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PubMed1994

Specific binding of dl-cloprostenol and d-cloprostenol to PGF2 alpha receptors in bovine corpus luteum and myometrial cell membranes.

Prostaglandin F2 alpha receptors (PGF2 alpha Rs) were measured in bovine corpus luteum and myometrial cell membranes using a radiometric method. The inhibition of labelled PGF2 alpha binding exerted by d-cloprostenol, dl-cloprostenol, PGF2 alpha and PGE1 (10(-11) M to 10(-4) M) was evaluated in vitro. Results strongly suggest that cloprostenol binding to PGF2 alpha Rs is stereospecific. d-Cloprostenol and PGF2 alpha were equipotent, about 150 times more potent than dl-cloprostenol (P < 0.05) and approximately 280 times more potent than PGE1 (P < 0.05) in inhibiting [3H]PGF2 alpha binding to corpus luteum cell membranes. Such differences were less evident in myometrial cell membranes, where d-cloprostenol and PGF2 alpha were about 10 times more potent than dl-cloprostenol (P < 0.05) and approximately 95 times more potent than PGE1 (P < 0.05).

Animals↗
PubMed2001

Comparison of oestrus synchronisation programmes in dairy cattle using oestradiol benzoate, short-acting progesterone and cloprostenol, or buserelin and cloprostenol.

AIM: 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.

Journal Article↗
PubMed2003

Effect of prostaglandin E2, DL-cloprostenol, and prostaglandin E2 in combination with D-cloprostenol on uterine motility during diestrus in experimental cows.

Prostaglandin F(2alpha) is used in dairy herd management because of its luteolytic properties and for its direct effect on the myometrium in cows diagnosed with endometritis. Prostaglandin E(2) has a contractile effect on the bovine uterus. In human medicine, prostaglandin E(2) is routinely used to maintain labor and to ripen the cervix. We hypothesized, that a combination of prostaglandin F(2alpha) and prostaglandin E(2) would provoke a long-lasting increase in intrauterine pressure (IUP) and uterine motility as compared to either prostaglandin group. Intrauterine pressure was recorded during the diestrus of eight lactating dairy cows using a transcervically placed intraluminal pressure microtransducer. After recording of physiologic uterine motility for 30min, prostaglandins (DL-cloprostenol, PGE(2), PGE(2) in combination with D-cloprostenol) or placebo were administered, followed by a 2h recording period. Significant differences were found for the area under the curve, the mean amplitude and the intrauterine pressure, whereas the number of pressure waves did not differ significantly among treatments. Peak values for area under the curve and mean amplitude were found during the first 15min for the combination of PGE(2) and D-cloprostenol. During the last 15min of the recording session, area under the curve and mean amplitude were increased only for the combination of PGE(2) and D-cloprostenol as compared to placebo. Although PGF(2alpha) and PGE(2) provoke an increase in intrauterine pressure, only their combination guarantees a significant effect over a 2h recording period.

Animals↗
PubMed2004

A sheer pharmacologic approach to compare the contractile effects of PGF2alpha, DL-cloprostenol and D-cloprostenol on isolated uterine, tracheal, ileal and arterial smooth muscle preparations.

The contractile effects of PGF2alpha and its cloprostenol analogs (D-enantiomer and racemate) were examined on isolated smooth muscle preparations (uterine, tracheal, ileal and arterial) from rat, guinea-pig and horse. DL- and D-cloprostenol were potent contractors of myometrium, but had negligible secondary effects on other types of smooth muscle, except artery whose response to the D-enantiomer may give rise to some concern.

Animals↗
PubMed1983

Fertility of dairy cattle following oestrus and ovulation controlled with cloprostenol, oestradiol benzoate and progesterone or progesterone and cloprostenol.

There have been several approaches to the control of the timing of the oestrous cycle and ovulation in dairy cattle in the last three decades. The first phase involved the use of progestins which were administered in various forms for prolonged periods. Although the timing of oestrus was controlled in most animals after withdrawal of the treatment, this control was not very precise and pregnancy rates from insemination at the first oestrus after treatment were reported to be below normal. Attempts were then made to combine short-term progestin treatments with oestrogens as luteolytic agents to gain better control of the timing of oestrus and ovulation. These studies resulted in some cases in better synchronization of oestrus and improved pregnancy rates. The discovery that prostaglandin F2 alpha (PGF2 alpha) and its synthetic analogue, cloprostenol were potent luetolytic agents in the cow led in the past decade to the use of these agents for oestrus and ovulation control in cattle. Prostaglandins for this purpose are ineffective in anovulatory cows, in cows with deficient luteal function and in the first 5 days of the oestrus cycle when a new corpus luteum is being formed. This limitation in their use has encouraged investigations into the combined use of short-term progestin treatment with prostaglandins to give more effective control of the timing of oestrus and ovulation and to avoid the adverse effects on fertility of long-term progestin treatment. Short-term progestin treatment combined with prostaglandins should mean that fewer cows would have ovulation suppressed for long periods and fertility of treated cows should be improved. A comparison of three procedures of ovulation control and fertility results shows the short-term progestin treatment combined with prostaglandin to be the most effective.

Animals↗
PubMed1979

The disposition of the synthetic prostaglandin analogue cloprostenol ('Estrumate') in the rat and marmoset.

1. Following subcutaneous administration of the synthetic prostaglandin analogue [14C]cloprostenol to the rat (200 micrograms/kg), the dose was quantitatively recovered from the excreta: 52% of the dose was present in the urine and 43% in faeces. After intravaginal administration (200 micrograms/kg) 42% of the dose was recovered from the excreta, equally divided between urine and faeces, and 40% (range 25--66%) of the dose was recovered from the site of application. The radiolabelled compounds present in faeces were eliminated initially via the bile. 2. The max. observed plasma concn. of total 14C in the rat was 84 ng equiv./ml at 30 min after subcutaneous administration of cloprostenol (200 micrograms/kg). A component which co-chromatographed with cloprostenol on t.l.c. was rapidly cleared from plasma with a half-life of 54 min. After intravaginal administration of cloprostenol (200 micrograms/kg), low and persistent plasma concn. of 14C were detected. 3. The metabolic fate of cloprostenol in the rat and marmoset has been studied with radiolabelled and non-labelled drug mixed such that fragments detected by mass spectrometry exhibited characteristic 12C:14C isotope clusters. Metabolites derived from cloprostenol contained these characteristic doublets. 4. In the rat cloprostenol is metabolized by beta-oxidation to tetranor-cloprostenol. Unchanged cloprostenol and a conjugate of tetranor-cloprostenol were minor urinary metabolites. In the rat biotransformation of cloprostenol in the cyclopentane ring occurred; the tetranor acid of 9-keto-cloprostenol was identified in urine. In the marmoset unchanged cloprostenol and dinor-cloprostenol were major urinary components.

Animals↗
PubMed1995

Effect of flunixin meglumine on endogenous prostaglandin F2 alpha secretion during cloprostenol-induced abortion in mares.

OBJECTIVE: To determine the relative role of endogenous prostaglandin F2 alpha (PGF2 alpha) secretion in cloprostenol-induced abortion in mares that no longer require luteal progesterone secretion for maintenance of pregnancy, and to evaluate the ability of a prostaglandin cyclooxygenase inhibitor (flunixin meglumine) to prevent cloprostenol-induced abortion. DESIGN: The effect of flunixin meglumine on PGF2 alpha secretion and outcome of pregnancy was compared between mares treated with cloprostenol only and mares treated with cloprostenol plus flunixin meglumine. ANIMALS: Five pregnant mares, aged 4 to 15 years, of light-horse type. PROCEDURE: Cloprostenol (250 micrograms) was administered at 24-hour intervals to 5 pregnant mares. Flunixin meglumine (500 mg, IV) was administered at 8-hour intervals starting 15 minutes before the first cloprostenol administration. Hourly blood samples were analyzed for 15-ketodihydro-PGF2 alpha, progesterone, and estrogen concentrations. Previously reported data on cloprostenol-induced abortion in 6 pregnant mares treated daily with cloprostenol only were used as historic controls. RESULTS: The mean (+/- SEM) interval from first cloprostenol administration to fetal expulsion 56.4 (+/- 13.7) hours and number of cloprostenol administrations 3.2 (+/- 0.6) in the 5 flunixin meglumine-treated mares were not significantly different, compared with values for 6 pregnant mares treated daily with cloprostenol only, 48.6 (+/- 5.6) hours and 2.8 (+/- 0.2) cloprostenol administrations. Flunixin meglumine did not inhibit endogenous PGF2 alpha secretion. Prostaglandin F2 alpha secretion rates on the day before and day of fetal expulsion were similar in both groups. CONCLUSION: Flunixin meglumine at a dosage of 500 mg/animal, administered IV every 8 hours, is ineffective in modulating uterine PGF2 alpha secretion during cloprostenol-induced abortion. CLINICAL RELEVANCE: Flunixin meglumine is ineffective in the modulation of prostaglandin-induced uterine PGF2 alpha secretion and, therefore, does not offer a viable alternative for the prevention of abortion in mares at risk of abortion because of systemic illness.

Abortion, Induced↗
PubMed1988

Reproductive performance of dairy cows following treatment with cloprostenol 26 and/or 40 days postpartum: a field trial.

One hundred and seventy Holstein Friesian cows were randomly assigned to receive either 500 ug cloprostenol or saline placebo on Day 26 postpartum followed by 500 ug cloprostenol or saline on Day 40 postpartum. Four treatment groups were formed: Group 1-saline (Day 26)/saline (Day 40); Group 2-cloprostenol/(Day 26) saline (Day 40); Group 3-saline (Day 26)/cloprostenol (Day 40); Group 4-cloprostenol (Day 26)/cloprostenol (Day 40). Double blind techniques were used in administering treatments and in assessing the response to treatment. Palpation of the reproductive tract per tectum and uterine biopsies were performed on 92 cows prior to each treatment at Day 26 and Day 40 postpartum. Progesterone concentrations were determined on milk samples collected prior to treatment. There were no significant differences among treatment groups with respect to services per conception, number of heats detected before first service and culling for infertility. Cloprostenol treatment at Day 26 appeared to delay the first estrus, but it reduced the number of days to conception after the first service. Cows receiving cloprostenol at Days 26 and/or 40 had a decreased calving-to-conception interval compared to controls (P=0.01). Sequential therapy with two doses of cloprostenol resulted in slightly better reproductive performance than either treatment on Day 26 or 40 alone. Treatment with cloprostenol resulted in a decrease in the subsequent incidence of pyometra (P<0.05). It is concluded that in the herd studied, cloprostenol therapy at Day 26 and/or 40 postpartum was beneficial to reproductive performance. Although it was anticipated that cloprostenol would be more effective in cows with elevated progesterone levels, the opposite was observed at the Day 26 cloprostenol treatment. Uterine biopsy at Days 26 and/or 40 had a detrimental effect on subsequent reproductive performance.

Journal Article↗
PubMed1984

Effects of Cloprostenol administration on neutral lipid and prostaglandin F metabolism by porcine luteal tissue.

The effects of Cloprostenol administration on porcine luteal lipid metabolism, progesterone production, and prostaglandin F production were examined in 32 pigs at day 12 of the estrous cycle. Pigs were killed between 0 and 18 hours after treatment. Recovered luteal tissue was incubated at 0 C and at 37 C in the absence and presence of dibutyryl cyclic AMP and indomethacin. Net in vitro release of progesterone from luteal tissue was depressed within 1 hour after Cloprostenol treatment whereas net in vitro release of prostaglandin F was accelerated 4 hours after Cloprostenol treatment. Inclusion of dibutyryl cyclic AMP in the incubation media did not alter progesterone production but did enhance prostaglandin F production at 0 and 1 hour after Cloprostenol treatment. Inclusion of indomethacin in the incubation media completely inhibited the Cloprostenol-induced acceleration of in vitro luteal PGF production. Cloprostenol treatment increased luteal triglycerides and decreased luteal free cholesterol and cholesterol esters within 1 hr after treatment. Arachidonic acid percentages in free fatty acids and triglycerides were also increased within 1 hr after treatment. When 37 C and 0 C incubations were compared, in vitro luteal accumulation of free fatty acids was maximum at 1 hr after Cloprostenol treatment. In vitro accumulation of triglycerides in luteal tissue was comparatively uniform at all times examined during the first 18 hr after Cloprostenol treatment. Comparison of 37 C and 0 C incubations further revealed that luteal triglycerides were active in accumulation of arachidonic acid. Inclusion of dibutyryl cyclic AMP and/or indomethacin in the incubation media did not alter luteal lipid contents or fatty acid compositions. Blood plasma progesterone was depressed at 4 hours after Cloprostenol whereas 13,14-dihydro-15-keto-prostaglandin F2a was elevated at 18 hours after treatment. Blood plasma free fatty acids increased 330 percent at 4 hours and free fatty acid compositions also changed at this time. In both luteal tissue and blood plasma, changes in steroid and fatty acid metabolism occurred prior to changes in prostaglandin metabolism, suggesting that Cloprostenol induced functional luteal regression prior to altering prostaglandin metabolism.

Animals↗
PubMed2002

Effects of dose and route of administration of cloprostenol on luteolysis, estrus and ovulation in beef heifers.

Four experiments were conducted (with crossbred beef heifers) to determine the effects of dose and route of administration of cloprostenol on luteolysis, estrus and ovulation. In Experiment 1, 19 heifers with a CL > or = 17 mm in diameter were randomly allocated to receive cloprostenol as follows: 100 microg s.c., 250 microg s.c., or 500 microg i.m. Heifers given 100 microg s.c. had a longer (P<0.03) interval (120.0 h+/-10.7 h; mean+/-S.E.M.) from treatment to ovulation than those given either 250 microg s.c. or 500 microg i.m. (92.0 h+/-7.4 h and 84.0 h+/-8.2 h, respectively). In Experiment 2, 28 heifers were given porcine LH (pLH), followed in 7 days by cloprostenol (same doses and routes as in Experiment 1), and a second dose of pLH 48 h after cloprostenol. Luteolysis occurred in all heifers, and no difference was detected among treatment groups in the interval from cloprostenol treatment to ovulation (mean, 101 h; P<0.9). In Experiment 3, 38 heifers at random stages of the estrous cycle (but with plasma progesterone concentrations > or =1.0 ng/ml) received 500 or 125 microg cloprostenol by either i.m. or s.c. injection (2/2 factorial design). There was no difference (P<0.4) among groups in the proportions of heifers that were detected in estrus or that ovulated. However, the interval from cloprostenol treatment to estrus was shorter (P<0.02) in the group that received 500 microg i.m. (58.5h) than in the other three groups (500 microg s.c., 75.0 h; 125 microg i.m., 78.0 h; and 125 microg s.c., 82.3h). In Experiment 4, 36 heifers were treated (as in Experiment 3) on Day 7 after ovulation. The proportions of heifers detected in estrus and ovulating after 125 microg s.c. (33 and 44%, respectively) or 125 microg i.m. (55 and 55%) were lower (P<0.05) than in those that received 500 microg s.c. (100 and 100%), but not different from those receiving 500 microg i.m. (78 and 89%, respectively). Overall, ovulation was detected in 9/18 heifers given 125 microg and 17/18 heifers given 500 microg of cloprostenol, on Day 7 (P<0.01) and was detected in 17/20 heifers given 125 microg and 18/18 heifers given 500 microg of cloprostenol, at random stages of the estrous cycle (P>0.05). Although there was no significant difference in luteolytic efficacy between i.m. and s.c. injections of the recommended dose (500 microg) of cloprostenol, variability in responsiveness to a reduced dose depended upon CL sensitivity, therefore, reduced doses cannot be recommended for routine use.

Animals↗
PubMed2006

The effect of dose and route of administration of R-cloprostenol on the parturient response of sows.

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.

Animals↗
PubMed1989

Effects of cloprostenol, human chorionic gonadotropin and estradiol benzoate treatment on estrus synchronization in dairy cows.

Two consecutive experiments were conducted. In Experiment 1, 24 Friesian lactating cows were randomly assigned to two groups. Cows in Group I received intramuscularly (i.m.) 500 mcg of cloprostenol, 1250 IU of human chorionic gonadotropin (hCG) and 5 mg of estradiol benzoate 12 h after cloprostenol treatment. Cows in Group II received 750 IU i.m. of hCG and 3 mg of estradiol benzoate 12 h after cloprostenol treatment. Treatment was given on Day 16 after estrus in both groups. All animals showed estrus within 24 to 48 h after cloprostenol treatment. The average interval from cloprostenol injection to the onset of estrus was not influenced by treatments. Four cows in Group I failed to ovulate and became cystic. In Experiment 2, 71 Friesian lactating cows were randomly assigned to two groups. Cows in Group I received 500 mcg i.m. of cloprostenol after corpus luteum detection by palpation per rectum. Cows in Group II received 500 mcg of cloprostenol plus 750 IU of hCG and 3 mg of estradiol benzoate 12 h after. When estrus ready for service was confirmed by rectal examination, cows were inseminated. The percentage of cows ready for service tended to be lower (P<0.06) between cows in Group I (88%) and those in Group II (100%). The average interval from cloprostenol treatment to service was longest (P<0.001) in Group I (78.7 h+/-14.9, X+/-SD) vs Group II (48 h+/-2.9). The degree of readiness for service synchrony was lowest (P<0.001) in Group I (59.3%) vs Group II (94.2%). The pregnancy rates of cows synchronized or treated were not altered by hCG-estradiol benzoate treatment (P>0.25). These results suggest that in dairy cows treated with cloprostenol following palpation per rectum of a corpus luteum and then with 750 IU of hCG and 3 mg of estradiol benzoate 12 h later, a single fixed-time insemination at 48 h after cloprostenol treatment should be performed.

Journal Article↗
PubMed1987

Induction of parturition, progesterone secretion, and delivery of placenta in beef heifers given relaxin with cloprostenol or dexamethasone.

Sixty primiparous beef heifers from a crossbreeding study were used to examine the effects of inducing parturition with relaxin (3,000 U/mg) combined with cloprostenol (500 micrograms, i.m., n = 30) or dexamethasone (20 mg, i.m., n = 30) at Day 273, 10 +/- 1 days before expected parturition (Day 283). Heifers were assigned at random within cloprostenol and dexamethasone groups to receive relaxin (1 mg, n = 5/treatment), i.m. or in the cervical os (OS), at 0 h (the same time as cloprostenol and dexamethasone) or 24 h later. Eleven and six first-calving heifers and sixteen and nine second-calving cows also received cloprostenol + relaxin and cloprostenol + phosphate-buffered saline, respectively. Radioimmunoassay of daily plasma samples indicated an abrupt decrease in progesterone with time (p less than 0.001), from 7.5 +/- 0.50 to 1.0 +/- 0.30 ng/ml (mean +/- SE) within 48 h for all groups. The mean rate of progesterone decrease (ng/ml in 24 h) was accelerated (p less than 0.01) in relaxin-treated heifers (5.3 +/- 0.36), in contrast to dexamethasone- and cloprostenol-treated control heifers (2.8 +/- 0.40). Relaxin combined with cloprostenol or dexamethasone shortened the calving period in these heifers by reducing the interval between treatment and calving (33 vs. 56 h; p less than 0.01). The incidence and duration of retained placenta were reduced by 22 vs. 75% and 14 vs. 34 h for relaxin combined with cloprostenol or dexamethasone as compared with cloprostenol- or dexamethasone-treated controls, respectively (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Comparison of the luteolytic action of gonadotrophin-releasing hormone antagonist and cloprostenol, and the ability of human chorionic gonadotrophin and melatonin to override their luteolytic effects in the marmoset monkey.

The effects of the luteolytic and luteotrophic agents cloprostenol, human chorionic gonadotrophin (hCG) and melatonin on the corpus luteum have been investigated in marmoset monkeys treated with an LHRH antagonist to reduce endogenous LH secretion. This has allowed the effects of these agents to be investigated in the absence of the principal endogenous luteotrophin. Administration of the LHRH antagonist ([N-acetyl-D beta Nal1-D-pCl-Phe2-D-Phe3-D-Arg6-Phe7-Arg8-D-Ala10]NH2-LHRH) or cloprostenol between days 7 and 11 after ovulation (preimplantation) resulted in luteolysis. A significant (P less than 0.05) decrease in progesterone concentrations had occurred by 4 h after administration of the LHRH antagonist and was indeed preceded by a fall in LH concentrations. Coadministration of hCG with the LHRH antagonist prevented the fall in progesterone. In contrast, administration of cloprostenol resulted in an immediate fall in progesterone concentrations, to less than half the initial level within 1 h, and co-administration with hCG did not prevent the fall. Administration of hCG stimulated progesterone production when given 8 h after the LHRH antagonist but not after 24 h. Cloprostenol prevented the stimulation by hCG. Co-administration of melatonin with the LHRH antagonist did not prevent the decrease in progesterone concentrations. Melatonin was also not effective in preventing the fall in progesterone induced by cloprostenol. However, co-administration of melatonin and cloprostenol between days 17 and 21 after ovulation (post-implantation) significantly (P less than 0.05) delayed the fall in progesterone seen with cloprostenol alone. These results suggest that while the LHRH antagonist and cloprostenol have different sites of action their effect is similar at the corpus luteum, that is in depriving the corpus luteum of luteotrophic support. The results also suggest that melatonin may be able to influence the luteolytic action of cloprostenol but that its effect varies with the stage of the cycle. The physiological role for such an action, if any, remains unknown.

Animals↗
PubMed1989

Farrowing induction with cloprostenol-xylazine combination.

Eighty crossbred, multiparous sows, weighing between 190 and 320 kg, were randomly assigned to the following four treatment groups of 20 sows each: 1) saline-saline, 2) cloprostenol-saline, 3) saline-xylazine and 4) cloprostenol-xylazine. The mean gestation length of each multiparous sow was calculated. Cloprostenol (250 ug/sow, i.m.) or saline was given 3 d prior to the calculated due date at 11:30 a.m. Xylazine (2 mg/kg, i.m.) or saline was given 20 h after either the cloprostenol or previous saline treatment. Cloprostenol-xylazine treated sows had the shortest mean farrowing interval (1.5 +/- 0.3 h) when compared with the rest of the treatment groups (saline-saline:66.0 +/- 8.1, cloprostenol-saline:10.5 +/- 1.9, saline-xylazine:60.6 +/- 5.6 h). Farrowing time, percentage of stillbirths, average birth weight, d-5 and d-21 postbirth weights, number of pigs born, number of pigs born alive, and number of pigs surviving at 5 and 21 d afterbirth were not significantly different among the four groups. This study demonstrated that cloprostenol-xylazine treatment decreases the time to onset of farrowing with less variation than cloprostenol or xylazine alone. Therefore, the use of a cloprostenol-xylazine combination is suggested as an alternative method for inducing farrowing.

Journal Article↗
PubMed2004

Reproductive performance of lactating dairy cows treated with cloprostenol at the time of insemination.

The effect of intravenous cloprostenol treatment at the time of insemination on reproductive performance was consecutively evaluated in three different subpopulations of high producing lactating dairy cows: Study (1) early postpartum synchronized and fixed-time inseminated (about 50 days in milk) cows (n = 379: 187 control and 192 treated cows); Study (2) presumed high fertility cows first inseminated between 90 and 120 days postpartum (n = 248: 124 control and 124 treated cows); and Study (3) heat stressed repeat breeder cows (n = 183: 93 control and 90 treated cows). Data were analyzed using multiple regression methods. Study 1: Parity (primiparous versus multiparous), milk production, body condition score at AI, insemination season (cool versus warm period) and treatment were included in the analysis as potential factors affecting ovulation, double ovulation, return to estrus, and pregnancy to first AI and to second AI (first AI plus return AI) rates. Logistic regression analysis indicated that the final model for ovulation rate only included the interaction (P = 0.002) between insemination season and treatment. Cloprostenol treatment at insemination led to a 4.2-fold increase in the ovulation rate in cows inseminated during the warm period. There were no significant effects of treatment, parity, milk production, body score or the insemination season on the return to estrus rate. The only variables included in the final logistic model for double ovulation and pregnancy to first AI rates were treatment and season, respectively. Treatment led to a 2.6-fold increase (P = 0.001) in the double ovulation rate, whereas cows inseminated in the warm period were 2.1 times less likely (P = 0.007) to become pregnant at first AI compared to those inseminated in the cool season. The variables included in the final logistic model for the pregnancy rate to second AI were treatment and season. Cloprostenol given at AI increased the risk of pregnancy 1.9 times (P = 0.002), and cows inseminated during the warm season were two times less likely to become pregnant (P = 0.003). No significant interactions were found among these three dependent variables (double ovulation and pregnancy to first and to second AI rates). Study 2: Logistic regression analysis of all the dependent variables: return to estrus, and pregnancy to first and to second AI (first AI plus return to AI) rates indicated no significant effects of treatment, parity, days in milk, milk production or body score at AI. No significant interactions were found. Study 3: The final model for the pregnancy rate only included the interaction between parity (primiparous versus multiparous) and treatment. Days in milk, milk production and insemination number showed no significant effect on pregnancy rate. Cloprostenol treatment at insemination increased the pregnancy rate in primiparous repeat breeder cows (odds ratio: 3.6). The treatment group and parity showed significant (P < 0.0001) interaction. This interaction suggests that cloprostenol treatment of primiparous cows at insemination might enhance pregnancy yet have no effect in multiparous cows. Our findings indicate that cloprostenol administered at insemination promotes ovulation and double ovulation in lactating dairy cows. Cloprostenol treatment showed no benefit in cows with acceptable reproductive performance, suggesting that cloprostenol treatment at AI may only be useful in cows in which stress factors affect ovulation and in repeat breeder cows.

Animals↗
PubMed1991

Preincubation of human granulosa cells with gonadotrophin prevents the cloprostenol-induced inhibition of progesterone production.

Human granulosa cells, from women undergoing ovum collection for in-vitro fertilization (IVF), will luteinize in vitro and provide a model for investigating the antigonadotrophic action of a prostaglandin F2 alpha (PGF2 alpha) analogue, cloprostenol, on granulosa-derived luteal cells. The granulosa cells were cultured in a defined medium and exposed to treatments during a preincubation period of 0 to 3 days and a final incubation with low density lipoprotein (LDL) from days 3 to 4. In the absence of human chorionic gonadotrophin (HCG), progesterone production was low, whereas exposure to HCG in the final incubation resulted in a 10-fold increase in progesterone concentrations. The inclusion of cloprostenol with HCG in the final incubation significantly (P less than 0.05) inhibited HCG-stimulated progesterone production. Exposure to HCG during the preincubation prevented the antigonadotrophic action of cloprostenol in the final incubation. The antigonadotrophic action of cloprostenol was retained when the granulosa cells were exposed to cloprostenol during the preincubation. Omission of LDL from the final incubation lowered the production of progesterone but the pattern of responses to HCG and cloprostenol were similar. Prevention of the antigonadotrophic action of cloprostenol after exposure to HCG may be a mechanism through which chorionic gonadotrophin can prevent regression of the corpus luteum in early pregnancy. Cloprostenol does not appear to inhibit LDL-stimulated steroidogenesis in human granulosa cells.

Cells, Cultured↗
PubMed1993

Roles of cyclic AMP and inositol phosphates in the luteolytic action of cloprostenol, a prostaglandin F2 alpha analogue, in marmoset monkeys (Callithrix jacchus).

The luteolytic response to a prostaglandin F2 alpha analogue, cloprostenol, was investigated in vivo and in vitro at defined stages of the luteal phase. In vivo administration of cloprostenol to female marmoset monkeys on day 3 after ovulation had no effect on plasma progesterone concentrations, whereas administration on day 14 after ovulation reduced plasma progesterone to preovulatory concentrations within 4 h. To identify the cellular basis for this luteolytic action, marmoset luteal tissue obtained on days 3, 6 and 14 after ovulation was incubated in vitro and progesterone production, cAMP accumulation and phosphoinositide (PI) turnover measured in response to cloprostenol, human chorionic gonadotrophin (hCG) with or without cloprostenol, or dibutyryl-cAMP with or without cloprostenol. Progesterone production was stimulated by both hCG and dbcAMP at all stages of the luteal phase. Although neither hCG nor dbcAMP had any significant effects on PI turnover, hCG also increased cAMP accumulation. In marmoset luteal tissue obtained on day 3 after ovulation, cloprostenol had no significant effect on basal or hCG/dbcAMP-stimulated progesterone production but significantly stimulated PI turnover. In contrast, on days 6 and 14 after ovulation, cloprostenol significantly inhibited hCG- and dbcAMP-stimulated progesterone production and the cAMP response to hCG, but had no significant effect on PI turnover. Since progesterone production by the marmoset corpus luteum depends on the luteotrophic support of luteinizing hormone (LH), these observations suggest that the luteolytic action of cloprostenol in vivo involves the inhibition of LH/hCG action at sites both prior and subsequent to cAMP accumulation. However, such luteolytic effects do not appear to require the generation of inositol phosphates by increased PI turnover.

Animals↗