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Circulating levels of obestatin and copeptin in obese and nonobese women with polycystic ovary syndrome

OBJECTIVE Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies, affecting 5-8% of reproductive-age women. It is associated with insulin resistance, central obesity, type 2 diabetes mellitus, dyslipidemia, and cardiovascular diseases. The current study was undertaken to evaluate serum copeptin and obestatin levels, carotid artery intima-media thickness, and brachial artery flow mediated dilatation in obese and nonobese women with PCOS and age-matched healthy controls and to investigate their relationship with each other and with clinical, metabolic, and hormonal parameters and cardiovascular risk factors. METHOD In the study population, we analyzed 60 patients with PCOS and 30 age-matched healthy women as controls. The patients with PCOS were divided into two groups based on body mass index (BMI): obese group (BMI>30kg/m(2), n=30) or nonobese group (BMI<30kg/m(2), n=30). History was obtained and a physical examination, peripheral venous blood sampling, and carotid and brachial artery ultrasonography were performed. Serum copeptin and obestatin levels, total testosterone, C-reactive protein (CRP), glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, homeostasis model assessment for insulin resistance (HOMA-IR), carotid artery intima-media thickness (CIMT), and brachial artery flow-mediated vasodilation (FMD) were determined and compared among the groups. RESULTS Women with PCOS, especially obese ones, had higher triglycerides, HOMA-IR, total testosterone, CRP, systolic and diastolic blood pressure, and waist-to-hip ratio (WHR), and lower HDL. Serum obestatin levels were significantly lower in the obese PCOS group than they were in the nonobese and control groups (p<0.001). Serum copeptin levels were significantly higher in the obese PCOS group than they were in the nonobese PCOS and control groups (p<0.001). CIMT values were similar among the groups (p>0.05). Brachial artery FMD was lower in the PCOS groups than it was in the control group (p<0.001). Obestatin and FMD values were negatively correlated with cardiovascular risk factors, whereas copeptin was positively correlated. A significant positive correlation was found between copeptin, BMI, WHR, hirsutism score, total testosterone, and HOMA-IR. There was no correlation between CIMT, copeptin, obestatin, and FMD. A positive correlation was seen between CIMT, BMI, triglycerides, and HOMA-IR. CONCLUSION Copeptin and obestatin may provide useful information regarding future cardiovascular risk in PCOS patients as copeptin was positively correlated and obestatin was negatively correlated with cardiovascular risk factors.

Effect of 2-aminoethoxydiphenyl borate on ischemia-reperfusion injury in a rat ovary model

OBJECTIVE The aim of this study is to evaluate the effects of 2-aminoethoxydiphenyl borate (2-APB) as an antioxidant and analyze biochemical and histopathologic changes in experimental ischemia-reperfusion (I/R) injury in rat ovaries. STUDY DESIGN Thirty female rats were utilized to create four groups. Group 1: I/R and 2-APB (2mg/kg); Group 2: I/R and 2-APB (4mg/kg); Group 3: I/R; Group 4: sham operation. Ovarian tissue and serum malondialdehyde, nitric oxide (NO) levels; ovarian tissue and serum total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI) were determined. In ovarian tissue samples histopathologic examination, immunoflourescence staining by TUNEL method was studied. RESULTS Tissue TOS, serum TOS, and OSI levels were elevated in I/R group. After treatment with 2-APB, tissue and serum TOS levels and OSI levels were markedly decreased. There was a significant difference in terms of tissue and serum NO levels between the sham group and I/R group. Elevation in tissue NO and serum NO levels were decreased after treatment with 2-APB. TUNEL-positive cell number gradually decreased with dose of 2-APB in groups 1 and 2. CONCLUSION Conservative treatment with 2-APB is beneficial for mitigation of I/R injury, and the ovarian protective effect of 2-APB appears to be mediated through its antiapopitotic and antioxidative effects.

Protective effects of sildenafil citrate administration on cisplatin-induced ovarian damage in rats

Abstract The aim of this study is to evaluate the effects of sildenafil citrate on cisplatin-induced ovarian toxicity. Thirty-two female rats were divided into four groups. Group 1: saline control; group 2: cisplatin; group 3: sildenafil citrate; and group 4: cisplatin plus sildenafil citrate group. In groups 2 and 4, the rats were injected with 5 mg/kg cisplatin intraperitoneally (i.p.). In groups 3 and 4, the rats were injected with 1.4 mg/kg sildenafil citrate i.p. The ovaries were removed two weeks later in all groups. Histopathologic examination, follicle counting and classification were performed. The expression of anti-Müllerian hormone (AMH) was detected immunohistochemically in the ovarian tissues. Sildenafil alleviated cisplatin-induced histopathological changes in the ovarian tissue. Primordial, secondary and tertiary follicles were diminished in group 2 compared with group 1 (p < 0.05). Pretreatment with sildenafil citrate preserved primordial follicle count in group 4 compared with group 2, and the difference was statistically significant (p < 0.05). According to our results, immunoreactivity intensity of AMH was lower in group 2 compared with group 1 (92.4 ± 3.97 versus 88.8 ± 1.77) but not significantly, whereas immunoreactivity intensity of AMH was higher in group 4 compared with group 2 (88.8 ± 1.77 versus 94.1 ± 2.36; p < 0.05). Our results demonstrated that pretreatment with sildenafil citrate is beneficial for protecting the ovaries from cisplatin-induced damage. Sildenafil citrate can be a choice for fertility preservation.

A Humanized Anti-Interleukin 6 Receptor Monoclonal Antibody, Tocilizumab, for the Treatment of Endometriosis in a Rat Model

Objective: The aim of this study was to investigate the efficacy of anti-interleukin 6 (IL-6) therapy in the treatment of endometriosis in a rat model. Study Design: After the peritoneal implantation of autologous endometrial tissue, 22 Wistar female rats were divided to create 2 intervention groups: the tocilizumab group (n = 13) and the control group (n = 9). After measuring implant volume, saline was administered to the rats in the control group and 8 mg/kg tocilizumab was administered intraperitoneally to the rats in the tocilizumab-treated group every 2 weeks. After a 4-week treatment period, the volumes and histopathological properties of the implants were evaluated. A scoring system was used to evaluate the preservation of epithelia. Fibrosis score was assessed between the groups. Ectopic and eutopic endometrium were evaluated immunohistochemically for IL-6 and vascular endothelial growth factor (VEGF). Results: There was a significant difference between the volumes of implants before and after treatment in the tocilizumab group (P < .05). The posttreatment volumes of lesions were smaller in the tocilizumab group than in the control group. Histologic and fibrosis scores were lower in the tocilizumab group than in the control group. Immunoreactivity intensity for VEGF was significantly decreased in the tocilizumab group for ectopic and eutopic endometrium (P < .05). Interleukin 6 levels and endometrial thickness for ectopic and eutopic endometrium were similar between the groups. Conclusion: Tocilizumab treatment had a regressive effect on the endometriotic implants.

Accessory spleen in the pelvis: A case report

Highlights • Ectopic splenic tissue can be either congenital (accessory spleen) or acquired (splenosis).• Accessory spleen (AS) is commonly located near the spleen’s hilum and in the pancreas tail.• Pelvic AS is a very rare entity.• AS is generally determined incidentally during radiological investigation or surgery.• Pelvic AS may be considered in differential diagnosis of adnexal masses.

NUCB2 gene polymorphism and its relationship with nesfatin-1 levels in polycystic ovary syndrome

Abstract Nesfatin-1, encoded by the nucleobindin-2 (NUCB2) gene, is an anorexigenic protein related to energy metabolism, obesity, and insulin resistance. The aim of this study was to evaluate NUCB2 gene polymorphism (rs757081) and its association with serum levels of nesfatin-1 in obese and non-obese women with polycystic ovary syndrome (PCOS). In the study population, we analyzed 60 patients with PCOS and 26 age-matched healthy women as controls. The patients with PCOS were divided into two groups based on body mass index (BMI): obese group (n = 28) or non-obese group (n = 32). NUCB2 was genotyped using the polymerase chain reaction-restriction (PCR) technique. Serum nesfatin-1 level was measured by enzyme-linked immunosorbent assay (ELISA). Nesfatin-1 levels in the obese PCOS group were significantly lower than those in the non-obese PCOS and control groups (p < 0.001). There was no statistically significant difference in the distribution of NUCB2 genotypes among the groups (p > 0.05), whereas nesfatin-1 levels in the CC and CG genotypes were lower than those in the GG genotype. Nesfatin-1 decreases in PCOS, especially in obese women, and is negatively correlated with cardiometabolic risk factors. Although genotype disturbances of NUCB2 were similar among the groups, CC and CG genotypes accompanied lower nesfatin-1 levels. C allele of NUCB2 gene polymorphism and nesfatin-1 may play a role in the pathophysiology of PCOS.

In vitro effects of estrogen and progesterone containing drugs on human erythrocyte carbonic anhydrase I and II isozymes in women smokers and nonsmokers

Background Carbonic anhydrases (CAs), a group of metalloenzymes, are involved in numerous physiological and pathological processes such as acid–base balance, gluconeogenesis, lipogenesis, ureagenesis, electrolyte secretion in various tissues, bone resorption and calcification, and tumorigenicity. In the current study, we aimed to determine and compare possible alterations in the activity of carbonic anhydrase I (CA I) and carbonic anhydrase II (CA II) isozymes by using estrogens and progestagens in female smokers and nonsmokers. Methods Blood samples from 30 smoker and 30 nonsmoker volunteers were drawn after obtaining informed consent. The blood samples were centrifuged to separate the plasma and erythrocytes. Thereafter, hemolysate was prepared from the red cells. CA I and CA II were purified from human erythrocytes with a simple one‐step procedure using Sepharose 4B‐l‐tyrosine‐sulfonamide affinity column. CAI and CA II isozymes were treated with estrogen and progesterone‐containing drugs, after which the inhibition or activation of the enzyme was determined. Results CA I and CA II enzyme activity was observed to be increased in female smokers. The results of this study show that dienogest is the most effective inhibitor for human erythrocytes CA I when compared with micronized progesterone, hydroxyprogesterone caproate, estradiol valerate, and estradiol hemihydrate in both female smokers and nonsmokers. All active ingredients have been shown to have a stronger inhibition in smokers than nonsmokers for CA I activity. Additionally, estradiol valerate and hydroxyprogesterone caproate have stronger inhibition against CA II enzyme activity in women who smoke. Conclusion The results of the current study provide important information to clinicians about how to consider the possible adverse effects of these drugs which are produced as a result of inhibition of CA I and CA II enzyme. Clinicians should take into consideration the side effects caused by CA I and CA II enzyme inhibition when prescribing these drugs in the treatment of different clinical conditions, especially in women who smoke.

The effects of IL-1A and IL-6 genes polymorphisms on gene expressions, hormonal and biochemical parameters in polycystic ovary syndrome

Abstract Polycystic ovary syndrome (PCOS) is a multifactorial disease characterised by chronic inflammation. We aimed to investigate an association between IL-1A and IL-6 gene polymorphisms and both hormonal/biochemical parameters and levels of IL-1A and IL-6. A total of 103 women diagnosed with PCOS according to ESHRE/ASRM criteria were investigated. The patients were divided into two groups as obese and non-obese. IL-1A and IL-6 genes polymorphisms as well as hormonal/biochemical parameters and levels of IL-1A and IL-6 were analysed in the same groups. Serum IL-1A and IL-6 levels were found to increase both in obese and non-obese groups. However, there was no association between IL-1A level and IL-1A polymorphism. A relationship was detected between H score, FSH, LH, total testosterone, HDL-C and TG levels and CG + GG genotypes of IL-6. Furthermore, an association was found between IL-6 levels and CC genotype of IL-6 in the obese PCOS patients. The abnormalities in hormonal/biochemical parameters detected in Turkish PCOS patients may be related with IL-6 gene polymorphism rather than IL-1A.

Prevention of ovarian hyperstimulation syndrome in a rat model: comparison of the efficacy of tocilizumab with that of ranibizumab, cabergoline, and a gonadotropin-releasing hormone antagonist.

Abstract The aim of the study is to investigate the effects of the interleukin-6 (IL-6) blocker tocilizumab in a hyperstimulated rat model and compare it with ranibizumab, a gonadotropin-releasing hormone antagonist (GnRHA), and cabergoline. Forty-seven rats were randomly divided into the following seven groups: Group 1: OHS; Group 2: OHS+ GnRHA; Group 3: OHS + ranibizumab; Group 4: OHS + cabergoline; Group 5: OHS + low-dose tocilizumab (TL); Group 6: OHS + high-dose tocilizumab (TH); Group 7: sham. Ovarian weight was significantly lower only in the ranibizumab group than in the OHS group. Estrogen levels were significantly lower in the GnRHA group than in the OHS and the treatment groups. Progesterone levels were significantly lower in the ranibizumab, cabergoline, and TL groups than in the OHS group. Among the treatment groups, corpus luteum counts were lower than in the OHS group. Corpus luteum counts were lowest in the tocilizumab groups. IL-6 intensity was lower in all treatment groups than in the OHS group. In the ranibizumab group IL-6 intensity was the lowest. The TL group did not significantly differ from the GnRHA and cabergoline groups regarding IL-6 expression. Ovarian VEGF expression was significantly lower in all treatment groups. For the TL, ranibizumab, and cabergoline groups VEGF intensity was similar. Tocilizumab may be a new strategy for preventing ovarian hyperstimulation syndrome by inhibition of IL-6.

Primary ovarian leiomyoma: A case report

Highlights • Primary ovarian leiomyoma is one of the rarest solid tumours of the ovary.• Many patients with ovarian leiomyomas are nulligravidas.• Differential diagnosis can be difficult from ovarian solid tumours.• The diffuse strong positive staining for SMA is characteristic of leiomyoma.• Unilateral and benign tumours can be treated with unilateral salpingo-oopherectomy.