INDUCTION OF PRETERM BIRTH IN MICE BY RU486

We hypothesized that treatment of pregnant mice with the progesterone receptor antagonist RU486 might cause preterm labor and result in the delivery of live pups. We also hypothesized that RU486 administration would alter prostaglandin production by decidual explants taken from t hese pregnancies. C3H/HeN females mated with C57Bl/6 males were inject ed with a single s.c. dose of RU486 on Days 12-14 of gestation. Three doses were tested (50 mu g, 150 mu g), and 250 mu g), and the mice wer e observed for evidence of delivery. The time course of delivery was d etermined in a second experiment using 150 mu g of RU486, and care was taken to observe the condition of the delivered pups. In a third expe riment, mice were killed when delivery commenced after injection with 150 mu g of RU486, and decidual explants were prepared. Controls that had received injections of vehicle were killed at the same time, and d ecidual explants were established. Media were removed after 24 h and a nalyzed for prostaglandin E(2) (PGE(2)) and prostaglandin F-2 alpha (P GF(2 alpha)) by RIA and for interleukin 6 (IL-6) by ELISA. Two of 3 mi ce given 50 mu g of RU486 delivered 16 pups prematurely. All 3 mice gi ven 150 mu g of RU486 delivered 22 pups prematurely, and 2 of 3 given 250 mu g of RU486 delivered 12 pups prematurely. Of mice treated with 150 mu g of RU486, none delivered within 12 h; 2 of 7 delivered within 15 h; and 6 of 7 delivered within 22 h. All pups appeared to be healt hy, with no evidence of placental infarction or death. PGE(2), PGF(2 a lpha), and IL-6 production by decidual explants was significantly grea ter in tissues taken from RU486-treated mice (n = 6) than in controls (n = 3). In summary, RU486 reliably induced preterm birth of the mice within 24 h after s.c. injection. This was associated with increased d ecidual prostaglandin and cytokine production and thus may mediate pre term labor. Inducing preterm birth with RU486 in a mouse model may be useful in investigations of the mechanism(s) of preterm labor.