Effect of alpha‐lipoic acid and myoinositol on endometrial inflammasome from recurrent pregnancy loss women

Problem: A significant increased expression/activation of one of the most well‐char‐ acterized inflammasomes, the NAcht leucine‐rich‐repeat protein‐3 (NALP‐3), in the endometrium from idiopathic recurrent pregnancy loss women (RPL) has been previ‐ ously 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 ex‐ pression 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 expres‐ sion 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 de‐ sign approaches to a personalized evaluation of endometrial status and, ultimately, a targeted medicine.