Altered DNA methylation and Dnmt expression in obese uterus may cause implantation failure.

Obesity is defined by increased adipose tissue volume and has become a major risk factor for reproduction. Recent studies have revealed a substantial link between obesity and epigenetics. The epigenome is dynamically regulated mainly by DNA methylation. DNA methylation, which is controlled by DNA methyltransferases (Dnmts), has been widely studied because it is essential for imprinting and regulation of gene expression. In our previous study, we showed that the levels of Dnmt1, Dnmt3a and global DNA methylation was dramatically altered in the testis and ovary of high-fat diet (HFD)-induced obese mice. However, the effect of HFD on Dnmts and global DNA methylation in mouse uterus has not yet been demonstrated. Therefore, in the present study, we aimed to evaluate the effect of HFD on the level of Dnmt1, Dnmt3a, Dnmt3b, Dnmt3l and global DNA methylation in uterus. Our results showed that HFD significantly altered the levels of Dnmts and global DNA methylation in the uterus. The total expression of Dnmt1, Dnmt3a and Dnmt3b was significantly upregulated, while level of Dnmt3l and global DNA methylation were dramatically decreased (p < 0.05). Furthermore, we observed that the expression of Dnmt3b and Dnmt3l was significantly increased in endometrium including gland and epithelium (p < 0.05). Although Dnmt3b was the only protein whose expression significantly increased, the level of global DNA methylation and Dnmt3l significantly decreased in stroma and myometrium (p < 0.05). In conclusion, our results show for the first time that obesity dramatically alters global DNA methylation and expression of Dnmts, and decreased DNA methylation and Dnmt expression may cause abnormal gene expression, especially in the endometrium.

The Role of Cannabinoid-1 Receptor Ligands in the Ovalbumin-Induced Mouse Model of Allergic Asthma: Is It Related to Transient Receptor Potential Vanilloid-1 Channels?

Objectives: The aim of this study was to investigate the role of cannabinoid (CB1) receptors on airway inflammation and hypersensitivity in allergic asthma and the potential interactions with TRPV1 channels. Materials and Methods: BALB/c mice were sensitized and provoked with ovalbumin to create a model of allergic asthma. CB1 selective agonist arachidonoyl 2'-chloroethylamide (ACEA) was administered intraperitoneally at doses of 0.5, 3, and 5 mg/kg. Receptor antagonism studies were performed utilizing selective CB1 antagonists AM251 at a dose of 3 mg/kg. TRPV1 channel was selectively blocked by capsazepine at a dose of 2.5 mg/kg. Penh values were recorded in vivo by a whole-body plethysmograph under methacholine challenge. Inflammatory cell count was performed in bronchoalveolar lavage fluid (BALF). Serum levels of proinflammatory cytokines were measured by Enzyme-Linked ImmunoSorbent Assay (ELISA). Inflammation in the lung tissue was scored histopathologically. Statistical significance was determined using one-way analysis of variance or Kruskal-Wallis test and expressed as p<0.05. Results: In sensitized animals, provocation with inhaled ovalbumin increased Penh values, serum interleukin (IL)-4, IL-5, IL-13 levels, eosinophil, neutrophil, lymphocyte, macrophage counts in BALF, and inflammation in the lung tissue. ACEA applications did not significantly alter Penh values, BALF inflammatory cell levels, and histological changes related to inflammation in the lung tissue according to the disease group; however, only at a dose of 5 mg/kg, it reduced the levels of the inflammatory cytokine IL-4. AM251 decreased Penh values, eosinophil and neutrophil migration in BALF, and inflammation score of lung tissue compared with the disease group. Although BALF inflammatory cell levels and Penh values were higher in the AM251+ACEA group than in the AM251 group, the differences were insignificant. In the CPZ+ACEA group, Penh values were significantly higher, and serum IL-4 and IL-13 levels and BALF eosinophil counts were lower than that in the CPZ group. Conclusions: This study demonstrated an important role of the CB1 receptors in allergic asthma. CB1 antagonism reduced airway hyperresponsiveness and inflammation and showed immunomodulatory effects. The effect of the CB1 agonist ACEA on asthma does not appear to be related to TRPV1 channels.

Antioxidant supplementation may effect DNA methylation patterns, apoptosis, and ROS levels in developing mouse embryos.

This study was designed to address the question: does antioxidant-containing embryo culture media affect DNA methyltransferases, global DNA methylation, inner cell mass/trophoblast differentiation, intracellular reactive oxygen species (ROS) levels, and apoptosis? Mouse zygotes were cultured in embryo culture media containing MitoQ, N-acetyl-L-cysteine (NAC), acetyl-L-carnitine (ALC), α-lipoic acid (ALA), or the mixture of NAC + ALC + ALA (AO) until the blastocyst stage, whereas in vivo-developed blastocysts were used as control. Protein expression levels of Dnmt1, 3a, 3b, and 3l enzymes were analyzed by immunofluorescence and western blot, while global DNA methylation, apoptosis, and ROS levels were evaluated by immunofluorescence. NAC, ALC, and MitoQ significantly increased the levels of all Dnmts and global methylation. ALA significantly induced all Dnmts, whereas global methylation did not show any difference. NAC and mixture AO applications significantly induced Nanog levels, ALA and MitoQ increased Cdx2 levels, while the other groups were similar. ALA and MitoQ decreased while ALC increased the levels of intracellular ROS. This study illustrates that antioxidants, operating through distinct pathways, have varying impacts on DNA methylation levels and cell differentiation in mouse embryos. Further investigations are warranted to assess the implications of these alterations on the subsequent offspring.

Malignant fibrous histiocytoma in a patient presenting with urinary system symptoms

Summary Malignant fibrous histiocytoma is a rare tumor. It is most commonly seen in individuals between the fifth and seventh decades of life, in extremities, and less frequently in the retroperitoneum. Although its etiology is not clearly known, radiotherapy, chemical agents, previous history of surgery, trauma and fracture, and Hodgkin lymphoma have been blamed. Leiomyosarcoma, liposarcoma and rhabdomyosarcoma should be taken into account in differential diagnosis. It is seen on computed tomography as a mass lesion with irregular borders and density similar to that of the surrounding muscle tissue. Necrotic and hemorrhagic components in the mass are characterized as heterogeneous low density areas. Fluid-fluid levels can be detected by computed tomography and magnetic resonance imaging.

Prevalence of congenital toxoplasmosis among a series of Turkish women / Prevalencia de toxoplasmosis congénita en una serie de mujeres en Turquía

Background: Toxoplasma gondii infection during pregnancy causes congenital malformations. Pregnant women should be screened for this infection since it is preventable and treatable. Aim: To study the sero prevalence of Toxoplasma gondii infection among pregnant women living in lzmir, Turkey. Material and Methods: A blood sample was obtained from 4651 women aged between 15 and 45years, during their first trimester of pregnancy. IgM and IgG antibodies against Toxoplasma gondii were measured using an ELISA assay. Among women with both IgG and IgM antibodies positive, an IgG avidity test was performed, using a VIDAS kit. Results: IgG antibodies were positive in 1871 (39.9%) participants. Of these, 48 (2.5%) also had positive IgM antibodies. In 41 ofthese 48 women, the IgG avidity test was performed and only one woman had a low avidity. This woman was treated with Spiramycin. Her offspring had an intrauterine growth retardation and oligohydramnios. A chorioretinitis was diagnosed in the offspring of other woman with both antibodies positive. Conclusions: In this series, the prevalence of congenital toxoplasmosis was low. However, women with positive antibodies against Toxoplasma Gondii should be further studied and followed during their pregnancy.

Antecedentes: La infección por Toxoplasma gondii durante el embarazo causa malformaciones congénitas. Se debe efectuar serologíapara esta infección en mujeres embarazadas ya que es prevenible y tratable. Objetivo: Estudiar la seroprevalencia de infección por Toxoplasma gondii en mujeres embarazadas que viven en Esmirna, Turquía. Material y Métodos: Se obtuvo una muestra de sangre en 4.651 mujeres cuyas edades fluctuaban entre 15 y 45, años, durante su primer trimestre de embarazo. Los anticuerpos IgM e IgG en contra de Toxoplasma gondii se midieron por ELISA. En mujeres que tenían anticuerpos IgG e IgM positivos, un ensayo de avidez de IgG se efectuó utilizando el kit VIDAS. Resultados: Los anticuerpos IgG fueron positivos en 1.871 participantes (39,9%). De estas, 48 (2,5%) también tenían anticuerpos IgM positivos. En 41 de estas 48 mujeres, se efectuó el test de avidez y sólo una tenía una baja avidez. Esta mujer se trató con espiramicina y su producto de concepción tuvo un retardo de crecimiento intrauterino y un oligohidroamnios. Una corioretinitis se diagnosticó en el producto de concepción de otra mujer con ambos anticuerpos positivos. Conclusiones: La seroprevalencia de toxoplasmosis congénita en esta serie de pacientes fue baja, sin embargo, las mujeres con anticuerpos positivos deben ser tratadas y seguidas.