The objective of this study was to determine the effect of exogenous progesterone administration at ovulation and during the early development of the CL, on its future sensitivity to a single administration of PGF2a in mares and cows. Horse Retrospective reproductive data from an equine clinic in the UK during three breeding seasons were used. Mares were divided into: control group, cycles with single ovulations; double ovulation group cycles with asynchronous double ovulations; and PRID group: cycles with single ovulations and treatment with intravaginal progesterone device (CIDR) immediately after the ovulation. All mares were treated with d-cloprostenol (PGF) at either: (i) 88 hr; (ii) 96 hr; (iii) 104 hr; or (iv) 112 hr after the last ovulation. Cattle A total of nine non-lactating Holstein cows were used. All cows were administered PGF14 d apart and allocated to one of two groups control group GnRH was administered 56 hr after the second PGF administration. CIDR group CIDR was inserted at the same time of GnRH administration. All cows were administered PGF at 120 hr post-ovulation. The complete luteolysis rate of mares with double ovulation (66.7%) and those treated with exogenous progesterone (68.4%) was significantly higher than the rate of mares with single ovulation (35.6%) at 104 hr. In the cow, however, the treatment with CIDR did not increase the luteolytic response in cows treated at 120 hr post-ovulation. In conclusion, the degree of complete luteolysis can be influenced by increasing the concentration of progesterone during the early luteal development in mares.

A luteolytic dose (500 micrograms) of cloprostenol was given four days before expected estrus to five mature cyclic cows of native Taiwan Yellow cattle. Blood samples were collected at hourly intervals for 60 hours and then twice daily (0800 h and 1600 h) until onset of the following estrus or Day 29 after prostaglandin (PG) injection. Plasma progesterone levels were quite low in the follicular phase and elevated over an 11-13 day period during the luteal phase for every animal. Two cows showed peak luteinizing hormone (LH) levels of 19.97 and 23.77 ng/ml of plasma at 120 and 127 h after PG injection. One cow did not show peak LH level during the 60-h sampling period, but had its highest concentration of 18.02 ng/ml at 0800 h on Day 8. Two cows showed no detectable peak LH during the 60-h sampling period or on subsequent days. But these two cows had increased concentrations of progesterone beginning on Day 6 and Day 12. All animals came back into estrus 23-28 days after PG treatment.

OBJECTIVE

To evaluate the efficacy of a programme using oestradiol benzoate, progesterone and the prostaglandin-F2 (PG) analogue, cloprostenol, to synchronise oestrus and ovulation in dairy cows, compared with a programme using a gonadotropinreleasing hormone (GnRH) agonist, buserelin, and cloprostenol.

METHODS

Twenty non-lactating dairy cows, at random stages of the oestrus cycle, were randomly assigned to 1 of 2 treatments. In Treatment 1 ( OPPG; n=10), cows were injected with 2 mg oestradiol benzoate intramuscularly (IM) plus 200 mg progesterone subcutaneously (SC) on Day 0, followed by 500 microg cloprostenol IM on Day 9 and 1 mg oestradiol benzoate on Day 10. In Treatment 2 (GPG; n=10), cows were injected with 10 microg buserelin IM on Day 0, 500 microg cloprostenol IM on Day 7 and 10 microg buserelin on Day 9. The ovaries of all cows were examined by ultrasonography, using an 8 MHz probe, from 5 days before the initial treatment until ovulation. Cows were observed for oestrus 3 times daily for 7 days after cloprostenol treatment. Blood samples were collected daily for determination of progesterone, and 6-hourly for 36 h after the second oestradiol or buserelin injection for the determination of follicle stimulating hormone (FSH) and luteinising hormone (LH) concentrations.

RESULTS

The percentage of cows observed in oestrus was higher in the OPPG group than in the GPG group (100% vs 55.6%, p=0.018). Treatment with either short-acting progesterone plus oestradiol benzoate or buserelin was followed by atresia or ovulation of the dominant follicle. Emergence of a new follicular wave occurred earlier (p>0.001) in the GPG group (2.2+/-0.2 days) than in the OPPG group (3.6+/-0.2 days). There was no significant difference between treatment groups in the variation of time of follicular wave emergence or size of the largest follicles at either the time of initial treatment (10.8+/-1.4 mm vs 11.1+/-0.8 mm), cloprostenol treatment (13.8+/-0.7 mm vs 14.0+/-1.3 mm) or of ovulation (15.4+/-0.7 mm vs 17.6+/-1.1 mm; p=0.10). The LH surge occurred sooner after the second injection of buserelin (4.0+/-1.0 h) than after the second injection of oestradiol benzoate (22.8+/-1.2 h; p>0.001). The interval between the second injection of oestradiol benzoate or buserelin and ovulation did not differ significantly between treatment groups (1.7+/-0.3 days vs 1.6+/-0.2 days; p=0.69).

CONCLUSIONS

The use of short-term progesterone treatment, combined with oestradiol benzoate for follicular wave synchronisation, and cloprostenol to cause lysis of residual luteal tissue, is a promising alternative to established methods of oestrus synchronisation in cows.

We conducted a progesterone-based timed AI protocol after follicular fluid aspiration using the ovum pick-up (OPU) technique to examine its applicability to the suckled beef cow. A total of 19 beef cows were randomly allocated to one of the following three groups based on the number of days postpartum: 13 to 60 days (Group A: suckled; early postpartum period, n=9), 61 to 150 days (Group B: suckled; mid postpartum period, n=6), or 151 to 281 days (Group C: non-suckled; prolonged open period, n=4) postpartum. These cows were treated with follicular fluid aspiration and insertion of a progesterone-releasing intravaginal device (PRID) on day 0. The PRID was removed and 500 microg of cloprostenol was intramuscularly administered on day 7. A dose (100 microg) of fertirelin acetate was injected intramuscularly 48 hours later, and this was followed by a timed AI (TAI) after another 18 hours (day 10). Serum samples were taken on days 0, 7, 9, 10, 12, 17, 24 and 31 for determination of the estradiol-17beta (E(2)) and progesterone concentrations. Pregnancy diagnosis was made by rectal palpation approximately 60 days after TAI. There was no significant difference in the peripheral E(2) concentrations among the three groups during the period of the hormonal treatment. The average progesterone concentrations in Group A on day 17 were significantly higher than those in Group B and exceeded 1.0 ng/ml on day 17 and thereafter. There was no significant difference in the numbers of collected immature oocytes among the three groups. The pregnancy rates in Groups A, B, and C were 77.8% (7/9), 83.3% (5/6) and 50.0% (2/4), respectively. In conclusion, this timed AI protocol is applicable to suckled beef cows within the period of 60 days postpartum.

Concentrations of progesterone before AI have had variable effects on fertility in both Bos indicus and Bos taurus cattle. The aim of this study was to determine if fertility and concentrations of progesterone after AI were affected in Bos indicus females when pre-ovulatory follicles develop in the absence or presence of a corpus luteum (CL). Between 6.5-7.5 days after a synchronised oestrus, all follicles ≥4 mm in diameter were aspirated (Day 0) and cloprostenol was administered on Days 0 and 1 (LP4, n = 36) or on Days 4 and 5 (HP4, n = 40). Animals were inseminated on detection of oestrus until Day 9. Breeding continued using natural mating between Days 9 and 19, AI on detection of oestrus between Day 19 and 29 and natural mating between Days 29-90. Mean concentrations of progesterone were less on Days 2-4 in the LP4 compared to the HP4-treated animals but similar on Days 14 and 20. In the LP4- compared to the HP4-treated animals, the odds of being detected in oestrus and ovulating close to the first AI were similar, but odds of pregnancy to first AI (OR = 0.19, 95% CI 0.07 - 0.52) and after 1, 4 and 13 weeks of breeding were less (P ≤ 0.051). Absence of a CL and relatively lesser concentrations of progesterone during emergence of pre-ovulatory follicles resulted in lesser pregnancy rates to AI in Bos indicus cattle but did not affect concentrations of P4 after ovulation.

Superluteinized rats were injected with the prostaglandin F2 alpha (PGF2 alpha) analogue cloprostenol to induce luteolysis. The treatment decreased progesterone production of ovarian homogenates from 8.9 +/- 0.5 to 4.0 +/- 0.7 nmol/ovary/10 min (mean +/- SEM) within 40 min. tochondrial fractions isolated from control and cloprostenol treated animals produced 4.7 +/- 0.4 and 2.8 +/- 0.3 nmol progesterone/ovary/10 min, respectively. Thus, the PGF2 alpha analogue treatment significantly reduced mitochondrial progesterone production. Addition of the 15 000 X g supernatant fraction did not influence the progesterone production rates of the mitochondrial fraction. The basal progesterone secretion from quartered ovaries decreased from 1.50 +/- 0.15 to 0.38 +/- 0.05 nmol/ovary during the initial 15 min of incubation following cloprostenol administration. hCG and N6,O2'-dibutyryladenosine 3':5'-cyclic monophosphate (DBC) stimulated the progesterone secretion from quartered ovaries, but the response was delayed in ovaries obtained from cloprostenol treated animals. Although the response was delayed, the progesterone secretion following cloprostenol treatment was re-activated with cAMP either directly or via hCG. The increment in progesterone secretion above unstimulated controls in response to DBC was not influenced by the cloprostenol treatment while the increment caused by hCG was decreased. Our data suggest that: 1) PGF2 alpha deactivates mitochondrial progesterone production, 2) this deactivation may be overcome by cAMP, and 3) PGF2 alpha decreases gonadotrophin responsive adenylyl cyclase.

Daily changes in the plasma progesterone concentrations were determined in eight mares treated with intramuscular injections of 250 mug cloprostenol, a prostaglandin analogue, followed five days later by 2500 I.U. human chorionic gonadotropin. A second cloprostenol injection was given 14 days after the first; the mares were then inseminated on the third and fifth day of the subsequent estrus and a second injection of human chorionic gonadotropin was administered on the fifth day. The onset of estrus following the second cloprostenol treatment was synchronized beginning three to four days after treatment in all eight mares. All eight ovulated, five mares conceived and only four foaled. Evaluation of the progesterone profiles provided reliable indicators of luteolysis, ovulation and luteal function. Decreasing plasma progesterone concentrations were associated with cloprostenol induced luteolysis or preceded spontaneous onset of estrus. The plasma progesterone concentrations increased consistently after ovulation, and in the pregnant mares, the progesterone concentrations remained high during the first month after insemination.

An experiment was conducted to test the hypothesis that the adrenal gland influences luteal activity in sheep. Twelve Finnish Landrace x Southdown ewes were either bilaterally adrenalectomized (n = 6) or sham adrenalectomized (n = 6) during the breeding season. At approximately 37 and 47 d after surgery, all ewes received intramuscular injections of cloprostenol to synchronize estrus. Blood samples were taken via jugular venipuncture at 48-h intervals between 1 and 19 d after the last cloprostenol treatment. Serum concentrations of progesterone were determined in each of these samples. Analysis of variance showed that concentrations of progesterone during the luteal phase were lower (P<0.05) in adrenalectomized ewes than in sham-operated controls, but that patterns of progesterone were similar for both groups of sheep. Based on these results, we conclude that the adrenal gland does not appear to be necessary for initiation of luteal regression in ewes.

Twenty-eight pluriparous and non-lactating Santa Inês sheep were synchronized with vaginal sponge and an intramuscular (IM) injection of 37.5 μg of cloprostenol on random days of the estrous cycle (D0); day 6 (D6), at 7:00 am, the devices were removed, and after 24 h (D7), GnRH analog (25 μg of lecirelin) was administrated. Fixed-time artificial insemination (FTAI) with cervical traction by the transcervical route was performed 52 to 58 h after sponge removal. Doppler velocimetry of both uterine arteries was performed on D0, D2, D4, and the morning of D6 (every 48 h), and then every 12 h from D6 to D8 (7:00 a.m. and 7:00 p.m.). We analyzed the peak systolic velocity (PSV), end-diastolic velocity (EVD), time-averaged maximum and mean velocity (TAMAX, TAMEAN), pulsatility index (PI), resistance index (RI), systolic/diastolic ratio (S/D), arterial diameter (AD), and blood flow volume (BFV), with the objective of evaluating the hemodynamic behavior of blood flow velocity parameters of the uterine artery during a short-term progesterone synchronization protocol in ewes. With respect to phases, we noted increases in the means of TAMAX and TAMEAN and decreases of EDV, PI, and RI (P < 0.05). S/D, EDV, TAMEAN, PI, RI, SD, AD, and BFV showed differences between the time of progesterone insertion and the estimated time of ovulation (which was considered the last evaluation) (P < 0.05). The PI and RI values were different when comparing the times of insertion and withdrawal of the progesterone device (PI 2.53-1.54 and RI 0.76-0.68) (P < 0.05). The PI was different with respect to side (P < 0.001), but no side effect was seen in the RI. In conclusion, the two uterine arteries behave differently under the effect of progesterone (intravaginal sponges) and the effect of estradiol during the follicular phase, and estrous phase was responsible for increasing uterine blood flow.

Seventy six ewes were treated with 7.5, 12.5, 25 or 50μg of cloprostenol on day 6 or 9 post-estrus to compare the luteolytic efficiency of the PGF2α analogue at each stage and to evaluate if progesterone concentrations at the time of treatment affect such efficiency. Blood samples were obtained before cloprostenol administration and 12, 24, 48, and 72h thereafter. There was an effect of dose (p<0.05) but not of day post-estrus on the proportion of animals completing luteolysis. As the dose increased, the proportion of ewes completing luteolysis also increased. Also, as the dose increased from 7.5 to 25μg, more ewes showed a transient progesterone decline instead of an absence of response, indicating that in some ewes reduced doses initiated luteolysis but were not able to finish the process. Since the dose of 25μg resulted in close to 50% luteolytic efficacy, this group was used to study the effects of progesterone concentrations at the time of treatment on the response to cloprostenol. Pre-treatment progesterone concentrations were higher (p<0.01) in ewes experiencing luteolytic failure than in those that completed luteolysis. There was a negative correlation between initial progesterone concentrations and their reduction by 12h post-treatment. It is concluded that high progesterone concentrations are associated with a reduction in sensitivity to small doses of cloprostenol. Possible mechanisms and implications of this luteoprotective effect are discussed.

Three experiments were conducted to test the abortifacient effects of PGF2 alpha analogues on mares during midgestation (average gestation length 141.5 days). The progesterone concentration was measured by radioimmunoassay. In experiment 1. five mares received an injection of PGF2 alpha analogue (fluprostenol: 500 micrograms intramuscularly) and a second injection either at 24, 48, of 72 h. Although the progesterone concentration decreased (P less than 0.05) an average of 44 per cent in 24 h, none of the pregnancies were terminated. In experiment 2, beginning at least 10 days after experiment 1, the same five mares were given PGF2 alpha analogue as follows: 250 micrograms intravaginally and 500 micrograms intramuscularly. The treatment was repeated 48 h later. Progesterone concentrations had not increased since experiment 1 and did not decrease during the 48 h following either injection. In experiment 3, six mares (average gestation length 162 days) were treated every 6 or 12 h with PGF2 alpha analogue (cloprostenol: 375 micrograms) until expulsion of the fetus occurred at 47 +/- 25 h after the initial injection; the mares received an average of 5 treatments. The progesterone concentration averaged 22 +/- 7 ng/ml before the initial PGF2 alpha treatment, decreased (P less than 0.05) to 8.4 +/- 2.7 ng/ml by 12 h before expulsion and 1-8 +/- 0.4 ng/ml 12 h after fetal expulsion. The progesterone concentration remained below 1.0 ng/ml for the next 4 days. However, only one of six mares exhibited estrual behavior after induced abortion.

The effects of treatment with intravaginal progesterone (PRID) oestradiol benzoate and cloprostenol at various stages of the oestrous cycle were examined in 2 experiments. In Exp. 1, PRIDs were inserted for 14 days commencing on Day 3, 10 or 17 of the oestrous cycle and half the animals in each group received 5 mg oestradiol benzoate at PRID insertion. Plasma samples were collected daily from the time of PRID insertion for 16 days, then every 4 days for a further 24 days. Samples were analysed for plasma progesterone concentration. In Exp. 2, heifers were treated on Day 10 as in Exp. 1, but half of each treatment group received 750 micrograms cloprostenol at PRID insertion. In Exp. 1, treatment with PRID alone appeared to inhibit endogenous progesterone production when treatment began on Day 3, but not when treatment began on Days 10 or 17. Treatment with oestradiol benzoate at the time of PRID insertion depressed progesterone levels, from about 2-5 days after injection. When treatment began on Day 10, the fall in progesterone levels after oestradiol benzoate was preceded by a marked rise in levels. In Exp. 2, treatment with cloprostenol markedly reduced peripheral concentrations of progesterone and also removed the effect of oestradiol. We suggest that oestradiol benzoate had a luteolytic effect, depressing luteal progesterone production when given on Days 3, 10 or 17 and that when given on Day 10 there was a transitory luteotrophic effect which preceded its luteolytic action.

The effect of a long run subclinic metabolic stress of acidotic and alkalotic nature was examined with respect to the course of cloprostenol induced estrus, ovulation and progesterone levels in blood and milk. The stress of acidotic nature was induced by widening the ratio of digestible crude protein to total dietary energy to the value 1:8.1 in 11 cows, while the alkalotic stress was due to narrowing the nutrient ratio to 1:2.81 in eight cows. Control group with the nutrient ratio 1:4.5-5 comprised 11 cows. The stress of acidotic nature was accompanied by ovulation disorders in 4 out of 11 cows (36.4%), in the group with the stress of alkalotic type it was in 2 out of 8 animals (25%). No ovulation disorders were observed in control group. Within 7 days after estrus, the average progesterone levels were 1.26 +/- 0.84 ng/ml in the blood of cows with stress of acidotic type, 3.48 +/- 2.99 in cows with stress of alkalotic type and 3.12 +/- 1.98 ng/ml in control cows. The differences between acidotic stress and control were statistically significant (P < 0.05). During the whole pregnancy (18 to 276 days), average progesterone levels were lowest in the group subjected to stress of acidotic nature. They ranged from 1.9 to 3.8 ng/ml with the average value 2.65 +/- 1.40 ng/ml. In the group with stress of alkalotic type they ranged from 2.55 to 5.43 ng/ml with the average value 3.67 +2- 2.29 ng/ml. In this control group, they ranged from 4.00 to 8.68 ng/ml with the average value 5.62 +2- 2.24 ng/ml. Variations in cortisol concentrations indicated a certain stressing effect of feeding rations on the internal environment of dairy cow organisms and activation of compensatory mechanisms.

The objective was to evaluate effects of prostaglandin (PG) F2α administration at the beginning of a progesterone and estradiol-based treatment period on ovarian response and pregnancy rate (P/AI) in Bos taurus beef heifers. Heifers were treated with 500 μg of cloprostenol administered: a) in two half-doses (250 μg) at the time of progesterone device insertion and removal (two-PG), or b) in a single dose at the time of device removal (one-PG). In the two-PG group, administration of PG at device insertion resulted in lesser serum progesterone concentrations during the 7-d treatment period (P < 0.05). Additionally, diameter of the follicle from which ovulation occurred was greater, and ovulation occurred earlier in the two-PG compared with one-PG group (P < 0.05). Fixed-time artificial insemination (FTAI) was performed in 3479 heifers with two times for FTAI (48 compared with 54 h from device removal). There was no effect on P/AI percentage for the PG treatment or the time of FTAI. The FTAI at 54 h resulted in a greater P/AI percentage in the one-PG than two-PG group (70.5%, 253/359 and 63.5%, 254/400, respectively; P < 0.05). There were no differences between PG treatments when FTAI was performed at 48 h after device removal. In conclusion, the administration of PG at the time of intravaginal progesterone device insertion results in lesser progesterone concentrations, and an increased size of the follicle from which ovulation occurs, and the time of ovulation is earlier after device removal. The pregnancy rate was not affected by the PG administration at the time of device insertion.

To investigate seasonal effects on the efficacy of estrus synchronization in mares, we administered a progesterone-releasing device (PRID) intravaginally to eight Haflinger mares for 11 days. In January 3 of 8 mares responded to the treatment with estrus and ovulation, in March 7 with estrus and 6 of 7 mares with ovulation, in June 6 of 7 and in October 7 of 8 mares with estrus and ovulation. Follicle distribution patterns at PRID insertion were different between January/October, March/June and June/October (P<0.05). Number of follicles decreased during PRID treatment in January, March and June (difference of number of follicles at Day 12 minus number of follicles at Day 1: -4.2+/-2.7, -0.9+/-0.9 and -4.9+/-1.5 follicles), while it increased in October (3.9+/-1.2 follicles; P<0.05). Mean progesterone concentrations were lowest in January (0.3+/-0.1 ng mL(-1)) when compared with March (3.5+/-1.8 ng mL(-1); P=0.063), June (4.4+/-1.4 ng mL(-1); P<0.05) and October (2.2+/-0.9 ng mL(-1); P<0.05). At Day 2 of PRID treatment, mean progesterone concentrations significantly increased in all mares. Except from January, mean LH concentrations decreased within one day after PRID insertion and remained at low levels during treatments in January and March. Total secretion of LH during PRID-treatment was significantly lower in January and March when compared with June and October. In the 5 of 7 mares that ovulated during PRID treatment a distinct increase of plasma LH concentrations after ovulation was detected. Administration of the progesterone releasing intravaginal device PRID combined with the PGF2alpha analogue cloprostenol was able to induce estrus and ovulation in mares at different times of the year. However, efficacy of the treatment was not satisfactory concerning effectiveness in relation to season and synchrony of intervals from removal of PRID to ovulation in mares.

A study was conducted on 35 East African shorthorned female goats to determine if a combination of buck teasing and low doses of a prostaglandin (PGF(2) alpha) analogue, cloprostenol, given intravulvo-submucosally (i.v.s.m.) would be suitable for synchronization of estrus. Goats were allotted, with the onset of estrus, to seven groups (n = 5 goats per group). Five of the seven groups received varying doses of cloprostenol: Group 1 (125 microg cloprostenol i.m. per goat); Group 2 (62.5 microg cloprostenol i.v.s.m. per goat); Group 3 (62.5 microg cloprostenol i.v.s.m. per goat plus buck teasing); Group 4 (31.25 microg cloprostenol i.v.s.m. per goat); Group 5 (31.25 microg cloprostenol i.v.s.m. per goat plus buck teasing); Group 6 (buck teasing); Group 7, (2 ml physiological saline i.v.s.m. per goat, control group). Plasma progesterone concentration was measured on day of treatment and for 6 d thereafter. All goats in groups 1, 2, 3 and 5 exhibited estrus within 68 h. Thus, the number of goats receiving low doses of PG-cloprostenol intravulvo-submucosally observed in estrus increased (P < 0.05) with exposure to bucks. Exhibition of behavioral signs of estrus was maximal between 2 and 20 h after onset of signs of estrus. The exposure of females to males prior to intrauterine penetration was an advantage because copious mucus eased penetration.

The effects of a synthetic prostaglandin analogue, cloprostenol, on luteal function in the guinea pig were studied. At a dose of 250 micrograms, cloprostenol administered I-P on day 9 of the cestrous cycle caused a reduction in the length of the oestrous cycle from 17.4 +/- s.d.0.9 to 14.5 +/- 1.1 days (p less than 0.01). Lower doses were ineffective, and post-treatment cycles were not different in length from pre-treatment cycles. Cloprostenol also caused a dose-dependent reduction in luteal weight, which fell from 3.52 +/- 0.82 to 1.82 +/- 0.41mg (p less than 0.01) 48 h after administration of a 250 micrograms dose on day 9. Plasma progesterone, measured by radioimmunoassay, was reduced from 4.67 +/- 0.59 to 2.69 +/- 0.66 ng ml-1 (p less than 0.01) 48 h after administration of 250 micrograms cloprostenol on day 9. 250 micrograms cloprostenol also reduced blood flow per corpus luteum, measured by 85Sr-labelled 15 microns microspheres, both at 3 h (20.20 +/- 10.36 to 9.40 +/- 4.20 microliters min-1; p less than 0.05) and at 48 h (18.47 +/- 8.27 to 5.23 +/- 1.90 microliters min-1; p less than 0.01) after administration on day 9. No adverse side-effects were observed at any dose level of cloprostenol used. It was concluded that cloprostenol is a useful experimental luteolysin in the guinea pig.

BACKGROUND

The present study describes the clinical features and plasma profiles of bovine pregnancy-associated glycoprotein 1 (bPAG1), the main metabolite of prostaglandin F2alpha (PG metabolite) and progesterone (P4) in heifers in which early abortions were induced.

METHODS

Early abortions were induced in four heifers with cloprostenol and monitored by ultrasonography. Blood samples were collected and the plasma were analyzed for bPAG 1, P4 and PG metabolite.

RESULTS

The foetal heartbeat rates varied from 170-186 beats per minute for all foetuses up to the date of cloprostenol treatment. Foetal death was confirmed within two days after cloprostenol treatment. Prior to cloprostenol injection, blood plasma concentrations of bPAG1, PG metabolite and P4 varied from 8.4-40.0 ng/mL, 158-275 pmol/L and 20.7-46.9 nmol/L, respectively. After the foetus expelled, the plasma level of bPAG1 began to decrease but the decrease was small and gradual. The estimated half-life of bPAG1 was 1.8-6.6 days. The plasma level of the PG metabolite started to have short lasting peaks (above 300 pmol/L) within three hours after cloprostenol treatment. The plasma concentrations of P4 dropped sharply to less than 4 nmol/L after 24 hours of cloprostenol injection.

CONCLUSIONS

The current findings indicated that after early closprostenol-induced foetal death, the plasma concentration of bPAG1 decreased gradually and showed a tendency of variation with the stages of pregnancy.

The aim of the study was to determine the luteolytic dose of cloprostenol administered directly into the corpus luteum (CL; intra-luteal treatment, ILT) in dairy cattle. Cows of two control groups were treated with 500 μg of cloprostenol (Estrumate®) intramuscularly (IM-500) or via ILT with 0.2 mL of physiological solution (ILT-0). Cows of four experimental groups were treated by ILT with cloprostenol in doses 5, 25, 50 and 100 μg (ILT-5, -25, -50 and -100 groups). Progesterone concentrations (P4) and size of CL were evaluated to assess luteolysis at 0, 0.5, 1, 2, 4, 8, 24 and 48 h or at 0, 24 and 48 h after ILT, respectively. Cows in the ILT-0 and -5 groups were unaffected by ILT. The P4 concentrations were less in cows of the IM-500, as well as ILT-25, -50 and -100 groups at 48 h subsequent to ILT. The size of the CL was less in cows of IM-500, as well as ILT-25, -50 and -100 groups at 48 h after ILT. There were P4 concentrations of about 1 ng/mL 48 h after ILT in cows of the IM-500, as well as ILT-50 and -100 groups. In conclusion, the cloprostenol dose of 50 μg administered intra-luteally is a luteolytic dose in cows.

Keywords: cloprostenol; corpus luteum; intraluteal treatment; luteolysis.

In the present study we have evaluated a possible stress reaction in response to two different PGF2α analogs-luprostiol and D-cloprostenol--and their effects on estrous cycle characteristics. In a cross-over-design eight mares received in alternating order either luprostiol (Treatment LUP; 3.75 mg im), D-cloprostenol (Treatment CLO; 22.5μg im) or saline (Treatment CON; NaCl 0.9% 0.5ml im) on day 8 after ovulation. Injection of either LUP or CLO, but not of CON resulted in a significant decline of progesterone concentration in plasma to baseline concentrations within two days (time: p<0.001, treatment: p<0.01, time × treatment: p<0.05). The treatment to ovulation interval was significantly shorter in LUP and CLO than in CON cycles (LUP: 9.4 ± 0.4 d; CLO: 9.4 ± 1.3 d; CON: 16.1 ± 0.8 d; p<0.001). Injection of either LUP or CLO, but not of CON significantly increased salivary cortisol concentration (immediately before injection: CON 1.3 ± 0.2, LUP 1.4 ± 0.3, CLO 1.4 ± 0.3 ng/ml; 60 min after injection: CON 1.0 ± 0.3, LUP 8.0 ± 1.4, CLO 4.2 ± 0.7 ng/ml; time: p<0.01, treatment: p<0.001, time × treatment: p<0.001). Heart rate decreased over time (p<0.05) independent of treatment and no changes in heart rate variability were detected. Injection of the PGF2α analogs CLO and LUP reliably induced luteolysis and apart from a transient increase in salivary cortisol concentration no signs of a physiological stress response or apparent side effects occurred.

The aims of the present study were to further examine the efficacy of different doses and routes of R-cloprostenol administration on the parturition response in sows. Fifty crossbred multiparous sows (Landrace x Yorkshire) with an average parity number of 4.7 +/- 2.4 were allocated to induce farrowing by one of the following treatments: Group I (control, n = 10) injection with normal saline 2 ml administered intramuscularly (i.m.); Group II (n = 10) injection with 75 microg of R-cloprostenol administered i.m. (at 7 AM); Group III (n = 10) injection with 75 microg of R-cloprostenol (at 7 AM) together with 10 IU of oxytocin (24 h after injection of R-cloprostenol) administered i.m.; Group IV (n = 10) injection with 37.5 microg of R-cloprostenol (at 7 AM) administered into perivulva region; Group V (n = 10) injection with 37.5 microg of R-cloprostenol (at 7 AM) administered into perivulva region together with 10 IU of oxytocin (24 h after injection of R-cloprostenol) administered i.m. The following parameters: pre-farrowing maternal behaviour, restless behaviour, R-cloprostenol or oxytocin injection to farrowing interval, expulsion intervals, duration of farrowing, total number of piglets born, litter birthweight, umbilical cord morphology and the degree of meconium staining were record. There were no significant differences among groups for the pre-farrowing maternal behaviours. In all the sows, the restless behaviour was not observed. There were no significant effect of oxytocin administration (10 IU, i.m.) on the percentage of umbilical cord morphology and the degree of meconium staining in different groups. There were no significant effect of route and dose of administration on the number of total piglet born, piglet born alive, stillbirth, mummy and litter birthweight. No significant effects of the different groups were found on the R-cloprostenol and oxytocin injection to farrowing interval, expulsion interval and farrowing duration. In conclusion, the present results demonstrated that a half dose (37.5 microg) of R-cloprostenol administered into the perivulva region was effective for inducing farrowing as the full recommended dose (75 microg) administered into the neck region (i.m.) and with no restless behaviour.

Although exercise and acupuncture are frequently used therapies to treat persistent postbreeding endometritis, their efficacy to date is unproven. The objective of this study was to determine if exercise and acupuncture are effective methods to reduce intrauterine fluid and compare the effectiveness of these treatments to the use of uterine ecbolics. Twelve mares susceptible to postbreeding endometritis were enrolled in the study with a randomized cross-over design using both positive and negative controls. During each estrous cycle, mares were randomized into one of six treatment groups, including stall rest (SR), oxytocin, cloprostenol, exercise, electroacupuncture, and oxytocin and exercise. Each mare was challenged with an insemination dose of 500 × 10⁶ dead sperm at time 0 hours. Intrauterine fluid measurements were taken at 0, 4, 24, 48, 72, and 96 hours postbreeding. Associations between treatment efficacy and fluid clearance were investigated using a random-effects logistic regression model that controlled for positive uterine culture. Compared with the SR negative control, exercise was the most effective treatment and had 29.7 times increased odds of fluid clearance. The second most effective treatment was oxytocin alone, with 16.9 times increased odds of fluid clearance. This was followed by cloprostenol that had 10.6 greater odds of fluid clearance, and finally, the treatment that combined exercise with oxytocin had 8.4 times greater odds of fluid clearance. Results from this study confirm that exercise and exercise combined with oxytocin are effective methods to clear intrauterine fluid.

Satisfactory results were obtained using estrumate in the following indications: (1) induction of oestrus in cows not showing any symptoms of oestrus; (2) treatment of cows with chronic endometritis; (3) expulsion of mummified foetuses; (4) termination of early pregnancy; (5) synchronisation of oestrus in heifers. It is conlcuded that estrumate may be regarded as a valuable addition to the armamentarium of therapy available to the veterinarian.

Peripheral plasma concentrations of oxytocin in female red deer during the luteal phase of the oestrous cycle (9.3 +/- 2.1 fmol/ml) exceeded those in the follicular phase (3.1 +/- 1.4) or during seasonal anoestrus (3.2 +/- 1.3). In both red and Père David's deer hinds during the mid-luteal phase of the cycle, systemic administration of a luteolytic dose of the prostaglandin F2 alpha analogue, cloprostenol, caused the concentration of oxytocin in the peripheral circulation to rise. Mean (+/- SEM) concentrations increased from 8.1 +/- 0.7 to 97 +/- 8 fmol/ml in red and from 6.2 +/- 0.7 to 153 +/- 30 fmol/ml in Père David's hinds within 5 min of treatment. During seasonal anoestrus oxytocin secretion in response to cloprostenol was reduced to less than 10% of that during the breeding season, in both species. Cloprostenol treatment raised circulating concentrations of prolactin in both species during the breeding season, and during anoestrus in red deer only. The concentration of oxytocin in a single corpus luteum removed at laparotomy from one red deer hind at the mid-luteal phase of the cycle was 66 nmol/g wet wt; identification was authenticated by HPLC. These results suggest that the corpus luteum secretes oxytocin in the Cervidae, as established previously in the Bovidae, and that luteal oxytocin secretion is stimulated by prostaglandin.