RU 486 induced suppression of placental neutrophil elastase inhibitor levels

After administration of RU 486 to pregnant cynomolgus monkeys, placental morphology varied from normal to pathological. In all cases (n = 5) circulating and placental PAPP-A levels were markedly suppressed by 76.0 per cent and 55.5 per cent, respectively. When fetal demise occurred within 24 h prior to caesarian section, morphological changes consistent with an active inflammatory (polymorphonuclear leukocytosis) reaction was readily observed at the utero-placental interface, degrading the chorionic villi. Whereas heparin-Sepharose fractionated aqueous extracts of placentae inhibited human neutrophil (or granulocyte) elastase (HGE) activity, extracts of placenta being degraded by host phagocytic-proteolytic defense system were rich in HGE activity. This study establishes: (1) the cynomolgus monkey as a model for PAPP-A studies, (2) that haemochorially implanted placentae produce PAPP-A, a heparin-binding inhibitor of HGE, (3) that administration of progesterone receptor antagonist suppressed placental PAPP-A synthesis, and (4) disrupted protease-protease inhibitor equilibrium at the feto-maternal interface. Thus supporting a role for progesterone in placental PAPP-A production and maintenance of a placental barrier against maternal phagocytic-proteolytic defenses.