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.
Purified porcine relaxin (3,000 U/mg) was administered either into the cervical os or by intra-muscular injection to crossbred beef heifers beginning 4 days before expected parturition, in an attempt to elucidate the physiological roles of relaxin in cervical dilatation, the pelvic area, and parturition. Relaxin (3,000 U in a gel vehicle), when administered into the cervical os during late pregnancy, induced significant dilatation of the cervix 8 and 16 h later, as compared to vehicle-treated controls. This induced cervical dilatation did not cause premature parturition in relaxin-treated heifers and was similar to controls. Exogenous relaxin during late gestation elicited an increased growth rate of the pelvic area, as determined by sequential measurements of height and width of the pelvic canal. These results indicate that, before parturition, pelvic width increased more rapidly than pelvic height and that exogenous relaxin elicited a greater response in both parameters. Highly significant nocturnal elevations in concentrations of progesterone in peripheral blood serum occurred in vehicle-treated control heifers during late pregnancy. These nocturnal elevations in serum levels of progesterone were significantly reduced after 8 and 16 h of relaxin treatment in experimental animals as compared to control heifers. The mechanisms by which porcine relaxin reduces ovarian progesterone secretion in beef heifers remain undefined.
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