Effect of inhibition of prostaglandin synthesis on cervical softening and uterine activity during ovine parturition resulting from progesterone withdrawal induced by epostane

Abstract

The effects of an inhibitor of 3 beta-hydroxysteroid dehydrogenase (epostane) on uterine activity and cervical softening have been studied in eight sheep during late pregnancy. Treatment with epostane led to a rapid decline in the concentration of progesterone measured in utero-ovarian venous plasma, to less than 10% of the pretreatment value within 30 min of bolus injection. This was followed by a significant (P less than 0.02) increase in the concentrations of metabolites of prostaglandins E and F in utero-ovarian venous plasma and uterine activity similar to that seen in the final stages of normal labour. Measurements of cervical tissue extensibility made ex vivo showed the cervix to have softened considerably. These changes occurred without any significant change in the concentration of oestradiol-17 beta in utero-ovarian venous plasma. Infusion of mefenamic acid, an inhibitor of prostaglandin synthesis, prevented the changes in uterine activity and cervical softening that occurred after injection of epostane alone. Mefenamic acid also reduced the increase in concentrations of metabolites of prostaglandins E and F in plasma, although the concentration of progesterone in these animals showed the same abrupt fall which occurred in sheep after injection of epostane alone. These results suggest that progesterone withdrawal, in the absence of any subsequent rise in circulating oestrogen concentrations, is sufficient stimulus to induce cervical softening in the ewe. Cervical softening following progesterone withdrawal can be prevented by inhibition of prostaglandin synthesis.