NR4A2 and NR4A3 expression differ in immune cells from RSA patients compared to normal fertile women

CARLOS DE LA TORRE HERNANDEZ; ERIKA RUDI; JOSEFINA STAGNARO; ELOISA I. ARANA; PABLO M. FERNANDEZ

Cancun

Congreso; ALAI; 2018

ALAI

BackgroundSpontaneous abortion is the most common complication of early pregnancy. Recurrent Spontaneous Abortion (RSA) is defined as three consecutive losses within the first 20 weeks of gestation. The majority of these recurrent losses remain unexplained. NR4A orphan receptors function as ligand-independent transcription factors that regulate the expression of target genes. These receptors have been implicated in broader functions within the immune system cells. NR4A receptors may play a role in restraining or increasing the effects of immune system cells in embryo development and implantation.MethodsPeripheral blood mononuclear cells (PBMCs) were obtained from RSA patients and control groups. NR4A mRNA expression was determined by real-time PCR. NR4A protein expression was determined by flow cytometry. Statistical analysis was performed using GraphPad Prism 5 software. Groups were compared by Mann-Whitney test.ResultsSamples from PBMCs in RSA group showed significant lower mRNA expression levels of NR4A2 (p=0.0174) and NR4A3 (p=0.027) nuclear orphan receptors, when compared to normal fertile women. NR4A2 protein expression was significantly higher in PBMCs from RSA patients when compared to normal fertile women (p=0.0014) and this was also observed when analyzing independent immune cells subsets CD3+CD4+ (p=0.0025), CD3+CD8+ (p=0.0015), CD3-CD56+ (p=0.002) and CD3-CD14+ (p=0.002). Similar significant higher protein expression levels were observed for NR4A3 in PBMCs (p=0.0066), or CD3+CD4+ (p=0.0066), CD3+CD8+ (p=0.0088), CD3-CD56+ (p=0.0106) and CD3-CD14+ (p=0.0118) immune cells subsets. NR4A1 mRNA or protein expression showed no significant difference between the analyzed groups.ConclusionThese results strongly support our hypothesis that NR4A orphan nuclear receptors play a role in the immune regulation mechanisms contributing to a successful pregnancy, and point to NR4A2 and NR4A3 as the main NR4A subfamily receptors that would participate as immune restrictive factors for embryo implantation or development.