RELEVANCE OF THE BLASTOCYST CONDITIONED MEDIA ON IMMUNOTOLERANCE: FOCUS ON THE CONTROL OF THE INFLAMMATORY RESPONSE.

ESTEBAN GRASSO; ELIZABETH SOCZEWSKI; DAIANA VOTA; LAURA FERNÁNDEZ; LUCILA GALLINO; CLAUDIA PÉREZ LEIRÓS; ROSANNA RAMHORST

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Congreso; LXIV REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI) LXI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC); 2016

SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI), SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC)

The decidualization of human endometrial cells involves changes in their secretome increasing the production of immunomodulatory mediators. It is associated with a sterile inflammatory response that should be later controlled to a tolerogenic microenvironment by maternal and bastocyst-derived factors. Here we focus on the production of immunomodulators during the decidualization process and we explored whether human Blastocyst Conditioned Media (BCM) could control the initial inflammatory response. As an in vitro model we used the Human endometrial stromal cell line (HESC) decidualized or not with medroxiprogesterone (10 -6 M)+dbcAMP (2,5 10 -3 M) during 8 days. We observed an increase in the production of IDO (indoloamine-2,3 di-oxigenase), CXCL8, CXCL12 and IL-1beta production (p<0.05 Studen T test) after the decidualization. Since IL-1beta can act as a ?double edge? mediator in early pregnancy, it is necessary for implantation but higher level display deleterious effects, we evaluated BCM effect on IL-1 production. BCM derived from human competent blastocyst reduced IL-1 intracellular production in decidualized cells, compared to BCM from blastocyst morphologically impaired. This effect was accompanied by decreased expression of ATF6 and PERK, two sensors of reticular stress, and TXNIP, a kinase/RNase associated with inflammasome activation by BCM and it was more pronounced with BCM derived from human competent blastocyst (p<0.05 Student t test). Finally, in an in vitro implantation model based on co-culture of blastocyst-like spheroids from trophoblast cells (BLS, from Swan-71 cell line) on decidualized-HESC cells, BLS were able to invade HESC decidualized monolayer and the BCM obtained from developmentally impaired blastocysts decreased their invasion index (p<0.05). In conclusion, the BCM might contribute to the cross-talk with decidualized cells controlling the inflammatory response and allowing blastocyst invasion accordingly with the blastocyst quality.