NR4A NUCLEAR ORPHAN RECEPTORS EXPRESSION DIFFER IN IMMUNE CELLS FROM URSA PATIENTS WHEN COMPARING LIVE BIRTH OUTCOMES

KAREN MIRA; PABLO FERNANDEZ

San Luis

Congreso; LXXI REUNIÓN CIENTÍFICA ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI); 2023

Spontaneous abortion is the mostcommon complication of early pregnancy in women. Recurrent Spontaneous Abortion (RSA) isdefined as three consecutive losses within the first 20 weeks of gestation. The majority of theserecurrent losses remain unexplained (URSA). The NR4A orphan receptors function as ligandindependent transcription factors that regulate the expression of target genes. These receptorshave been implicated in broader functions within the immune system cells. NR4A orphan nuclearreceptors may play a role in restraining or increasing the effects of immune system cells in embryodevelopment and implantation. Our goal is to unveil if these orphan receptors integrate thenumerous mechanisms of various origins responsible for the maternal tolerance towards theembryo/foetus, through their involvement in immune cell functions. We have previously reportedthat URSA patients show significant lower mRNA expression levels of NR4A2 and NR4A3 nuclearorphan receptors, when compared to control fertile women. Here we report a new retrospectivestudy analysing the mRNA expression levels in primary and secondary URSA patients, andcompared to their results in achieving a successful pregnancy up to two years after consultation,regardless any treatment or strategy they followed. NR4A mRNA expression levels weredetermined by real-time PCR in peripheral blood mononuclear cells (PBMCs), and women weredivided in two groups considering our medical records indicating successful pregnancies (Yes or Nolive-birth). Statistical analysis was performed using GraphPad Prism 5 software. Groups werecompared by MannWhitney test. The significance threshold was set at 0,05. When analysing thisoutcome, URSA women who reversed their condition had, at the time of consultation, significantlower mRNA expression levels of NR4A2 (p=0.0324) and NR4A3 (p=0.0162) compared to URSAwomen that did not reverse. Even if NR4A1 expression levels showed a similar tendency, thecomparison of the two groups for this nuclear orphan receptor levels did not result statisticalsignificant (p=0.0957). We also tested for NR4A expression levels differences between successfulpregnancies or not in unexplained infertility patients. In these comparisons, none of the nuclearorphan receptors resulted in differences statistically significant. Our results, obtained from PBMCs,strengthen our hypothesis that members of the NR4A subfamily, particularly NR4A2 and NR4A3,would participate as immune restrictive/promotive factors for embryo/foetus development inprimary and secondary URSA patients. These results point the NR4A transcription factor subfamilyas being involved in reversible pathways leading to RSA or live birth according to their expressionlevels and further encourage our efforts to extend the study in endometrial infiltrated immunecells.