FOXM1 is lower in human fetal membranes after spontaneous preterm labour and delivery

Spontaneous preterm birth is usually associated with infection, inflammation or both. Forkhead box (FOX) M1 (FOXM1), a member of the FOX family of transcription factors, has been associated with inflammation. The aim of this study was to determine whether FOXM1 regulates the expression and release of pro-labour mediators in human gestational tissues. FOXM1 mRNA and protein expression were determined in fetal membranes from women at (1) preterm no labour: Caesarean section with no labour and (2) preterm labour: after spontaneous labour and delivery. Primary amnion cells were utilised to investigate the effect of small interfering RNA (siRNA)-mediated gene silencing of FOXM1 on pro-labour mediators. Spontaneous preterm labour decreased FOXM1 gene and nuclear protein expression. FOXM1 silencing in primary amnion cells increased interleukin (IL)-1β-induced pro-inflammatory cytokines (IL-6 and IL-8 mRNA expression and secretion), cyclooxygenase (COX)-2 expression and subsequent prostaglandin (PG)E2 and PGF2α release as well as gene expression and secretion of the matrix-degrading enzyme matrix metalloproteinase 9 (MMP-9). In conclusion, spontaneous preterm labour is associated with decreased FOXM1 expression in fetal membranes.