Fiorella Di Nicuolo1, Silvia D'Ippolito2,3, Roberta Castellani3, Esther Diana Rossi4, Valeria Masciullo3,5, Monia Specchia3, Marco Mariani6, Alfredo Pontecorvi1,7,8, Giovanni Scambia3,5, Nicoletta Di Simone2,3. 1. Paolo VI International Scientific Institute, Università Cattolica del Sacro Cuore, Roma, Italia. 2. U.O.C. di Ostetricia e Patologia Ostetrica, Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia. 3. Istituto di Clinica Ostetrica e Ginecologica, Università Cattolica del Sacro Cuore, Roma, Italia. 4. U.O.C. di Anatomia Patologica, Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia. 5. U.O.C. di Ginecologia Oncologica, Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia. 6. Istituto di Sanità Pubblica, Sezione di Igiene, Università Cattolica Del Sacro Cuore, Roma, Italia. 7. U.O.C di Endocrinologia e Diabetologia, Dipartimento di Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia. 8. Istituto di Patologia Medica, Università Cattolica del Sacro Cuore, Roma, Italia.
Abstract
PROBLEM: A significant increased expression/activation of one of the most well-characterized inflammasomes, the NAcht leucine-rich-repeat protein-3 (NALP-3), in the endometrium from idiopathic recurrent pregnancy loss women (RPL) has been previously found by our research group. We therefore, suggested this event as being one of the molecular mechanisms altering endometrial inflammatory status during early pregnancy. In the present research, we attempt to investigate whether molecules with anti-inflammatory activity, alpha-lipoic acid (ALA), and/or myoinositol affect the endometrial NALP-3 expression and activation. METHOD OF STUDY: Women with a history of idiopathic RPL (n = 30) were included in the study and compared to a control group (n = 15). Endometrial tissues were collected by hysteroscopy during the mid-luteal phase. RPL women underwent a three-month prescription of tablets containing ALA plus myoinositol (Sinopol® ). After treatment, hysteroscopic biopsies were repeated in RPL patients. Inflammasome expression was evaluated by immunohistochemical and Western blot analysis. NALP-3 activation was studied by quantifying the secretion of both caspase-1 and interleukin (IL)-1ß and IL-18 through ELISA. In ex vivo experiments, the effects of each molecule on endometrial inflammasome were studied. RESULTS: Sinopol® significantly reduced the RPL endometrial inflammasome expression and activation. ALA, but not myoinositol, significantly reduced the endometrial inflammasome expression and activity. CONCLUSION: Our data suggest a role for ALA on RPL inflammasome. Understanding the mechanisms involved in RPL and the observation that specific molecules are able to interfere with such complex at the endometrium might provide new rational design approaches to a personalized evaluation of endometrial status and, ultimately, a targeted medicine.
PROBLEM: A significant increased expression/activation of one of the most well-characterized inflammasomes, the NAcht leucine-rich-repeat protein-3 (NALP-3), in the endometrium from idiopathic recurrent pregnancy loss women (RPL) has been previously found by our research group. We therefore, suggested this event as being one of the molecular mechanisms altering endometrial inflammatory status during early pregnancy. In the present research, we attempt to investigate whether molecules with anti-inflammatory activity, alpha-lipoic acid (ALA), and/or myoinositol affect the endometrial NALP-3 expression and activation. METHOD OF STUDY: Women with a history of idiopathic RPL (n = 30) were included in the study and compared to a control group (n = 15). Endometrial tissues were collected by hysteroscopy during the mid-luteal phase. RPLwomen underwent a three-month prescription of tablets containing ALA plus myoinositol (Sinopol® ). After treatment, hysteroscopic biopsies were repeated in RPLpatients. Inflammasome expression was evaluated by immunohistochemical and Western blot analysis. NALP-3 activation was studied by quantifying the secretion of both caspase-1 and interleukin (IL)-1ß and IL-18 through ELISA. In ex vivo experiments, the effects of each molecule on endometrial inflammasome were studied. RESULTS:Sinopol® significantly reduced the RPL endometrial inflammasome expression and activation. ALA, but not myoinositol, significantly reduced the endometrial inflammasome expression and activity. CONCLUSION: Our data suggest a role for ALA on RPL inflammasome. Understanding the mechanisms involved in RPL and the observation that specific molecules are able to interfere with such complex at the endometrium might provide new rational design approaches to a personalized evaluation of endometrial status and, ultimately, a targeted medicine.
Authors: Fiorella Di Nicuolo; Roberta Castellani; Alessandra De Cicco Nardone; Greta Barbaro; Carmela Paciullo; Alfredo Pontecorvi; Giovanni Scambia; Nicoletta Di Simone Journal: Molecules Date: 2021-01-08 Impact factor: 4.411
Authors: Antonio Aversa; Sandro La Vignera; Rocco Rago; Alessandra Gambineri; Rossella E Nappi; Aldo E Calogero; Alberto Ferlin Journal: Front Endocrinol (Lausanne) Date: 2020-08-11 Impact factor: 5.555