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.

Effects on maternal and fetal steroid concentrations of induction of parturition in the sheep by inhibition of 3 -hydroxysteroid dehydrogenase

“…The rapid sustained drop in maternal plasma progesterone concentrations after epostane con¬ firmed previous observations with trilostane and epostane on pregnant sheep (Taylor et al, 1982;Jenkin & Thorburn, 1984;Ledger et al, 1985). This persistent inhibition of placental 3ß-HSD is difficult to explain and is in marked contrast to the action of epostane in two other species.…”

“…A feature of the rapid drop in circulating progesterone in this and earlier studies was the equally fast increase in maternal plasma PGFM concentration (Taylor et al, 1982;Jenkin & Thorburn, 1984;Ledger et al, 1985). This raises the question of whether a rise in oestrogen is in fact required for the induction of uterine PGF production in the sheep: a view which is widely held (Liggins et al, 1973; Thorburn & Challis, 1979).…”

Regulatory effect of steroid hormones and fetal tissues on expression of oxytocin receptor in the endometrium of late pregnant ewes

“…The present study and other reports on endometrial expiants of nonpregnant sheep and endometrial epithelial cultures of cows (Horn et (Vallet et al, 1990;Larcher et al, 1995;Wathes et al, 1996b (Breton et al, 1996) (Vallet et al, 1990;Wathes et al, 1996b (Ledger et al, 1985;Li et al, 1991) and similar experiments with RU486 in rats showed that treatment resulted in an increase in uterine oxytocin receptor expression (Fang et al, 1996(Fang et al, , 1997. In the present study, disruption of the progesterone-dominated environment for as little as 4 h was sufficient to remove the inhibitory effect of progesterone.…”

Prenatal maturation, the timing of birth and how it may be regulated in domestic animals

“…Cervical compliance is certainly affected by the maternal hormonal environment (Fitzpatrick, 1977). In the sheep a sudden drop in progesterone in the absence of any rise in oestrogen will induce cervical ripening within a few hours (Ledger, Webster, Anderson & Turnbull, 1985) while oestrogen alone will also elicit softening (Fitzpatrick & Dobson, 1981). That prostaglandins are the primary factors in cervical ripening is shown by the effectiveness of exogenous PGE and by the inhibitory action of PG synthetase inhibitors (Fitzpatrick & Dobson, 1981;Ledger, Ellwood & Taylor, 1983).…”