Effect of Inflammatory Signals on Progesterone Production at the Maternal-Fetal Interface

Introduction: In explant cultures of human fetal membranes (FM) granulocyte-macrophage-colony-stimulating-factor (GM-CSF) mediates the inflammation-induced FM weakening seen in preterm premature rupture (pPROM) and exogenous progesterone (P4) inhibits GM-CSF weakening. Here we report that induces P4 production within which then acts a paracrine manner to counteract GM-CSF-induced Methods: explants mounted Transwell inserts were cultured with control media increasing GM-CSF, RU486 (blocks action), or trilostane production). production, matrix metalloproteinase-2 (MMP-2) strength determined. Effects on abundance 3ß-hydroxysteroid dehydrogenase (3ßHSD) enzyme BeWo trophoblast cell line also Results: induced both cells concentration-dependent manner. increased 3βHSD protein cells. Incubation FMs RU486, trilostane, each caused Trilostane MMP-2. Exogenous repressed MMP-2 restored strength. Conclusion: by trophoblastic suggesting locally produced is factors weaken FM. Inhibition local action resulted concomitant induction maintains structural integrity. This reversed P4. These data are consistent negative-feedback system whereby mediator weakening, counteracts inhibiting its downstream resultant preservation