Prevention of the retained fetal membrane syndrome (retained placenta) during induced calving in dairy cattle

Sixty-six dairy cattle were induced to calve with dexamethasone treatment at 5 d prior to expected time of calving. Each animal was assigned randomly to one of two treatments, saline (2 ml) or PGF(2)alpha (10 mg), which were administered within 1 h postpartum. With the saline treatment, 90.5 % of the animals had placental retention, whereas only 8.8 % of the PGF(2)alpha-treated animals had placental retention. The PGF(2)alpha-treated cows released the fetal membranes in 7.4 +/- 1.35 h postpartum, whereas the saline-treated cows released the membranes in 98.3 +/- 10.93 h postpartum. These data demonstrate that treatment with PGF(2)alpha within the immediate postpartum period is effective (P < 0.001) in the prevention of placental retention in the dairy cow induced to calve with dexamethasone.     

Opposite effects of glucocorticoid on estrogen-induced growth and differentiation of quail oviduct: demonstration by sequential treatments

Control of the development and functions of avian oviduct is monitored by four classes of steroid hormones, including glucocorticoids. The effects of dexamethasone (DEX), a synthetic glucocorticoid, were studied via sequential treatments with estradiol benzoate, paying special attention to changes in estrogenic oviduct responses involving DNA synthesis and cell proliferation, ovalbumin accumulation and cell differentiation. DEX exerted an antagonistic effect upon estrogen stimulation when administered separately before or after estradiol benzoate (EB). Given before EB, DEX was more strongly antagonistic for DNA synthesis than when given simultaneously with EB. Administered after EB, DEX reversed EB-induced cell proliferation: the DNA content declined and the oviduct regressed. In the same way, protein and ovalbumin synthesis was inhibited and delayed by first intervention of DEX, and accelerated catabolism of ovalbumin and proteins was observed when DEX followed EB. DEX, which was ineffective alone, but synergistic on ovalbumin synthesis when given concomitantly with EB, prevented or dissipated the estrogenic effects, cell proliferation and secretory process when administered in sequential treatments.     

Spontaneous and oxytocin-induced uterine motility in cyclic and postpartum mares

Intrauterine pressure was measured in three cyclic and two postpartum mares. Pressure was recorded using a catheter tip pressure transducer. The transducer was passed transcervically into the uterus.. In cyclic mares recordings were started on Day 1 of estrus and continued daily until ovulation as well as on Days 1 and 8 of diestrus. In postpartum mares recordings were started within 48 h after foaling and continued until the mares ovulated. The intrauterine pressure changes in postpartum mares was also recorded on Days 1 and 8 of diestrus. Spontaneous uterine contractions were recorded in cyclic mares for 30 min and in postpartum mares for 10 min. Induced uterine motilities were recorded for 30 min in both groups after the administration of oxytocin (40 USP, i.v.). Total area under the contraction curve in a 10-min period was used as a uterine motility quantitating unit. All mares demonstrated uterine contractions during estrus and diestrus. All mares demonstrated significant responses to oxytocin during estrus and diestrus. It appears that estrogen priming is not necessary for a significant uterine response to oxytocin.     

Luteinizing hormone response to estradiol benzoate in cows postpartum and cows with ovarian cysts

Twenty-seven dairy cows were evenly assigned to one of three groups and given an intramuscular injection of 2 mg estradiol benzoate. Cows in group 1 were greater than 30 days postpartum at treatment and had been diagnosed via rectal palpation to have ovarian cysts. Cows in groups 2 and 3 were 12 to 14 and 30 to 40 days postpartum, respectively. Blood plasma was collected from all cows before treatment and then every three hours for 36 hours post-treatment. Concentrations of LH, estradiol-17 beta and progesterone in plasma were determined by radioimmunoassay. Four, zero and five cows in groups 1, 2 and 3, respectively, had concentrations of progesterone greater than 1.0 ng/ml before estradiol benzoate treatment. None of these cows had a peak LH release greater than 5 ng/ml following estradiol benzoate treatment. The numbers of cows with progesterone concentrations less than 1 ng/ml that released LH (>5 ng/ml) in response to estradiol benzoate were 3 of 5, 3 of 9, and 4 of 4 for groups 1, 2, and 3, respectively; the proportion for group 3 was higher (P<.05) than for group 2. Of the cows that released LH, mean peak LH concentrations were 33.3+/-5.4, 14.8+/-7.2 and 24.6+/-9.8 ng/ml for groups 1, 2 and 3, respectively, and the duration of the LH increase was 8.0+/-1.0, 8.0+/-2.0 and 13.0+/-4.0 hours. The time from estradiol benzoate treatment to peak LH release for cows with ovarian cysts (25+/-2 hours) was delayed (P<.05) compared with that for cows 30 to 40 days postpartum without ovarian cysts (16+/-1 hour). In summary, responsiveness to estradiol benzoate is regained between 2 to 4 weeks postpartum in most cows. In addition, some cows with ovarian cysts can release LH in response to estradiol benzoate, but peak LH release is delayed compared to cows at a comparable stage postpartum without ovarian cysts.     

Characteristics of bovine early puerperal uterine contractility recorded under farm conditions

A non-invasive, digital technique was used to measure and quantify intrauterine pressure (IUP) changes in early postpartum dairy cows kept under farm conditions in order to document physiological changes in uterine contractility after uncomplicated calvings. In addition, possible relationships between characteristics of uterine contractility and blood ionized calcium (Ca(2+))-concentrations were investigated. Recordings of uterine contractility were made by using a transcervically inserted open tip catheter in 12 healthy cows during their first 48h after calving. The IUP recording technique appeared easily applicable under farm conditions. Although mean frequency (FREQ), amplitude (AMP) and area under the curve (AUC) of the myometrial contractions significantly decreased due to time, untreated early postpartum cows showed a high variability in characteristics of uterine contractility. There was no correlation between blood Ca2+ -concentrations and any of the contractility parameters.     

Uterine cyclic AMP formation: biphasic effect of estrogen on catecholamine sensitivity.

Female, ovariectomized rats were treated with estradiol and then, after various time periods, given an intravenous injection of isoproterenol or epinephrine. 30 seconds later uteri were frozen $\text{in}$$\text{situ}$ and assayed for cyclic AMP and glycogen phosphorylase. The cyclic AMP response to catecholamines was significantly depressed as early as 30 minutes after estrogen and at 6, 12 and 24 hours was 50% of that in non-estrogen-treated controls. Catecholamine-induced glycogen phosphorylase activation was unchanged until 24 hours after estrogen when it was significantly increased over controls. At 48 hours of estrogen both the cyclic AMP and phosphorylase responses to catecholamines were greater than controls. Estrogen regulates uterine β-adrenergic sensitivity but the time courses of estrogen effects on the cyclic AMP and glycogen phosphorylase response changes are different. Catecholamine-induced uterine cyclic AMP formation is biphasic: suppression during the first 24 hours of estrogen followed by recovery and finally augmentation by 48 hours. Catecholamine-induced glycogen phosphorylase activation shows only augmentation after 24–48 hours of estrogen. It is concluded that estrogen has independent effects on the β-adrenergic-glycogen phosphorylase activation pathway at two different points; one prior to cyclic AMP formation and another after cyclic AMP formation.     

Dexamethasone and estradiol benzoate induced parturition in dairy cattle

Fifteen 2-year-old Holstein cows and 21 mature Holstein cows were assigned to one of three groups. Cows in Group I calved spontaneously. Cows in Groups II and III received single intramuscular injections of 20 mg dexamethasone and 25 mg estradiol benzoate to induce parturition prematurely. In addition, cows in Group III received a single intramuscular injection of 12.5 mg estradiol benzoate 48 hr prior to dexamethasone and estradiol benzoate. The objective of the experiment was to determine the effectiveness of estradiol benzoate in combination with dexamethasone on traits at parturition and on productive and reproductive characteristics following parturition. Induction of parturition shortened gestation length and increased the incidence of retained placentas (both P < .01). All induced cows calved between 21 and 59 hr postinjection with less (P < .05) udder edema when compared to control cows. Mean plasma estrogen concentrations, using an assay system which does not measure estradiol benzoate, were not different among groups following injections of estradiol benzoate. Mean estradiol-17β concentrations in induced cows, however, using an assay system which does recognize estradiol benzoate (70.8% crossreactivity), were higher (P < .01) following estradiol benzoate injection, tended to be higher through parturition, and remained elevated (P < .01) at 12 and 24 hr following parturition when compared to cows calving spontaneously. Mean monthly milk production and the 2x, 305-ME records for milk, fat and FCM were not different among groups.     

Inhibition of postpartum uterine involution in the rat by relaxin

The possible contribution of relaxin to the support of uterine accommodation during late gestation by retarding tissue lysis was examined using the involuting postpartum uteri of unilaterally pregnant rats. In otherwise intact animals, twice-daily administration of 0.1 mg of relaxin (porcine fraction B) significantly retarded the regression of both gravid and, to a greater extent, nongravid tissue during the first 4 days postpartum, and collagenolysis was similarly delayed. Immediate postpartum ovariectomy had little effect on the uterus, although 5 micrograms estradiol benzoate daily suppressed uterine involution in the gravid tissue to about 50% and was even more effective in the nongravid uterus. Relaxin alone had little effect on the gravid uterus following ovariectomy, but augmented estrogen to the extent that less than half of the tissue and its collagen were lost during 4 days. The effect on nongravid tissue was even more striking in that the combination of estrogen and relaxin prevented any degradation of tissue in general or of collagen. Although we have reported that relaxin can stimulate uterine collagen synthesis as well as uterine growth, the magnitude of its postpartum effect in the presence of estrogen suggests a stabilizing or anticatabolic effect upon the uterus.     

The effect of intrauterine administration of estradiol on postpartum uterine involution in cattle

In cattle, the first postpartum dominant follicle has a predilection for the ovary contralateral to the previously gravid uterine horn. However, the presence of an estradiol-secreting dominant follicle in the ipsilateral ovary is a marker of subsequent fertility, possibly due to a localized effect of ovarian estradiol on uterine involution. The present study tested the hypothesis that estradiol increases the rate of uterine involution when administered into the previously gravid uterine horn around the expected time of selection of the first postpartum dominant follicle. Dairy cows were treated with 10 mg estradiol benzoate (n=15) or saline (n=14) administered through the cervix into the previously gravid uterine horn lumen on Days 7 and 10 postpartum. Uterine involution was monitored by daily transrectal ultrasonography and estimation of peripheral plasma concentrations of PGFM and acute phase proteins, while ovarian function was monitored by ultrasonography and measurement of plasma hormone concentrations. There was no effect of estradiol treatment on the diameter of the previously gravid or nongravid uterine horns, nor on the plasma concentrations of PGFM or acute phase proteins. However, cows in which the first postpartum dominant follicle ovulated during the study period had a smaller diameter of the previously gravid (P<0.01) or nongravid uterine horns (P<0.001) compared with cows in which the follicle regressed. Thus, our hypothesis was not proven, and the opposite pathway of utero-ovarian signaling may be more important during the postpartum period.     

Reduced incidence of retained placenta with induction of parturition in the cow

Two experiments were designed to determine whether pretreatment with Opticortenol (OPT), a long-acting corticosteroid, prior to induction of parturition with 25 mg of dexamethasone (DEX) alone or in combination with 500 mug cloprostenol (CLO) would result in a reduced incidence of retained placenta. In Experiment 1, 70% of the cows pretreated with 25 mg OPT on Day 270 of gestation calved before or within 24 hours of the scheduled induction treatment on Day 277. Cows induced to calve with DEX plus CLO without OPT pretreatment had an increased rate of placental retention (P<0.05), whereas, cows that received OPT were not different from the controls. In Experiment 2, cows received either 1 mg/25 kg OPT (high dosage) or 1 mg/50 kg OPT (low dosage) on Day 270 of gestation and were induced with DEX plus CLO on either Day 274 (4 days) or Day 276 (6 days). Cows claved 29.0 to 31.8 hours after induction treatment with 95% beginning to calve between 0700 and 1900 hours. The interval from calving to placental release and the incidence of retained placenta was not different between the high dosage 6-day group (29.4+/-8.2 hours, 29%) and the non-induced control cows (16.1+/-10.7 hours, 5%). When three cows in the high dosage 6-day group that retained their placentas for 30 to 36 hours were considered as not retained, the incidence of placental retention for that group was reduced still further to 17%. First service conception rates and pregnancy rates were lower in cows with retained placentas. Differences were significant (P<0.01) in Experiment 1 but not in Experiment 2. It was concluded that pretreatment with 1 mg/25 kg OPT 6 days prior to induction of parturition with DEX plus CLO in combination results in a predictable calving time, high calf viability, and a low incidence of placental retention.     

The effect of intravenously administered prostaglandin E2 on rat uterine 3′, 5′-adenosine monophosphate

PGE₂ administered intravenously increased levels of cyclic AMP in uterine tissue of rats ovariectomized 12 days before treatment. This action of PGE₂ on uterine tissue was dose-dependent, with a dose response curve from 50 to 600 μ/Kg and the maximum effect was seen 10 minutes after PGE₂ administration. Delay of prostaglandin treatment until 25 days post-ovariectomy prevented this response. Administration of estradiol benzoate to such animals however, allowed the rat uterus to respond with elevated cyclic AMP levels at 3 minutes but not at 10 or 45 minutes after PGE₂ treatment.     

GnRH induced LH release in suckled beef cows. II. The effects of exogenous corticoids and estradiol benzoate on luteinizing hormone release by GnRH

In Experiment 1, 24 suckled beef cows were assigned to 4 treatment groups (6 cows/group). Group I cows calved spontaneously. Parturition was induced in Groups 2, 3 and 4 with 20 mg dexamethasone (DEX) 8 to 12 days prior to expected calving date. Additionally, cows in Groups 3 and 4 received 8 mg triamcinalone acetonide (TA) 6 days prior to DEX treatment. Animals in Group 4 also received 10 mg estradiol benzoate (EB) with TA, and on alternate days until DEX, when 20 mg EB was given. Gonadotropin releasing hormone (GnRH, 100 mug) was given intramuscular (IM) to all cows on days 2 or 3 postpartum. Plasma LH increased (P< .05) following GnRH treatment in Groups 2, 3 and 4, but not in Group 1. LH release (area under the curve) following GnRH was greater (P< .05) for cows in Group 4 compared to cows in Groups 1, 2 or 3, and differences in LH release between Groups 1, 2 or 3 were not significant. In Experiment II, 36 mature Hereford cows were assigned to a 2 x 3 factorial experiment (6 cows/group). Groups 1 and 2, 3 and 5, and 4 and 6 received 0, 100, or 200 mug GnRH (IM) at 78 hr postpartum, respectively. In addition, cows in Groups 2, 5 and 6 received 5 mg EB at 36 hr postpartum. Plasma LH concentrations were not different (P <.05) among groups from 36 to 78 hr postpartum. A surge of LH in response to EB treatment was not detected at 54 to 62 hr (18 to 26 hr post EB), indicating a lack of response by the positive feedback mechanism at this early time postpartum. Mean plasma LH concentrations were elevated 78 to 82 hr postpartum for Groups 3 through 6. Treatment with EB at 36 hr caused a significantly greater (P< .05) response to GnRH with 200 mug of GnRH releasing more LH than 100 mug of GnRH.     

The use of dimenhydrinate in conjunction with dexamethasone for induction of parturition in beef cattle

Forty-eight crossbred Chianina cows (3 to 5 years of age), with an expected gestation length of 288 days, were randomly divided into four treatment groups to evaluate the use of dimenhydrinate (an antihistamine agent) in conjunction with dexamethasone (DEX) for inducing parturition in beef cattle. Group (A) received a 20 mg dose of DEX (im) on day 282 of gestation and a carrier vehicle (iv) 24 hours later (day 283); Group (B) was given a carrier vehicle (im) on day 282 and 500 mg of dimenhy-drinate (DMH) diluted in 200 ml of 2.5% dextrose-0.9% saline solution given (iv) on day 283 and Group (C) received 20 mg of DEX (im) on day 282 and 500 mg of DMH in solution (iv) on day 283 of gestation. The remaining 12 cows assigned to Group (D) were not handled and were allowed to calve under natural conditions. The number of cows calving and percent calving within 60 hours after the first injection were: 10(91%), none(0%) and 12(100%) for the DEX, DMH and DEX plus DMH groups, respectively. The mean gestation length of the control cows in Group (D) was 288.6 days. Frequency of dystocia was: 18.2, 8.3, 0 and 0% and retained placentae (>/=24 hours) was: 72.8, 16.6, 33.3 and 0% for DEX, DMH, DEX plus DMH and control groups, respectively. In this study, a 20 mg dose of DEX (im) followed 24 hours later with 500 mg of DMH (iv) was more successful for calving induction than when DEX or DMH was used alone. The combination DEX and DMH treatment induced calving in a shorter interval from treatment (P<.05) and decreased the incidence of retained placentae (P<.01) when compared with those induced following DEX treatment.     

Maturation of spontaneous and agonist-induced uterine contractions in the peripartum mouse uterus.

This study tested the hypothesis that the uterus achieves maximum contractile capabilities before the onset of labor. Basal and agonist-stimulated contractions were assessed in uterine strips on Day 15 or 18 of pregnancy, the day of parturition, or 1 day postpartum (n = 4-13 per group). Spontaneous contractions were evident in all groups (n = 4-13 per gestational group); contraction frequency was greater in peripartum groups than in virgin controls ( approximately 4.6 versus 2.8/200 sec). Peak amplitude was nearly 9-fold higher on Days 15 and 18 and over 30-fold higher in the postpartum and 1 day postpartum groups than in nonpregnant mice. Maximum frequency and peak amplitude were achieved in response to 10(-6) to 10(-8) M oxytocin or arginine vasopressin (OT(max) or AVP(max)). Frequency of contractions in response to OT(max) peaked on Day 18 and then declined. Contraction amplitude increased 5-fold on Day 15, declined on the day of birth (equivalent to nonpregnant level), then rebounded to peak on postpartum Day 1. AVP(max) similarly increased frequency and amplitude of contractions, except that maximum contraction amplitude occurred postpartum. Thus, an endogenous oscillator, residing in the uterus, sustains high basal and agonist-induced contraction frequency during pregnancy. Although acceleration of this pacemaker occurred before term, the data suggest that peripartum increases in contraction amplitude characterize the transition to the powerful synchronous contractions of parturition.     

Early induction of parturition and initiation of lactation in sheep

Dexamethasone and estradiol benzoate were used to induce parturition in ewes at about day 120 of gestation as part of a program to reduce the time taken to progeny-test carpet-wool rams by evaluating the birthcoats of their offspring. Ten ewes received 5 injections of 12 mg dexamethasone over 2.5 days commencing on day 117. Eight lambed 3.1 +/- 0.53 days after the final injection. Of 14 ewes which received 20 mg estradiol benzoate on day 118, three delivered lambs, 2.0 +/- 0.41 days after injection. All lambs were born dead or died within 2 hours of birth. Following parturition all ewes came into lactation. The dexamethasone group produced more colostrum, with higher total solids content than the estradiol group. However, the volume was less than in a control group which lambed at full term. It was concluded that dexamethasone could be used successfully to induce parturition at 120 days and that onset of lactation was similar to that which occurs at full term.     

Effect of 17-alpha-hydroxy-progesterone capronate on the motility of the human uterus in puerperium following abortion

The effects of 17alpha-hydroxyprogesterone capronate (17-OH-P) on spontaneous uterine motility and on oxytocin-induced uterine contraction during the postabortion period were studied in 22 women. The effects of 17-OH-P were present 8 hours after administration and still appreciable after 12 hours, but were considerably diminished after 24 and 48 hours. The efficiency of 17-OH-P in inhibiting uterine contraction after administration of oxytocin is clearly inferior to that of natural progesterone.     

Effect of corticoid induced parturition on lactation and on prepartum profiles of serum progesterone and the estrogens among cows retaining and not retaining fetal membranes

Twenty-one mature F1 Brahman-Hereford cows were treated with 25 mg of dexamethasone (DEX) on day 279 or 280 of gestation to induce birth prematurely. Eigth cows were untreated (UT). Blood was sampled on day 279 or 280 of gestation just prior to treatment of cows with DEX (0 hr), at least daily thereafter to calving and within 1 hr postpartum. Concentrations of progesterone (P₄), estrone (E₁) and estradiol-17β (Eβ) and -17α (Eα) in blood serum were measured by radioimmunoassay. Among 21 cows treated with DEX, 16 (76%) calved within 78 hr (52±3 hr). Eleven of the 16 cows retained fetal membranes more than 12 hr (RFM) and five cows did not retain fetal membranes (NRFM). Five cows (24%) treated with DEX calved 266±46 hr later (NOR) on day 290±1 of gestation compared to day 286±2 for cows in group UT. No cow in groups NOR or UT had RFM. Failure of group NOR to calve prematurely appeared due to elevated serum P₄ (P<.05), low serum Eβ (P<.10) and other estrogens (P>.10) pretreatment, and to only a 32% decrease in serum P₄ within 72 hr after treatment. Serum estrogens, especially Eβ, were next lowest pretreatment in group RFM. However, in group RFM, all serum estrogens increased (P<.10 to P<.01) within 48 hr after treatment, reached higher concentrations and peaked later in relation to calving than in other groups (NRFM, NOR and UT). Synchronization of placental maturation and parturition may require a longer period of elevated serum estrogens prior to calving than was observed in group RFM. Treatment of cows prepartum with DEX had no effect on gain of calves, milk yield or yields of fat, total protein and total solids in milk during the first 12 weeks of lactation.     

Endothelin and sarafotoxin: influence on steroid-regulated motility of rat uterus.

The sarafotoxins (SRTX) and endothelins (ET) were shown to influence the motility of the isolated rat uterus by inducing an increase in the rate and in the maximum tension of the spontaneous rhythmic contractions and a suppression of the relaxation phase of these contractions. Ovariectomized rats, 24 weeks post-operation, show no spontaneous motility of their uteri and the SRTX/ET peptides induce only a slight tonic increase in the uterine tension. Treatment with 17 beta estradiol restores spontaneous motility and sensitivity to the SRTX/ET peptides in all three contraction modes. It is concluded that the influence of the SRTXs and ETs on uterine motility depends on the hormonal status of the animal.     

Dexamethasone suppression of sexual behavior in the ovariectomized mare

The influence of steroids of adrenal cortical origin on estrous behavior in the ovariectomized mare was evaluated by adrenal suppression via dexamethasone (DEX) administration in two experiments. In Experiment I, 12 mares (six DEX, six control) were tested for sexual behavior in harem groups (two DEX and two control mares plus one stallion per group) for 9 consecutive days. In Experiment II, estradiol (E₂) was given to a group of DEX-treated mares as an additional control. Twelve mares (four DEX, four DEX + E₂, and four control) were tested in harem groups (one DEX, one DEX + E₂, and one control mare plus one stallion per group) for 10 days. All DEX mares showed a clear suppression of sexual response compared to control or DEX + E₂ mares, indicating that the estrous behavior seen in ovariectomized mares may be due to steroids from the adrenal cortex. The control and DEX + E₂ mares were similar in all measures of proceptivity. Despite being more receptive, as indicated by fewer negative responses, the DEX + E₂ mares received fewer intromissions and ejaculations than did the control animals. The ability of estradiol to induce estrous behavior in the dexamethasone-suppressed mare notwithstanding, other adrenal steroids, e.g., androgens, may be involved in estrous behavior in the untreated, ovariectomized mare.     

Estradiol effect on indomethacin and prostaglandin E2-modulation of adrenergic transmission in rabbit oviduct.

The effect of prostaglandin E2 /PGE2/ and indomethacin on 3H-noradrenaline (3H-NA) release- and on contractions-evoked by field electrical stimulation (FES) was studied in vitro in oviductal isthmus of mature rabbits (untreated and treated with estradiol). FES evoked guanethidine-sensitive contractions and calcium-dependent tritium overflow, which reflected 3H-NA overflow. Marked and concentration-dependent decrease of FES-evoked contractions by PGE2 (0.1-100 nM) was observed in both groups of animals. The inhibitory effect of PGE2 was more pronounced in estradiol treated animals (IC50 1.5 nM, n = 9) than in untreated animals (IC50 18 nM, n = 6). Indomethacin, 1 microM, induced a remarkably pronounced increase of FES-evoked contractions in estradiol treated (by 57.3 +/- 6.3%, n = 8) in comparison with untreated rabbits (21.4 +/- 3.8%, n = 7). The amount of FES-evoked release of tritium was significantly higher in untreated than in estradiol treated rabbits. PGE2 decreased and indomethacin increased tritium-evoked release. The effects of PGE2 and indomethacin on tritium-evoked release showed no estradiol dependence. The competitive results of PGE2 and indomethacin on both evoked contraction and 3H-NA release suggest that endogenous prostaglandin E2 takes part in modulation of adrenergic mediated contraction and that estradiol enhanced the prostaglandin effect.