristics, metabolic features, and phenotype of Chinese women with polycystic ovary syndrome: a large-scale case-control study.

AIM: The Rotterdam criteria extend the phenotypic spectrum of polycystic ovary syndrome (PCOS). The study was to investigate the clinical and biochemical features of a large-scale clinic based on the samples of Chinese women and to evaluate the value of Rotterdam criteria on Chinese PCOS women. METHODS: One thousand four hundred and four Chinese women were involved in our study, among whom, 719 cases were diagnosed as PCOS based on 2003 Rotterdam criteria, and 685 women without history of hyperandrogenism and with regular menstrual cycles were recruited as control. Clinical features, ultrasonographic (ovarian follicle number and volume), hormonal and metabolic parameters were commenced as outcome measures. RESULTS: Among 719 PCOS women, 6.1 % had hirsutism, 13.3 % had acne, 21.1 % had hyperandrogenism, 94.2 % had polycystic ovaries on ultrasonographic examination, and 88.6 % had menstrual abnormality. About one-third of the total PCOS patients were insulin resistant. The most frequent PCOS phenotype is the non-hyperandrogenic phenotype (O + P). Total testosterone, LH/FSH ratio, body mass index (BMI), and Ferriman and Gallwey scores (F-G) were all significantly higher in PCOS groups compared with non-PCOS group. Women with PCOS and obesity had higher serum testosterone, fasting insulin, longer menstrual cycle and larger ovarian follicle number, and LH/FSH ratio, estradiol or ovarian volume were similar between obese and normal BMI women. The LH level was statistically lower in the obese PCOS group. CONCLUSIONS: Rotterdam criteria are generally applicable to Chinese population. Chinese women with PCOS showed lower rates of hyperandrogenemia, hirsutism, obesity, and insulin resistance. Obesity aggravates menstrual irregularity and increases the follicle number and serum total testosterone level.

Hepatoid carcinoma of the ovary: A case report and review of the literature.

Hepatoid carcinoma of the ovary is a type of tumor resembling hepatocellular carcinoma that arises from the ovary. Hepatoid carcinoma patients are predominantly elderly females ranging between 35 and 78 years of age, with an average age of 56 years. It was suggested that, microscopically, bile canalicular structures are rare, but among nine cases examined for bile canalicular structures, four demonstrated a positive result. Here, we report a case of a 55-year-old female who presented to the Second Xiangya Hospital, Changsha, China, with lower abdominal pain, abdominal distention and increasing abdominal girth. The patient underwent total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, tumor debulking and postoperative chemotherapy. A mass in the left ovary measuring approximately 11 cm in diameter was identified. Microscopic and immunohistochemical results suggested that it was a hepatoid carcinoma of the left ovary.

Quantitative proteome analysis of multidrug resistance in human ovarian cancer cell line.

In order to understand the molecular mechanisms of multidrug resistance (MDR) in ovarian cancer, we employed the proteomic approach of isobaric tags for relative and absolute quantification (iTRAQ), followed by LC-MS/MS, using the cisplatin-resistant COC1/DDP cell line and its parental COC1 cell line as a model. A total number of 28 proteins differentially expressed were identified, and then the differential expression levels of partially identified proteins were confirmed by Western blot analysis and/or real-time RT-PCR. Furthermore, the association of PKM2 and HSPD1, two differentially expressed proteins, with MDR were analyzed, and the results showed that they could contribute considerably to the cisplatin resistance in ovarian cancer cell. The differential expression proteins could be classified into eight categories based on their functions, that is, calcium binding proteins, chaperones, extracellular matrix, proteins involved in drug detoxification or repair of DNA damage, metabolic enzymes, transcription factor, proteins related to cellular structure and proteins relative to signal transduction. These data will be valuable for further study of the mechanisms of MDR in the ovarian cancer.

[Role of platelet-derived growth factor in the pathogenesis of preeclampsia].

OBJECTIVE: To study the role of platelet-derived growth factor (PDGF) in the pathogenesis of preeclampsia (PRE). METHODS: Thirteen normal and 20 PRE late-pregnancy women were enrolled in this study. The serum PDGF-BB levels were measured with enzyme-linked immunosorbent assay, and the expression of PDGF-B mRNA in the decidual blood vessel was determined using in situ hybridization. RESULTS: PDGF-BB levels in PRE group was significantly higher than that in normal pregnant women (83.54 -/+34.52 vs 39.61-/+18.20, P<0.001), and the expression of PDGF-B mRNA in decidual blood vessel was also significantly higher in PRE group (P<0.001), showing a positive correlation between serum PDGF and PDGF-B mRNA expression (r=0.603, P<0.001). CONCLUSION: PDGF is associated with the pathology of decidual blood vessel. Elevated serum PDGF levels and PDGF-B mRNA expression in the decidual blood vessel may play an important role in the pathogenesis of PRE.

[Management of heart failure and timing of delivery in pregnancy].

OBJECTIVE: To explore the management of heart failure, the timing of delivery in pregnancy, and the influence on pregnant prognosis. METHODS: We retrospectively analyzed the incidence of heart failure, treatment results, pattern of termination, and time of termination in 356 cases of pregnancy with heart disease. RESULTS: One hundred and thirty-six (38.20%) cases were diagnosed as heart failure and 76 (55.88%) were moderate or severe heart failure. Heart failure tends to occur more easily in rheumatic heart diseases than in congenital heart diseases. Heart failure occurred more frequently in pregnancy with rheumatic heart diseases without the heart operation before pregnancy than that of pregnancy with congenital heart diseases. The occurence of the moderate and severe heart failure in pregnancy decreased in rheumatic heart diseases with surgical therapies compared with those without surgical therapies (P <0.05). Compared with pregnancy with heart failure controlled inadequately, pregnancy with effectively controlled heart failure had better tolerance during delivery and through the pregnancy, and puerperium. CONCLUSION: Congenital heart diseases and rheumatic heart diseases are the chief causes of heart failure during the gestation. Therapy before pregnancy, especially surgery to the rheumatic heart diseases, may improve the cardiac function during pregnancy. Monitoring heart function and selecting the proper timing to terminate pregnancy after controlling the heart failure in late pregnant period will be helpful to improve the prognosis of pregnant and perineonate.

[Characteristics of blood dynamic parameters in pregnant women with anticardiolipin antibodies and history of adversely pregnant complications].

OBJECTIVE: To study the characteristics of blood dynamic parameters in pregnant women with anticardiolipin antibody (aCL) and a history of adversely pregnant complications. METHODS: The study included a prospective cohort of pregnant women with (272 cases) and without (186 cases) aCL. Among the aCL positive pregnant women, 91 cases had the history of adversely pregnant complications including spontaneous abortion, still fetus. Serum antibodies to cardiolipin (CL) were measured by a specific enzyme linked immunosorbent assay. Blood dynamics parameters were measured by non-invasive cardiovascular parameters surveyor (TP-CBS). RESULTS: The women were divided into three groups: group A (91 cases)included women with both the history of adversely pregnant complications and positive aCL, group B (181 cases) with positive aCL alone and group C (186 cases) without either of them. In group A maximum blood viscosity (Vmax) was (4.7 +/- 0.5) mPa x s and in group B it was (4.6 +/- 0.7) mPa x s. Both was higher than normal. In group B the Vmax was higher (P < 0.05) than in group C [(4.4 +/- 0.4) mPa x s]. The wave form coefficient(K) was different in three groups: group A was 0.41 +/- 0.04, group B was 0.39 +/- 0.05 and group C was 0.39 +/- 0.04. In group A their wave form coefficient was higher than in group B (P < 0.05). Their total peripheral resistance (TPR) was higher (P < 0.05) in group A [(1.3 +/- 0.4) mm Hg x s x ml(-1)] than in group B [(1.2 +/- 0.4) mm Hg x s x ml(-1)]. The cardiac index (CI) was in group A [(43 +/- 15) ml/(s x m(2))], in group B [(48 +/- 16) ml/(s x m(2))] and in group C [(48 +/- 14) ml/(s x m(2))], lower in group A than in group B (P < 0.05). CONCLUSIONS: An important change of blood dynamic parameters of pregnant women with aCL is the increase of Vmax. If Vmax, K and TPR were increased and CI was decreased simultaneously in women with aCL, it would result in more chances of adversely pregnant complications. Measuring the blood dynamics parameters will help us discover the sub-clinical hypercoagulable state of patients with aCL and guide us to treat them promptly, so that to improve successful pregnancy rate.

[Relationship between anticardiolipin antibodies and abortion].

OBJECTIVE: To explore the relationship between anticardiolipin antibodies (ACA) and abortion. METHODS: The level of serum ACA in 93 abortion women (abortion group) and 80 normal pregnant women (control group) was determined by the enzyme linked immunoabsorbent assay. The abortion group included threatened abortion (n = 62), inevitable abortion (n = 21), and missed abortion (n = 10). RESULTS: The positive rate of ACA in the abortion group was significantly higher than that in the control group (P < 0.05). The positive rate of ACA in pregnant women with a history of abortion was significantly higher than that in those women without a history of abortion (P < 0.05). The positive rate of ACA was not significantly different between habitual abortion and spontaneous abortion (P > 0.05). CONCLUSION: Anticardiolipin antibodies may induce abortion, but it is not related to habitual abortion.

[Meconium-stained amniotic fluid and intra-amniotic infection].

OBJECTIVE: To explore the relationship between meconium-stained amniotic fluid and Fifty-six women of cesarean section with intact membrane and intra-amniotic infection. METHODS: without parturient were divided into 3 groups according to the property of amniotic fluid (no meconium, I to approximately II degree meconium stainedness, and III degree mecomium stainedness). The content of interleukin-6 in amniotic fluid was measured with ELISA. The infiltration of inflammatory cells in the placenta and its membrane was determined by the pathological diagnosis. The neonatal Apgar score and puerperial infection after the surgery were analyzed. RESULTS: There were no significant differences in the content of IL-6 in amniotic fluid and in the infiltration of inflammatory cells among the 3 groups. But the rate of neonatal asphyxia in the meconium-stained cases was significantly higher than that without meconium. CONCLUSION: Meconium-stained amniotic fluid is a marker of fetal distress, but it is not related to intra-amniotic infection.

[Clinical analysis of 242 cases of controlled preterm delivery].

OBJECTIVE: To understand the effect of controlled premature delivery and its termination method of pregnancy. METHODS: The clinical data of 242 cases of controlled premature delivery were retrospectively analyzed. RESULTS: The incidence of premature delivery was 5.75% and the incidence of controlled premature delivery was 46.81%. Pregnancy induced hypertension (PIH) was the first-place reason of controlled premature delivery. The cesarean section rate of controlled premature delivery was 64.88%, which was significantly higher than that of natural premature delivery (16.45%, P < 0.05); the rate of postpartum hemorrhage and neonatal suffocation in controlled premature delivery was significantly lower than that of natural premature delivery (P < 0.05). CONCLUSION: Appropriately controlled premature delivery can be beneficial to the newborn's survival rate and can lower the mortality of pregnant women.