Induction of labor and cervical maturation using mifepristone (RU 486) in the late pregnant rat. Influence of a cyclooxygenase inhibitor (Diclofenac).
The mechanism of action of RU 486 (Mifepristone), an antiprogesterone compound, on labor induction and on cervical maturation, is still not well documented. We have investigated the effect of RU 486, alone and in association with a cyclooxygenase inhibitor (Diclofenac) on the induction of preterm delivery and on concomitant changes in the distribution of cervical glycosaminoglycans (GAGs) in pregnant Wistar rats: a control group (n = 18), a RU 486 treated group (n = 36), and a RU 486 and Diclofenac treated group (n = 15). The results of this study confirm the ability of this antiprogesterone treatment to induce preterm delivery in the rat. This effect was antagonized by cyclooxygenase inhibition, suggesting that the action of RU 486 on labor induction could be mediated by prostaglandins. The absence of an increase in plasma prostaglandin E2 (PGE2) levels in RU 486 treated animals could be explained by local uterine changes in prostaglandin concentrations. Mifepristone also induced some of the biochemical features of cervical maturation (i.e. increased hydration and hyaluronic acid concentration). This effect was not inhibited in Diclofenac treated animals suggesting that factors other than prostaglandins play a role in this phenomenon.
Cabrol
D
D
INSERM U 166, Paris, France.
Carbonne
B
B
Bienkiewicz
A
A
Dallot
E
E
Alj
A E
AE
Cedard
L
L
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D002584:Cervix Uteri / Q000187:drug effects*; D004008:Diclofenac / Q000494:pharmacology*; D015232:Dinoprostone / Q000097:blood*; D004588:Electrophoresis, Cellulose Acetate; D005260:Female; D006025:Glycosaminoglycans / Q000378:metabolism*; D007751:Labor, Induced; D007975:Leukotriene B4 / Q000097:blood*; D015735:Mifepristone / Q000494:pharmacology*; D011247:Pregnancy; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains
D001095:Arachidonic Acids; D006025:Glycosaminoglycans; D004008:Diclofenac; D007975:Leukotriene B4; D015735:Mifepristone; D015232:Dinoprostone