Search

Endometriosis is an estrogen-linked gynecological disease defined by the presence of endometrial tissue on extrauterine sites where it forms invasive lesions. Alterations in estrogenmediated cellular signaling seems to have an essential role in the pathogenesis of endometriosis. Higher estrogen receptor (ER)- levels and enhanced ER- activity were detected in endometriotic tissues. It is well known that ER- interacts with components of the cytoplasmic inflammasome-3 (NALP-3), the NALP-3 activation increases interleukin (IL)-1 and IL-18, enhancing cellular adhesion and proliferation. Otherwise, the inhibition of ER- activity suppresses the ectopic lesions growth. The present study aims to investigate the potential effect of -lipoic acid (ALA) on NALP-3 and ER- expression using a western blot analysis, NALP-3-induced cytokines production by ELISA, migration and invasion of immortalized epithelial (12Z) and stromal endometriotic cells (22B) using a 3D culture invasion assay, and matrix-metalloprotease (MMPs) activity using gelatin zymography. ALA significantly reduces ER-, NALP-3 protein expression/activity and the secretion of IL-1 and IL-18 in both 12Z and 22B cells. ALA treatment reduces cellular adhesion and invasion via a lower expression of adhesion molecules and MMPs activities. These results provide convincing evidence that ALA might inhibit endometriosis progression.

Background: Pinopode expression has been suggested as a marker of endometrial receptivity. Methods: We set up an experimental study comparing endometrial tissue from recurrent pregnancy loss (RPL, n = 30) and fertile control (CTR, n = 20) women in terms of pinopode expression/morphology; expression of thrombomodulin (TM) and ezrin; cytoskeletal organization. Endometrial samples were collected during implantation window and evaluated by scanning electron microscopy, western blot, and immunofluorescence. Results: We found that RPL endometrial tissue showed: (i) increased pinopodes density (* p < 0.05); (ii) a reduced diameter of pinopodes (* p < 0.05); (iii) a decreased TM and ezrin expression (p < 0.05). Additionally, confocal images showed a significantly reduced expression of phosphorylated (p)-ezrin, confirming the results obtained through immunoblot analysis. Immunofluorescence staining showed that in CTR samples, junctions between cells are intact and clearly visible, whereas actin filaments appear completely lost in RPL endometrial samples; this suggests that, due to the impaired expression and activity of TM and ezrin, actin does not bind to plasma membrane in order to orchestrate the cytoskeletal actin filaments. Conclusions: Our findings suggest that an impaired expression of TM and expression/activation of ezrin may aect the connection between the TM and actin cytoskeleton, impairing the organization of cytoskeleton and, eventually, the adequate pinopode development.

Celiac disease (CD) is an autoimmune disorder that occurs in genetically predisposed people in which the ingestion of gluten leads to damage in the small intestine that clinically presents with malabsorption-related symptoms. CD can also be the underlying cause of several nongastrointestinal symptoms. This review summarizes evidence on the relationship between CD and gynecological/obstetric disorders like reproductive failures. Although much has been reported on such a linkage, the pathogenic mechanisms remain unclear, especially those underlying extra-gastrointestinal clinical manifestations. Studies conducted on celiac subjects presenting gynecological/obstetric disorders have pointed to intestinal malabsorption, coagulation alterations, immune-mediated tissue damage, and endometrial inflammation as the main responsible pathogenic mechanisms. Currently, however, the knowledge of such mechanisms is insufficient, and further studies are needed to gain a more thorough understanding of the matter.

OBJECTIVE: To investigate whether miscarried embryo/fetal crown rump length (CRL) measurement may yield a practical application for predicting a conclusive result at the cytogenetic analysis of miscarriage tissue. Our study might help in improving the cytogenetic method, the results of which may be affected by maternal cell contamination (MCC). In particular, we aimed at establishing whether the miscarried embryo/fetal CRL measurement shows accuracy in predicting the possibility of MCC and the scan cut-off value useful to this purpose and, as a result, suggest a multi-step procedure for the genetic ascertainment. METHODS: Women experiencing at least two miscarriages of less than 20 weeks size at the Pregnancy Loss Unit at Fondazione Policlinico A. Gemelli underwent a scan before surgery. The CRL value was recorded. After the dilatation and courettage (D&C) procedure, miscarriage tissue was processed through the proposed multi-step procedure before performing oligo-nucleotide-based and SNP (single nucleotide polymorphisms)-based comparative genomic hybridization (CGH+SNP) microarray analysis. RESULTS: 63 women and 63 miscarriages met the criteria. By using the Receiving Operator Characteristic (ROC) curves, CRL showed an AUC of 0.816 (95%CI:0.703-0.928,p<0.001). A CRL≥24.5 mm cut-off value showed a higher positive likelihood ratio (5.27) but, conversely, a higher negative likelihood ratio (0.64) in predicting the possibility of MCC. Microarray analysis was successful in the totality of cases in which the embryo/fetal origin of miscarriage tissues was proven. CONCLUSIONS: The 24.5 mm CRL value emerges as the most suitable cut-off enabling the identification of cases in which the embryo-fetal component can be isolated in the absence of MCC and the chromosomal array provide informative results