Comparison of the use of cabergoline and gonadotrophin to treat primary and secondary anoestrus in bitches

Objective To determine the efficacy and reliability of cabergoline and pregnant mare's serum gonadotrophin (PMSG) for induction of oestrus in bitches with primary or secondary anoestrus. Procedures We studied 39 healthy bitches of various breeds aged 2–6 years and in primary or secondary anoestrus: 20 bitches were administered 5 µg/kg/day cabergoline orally until day 2 after the onset of pro‐oestrus or for a maximum of 42 days, and 19 bitches were administered 20 IU/kg/day PMSG intramuscularly for 5 consecutive days, followed by an additional single injection of 25 IU/kg of human chorionic gonadotrophin on the fifth day. Results The rates of oestrus induction in the primary and secondary anoestrous bitches treated with cabergoline and PMSG were found to be similar. Pregnancy and whelping rates in the cabergoline group were statistically different from the rates in the PMSG group (P < 0.001). Conclusion Cabergoline is more effective and reliable for the induction of a fertile oestrus in bitches with primary or secondary anoestrous.     

Coat colour changes associated with cabergoline administration in bitches

Cabergoline or bromocriptine were administered orally to 60 bitches at doses of 5 microg/kg and 15 microg/kg daily, respectively, for two to 45 days for the treatment of pseudopregnancy or for oestrus induction. Seven of the dogs which received cabergoline for more than 14 days developed coat colour changes from the second week of administration to the next coat shedding. Of these, fawn-coloured bitches developed a yellowish coat colour while Argentine boar hounds became black spotted, mainly on their extremities. In previous untreated oestrous periods, these bitches had shown no coat colour changes. It is concluded that a colour shift in certain haircoats of particular breeds could be mediated through the inhibition of the secretion of melanocyte-stimulating hormone by the administration of the dopaminergic agonist cabergoline for more than two weeks. Transient coat colour changes should be considered a possible side effect when planning long-term treatment with dopaminergic agonists in dogs.     

Comparisons of different combinations of analogues of PGF2 alpha and dopamine agonists for the termination of pregnancy in dogs.

Groups of five pregnant bitches were treated to terminate the pregnancy with four combinations of drugs, starting 28 days after the estimated surge of luteinising hormone (LH), 22 to 28 days after the first mating. The treatments were: cabergoline administered orally for 10 days at a dose of 5 micrograms/kg and a single subcutaneous injection of 2.5 micrograms/kg cloprostenol at the start of the treatment; the same dose of cabergoline plus two doses of 1 microgram/kg cloprostenol administered on days 28 and 32 after the LH surge; bromocryptine administered orally at a dose of 30 micrograms/kg three times a day for 10 days plus a single dose of 2.5 micrograms/kg cloprostenol; the same dose of bromocryptine plus two doses of 1 microgram/kg cloprostenol; and a group of five pregnant bitches was left untreated. The pregnancies were terminated in all but one of the treated bitches, in each case by resorption of the fetuses. There were few side effects in the bitches treated with two doses of 1 microgram/kg cloprostenol, and were present but acceptable in those treated with one dose of 2.5 micrograms/kg. Plasma progesterone concentrations decreased to less than 1 ng/ml within 72 hours of the start of treatment and remained low except in the bitch in which pregnancy was not terminated. In the five untreated bitches, plasma progesterone remained high and they whelped normally. In the treated groups, the intervals between successive displays of oestrus were reduced by approximately 70 days in comparison with previous cycles or with the control group, but the fertility of the dogs was not affected adversely.     

A Review of Canine Pseudocyesis

The purpose of this article is to review the most relevant features of the physiology, clinical signs, diagnosis, treatment and prevention of canine pseudocyesis (PSC). This is a physiological syndrome, characterized by clinical signs such as: nesting, weight gain, mammary enlargement, lactation and maternal behaviour, which appears in non‐pregnant bitches at the end of metaoestrus. PSC is a frequent finding in domestic dogs. Although it is generally admitted that prolactin (PRL) plays a central role in the appearance of PSC, its precise aetiophysiology is not completely understood yet. A number of clinical studies suggest that at some point of metaoestrus circulating PRL levels rise in overtly pseudopregnant bitches. Individual differences in sensitivity to PRL as well as the existence of molecular variants of canine PRL with different bioactivity versus immunoreactivity ratios may help clarify the aetiopathology of PSC. Diagnosis of PSC is based on the presence of typical clinical signs in metaoestrous non‐pregnant bitches. Considering that PSC is a self limiting physiological state, mild cases usually need no treatment. Discouraging maternal behaviour and sometimes fitting Elizabethan collars to prevent licking of the mammary glands may suffice in these cases. Sex steroids (oestrogens, progestins and androgens) have been traditionally used to treat PSC but the side‐effects usually outweigh the benefits of these medications. Inhibition of PRL release by ergot derivatives [ bromocriptine (10–100 μg/kg per day for 10–14 days], cabergoline (5 μg/kg per day during 5–10 days), metergoline (0.2 mg/kg per day during 8–10 days) has proved to be effective for the treatment of canine PSC. Although some of these ergot derivatives present some untoward side‐effects, they are transient and can usually be managed. Predisposed bitches not intended for breeding should be spayed as ovariectomy is the only permanent preventive measure.     

Equine Chorionic Gonadotropin and Human Chorionic Gonadotropin Stimulation Increase the Number of Luteinized Follicles and the Progesterone Level Compared with Cabergoline Stimulation in Anoestrus Bitches

In this study, ovarian morphologies and blood progesterone concentrations following oestrous induction in bitches were examined. Fifty‐three clinically healthy anoestrus bitches received cabergoline at a daily dose of 5 μg/kg of body weight per os for 21 days (group I) or subcutaneous equine chorionic gonadotropin at a dose of 20 IU/kg of body weight for five consecutive days with an additional 500 IU s.c. per bitch of human chorionic gonadotropin on the last day of treatment (group II). Twenty bitches that spontaneously displayed oestrous signs were left untreated and served as controls (group III). The induced oestrous rates and ovulation rates in groups I and II were 60.0% vs 64.3% and 86.7% vs 83.3%, respectively. Morphological assessments of the ovarian structures after ovariohysterectomy revealed an increase in the number of luteinized follicles and cysts in group II compared with the two other groups (p < 0.001). In contrast, the numbers of corpora lutea and follicles were similar in all groups. In accordance with the above‐mentioned alteration, the progesterone concentration in the gonadotropin group (II) was increased (p < 0.001) in the periovulatory period compared with the other two groups. During the entire sampling period, the progesterone profiles in the cabergoline (I) and control (III) groups were similar and typical of normally cycling bitches. In conclusion, gonadotropin treatment is associated with an increased progesterone level during the periovulatory period that probably originates from luteinized follicles, whereas cabergoline treatment induces cycles with both physiological progesterone concentrations and ovarian morphologies.     

Treatment of spontaneous pyometra in 22 bitches with a combination of cabergoline and cloprostenol

Twenty-two bitches with ultrasonographically diagnosed spontaneous pyometra were treated with a combination of 5 microg/kg cabergoline per day and 5 mug/kg cloprostenol every third day, and potentiated sulphonamide twice a day. Bitches with either open-cervix or closed-cervix pyometra showed a rapid clinical improvement, associated with a reduction in plasma progesterone concentration, increased vulval discharge and a reduction in the diameter of the uterus. The haematological profiles of 21 of the bitches returned to normal within six days of treatment, and their biochemical profiles returned to normal within nine days; 19 of the bitches were managed successfully by a 10-day period of treatment. Two bitches required a further three days of treatment, and in one bitch with a partial uterine torsion the treatment was not successful. Adverse effects of the treatment were limited to the 60 minutes immediately after the administration of prostaglandin, and included retching, vomiting, mild abdominal straining, diarrhoea and panting. The incidence of adverse effects was reduced after each successive dose of prostaglandin. Eleven of the 21 successfully treated bitches were mated at the next oestrus, and seven became pregnant; their litters were smaller than the published breed averages. In four of the bitches the pyometra recurred after the next oestrus.     

Influence of Gonadotrophin‐Induced First Oestrus on Gilt Fertility

The aim of this study was to determine the association between the oestrous response of pre‐pubertal gilts to gonadotrophin injection or boar exposure and their subsequent farrowing rate and litter size. At 154 days of age, randomly selected pre‐pubertal gilts received an intramuscular injection of 400 IU equine chorionic gonadotrophin plus 200 IU human chorionic gonadotrophin (PG600^®; Merck Animal Health; n = 181). From the remaining pool of animals not treated with hormones, the first gilts showing signs of oestrus were selected to act as controls (n = 201). Boar exposure began at 155 days of age for both groups, and gilts were bred at a weight of approximately 130 kg. Comparisons were made between PG600^®‐treated gilts exhibiting oestrus or not within 7 days post‐injection (early and late responders, respectively) and control gilts exhibiting oestrus or not within 30 days after beginning of boar exposure (select and non‐select control gilts, respectively). By 162 days, oestrus was detected in 67.5% of PG600^®‐treated gilts compared with 5.7% of control gilts (p < 0.0001). The proportion of animals observed in oestrus at least three times before breeding was greater for select control gilts compared with early and late responder PG600^®‐treated gilts (p ≤ 0.001). There were no significant differences in farrowing rate and litter size between the four treatment groups. These data indicate that PG600^® is an effective tool to induce an earlier oestrus in gilts, that subsequent farrowing rate and born alive litter size compare favourably to that of select gilts and that gilts failing to respond promptly to hormonal stimulation do not exhibit compromised fertility.     

Effect of an Injectable Cabergoline Formulation on Serum Prolactin (PRL) and Milk Secretion in Early Postpartum Beagle Bitches

This study was conducted in order to evaluate effects on prolactin (PRL) concentration and mammary milk secretion of an injectable cabergoline formulation administered to five lactating Beagle bitches during early postpartum (PP). Bitches were bled twice daily (from PP day 3 to PP day 12) and then daily (from PP day 13 to PP day 16) to assay serum PRL. On PP day 6, a subcutaneous (SC) injection of 0.1 ml/kg of placebo was administered. On PP day 9, a SC 0.1 ml/kg dose of injectable cabergoline was administered. All bitches were checked for milk production, using a clinical scoring in order to quantify milk expression from each teat. A circadian variation of serum PRL was evident during the 6 days of pre-treatment monitoring. The day after cabergoline injection, an 80% decrease of PRL serum concentration was observed (p < 0.05). The circadian oscillatory pattern of PRL secretion disappeared after administration of cabergoline, and PRL values remained significantly lower than in the previous days for the first 60 h following treatment (p < 0.001). Milk production was drastically reduced when comparing pre-treatment to post-treatment scores (p < 0.001). A single dose of injectable cabergoline caused a significant reduction in serum PRL concentration and a significant reduction in milk flow. The injectable formulation of cabergoline appeared to be safe and well tolerated.     

In vivo investigation of luteal function in dogs: Effects of cabergoline,a dopamine agonist,and prolactin on progesterone secretion during mid-pregnancy and -diestrus

The role of prolactin on luteal function in dogs was investigated in vivo. The function of prolactin in mid-luteal phase was compared in pregnant and nonpregnant dogs. A dopamine agonist, cabergoline, known for its prolactin secretion inhibitory effects, was injected subcutaneously at a dose of 5 μg/kg body weight in five pregnant and five nonpregnant Beagle bitches. Mean plasma prolactin and progesterone were dramatically suppressed for 4 to 5 days after injection in both groups when compared with control pregnant and non-pregnant animals, whereas no effect on luteinizing hormone (LH) secretion was observed. The decline in plasma progesterone occurred after that in prolactin, suggesting plasma progesterone was impaired by inhibition of prolactin secretion. These results confirm the luteotropic importance of prolactin in pregnant bitches, and also demonstrate its importance in luteal phase of the nonpregnant dog.Second, to demonstrate that the effects of cabergoline were mediated by prolactin inhibition and not by a direct action on the corpus luteum, concomitant administration on Day 30 of cabergoline and prolactin (375 μg IV twice daily on Days 30 and 31) or cabergoline and LH (750 μg IV twice daily on Days 30 and 31) was affected in two groups of five pregnant animals each. Results showed that only prolactin was able to reverse the negative effects of cabergoline on circulating progesterone. This confirms the indirect mode of action of the dopamine agonist, cabergoline on corpus luteum function.Third, further investigation on the precise luteotropic role of prolactin was made by IV injection of 375 μg pure canine prolactin twice daily in five pregnant bitches on Days 30 and 31, and in five pregnant bitches on Days 40 and 41. No direct stimulatory effect of prolactin on plasma progesterone secretion occurred. Nor was there a noticeable effect on plasma LH secretion. These results suggest that prolactin is unable to directly stimulate progesterone secretion by the corpus luteum of pregnancy.The results of this study suggest that prolactin is an essential luteotropin in the dog from mid-luteal phase in both pregnant and nonpregnant animals. However, it appears to act by sustaining corpus luteum lifespan and function rather than by direct stimulatory effects on progesterone secretion.     

Termination of mid-term pregnancy in the dog with oral RU 486

A total of four pregnancies were terminated in three bitches (two beagles and one flatcoated retriever) with a single dose of 20 mg/kg (one case), two doses of 8-3 mg/kg (one case) or 20 mg/kg plus 40 mg/kg (two cases) RU 486 by mouth (Mifepristone; Roussel-Uclaf, France) from day 26 to day 36 after the first day of mating of the bitch. Abortions occurred within two, four, 11 and 11 days after the initial treatment, respectively. The clinical status of the bitches was similar to that observed during a normal parturition, ie, lowering of the body temperature, shivering, panting and nesting behaviour. No side effects were seen. The beagle bitch that aborted twice, was mated at the first oestrus after the first abortion, conceived and aborted the same number of puppies the second time. The peripheral plasma progesterone concentration at the time of treatment in all bitches was < 75 nmol/litre. It had decreased to between 24-2 and 13-1 nmol/litre at the time of abortion and to between 4-0 to 0–5 nmol/litre at four to 15 days after the initial treatment. Peripheral plasma levels of prolactin increased three- to fourfold within 24 to 48 hours after treatment, concomitant with the drop in progesterone and had returned to basal levels within two to three days. Prolactin concentrations also increased around the time of intrauterine fetal death. Prostaglandin F_2aα-metabolite concentrations increased slowly after treatment, and around the time of abortion the levels increased five- to 10-fold. RU 486 seems to be a safe and effective abortifacient for use during mid-term pregnancy in the dog.     

Oestrus control in bitches with proligestone, a new progestational steroid

A study of oestrus control in bitches with a new type of progestagen, proligestone, in six Dutch and three UK practices is reported. The product was given subcutaneously, regardless of the stage of the sexual cycle and of the usual contraindications for progestagens. A 97% efficacy was obtained with dosages varying from 20–33 mg/kg for the smallest animals to 10–13 mg/kg for the largest animals, when the first treatment was given in anoestrus with repeated treatments after 3 months, 4 months and thereafter every 5 months.
Following treatment in pro–oestrus, heat symptoms disappeared in 96% of the animals within 5 days. By retreatment after 3 months, oestrus prevention could be maintained in 97% of these cases.
Where the animals had been treated only with proligestone (1608 treatments in 776 bitches) there were five cases of the cystic hyperplasia pyometra complex; none of these occurred after treatment in pro–oestrus. Of the animals previously treated with other progestagens for oestrus control (814 treatments in 307 bitches) there were 11 cases.
Forty–one out of 46 bitches which had a history of reproductive disorders did not show signs again.
Other side–effects were also negligible (<0–5%). Fertility at the first oestrus after treatment appeared normal.     

Inhibitory Effects of Pergolide and Cabergoline Formulations on Daily Plasma Prolactin Concentrations in Geldings and on the Daily Prolactin Responses to a Small Dose of Sulpiride in Mares

Two experiments were conducted to assess the efficacy and duration of action of two dopaminergic compounds, pergolide and cabergoline, on daily prolactin secretion in geldings and on prolactin responses to a small dose of sulpiride over 10 days. In the first experiment, oral administration of 2 mg of pergolide was compared to a single injection of 2 mg of pergolide in a slow-release vehicle and a single injection of 5 mg of cabergoline in slow-release vehicle. Controls received vehicle only. All drug treatments reduced (P < .05) prolactin concentrations relative to that in controls but differed substantially in duration of action (oral pergolide approximately 6 hours or less, injected pergolide 6 to 24 hours, and injected cabergoline at least 6 days). In the second experiment, repeated small doses of sulpiride (2 μg/kg of body weight intravenously) were used to stimulate prolactin release in mares, and the ability of seven daily injections of pergolide (2 mg each) and a single injection of cabergoline (5 mg) in slow-release vehicle to suppress this release were compared. Control mares receiving vehicle injections had robust prolactin responses to the sulpiride injections on all days of injection (days 1, 0, 1, 2, 3, 4, 6, 8, and 10 relative to treatment). Prolactin responses were muted (P < .05) by pergolide and cabergoline treatments on the first day of injection (day 0, 30 min after treatment) and were basically absent on days 1 to 8. The single injection of cabergoline continued to be suppressive through day 10, whereas mares previously treated with pergolide (through day 6) had begun to recover a prolactin response by day 10. We conclude that either daily 2-mg pergolide injections in slow-release vehicle or a single injection of 5 mg of cabergoline in slow-release vehicle is an effective way to apply dopaminergic activity to horses for approximately 7 to 10 days and may have application in the treatment of pituitary pars intermedia dysfunction in affected horses.     

Changes in luteinizing hormone pulse frequency and prolactin levels in bitches in response to estrus induction by cabergoline-its cases where it is delayed to induce estrus

The effect of estrus induction by cabergoline on gonadotropin and steroid hormone responses was examined in anestrous bitches. Eleven beagles were used in the study; seven were included in the estrus induction group and four were included in the spontaneous estrus group. Cabergoline was orally administered to the estrus induction group at 5 µg/kg once daily for four weeks, or until hemorrhagic discharge was detected. The inter-estrus interval in the estrus induction group was significantly shorter than the previous estrus interval. Bitches that showed proestrus within four weeks of treatment showed increased luteinizing hormone (LH) pulse frequency and, subsequently, increased estradiol (E₂) levels. Prolactin (PRL) levels declined promptly after treatment, except in one bitch that did not show proestrus during the cabergoline treatment period. There was a significant correlation between the time to proestrus induction and the reduction in PRL levels. A positive correlation was found between the LH levels two weeks after cabergoline administration and PRL reduction. This study demonstrates that an abrupt reduction in PRL is likely to be important for initiation of estrus in bitches. A reduction in PRL indirectly leads to an increase in LH pulse frequency, which regulates follicular development in bitches. However, if the period from the end of the previous estrus to the cabergoline treatment is short, it may take some time to show proestrus without increasing E₂ levels, even if the LH level increases after cabergoline administration.     

Some observations on the aerobic bacterial flora of the genital tract of the dog and bitch

The aerobic bacterial flora from the genital tracts of 143 bitches and 51 dogs was investigated. Beta haemolytic streptococci (group G), Staphylococcus aureus and Escherichia coli were among the organisms isolated from normal bitches in heat, abnormal bitches and normal dogs. Repeated sampling of two bitches during oestrus, and the dog to which they were mated, showed that bacteria were transmitted from bitch to dog, but did not become established. Guarded swab samples taken from the vagina collected less bacteria than samples from the vestibule. Numerous bacteria were seen in vaginal smears taken from bitches during oestrus, but numbers fell rapidly with the appearance of leucocytes in the smear at the onset of metoestrus.     

Long-term Treatment of Insulin-insensitive Mares with Cabergoline: Effects on Prolactin and Melanocyte Stimulating Hormone Responses to Sulpiride and on Indices of Insulin Sensitivity

The main experiment assessed whether the inhibitory effects of the dopamine agonist, cabergoline, on prolactin and α-melanocyte stimulating hormone (MSH) concentrations would persist throughout a longer-term administration (65 days). The possible effect of cabergoline on insulin sensitivity was also studied. Ten mares known to be insulin insensitive were allotted to two groups (treated vs. control). An insulin challenge, a glucose tolerance test, and a sulpiride challenge were administered before treatment. On day 0, treated mares (n = 5) received an injection of 5 mg cabergoline in slow-release vehicle; control mares (n = 5) received an equivalent vehicle injection. Injections were repeated every 10 days for a total of seven injections. Sulpiride challenges were done 1 day before each cabergoline treatment to assess possible refractoriness to the treatment. Behavior and hair coat density were also monitored. Plasma prolactin was suppressed (P < .01) to undetectable levels in mares receiving cabergoline; control mares had robust prolactin responses to each sulpiride injection. There was no indication of refractoriness to cabergoline over time. Plasma MSH concentrations after sulpiride were also suppressed (P < .05) by cabergoline. After treatment, neither the glucose response to insulin nor the insulin response to glucose differed (P > .1) between groups. No behavioral changes were noted because of treatment. Weight of hair samples indicated that cabergoline perturbed (P < .05) winter coat growth. It is concluded that 5 mg of cabergoline in slow-release vehicle administered every 10 days is an effective way of delivering dopaminergic activity to mares that results in no noticeable detrimental effects and no refractoriness to the drug.     

Effect of Oestrous Synchronization with Estradiol 17β and Progesterone on Follicular Wave Dynamics in Dairy Heifers

An experiment was designed to evaluate the effects of estradiol‐17β (E17β) on follicular wave dynamics and ovulatory response in Holstein heifers receiving either a progestogen ear‐implant (Crestar^®; Intervet International b.v. Boxmeer, The Netherlands) or an intravaginal progesterone‐releasing device [controlled internal drug release‐bovine device (Eazibreed, CIDR‐B^®; Bodinco BV, Alkmaar, The Netherlands)]. For comparison, another group of heifers was also synchronized using Crestar plus an injection of estradiol valerate (EV) and norgestomet as recommended by the pharmaceutical company. Twenty 20–22‐month‐old cycling Holstein heifers were allocated to one of the following treatment groups at random stages of the oestrous cycle: (I) simultaneous insertion of Crestar and intramuscular injection of 3 mg norgestomet and 5 mg EV (Crestar 9 + EV 9); (II) simultaneous insertion of Crestar and intramuscular injection of 5 mg E17β (Crestar 9 + E17β 9); (III) insertion of Crestar followed 2 days later by intramuscular injection of 5 mg E17β (Crestar 9 + E17β 7); or (IV) insertion of CIDR‐B device followed 2 days later by intramuscular injection of 5 mg E17β (CIDR 9 + E17β 7). The CIDR‐B or Crestar implants were removed after 9 days and all heifers received 500 μg Cloprostenol (Estrumate^®, Pitman‐Moore Nederland BV, Houten, The Netherlands). Ovarian ultrasonographic examinations were performed once daily during the synchronization period using a B‐mode scanner equipped with a 7.5 MHz linear‐array transrectal transducer. In addition, heifers were scanned every 12 h after implant/device withdrawal until 3 days after ovulation in order to monitor follicular activity, detect ovulation and subsequent early luteal formation. Detection of oestrus was performed every 6 h for 4 days after device/implant removal. Oestrus was observed 24–32 h before ovulation in all heifers. The mean hours interval from treatment withdrawal to ovulation was not significantly different (84.0 ± 16.5, 77.6 ± 4.1, 73.6 ± 4.1 and 64.0 ± 4.4 h for treatments I, II, III and IV, respectively; p > 0.1). However, the variance for heifers treated with EV + norgestomet was significantly larger (Levene’s Test; p < 0.01) than those treated with E17β. All E17β treatments resulted in dominant follicle suppression and a new wave emerged 4.1 days after treatment compared with 6.6 days for the EV + norgestomet treatment (p < 0.05). The time from emergence of the new ovulatory wave to ovulation was longer for the new wave that emerged after E17β treatment (9.2 ± 0.3 days) than after EV + norgestomet treatment (6.9 ± 0.4 days; p < 0.05). The results of this study suggest that the four treatments used were effective in inducing synchronous behavioural oestrus and ovulation. However, a higher degree of oestrus and ovulation synchrony was observed in heifers treated with E17β than in heifers treated with EV + norgestomet. Synchronization treatments with exogenous E17β or EV + norgestomet at the time of progestin device insertion (Crestar or CIDR‐B) or 2 days later in heifers can regulate a different emergence pattern of ovarian follicular development in randomly cyclic heifers. The E17β was effective in inducing follicular suppression and resulted in the consistent emergence of a new follicular wave.     

Effect and mechanisms of the anti-prolactin drug cabergoline on pseudopregnancy in the bitch

A potent anti-prolactin drug, cabergoline, administered orally for five days, was clinically successful in treating three different clinical manifestations of pseudopregnancy in referred bitches. The clinical conditions treated were categorised as standard pseudopregnant bitches (n=8), those previously unsuccessfully treated with hormones (n=10) and those which had behavioural pseudo pregnancy following ovariohysterectomy (n=8). The number of bitches whose owners reported a 'good'response was seven out of eight, six out of 10 and six out of eight, respectively. There were very few side effects in that only one bitch vomited following treatment. The clinical response did not necessarily appear to be related to an alteration in circulating prolactin concentrations, suggesting that the drug may have a direct effect on the tissues as well as in most cases reducing the plasma prolactin concentrations.     

Molecular studies on oestrogen α and progesterone receptors and histomorphometric analysis of canine uteri following aglepristone treatment

Aglepristone, a competitive progesterone antagonist, is successfully used in various progesterone-dependent conditions. This study investigated uterine histomorphometric analysis, and expressions of the oestrogen α receptor (ERα) and progesterone receptor (PR) in uteri of bitches following the single dose of aglepristone treatment. Twelve client-owned healthy diestrous bitches were used in the study. The single dose of aglepristone (Alizine^®, 10 mg/kg) was injected subcutaneously 5 days before ovariohysterectomy in the treatment group (n = 6); bitches without treatment served as a control group (n = 6). Uteri were collected for histomorphometric analysis, ERα and PR gene, and protein expressions studies. The mRNA expressions of ERα and PR were determined by RT-qPCR. Immunohistochemical analysis was used to evaluate the ERα and PR protein expressions using an H-score in five parts of the uterus. The results demonstrated glandular epithelium height significantly decreased (p < .05) and ERα mRNA increased (p < .01) in treated dogs. Of the treated bitches, lower expression levels of ERα were observed in the luminal epithelium, crypt and glandular epithelium, with higher expression in the endometrial stroma and myometrium (p < .05); however, PR expression decreased in the luminal epithelium, crypt and glandular epithelium (p < .01). In conclusion, reduction of the uterine glandular epithelium and ERα mRNA upregulation together with changes in ERα and PR expressions were observed in the treated bitches. However, changes in uterine ERα and PR expressions in the treated bitches depended on tissue layers. The treatment had no effect on serum oestradiol and progesterone levels.     

Induction of oestrus by administering Inhibin antiserum along with equine chorionic gonadotropin in anoestrous bitches

As dogs experience oestrus only once or twice a year, it is necessary to establish an effective method of oestrous induction for efficient breeding. In the present study, we evaluated inhibin antiserum (IAS) on oestrous induction in anoestrous females. Bitches were administered 0.5 ml/kg IAS or a mixture of 50 IU/kg equine chorionic gonadotropin (eCG) and 0.5 ml/kg IAS and 500 IU human chorionic gonadotropin (hCG) administered 7 days after the mixture injection. As a control, bitches received 50 IU/kg eCG, with 500 IU hCG administered 7 days after eCG injection. Blood-tinged vaginal discharge, vulvar swelling, plasma progesterone concentrations and ovarian follicular development were assessed from day 0 to day 14. IAS alone injection did not induce oestrus in bitches at the anoestrous stage. Conversely, vulvar swelling, blood-tinged vaginal discharge and an estimated luteinizing hormone (LH) surge appeared on days 3–7, days 3–6 and days 7–9 after the IAS+eCG mixture injection, respectively, in all five bitches at the anoestrous stage. The average number of developing and ovulated follicles in bitches administered IAS+eCG was 8.8 and 9.6 respectively. A single eCG injection followed by hCG induced oestrous signs, with an average of 8.3 developing follicles and 4.5 ovulated follicles. This study revealed that IAS alone did not induce oestrus, but when IAS was used in combination with eCG, it induced oestrus and promoted a considerable number of ovulations in anoestrous dogs.     

Fixed‐time post‐cervical artificial insemination in weaned sows following buserelin use combined with/without eCG

Fixed‐time post‐cervical artificial insemination (FTAI) drastically reduces labour requirements and increases the use of boars with higher genetic merit. This study evaluated the efficiency of eCG administration combined with/without the GnRH agonist buserelin for the induction and synchronization of ovulation in weaned sows submitted to FTAI. The sows were allocated into three groups. In the control group, the first artificial insemination was performed at the onset of oestrus and repeated every 24 hr. In the eCG+GnRH group, sows received 600 IU eCG at weaning and buserelin (10 μg) after 86–89 hr of eCG, and in the GnRH group, sows received only buserelin after 86–89 hr of weaning. The hormone‐treated sows received a single FTAI after 30–33 hr of buserelin application. All the sows were inseminated with homospermic doses (1.5 × 10⁹ sperm cells/50 ml). The interval between weaning and ovulation was shorter (p < .05) in the eCG+GnRH (133.3 hr) and GnRH (135.9 hr) groups than the control (141.5 hr) group. In the eCG+GnRH group, the sows ovulated earlier (p < .05) than those in the GnRH group (44.5 vs. 48.2 hr after buserelin administration). The reproductive performance of GnRH sows was not compromised when only sows exhibiting oestrus at the time of insemination were considered, but lower farrowing rate and smaller litter size were observed in eCG+GnRH sows. The reproductive performance of eCG+GnRH sows was primarily compromised because the insemination was performed outside the optimal time relative to ovulation; therefore, it is advisable to inseminate them before 116–122 hr after weaning.