Modulation of the Inflammatory Response in Polycystic Ovary Syndrome (PCOS)-Searching for Epigenetic Factors.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. Despite its incidence, the syndrome is poorly understood and remains underdiagnosed, and female patients are diagnosed with a delay. The heterogenous nature of this complex disorder results from the combined occurrence of genetic, environmental, endocrine, and behavioral factors. Primary clinical manifestations of PCOS are derived from the excess of androgens (anovulation, polycystic ovary morphology, lack of or scanty, irregular menstrual periods, acne and hirsutism), whereas the secondary manifestations include multiple metabolic, cardiovascular, and psychological disorders. Dietary and lifestyle factors play important roles in the development and course of PCOS, which suggests strong epigenetic and environmental influences. Many studies have shown a strong association between PCOS and chronic, low-grade inflammation both in the ovarian tissue and throughout the body. In the vast majority of PCOS patients, elevated values of inflammatory markers or their gene markers have been reported. Development of the vicious cycle of the chronic inflammatory state in PCOS is additionally stimulated by hyperinsulinemia and obesity. Changes in DNA methylation, histone acetylation and noncoding RNA levels are presented in this review in the context of oxidative stress, reactive oxygen species, and inflammatory signaling in PCOS. Epigenetic modulation of androgenic activity in response to inflammatory signaling is also discussed.

Anti-inflammatory Action of Metformin with Respect to CX3CL1/CX3CR1 Signaling in Human Placental Circulation in Normal-Glucose Versus High-Glucose Environments.

Upregulation of chemokine CX3CL1 and its receptor CX3CR1 occurs in the diabetic human placenta. Metformin, an insulin-sensitizing biguanide, is used in the therapy of diabetic pregnancy. By preventing the activation of NF-κB, metformin exhibits anti-inflammatory properties. We examined the influence of hyperglycemia (25 mmol/L glucose; HG group; N = 36) on metformin-mediated effects on CX3CL1 and TNF-α production by placental lobules perfused extracorporeally. Additionally, CX3CR1 expression and contents of CX3CR1, TNF-α receptor 1 (TNFR1), and NF-κB proteins in the placental tissue were evaluated. Placentae perfused under normoglycemia (5 mmol/L glucose; NG group; N = 36) served as the control. Metformin (2.5 and 5.0 mg/L; subgroups B and C) lowered the production of CX3CL1 and TNF-α in a dose-dependent and time-dependent manner. Hyperglycemia did not weaken the strength of these metformin effects. Moreover, CX3CL1 levels after perfusion with 5.0 mg/L metformin were reduced by 33.28 and 33.83% (at 120 and 150 min, respectively) in the HG-C subgroup versus 24.98 and 23.66% in the NG-C subgroup, which indicated an augmentation of the metformin action over time in hyperglycemia. CX3CR1 expression was significantly higher in the HG-B and HG-C subgroups compared to that in the NG-B and NG-C subgroups. Increased CX3CR1 protein content in the placental lysates was observed in subgroups B and C. The two higher metformin concentrations significantly decreased the levels of NF-κBp65 protein content in both groups. However, the decrease was significantly stronger in hyperglycemia. TNFR1 upregulation in the HG group was not affected by metformin. Further studies on metformin therapy during pregnancy are needed, including safety issues.

Presurgical diagnostic difficulties in an asymptomatic patient with primary transitional cell carcinoma of the oviduct: case report.

Primary transitional cell carcinoma of the fallopian tube is a very rare condition. We present a case of a 70-year-old asymptomatic Caucasian patient with an irregular solid right adnexal mass of 67 × 35 × 59 mm which was discovered during routine ultrasound pelvic examination. There was no acoustic shadow and the patient did not feel pain during examination. No evidence of metastases or ascites was found by ultrasound. There was moderate vascularization of the mass. The mass was considered malignant according to the subjective assessment of the examiner. Serum level of CA125 was elevated to 519 U/ml. The results of logistic regression model LR2 according to the International Ovarian Tumor Analysis (IOTA) group was 64.4%, suggesting the malignant nature of the mass. The IOTA-ADNEX model showed 97% probability of malignancy, probably (85.5%) stage II-IV ovarian cancer. The risk of malignancy being borderline, stage I and metastatic was 0.6%, 3.9% and 7%, respectively. Omitting CA125 in the IOTA-ADNEX model slightly decreased the probability of malignancy to 81.3%, still most likely (54.2%) stage II-IV ovarian cancer. The results of risk of malignancy indices RMI I-IV were 1557, 2076, 1557 and 2076, respectively, reflecting the malignant nature of the mass. The final diagnosis was transitional cell carcinoma of the fallopian tube, stage IIIc according to FIGO.

High Glucose Level Disturbs the Resveratrol-Evoked Curtailment of CX3CL1/CX3CR1 Signaling in Human Placental Circulation.

Hyperglycemia-induced hyperactivity of chemokine CX3CL1 (fractalkine) occurs in the human placenta. Anti-inflammatory/antioxidant activities of resveratrol (3,5,4'-trihydroxy-trans-stilbene) are related to the modulation of chemokine CX3CL1 and its receptor, CX3CR1, signaling pathways. We examined the influence of high glucose (25 mmol/L glucose; HG group; N = 36) on resveratrol-mediated effects on CX3CL1 and TNF-α production by the placental lobule, CX3CR1 expression and contents of CX3CR1, TNF-α receptor 1 (TNFR1), and NF-κB proteins in placental tissue. The placental lobules perfused under normoglycemic conditions formed the control NG group (N = 36). Resveratrol (50 and 100 µM; subgroups B and C) administered into the perfusion fluid lowered the production of both CX3CL1 and TNF-α. The reductions in CX3CL1 levels were more evident in the NG group. CX3CR1 expression was significantly higher in the NG subgroups B and C compared to the HG subgroups B and C (385.2 and 426.5% versus 199.3 and 282.4%, resp.). An increase in CX3CR1 protein content in placental lysates was observed in the NG subgroups B and C. Also, resveratrol significantly decreased NF-κBp65 protein content only in the NG group, not affecting hyperglycemia-elicited TNFR1 upregulation. In conclusion, euglycemia assures optimal effects of resveratrol pertaining to CX3CL1/CX3CR1 signaling in the placenta. Future studies on resveratrol are needed, especially those including maternal-fetal risk assessments.

Spontaneous rupture of the pregnant uterus following salpingectomy: a literature review.

BACKGROUND: Spontaneous rupture of the uterus is a life-threatening obstetric complication in rare cases associated with previously performed salpingectomy. AIM: This paper presents an analysis of uterine rupture cases during pregnancy in patients after surgical removal of the fallopian tubes. METHODS: The English and Polish language literature was reviewed for studies published between January 1, 1980 and September 30, 2014 to identify articles that described rupture of the uterus in women with a previous history of salpingectomy. RESULTS: Thirteen case reports and case series studies in 18 women were identified. 33% of cases of uterine rupture following salpingectomy occurred during intrauterine pregnancy, whereas the rest was associated with interstitial ectopic pregnancy. Laparoscopic salpingectomy more often resulted in rupture of the uterus during non-ectopic pregnancy as compared to laparotomy (4 vs. 2 cases, respectively). When interstitial pregnancies were excluded, uterine rupture was a cause of fetal death in 67% of reported gestations. There were no cases of maternal mortality. Conservative treatment was the preferred management option, and total hysterectomy was performed in only 2 patients. CONCLUSION: Particular attention should be paid to patients with a previous history of salpingectomy due to the risk of uterine rupture throughout the entire pregnancy.

Placental tumor (chorioangioma) as a cause of polyhydramnios: a case report.

Placental chorioangioma is the most common type of placental tumor. It is usually symptomless and may be associated with serious maternal and fetal complication when it reaches a large size. We presented a case of an angiomatous type of placental hemangioma diagnosed in the second trimester of pregnancy in a patient with polyhydramnios. A normal volume of amniotic fluid was successfully achieved by three amnioreductions with conservative management. The size of the placental tumor remained the same from the time of diagnosis to the end of pregnancy. A term labor was uncomplicated and a healthy newborn was delivered. Macroscopic and microscopic examination of the placenta confirmed the diagnosis. Despite the rarity of placental tumors, they should be considered as differential diagnosis in cases of polyhydramnios.

Diagnostic value of ultrasound indicators of neoplastic risk in preoperative differentiation of adnexal masses.

AIM: To assess the diagnostic value of the risk of malignancy indices and simple ultrasound- based rules in preoperative differentiation of adnexal masses. MATERIAL AND METHODS: Retrospective examination of 87 patients admitted to hospital due to adnexal tumors. The lesions were evaluated on the basis of international ultrasound classification of ovarian tumors and four risk of malignancy indices were calculated based on ultrasound examination, concentration of CA 125 and menopausal status. RESULTS: The patients were aged between 17 and 79, the mean age was 44.5 (standard deviation SD=16.6). Most of the patients (60.91%) were before their menopause. The sensitivity of the simple ultrasound-based rules in the diagnosis of malignancies equaled 64.71% and the specificity constituted 90.00%. A significant statistical difference in the presence of the malignant process was demonstrated in relation to age, menopausal status, CA 125 concentration and analyzed ultrasound score. All indices were characterized by similar sensitivity and specificity. The highest specificity and predictive value of malignant lesions out of the assessed ones was demonstrated by the risk of malignancy index proposed by Yamamoto. The risk of malignancy index according to Jacobs, however, showed the highest predictive value in the case of non-malignant lesions. CONCLUSIONS: The multiparametric ultrasound examination may facilitate the selection of patients with adnexal tumors to provide them with an appropriate treatment - observation, laparotomy and laparoscopy. These parameters constitute a simple ambulatory method of determining the character of adnexal masses before recommending appropriate treatment.