Effect of spontaneous term labour on the expression of the NR4A receptors nuclear receptor related 1 protein (Nurr1), neuron-derived clone 77 (Nur77) and neuron-derived orphan receptor 1 (NOR1) in human fetal membranes and myometrium

Inflammation has been implicated in the mechanisms responsible for human labour. Emerging evidence indicates that nuclear receptor subfamily 4A (NR4A) receptors regulate the transcription of genes involved in inflammation. The aim of the present study was to determine the effect of spontaneous term labour, Toll-like receptor (TLR) ligands and nucleotide-binding oligomerisation domain-containing (NOD) ligands on the expression of nuclear receptor related 1 protein (Nurr1), neuron-derived clone 77 (Nur77) and neuron-derived orphan receptor 1 (NOR1) in human fetal membranes and myometrium. Human fetal membranes and myometrium were collected from term non-labouring women and women after spontaneous labour onset. Tissue explants were used to determine the effect of the bacterial products lipopolysaccharide (LPS; TLR4 ligand), flagellin (TLR5 ligand), fibroblast-stimulating lipopeptide (FSL-1) (TLR2 ligand), γ-D-glutamyl-meso-diaminopimelic acid (iE-DAP) (NOD1 ligand) or minimal peptidoglycan muramyl dipeptide (MDP; NOD2 ligand) on Nurr1, Nur77 and NOR1 expression. Term labour was associated with significantly higher Nurr1 and Nur77, but not NOR1, expression in fetal membranes and myometrium. LPS and MDP increased Nurr1, Nur77 and NOR in fetal membranes; flagellin increased Nurr1 in fetal membranes and the myometrium, as well as NOR1 in the myometrium; and FSL-1 increased Nurr1 expression in fetal membranes. In summary, human labour and bacterial products increase Nurr1, Nur77 and/or NOR1 expression in human fetal membranes and myometrium. This increase in NR4A receptors may contribute to the expression of proinflammatory and pro-labour genes associated with fetal membrane rupture and myometrial contractions.