PO-OB22 : Impact of progesterone on mechanism of preterm premature rupture of membrane

Objective: The role of the TLR/NLR family of proteins in maintaining placental homeostasis and contribution of altered TLR/NLR signaling to pathological states such as chorioamnionitis and PPROM remain understudied. Only a few researchers have been reported about the role of progesterone and its mechanism related to fetal membrane weakening and PPROM. Therefore, this study aim to investigate roles and molecular mechanisms of progesterone in fetal membranes under basal condition and stimuli with TLR/NLR agonists. Methods: Fetal amniotic membranes were collected from uncomplicated pregnant women who had an elective cesarean at term prior to the onset of labor (n = 30). Human primary amnion epithelial cells (hAECs) were pretreated with/without medroxyprogesterone acetate (MPA, 10 or 50M) for 24 hours. After, TLRs/NLRs agonist alone or combination with MPA and agonist were treated under each of the following bacterial agonists: PDG for TLR2; MDP for Nod2. Expressions of TLRs/NLRs and their effects on pro-inflammatory cytokines in hAECs and effects of progesterone were evaluated with Quantitative real-time RT-PCR. Results: Expressions of TLR2 and Nod2 genes were increased with treatment of each specific agonist. Co-stimulation of progesterone decreased expressions of TLR2 and Nod2 genes. Stimulation of specific agonists for TLR2 and Nod2 increased expressions of IL-1 and IL-8 genes. Co-stimulation of each specific agonist and progesterone decreased expressions of IL-1 and IL-8 genes. Expressions of TLR2 genes were decreased by progesterone stimulation alone compared with no treatment, whereas expressions of Nod2 genes were not changed. Expressions of IL-1 and IL-8 genes in treatment of all agonists were not changed by progesterone stimulation alone compared with no treatment. Conclusion: This study demonstrate progesterone is protective against PPROM through anti-inflammatory action.