Different Expression Pattern of TIM-3 and Galectin-9 Molecules by Peripheral and Peritoneal Lymphocytes in Women with and without Endometriosis.

Endometriosis is a gynecological condition that is associated with chronic pelvic inflammation, pain, and infertility. Although substantial evidence supports that immunological alterations contribute to its pathogenesis and we previously posed a pivotal role of Galectin-9 (Gal-9) in this disorder, the involvement of the TIM-3/Gal-9 pathway in the development of endometriosis-associated immunological abnormalities is not yet known. In the present study, multicolor flow cytometry was used to compare the immunophenotype and cell surface expression of TIM-3 and Gal-9 molecules on peripheral blood (PB) and peritoneal fluid (PF) lymphocytes of women with and without endometriosis. We found an altered distribution of different lymphocyte subpopulations, a markedly decreased TIM-3 labeling on all T and NK subsets and a significantly increased Gal-9 positivity on peripheral CD4+ T and Treg cells of the affected cohort. Furthermore, a significantly increased TIM-3 expression on CD4+T-cells and elevated Gal-9 labeling on all T and NK subsets was also revealed in the PF of the examined patients. In conclusion, our results suggest a persistent activation and disturbed TIM-3/Gal-9-dependent regulatory function in endometriosis, which may be involved in the impaired immune surveillance mechanisms, promotes the survival of ectopic lesions, and aids the evolution of reproductive failures in endometriosis.

Levels of total antioxidant capacity and 8-hydroxy-2'-deoxyguanosine of serum and follicular fluid in women undergoing in vitro fertilization: focusing on endometriosis.

This study was designed to evaluate the levels of oxidative stress (OS) markers, total non-enzymatic antioxidant capacity (TAC) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the serum and follicular fluid (FF) of patients undergoing in vitro fertilization (IVF). The impact of these biomarkers on IVF outcome was also analysed. Samples were obtained from 61 patients (age: 36.40 ± 4.99 years; BMI: 22.54 ± 2.46; infertility: 3.7 ± 2.5 years [mean ± SD]) before and after controlled ovarian hyperstimulation (COH). Patients with and without endometriosis were also evaluated separately. TAC was quantified by enhanced chemiluminescence assay and 8-OHdG was measured by enzyme-linked immunosorbent assay. It was demonstrated that these biomarkers responded to COH differently. No relationship could be detected in their FF levels, although their cumulative serum levels were inversely related. Both FF TAC and FF 8-OHdG had a negative impact on the number of good quality embryos, but an effect of Serum TAC and 8-OHdG could not be observed. When women with and without endometriosis were evaluated separately, inconsistent results were obtained. However, women without endometriosis had higher levels of serum and FF TAC when they progressed to clinical pregnancy. Our findings support the notion that OS has an important contribution to the reproductive potential in IVF patients, the ideal biomarkers of outcome measures, however, need to be further explored.

Local upregulation of transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1 ion channels in rectosigmoid deep infiltrating endometriosis.

Transient Receptor Potential Vanilloid 1 (TRPV1) and Transient Receptor Potential Ankyrin 1 (TRPA1) expressed mainly by primary sensory neurons function as major nociceptive integrators. They are also present on the rat endometrium in an oestrogen-regulated manner. TRPV1 is upregulated in peritoneal and ovarian endometriosis patients, but there is no information about TRPA1 and their pathophysiological significances. In this study, patients undergoing laparoscopic surgery were investigated: severe dysmenorrhoea due to rectosigmoid deep infiltrating endometriosis ( n = 15), uterine fibroid-induced moderate dysmenorrhoea ( n = 7) and tubal infertility with no pain ( n = 6). TRPA1 and TRPV1 mRNA and protein expressions were determined by quantitative polymerase chain reaction and semi-quantitative immunohistochemistry from the endometrium samples taken by curettage. Results were correlated with the clinical characteristics including pain intensity. TRPA1 and TRPV1 receptors were expressed in the healthy human endometrium at mRNA and protein levels. Sparse, scattered cytoplasmic TRPA1 and TRPV1 immunopositivities were found in the stroma and epithelial layers. We detected upregulated mRNA levels in deep infiltrating endometriosis lesions, and TRPV1 gene expression was also elevated in autocontrol endometrium of deep infiltrating endometriosis patients. Histological scoring revealed significant TRPA1 and TRPV1 difference between deep infiltrating endometriosis stroma and epithelium, and in deep infiltrating endometriosis epithelium compared to control samples. Besides, we measured elevated stromal TRPV1 immunopositivity in deep infiltrating endometriosis. Stromal TRPA1 and TRPV1 immunoreactivities strongly correlated with dysmenorrhoea severity, as well TRPV1 expression on ectopic epithelial cells and macrophages with dyspareunia. Epithelial TRPA1 and stromal TRPV1 immunopositivity also positively correlated with dyschezia severity. We provide the first evidence for the presence of non-neuronal TRPA1 receptor in the healthy human endometrium and confirm the expression of TRPV1 channels. Their upregulations in rectosigmoid deep infiltrating endometriosis lesions and correlations with pain intensity suggest potential roles in pathophysiological mechanisms of the disease.