RU 486 mediated leukocytic inflammatory reaction at the utero-placental interface.
Placentae obtained from RU 486 treated cynomolgus monkeys, with successful pregnancy outcome, could not be distinguished, by microscopic or macroscopic examination, from normal placental morphology of untreated females. However, circulating PAPP-A levels were markedly depressed in RU 486 treated (114.8 +/- 13.1 IU/l) than in control animals (477.2 +/- 150 IU/l), suggesting compromised placental physiology. Microscopic examination of placental tissue obtained from animals with fetal demise, after RU 486 administration, revealed pathological changes. When fetal demise occurred recently (less than 24 h), active villus destruction by infiltrating polymorphonuclear leukocytes was readily observed. Whereas aqueous extracts of placentae, whether obtained by cesarean section or spontaneous delivery, inhibited neutrophil elastase (HGE) activity, extracts of placenta being degraded by host phagocytic-proteolytic defense system were rich in HGE activity. Thus suggesting that parturition was not mediated by leukocyte lysosomal proteases, such as HGE, and that hemochorrially implanted placentae produce PAPP-A, a specific inhibitor of HGE. Administration of RU 486 decreased placental PAPP-A production and secretion, culminating with a neutrophilic infiltration into placental intervillous blood spaces, destruction of villus structure and fetal demise.
Sinosich
M J
MJ
Wolf
J P
JP
Williams
R F
RF
Hodgen
G D
GD
D000818:Animals; D005260:Female; D007249:Inflammation / Q000473:pathology; D008431:Maternal-Fetal Exchange; D015735:Mifepristone / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D010920:Placenta / Q000033:anatomy & histology / Q000187:drug effects / Q000473:pathology*; D011247:Pregnancy; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism; D011374:Progesterone / Q000037:antagonists & inhibitors; D014599:Uterus / Q000033:anatomy & histology / Q000187:drug effects / Q000473:pathology*
D015735:Mifepristone; D011374:Progesterone; D011266:Pregnancy-Associated Plasma Protein-A