Antiprogesterone, RU 486, Facilitates Parturition in Cattle*

Abstract

RU 486, a potent progesterone antagonist with high affinity for progesterone receptor, was used alone or in combination with relaxin in late pregnant cattle to determine its effect on induction of parturition. Cross-bred beef cattle were bred by artificial insemination. An indwelling cannula was inserted into a jugular vein on day 269 (expected term = day 283) for repeated blood sample collection. On day 277, the cattle were assigned randomly to three groups (n = 6 each): group 1 received RU 486 (2 mg/kg BW, im) at 0800 h on days 277 and 278; group 2 received the same RU 486 treatment plus 3000 U relaxin, injected sc at 0800 h on day 278; and group 3 served as controls and received vehicle injection. Parturition occurred 55 h after treatment in group 1 and 53 h after treatment in group 2 compared with 210 h in the controls (P less than 0.01). The calves from treated groups were vigorous at birth, and their birth weights (32 and 33 kg in groups 1 and 2) were less than those of control calves (38 kg; P less than 0.01). There was no incidence of difficult birth (dystocia) with RU 486 treatment compared with that in the controls. Placenta delivery averaged 6.5 h after birth in both RU 486-treated groups and did not differ from the control value (5 h). Plasma progesterone concentrations averaged 8.2 ng/ml during the pretreatment period for all animals. Progesterone started to decrease markedly by 1200 h on day 278, dropped to about 4 ng/ml by 2400 h that same day, and was at basal levels on day 279, the day of calving, in two hormone-treated groups. In sharp contrast, progesterone was maintained at about 6 ng/ml in placebo-treated controls during this period and did not decrease to basal levels until 2 days before parturition on day 286 (P less than 0.01). Peak RU 486 in plasma was 7.2 ng/ml after the first injection and 14.3 ng/ml after the second injection, and averaged 7.9 ng/ml on the day of induced calving (day 279). Peak relaxin was 4.1 ng/ml after hormone injection. The results indicate that RU 486 alone or combined with relaxin precisely controlled the time of parturition in cattle in late pregnancy. Such treatment can be used to facilitate parturition and increase survival rates of neonatal calves without detrimental effects of dystocia, retention of placenta, and delayed postpartum fertility.

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.…”

Use of the progesterone (P4) receptor antagonist aglepristone to characterize the role of P4 withdrawal for parturition and placental release in cows

“…Clinical observations indicated that dystocia was due to an insufficient myometrial activity and a poor widening of the posterior birth canal. In contrast to our study, no dystocia was observed after the induction of parturition in multiparous beef cows using mifepristone starting on day 277 (Li et al 1991), and the incidence was low in beef heifers (Dlamini et al 1995). The reason for this significant difference between these results is not clear but may be related to the time when antiprogestin treatment was started.…”

“…The prepartal course of body temperature in D272CAp cows clearly resembles features described for the phase preceding normal term characterized by a transient decrease of 0.4 8C (48-22 h; Birgel et al 1994) and the absence of diurnal variation (48-8 h; Lammoglia et al 1997). The time between the onset of antiprogestin treatment and birth (48.7G7.5 h) is in the same range as reported after the initiation of parturition using the similar type antiprogestin, mifepristone, on days 277 and 278 in beef cows (55G3 h; Li et al 1991) or beef heifers (43G7 h; Dlamini et al 1995).…”

Pregnancy, parturition, and lactation in hypophyseal stalk-transected beef heifers

“…Ovarian production of progesterone is required to maintain pregnancy in cattle; ovariectomy causes an abrupt drop in circulating progesterone levels with abortion occurring in most cases (Tanabe 1966, Estergreen et al 1967, Chew et al 1979. Furthermore, the antiprogestin, RU 486, causes an abrupt decrease in progesterone and precisely induces premature parturition in cattle (Li et al 1991b). Although PRL secretion in cattle is tonically inhibited by the hypothalamus and remains significantly greater during the first 14 days after HST than seen in SOC animals, circulating PRL concentration gradually drifts lower but remains seasonally regulated (Benoit et al 1989, Cho et al 1998.…”