ENDOPLASMIC RETICULUM STRESS INDUCES AN INFLAMMATORY RESPONSE DURING DECIDUALIZATION: POTENTIAL REGULATION BY miR-17-5p, miR-21-5p AND miR-193b-3p

ELIZABETH SOCZEWSKI; JOSÉ MARTÍN MURRIETA-COXCA; PAULINA FUENTES-ZACARIAS; RUBY GUTIÉRREZ-SAMUDIO; LUCAS MIRANDA; ESTEBAN GRASSO; MARCELO MARTÍ; CLAUDIA PÉREZ LEIRÓS; DIANA MORALES-PRIETO; UDO MARKERT; ROSANNA RAMHORST

Mar del Plata

Congreso; REUNIÓN CONJUNTA SAIC SAI&FAIC SAFIS 2022; 2022

SAIC, SAIC, SAFIS

Considering that differentiation of endometrial stromal cells involves the induction of the endoplasmic Reticulum Stress (RS) and Unfolded Protein Response (UPR), here we identified and explored the contribution of miRNAs in the regulation of these processes. We used an in vitro model of decidualization based on the endometrial stromal cell line St-T1b, treated with 8-Br-cAMP during 5 days, or Thapsigargin (Tg, a RS-inducer). After decidualization St-T1b, increased the RS-sensors ATF6a, PERK and IRE1a, and the UPR marker CHOP, in comparison with non-decidualized cells (p<0.05,t-test). Moreover, thioredoxin-interacting protein (TXNIP), a link between the RS-pathway and inflammation increased in decidualized cells, and also the inflammasome NLRP3 and IL-1β expression (p<0.05, t-test). Then, by performing an in silico analysis using miR-Net 2.0 we identified three miRNAs able to regulate the RS/UPR pathways and the inflammation associated to embryo implantation: miR-17-5p, miR-21-5p and miR-193b-3p. The three miRNAs significantly decreased in non-decidualized cells in the presence of Tg.Finally, to validate the present results we used endometrial biopsies from patients with recurrent pregnancy loss (RPL) and recurrent implantation failures (RIF). Using in situ hybridization technique in endometrial samples we confirmed the localized of the three miRNAs in stromal and epithelial glandular cells in both group of patients. In fact, stromal cells from RPL patients displayed lower intensity in comparison with those from RIF patients indicating an alteration in the regulation of the RS/UPR processes. The key message is that decidualization is accompanied by the induction RS/UPR processes associated with a sterile inflammatory response to sustain embryo implantation. We identified novels miRNAs, miR-17-5p, miR-21-5p, and miR-193b-3p that might be involved in the regulation of these processes and are differentially expressed in endometrium from RPL and RIF patients