Abstract
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 (5x106 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 (PGE2) 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.
Highlights
Preterm birth (PTB) and preterm premature rupture of membranes (PPROM) remain major public health problems worldwide [1]
The depletion of progesterone receptor membrane component 1 (PGRMC1) mRNA and protein by siRNA transfection from amnion and chorion cells was confirmed by quantitative PCR (qPCR) and Western blotting respectively (Fig 1B)
At the maximal multiplicity of infection (MOI), U. parvum had a mean adherence of 15.0±0.6% in cultured primary amnion cells and 16.9± 3.7% in cultured primary chorion cells
Summary
Preterm birth (PTB) and preterm premature rupture of membranes (PPROM) remain major public health problems worldwide [1]. The exact mechanisms of PTB and PPROM are not well understood, infection of the fetal membranes has been implicated as an early event in their pathogenesis [2,3,4]. Bacteria are present in the fetal membranes irrespective of gestational age, labor, or rupture status. Increasing evidence suggests that U. parvum is an important pathogen in pregnancy and is associated with PPROM, PTB, and chorioamnionitis. U. parvum is the most frequently isolated pathogen in the amniotic fluid of women who deliver preterm [12], and U. parvum colonization in neonates is inversely related to gestational age at delivery [13]. The most recent study of the human microbiota during pregnancy indicated that elevated vaginal Ureaplasma abundances were associated with PTB [14]. To date, the pathogenicity of U. parvum and host susceptibilities to U. parvum in fetal membranes are poorly understood [17]
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