Endometriosis is an inflammatory disease depending on estradiol, with TNF-α being one of the most representative cytokines involved in its pathogenesis. TNF-α acts through its bond to the TNFRp55 and TNFRp75 membrane receptors. The aim of this study was to analyze the effect of the TNFRp55 deficiency on the development of ectopic endometriotic-like lesions. Endometriosis was induced surgically in mice of the C57BL/6 strain, wild type (WT) and TNFRp55−/− (KO). After four weeks, the peritoneal fluid was collected and the lesions were counted, measured with a caliper, removed, weighed, fixed or kept at −80°C. We evaluated the cell proliferation by proliferating cell nuclear antigen (PCNA) immunohistochemistry and apoptosis by TUNEL technique in the ectopic lesions. MMP-2 and MMP-9 activities (factors involved in invasiveness) were measured by zymography in the peritoneal fluid; estradiol and progesterone levels were measured by radioimmunoassay in the lesions and in the peritoneal fluid. We found that in KO animals the mean number of lesions established per mouse, the lesion volume, weight and cell proliferation increased and apoptosis decreased. In addition, the activity of MMP-2 and the estradiol level increased, whereas the progesterone level was not significantly modified. In conclusion, the deficiency of TNFRp55 promoted the establishment and development of endometriosis through an increase in the lesion size and high levels of estradiol which correlate with an increase in the MMP-2 activity. This is evidence of the possible association of the deregulation of the TNFRp55 expression and the survival of the endometriotic tissue in ectopic sites.
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Sandra Vallcaneras, Federica Ghersa, Juan Bastón, María Belén Delsouc, Gabriela Meresman, and Marilina Casais
Antonella Rosario Ramona Cáceres, Fiorella Campo Verde Arboccó, María de los Ángeles Sanhueza, Daniela Alejandra Cardone, Graciela Beatriz Rodriguez, Marilina Casais, Adriana Soledad Vega Orozco, and Myriam Raquel Laconi
Neuroactive steroids can rapidly regulate multiple physiological functions on the central and peripheral nervous systems. The aims of the present study were to determine whether allopregnanolone (ALLO), administered in a low nanomolar and a high micromolar concentrations, can: a) induce changes in the ovarian progesterone (P4) and estradiol (E2) release, b) modify the ovarian mRNA expression of 3 β-HSD, 20 α-HSD and 3 α-HSD, c) modulate the ovarian expression of progesterone receptors A and B, α and β estrogenic receptors, LH receptor (LHR) and FSH receptor (FSHR). To further characterize ALLO peripheral actions, the effects were evaluated using a superior mesenteric ganglion-ovarian nervous plexus-ovary (SMG-ONP-O) and a denervated ovary (DO) systems. ALLO SMG administration increased P4 concentration in the incubation liquid, by decreasing ovarian 20α-HSD mRNA, it also increased ovarian 3α-HSOR mRNA expression. In addition, ALLO neural peripheral modulation induced an increase in the expression of ovarian LHR, PRA, PRB, and ERα. Direct ALLO administration to the DO decreased E2 and increased P4 concentration in the incubation liquid. The mRNA expression of 3β-HSD decreased, and 20α-HSD increased. Further, ALLO in the OD significantly changed ovarian FSHR, and PRA expression. This is the first evidence of ALLO direct effect on ovarian steroidogenesis. Our results provide important insights about how this neuroactive steroid interacts both with the PNS and the ovary, these findings might help devise some of the pleiotropic effects of neuroactive steroids on female reproduction. Moreover, ALLO modulation of ovarian physiology might help uncover novel treatment approaches for reproductive diseases.
