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Ureaplasma parvum  ( U .  parvum ) is gaining recognition as an important pathogen for chorioamnionitis and preterm premature rupture of membranes. We aimed to investigate the roles of progesterone (P4) and a novel progesterone receptor, progesterone receptor membrane component 1 (PGRMC1), in the response of fetal membranes to  U .  parvum . Fetal membrane cells (amnion, chorion and decidua) were isolated and confirmed to be free of  Mycoplasmataceae . Cells were treated with  U .  parvum  (5x10 6  CFU), and adherence was quantified by qPCR. Amnion and chorion cells were transfected with scrambled siRNA or validated PGRMC1 siRNA for 72h. Cells were then treated with  U .  parvum  for 4h with or without pretreatment with P4 (10 −7  M) or ethanol for 1h. Interleukin-8 (IL-8), matrix metalloproteinase 9 (MMP9) and cyclooxygenase (COX-2) mRNA expression were quantified by qRT-PCR. Culture medium was harvested and analyzed for IL-8 and prostaglandin (PGE 2 ) secretion by ELISA and MMP9 activity by zymography.  U .  parvum  had a mean adherence of 15.0±0.6%, 16.9± 3.7% and 4.7±0.3% in cultured amnion, chorion and decidua cells, respectively. Exposure to  U .  parvum  elicited significant inflammatory responses including induction of IL-8, COX-2, PGE2 and MMP9. A possible role of PGRMC1 was identified in the inhibition of  U .  parvum- stimulated COX-2 and MMP9 mRNA expression in chorion cells and MMP9 activity in amnion cells. On the other hand, it might enhance the  U .  parvum- stimulated IL-8 protein secretion in amnion cells. P4, mediated through PGRMC1, significantly inhibited  U .  Parvum -induced MMP9 mRNA and COX-2 mRNA expression in chorion cells. P4 appeared to attenuate  U .  parvum  induced IL-8 mRNA expression in chorion cells, but this P4 effect might not mediated through PGRMC1. In summary,  U .  parvum  preferentially adheres to and induces inflammatory responses in chorion and amnion cells. P4 and PGRMC1 appear to differentially modulate the inflammatory responses induced by  U .  parvum  among amnion and chorion cells.

plos one

The Role of Progesterone and a Novel Progesterone Receptor, Progesterone Receptor Membrane Component 1, in the Inflammatory Response of Fetal Membranes to Ureaplasma parvum Infection