anoestrus and to enhance breeding efficiency

Cloprostenol is a synthetic prostaglandin F analogue. It is a FP (Prostaglandin F) receptor agonist, which shows 2· powerful luteolytic effects. It also stimulates the contraction of uterine and bronchial smooth muscle and produces vasoconstriction in some vessels. Anoestrous may be due to some conditions like abnormal pregnancy, early pregnancy, pyometra, endometritis, retention of placenta, maceration and mummification. So, get rid of this conditions cloprostenol is widely used. It has been now in vogue to administer PGF or its analogue in early 2· postpartum cows and buffaloes in order to hasten early resumption of cyclic ovarian activity and thereby to increase the reproductive efficiency. To improve reproductive efficiency, it is necessary to inseminate cows early in the breeding season so that, thereby achieving a more compact calving season. Breeding efficiency is increased by means of synchronization of estrus, conception rate and pregnancy rate. Estrus synchronization can be achieved by lysis of corpus luteum by administration of prostaglandin (PGF ) or its synthetic analogue on 5-17 2· days of the estrus cycle. The cows will return to estrus within 3-5 days. The effective therapeutic doses for cloprostenol are 500 µg in cattle and 175 µg in pigs. However, for R-cloprostenol, the recommended doses are: 150 µg in cattle and 75 µg in pigs. In both cases, it is administered by the intramuscular route.


Introduction
advantageous for maximal milk yield per cow per year [1].It is accepted that bovine genital infections, either The successful economics of a dairy farm specific or non-specific in nature, account for large production lies in ensuing proper and optimal number of pregnancy failure in cows [2].Generally, reproductive rhythm of each individual cow and non-specific infection of the genitalia is considered to buffaloes in the herd, within the normal physiological be the main cause of repeated conception failure [3].range.Any deviation in the breeding rhythm results in Bacterial infection is the most important among the a progressive economic loss due to widening of dry various causes of the sub-fertility [4].Such a condition period, reduced calving and lactation during the life may cause cervicitis or endometritis of various span of animal.Infertile animal means a direct loss in degrees, which in turn may lead to embryonic death milk production, whereas reduced calf crops hamper and repeat breeding problems [5].These infections the selection efficiency in long-term dairy herd affect fertility by altering the uterine environment, improvement.Thus, fertility and breeding efficiency resulting in impairment of sperm transport, sperm of dairy animals plays a pivotal role in dairy economics.The goals for the reproductive death and hostile environment to the subsequent management are to increase the milk productivity and development and maintenance of the conceptus reproductive capabilities of cows and young stocks.leading to early embryonic death.Early embryonic Economy of dairy farming largely depends on death is a major factor in reproduction failure [6].pregnancy rate.The twelve-month calving interval is Immediately after calving, the uterus of over 90% of all dairy cows becomes infected with bacteria The molecular formula and molecular weight of [7].Delayed uterine clearance which leads to retention cloprostenol sodium are C H ClNaO and 446.90 22 28 6 of placenta and subsequent development of anoestrus respectively.In IUPAC Cloprostenol is (Z)-7condition, reduced breeding efficiency, endometritis [(1R,3R,5S)-2-[(E,3R)-4-(3-chlorophenoxy)-3and pyometra are major problems contributing to subhydroxybut-1-enyl]-3,5-dihydroxycyclopentyl]-heptfertility and infertility in farm animals.The clinical 5-enoic acid.syndrome of delayed uterine clearance is characterized Cloprostenol is a synthetic racemic analogue of by an accumulation and retention of fluid or pus within prostaglandin F .Normally a racemic mixture of both 2α the uterine lumen, suppression of the estrous cycle and the enantiomers R-cloprostenol and S-cloprostenol is in severe condition animals may die.There is often a obtained by the chemical synthesis.By means of a negative effect on fertility, milk production and specially designed synthetic path and a chromatooverall health of the farm animals.
graphic method, the enantiomers can be separated and Prostaglandins are tissue hormones and are also pure R-cloprostenol can be isolated.Both cloprostenol known as 'autocids'.There are four prostaglandin and the pure R-cloprostenol are used in veterinary groups, which are A, B, E and F according to their structure medicinal products.and function.Out of these, PGF and Prostaglandin E 2α In body it get metabolized to 9, 11-dihydroxyare the most important ones which have direct effect 15-cetoprost-5 -enoic acid and 9, 11, 15on reproductive organs and fertility.Prostaglandins trihydroxyprost-5-enoic acid which rapidly get are synthesized from arachidonic acid.Fluprostenol, excreted from the blood through urine.Its half life is 1-Cloprostenol, Dinoprost, Tiaprost and Luprostiol are 3 hours.synthetic PGF analogues [8].Prostaglandins have 2α

Mechanism of Action
ecbolic properties and used to expel intraluminal uterine contents as well as cause lysis of the corpus luteum [9].
Prostaglandins are assumed to be important local regulators of luteal function in almost all PGF and its analogues are applied in different ways 2α mammals.Production of both luteotrophic and luteolytic including intramuscular, intrauterine, intravenous, prostaglandins and expression of specific intraovarian, intracervical and intravulvo-submucosal prostaglandin binding sites have been verified in the routes [10].The cloprostenol (a synthetic prostaglandin corpora lutea of non-primate [13] and primate species analogue) has been used to treat the condition like [14].PGF has been found to reduce the concentration anoestrus, retained placenta, endometritis and pyometra. of progesterone released by luteal tissue in vivo [15] It has been also used to improve breeding efficiency.and in vitro [16] via stimulation of Protein Kinase-C.This essay will illustrate the role of cloprostenol in Cloprostenol acts as a potent luteolytic agent, anoestrus and to improve breeding efficiency.
which causes functional and morphological regression

Structure and Properties
of the corpus luteum in cattle and horses [17].It also causes the myometrium contraction [18] and partial Prostaglandin is a group of components derived cervical relaxation.Cloprostenol exhibit luteolytic from unsaturated C-20 fatty acids, primarily activity during the 5 to 15 day of estrus cycle.arachidonic acid.Most prostaglandins have double Progesterone, by its inhibitory effect, inhibits the bonds at 5-6 and 13-14 carbons.Double bonds at myometrial contraction and the corpus luteum is the carbons 13-14 and an -OH group at C-15 are essential main source of progesterone in estrus animals.for biological activity [11].Cloprostenol is a synthetic Luteolytic effect of PGF occurs via luteal membrane prostaglandin F analogue.It is a FP (Prostaglandin F) 2α 2α PGF receptor [19].Administration of PGF and its receptor agonist [12], which shows powerful luteolytic 2α 2α agonist (cloprostenol) is the treatment of choice for effects.Prostaglandin PGF analogue also stimulates 2α cases of endometritis and pyometra in which corpus the contraction of uterine and bronchial smooth muscle luteum is present.Only 1 mg of PGF given 2α and produces vasoconstriction in some vessels.intramuscularly is required to induce luteolysis in the Cloprostenol sodium salt is a white or off-white mare, but 25 mg intramuscularly is required in cows hygroscopic powder; freely soluble in water and [11].alcohol.Cloprostenol sodium salt is soluble in organic Apart from luteolytic action cloprostenol may solvents such as ethanol, DMSO (Dimethyl also be used for the induction of parturition in pregnant Sulfoxide) and dimethyl formamide.The solubility of cows, sows and mares.It was demonstrated that only cloprostenol sodium salt in these solvents is 50, 60, the R-enantiomer of cloprostenol exhibits the and 130 mg/ml, respectively.luteolytic activity.The biological activity of its major The deficiency in myometrial contractility after metabolite is at most one hundredth of that of breeding is responsible for the delay in uterine cloprostenol.
clearance and may also account for the retention of placenta, endometritis and pyometra which is

Role in Treatment of Anoestrus
responsible for the absence of cyclic activity in Systematic reproductive management programs domestic animals.The incidence of endometritis is are increasingly being applied on modern dairy farms.highest during the first 14 days post-partum.These programs permit control of time to first Progesterone makes the uterus more prone to uterine Artificial Insemination and reduction or elimination of infection [26], which increases the chance to develop detection of estrus.Reduction in pregnancy risk is the condition like endometritis and pyometra.exaggerated among cows diagnosed as anovulatory at Retained placenta is also one of the main risk factor for the start of an ovulation-synchronization protocol.the acute post-partum endometritis, pyometra and Failure to display estrus before the end of the delay uterine involution.Cows with retained placenta voluntary waiting period was predictive of future have been shown to contain relatively higher level of reproductive failure.Cows diagnosed as anestrous progesterone and lower PGF in their placentomes 2α include cows that fail to ovulate and those that ovulate [27].Musah et al. [28] suggested that relaxin in the absence of behavioral estrus.Anoestrous may combined with cloprostenol reduces the incidence of also be due to some conditions like abnormal pregnancy, retained placenta in heifers.Now a day cloprostenol is early pregnancy, pyometra, endometritis, retention of drug of choice for the uterine cleanser in retention of placenta, maceration and mummification.So, for the placenta, endometritis and pyometra.get rid of this conditions cloprostenol (synthetic Abortion induction can be necessary in some analogue of PGF ) is widely used.
cases, such as incompletion of maternal growth at the 2α In recent years, routine preventive procedures first gestation in heifers because of higher risk for have been developed to optimize and maintain a high dystocia and retention of placenta.Moreover, degree of breeding efficiency in dairy herds.All the termination of gestation is necessary for eliminating buffaloes and cows under such programs are usually low producing cows from herds and in cases of examined routinely at approximately 25 -30 days after stillbirth and pathological developments including maceration and mummification of foetus, calving to determine the degree of ovarian activity and hydroamnion and hydoallantios during prenatal life.uterine involution and changes in the reproductive PGF and its analogues are used to terminate gestation.tract that has as early as occurred since parturition.Frequent examinations may be carried out during the Mechanism by which PGF induces abortion includes 2α course of postpartum phase on buffaloes and cows depressing peripheral progesterone level through with any abnormalities in the genital discharge, estrus leuteolysis and stimulating abdominal contraction and rhythm and in those that suffered from anoestrus, partial cervical relaxation [29].Prostaglandin F and 2α suboestrus or repeat breeding to arrive at an accurate its analogues have been shown to be reliable early diagnosis and implement proper therapy.It has abortifacients when administered in the first 150 days been now in vogue to administer PGF or its analogue of pregnancy [30] and were effective in the induction 2α in early postpartum cows and buffaloes in order to of parturition after 255 days of gestation [31].hasten early resumption of cyclic ovarian activity and Cloprostenol and other PGF analogues will cause 2α thereby to increase the reproductive efficiency [20].
leuteolysis in nonpregnant sheep and by similar Treatment with PGF [21] or synthetic analogues mechanisms should cause absorption or abortion of 2α of PGF (cloprostenol) [22] is effective in causing embryos in sheep during early pregnancy (up to 55 2α days) [32].Cloprostenol (an analogue of luteolysis in heifers or cows except for 4 or 5 days after prostaglandin F ) and dexamethasone in combination estrus [23].During anoestrus, fluorogestone acetate 2α would induce abortion in feedlot heifers, regardless of (FGA) intravaginal sponges for 11 days in conjuction the stage of gestation [33].with PMSG (Pregnant Mare Serum Gonadotrophin) (750 IU) and cloprostenol (50 µg) 48 hours before Use to enhance Breeding Efficiency sponge removal resulted in 87.5% and 93.8% estrus Breeding efficiency is one of the key factors for response and fertility, respectively in Alpine does [24].
the determination of economic success of a cow-calf Two intramuscular injections of cloprostenol (125 µg) operation.In general, to obtain maximum economic administered 10 days apart in Mehsana does were as benefit cattle should calve once per year.It is a critical effective as the progestagen treatments tested [25].component of a successful dairy operation, whereas tromethamine, 5 mg or 10 mg) or its analogue reproductive inefficiency is one of the most costly cloprostenol (62.5 µg, 125 µg or 250 µg) can be used problems facing the dairy industry today.for synchronization of estrus in cyclic does.A double Reproductive disorders occur frequently in lactating injection regimen with an interval of 10 to 14 days dairy cows and can dramatically affect reproductive between injections is usually used.Two injections of efficiency in a dairy herd.Some of the most common cloprostenol at the rate of 62.5 µg, 125.0 µg and 250.0 disorders include ovarian cysts, twinning, early µg administered 14 days apart, were effective in embryonic loss and retained placenta.These are synchronizing doe during breeding season [39].The diverse disorders that are similar in that they all can response rate approaches 90 to 100% with conception result in impaired reproductive function.Twinning is rates varying from 65 to 75%.Onset of estrus is an unavoidable outcome of reproduction in dairy usually expected 55 to 65 hours after treatment [40].cattle and is undesirable in a dairy operation because it Approximately 80% of the gilts inseminated at a PGF 2α reduces overall profitability and reproductive synchronized estrus had embryos 4-7 days or 24-30 efficiency [34].To improve reproductive efficiency, it days later [41]. is necessary to inseminate cows early in the breeding Estrus synchronization schedule in mares involves season so that repeat inseminations can be performed the administration of PGF or one of its analogues and 2α early, thereby achieving a more compact calving gonadotropic hormones [42].In randomly cycling season.Breeding efficiency is increased by means of mares, this method occur variations of results in a synchronization of estrus, conception rate and reasonably well synchronized onset of estrus and pregnancy rate.Estrous synchronization together with occurrence of ovulation.Conception rates in mares Artificial Insemination in ewes is important in the following such treatment have been variably reported improvement of reproductive efficiencies and as 39.9% [43], 40% [42], 58% [44] and 68% [45].management processes.
Synchronization of ovulation using prostaglandins or Estrus synchronization means to bring a group its analogues (cloprostenol) requires the presence of of animals in a same stage of estrus cycle so that they active corpora lutea and thus a previous knowledge of may come into estrus and ovulate at the same time.It is the seasonal ovulatory activity of ibex females in good managemental tool for programmed breeding, December-January [46].hence leading to programmed feeding and easier Cloprostenol have been used widely for the management of the cows being at the same stage of controlled induction of farrowing.The advantages are gestation.Finally, the calving will also be easy and to improve batch farrowing and to induce farrowing in convenient due to expected date of calving spread over the daytime (24-36 hours after injection), when labour a shortest possible period.Estrus synchronization can is more readily available and farrowing can be better be achieved by lysis of corpus luteum by adminissupervised.This enables prompt assistance to be given tration of Prostaglandin (PGF ) or its synthetic analogue 2α to a sow, which may have difficulty and ensures safer on 5-17 days of the estrus cycle.The cows will return delivery of the piglets and reduces stillbirths.It also to estrus within 3-5 days [35].Most estrus synchrofacilitates colostrum management, with supervisors nization programs in dairy cattle mainly involve the ensuring piglets start to suckle.Cloprostenol act on the use of the luteolytic agents prostaglandin or its corpora lutea of pregnancy in the sow's ovaries and analogues.Prostaglandin is only effective in diestrus cause them to regress, signaling to the body that it is cows; a double prostaglandin protocol applied 11-14 time to give birth.The injection is normally given days apart seems to be capable of bringing most cows within two days of the individual farm's calculated to estrus [36].The double-injection regimen of average farrowing date (approximately 115 days but Cloprostenol was highly effective in synchronizing range 111-119 days) to avoid problems with weak estrus in heifers and the time of onset of estrus was piglets, which may affect viability.The majority of similar to that reported by Cooper [10].treated sows had farrowed by 35 hours after treatment Estrus synchronization in Sudanese Nubian does [47].was achieved with double dose of cloprostenol ( 125Armstrong et al. [48] also observed significant µg) together with intravaginal sponges impregnated increase in first service conception rate in cows with progesterone inserted for 16 days [37].During receiving PGF treatment during early postpartum 2α the breeding season, when goats are actively cycling, and similar were the observations of Shah [49] in estrus can be synchronized with PGF or one of its 2α buffaloes.Moment and Seguin [50] showed a high analogues, such as cloprostenol [38].PGF (dinoprost conception rate (73 %) in heifers treated with PGF 2α 2α 2α hormones has proved to be efficient in treating differentiation inhibitors for primary culture of anoestrous, synchronizing estrus in postpartum dairy adipocyte precursors in defined medium.Biochem.cows, improving reproductive efficiency in dairy Biophys.Res.Commun.233: 200-202.13.Poyser, N. L. (1992).Prostaglandins in animal farms.It has been proved to administer PGF or its 2α reproduction.Agricultural Biotechnology News and analogue in early postpartum cows and buffaloes in Information.4: 17-25.order to hasten early resumption of cyclic ovarian 14.Fisch, B., Rose, M. P., Elder, M. G., Winston, R. M., activity and thereby to increase the reproductive Margara, R. A. and Hillier, S. G. (1994).Effects of efficiency.For the purpose of treatment of anoestrus oestrogen and progesterone synthesis and arachidonic and to improve breeding efficiency Cloprostenol is acid metabolism in human luteal cells.Clinical one of the most effective drug.