Effects of flunixin meglumine on endotoxin-induced prostaglandin F2 alpha secretion during early pregnancy in mares

The role of prostaglandin F2 alpha (PGF2 alpha) in embryonic loss following induced endotoxemia was studied in mares that were 21 to 44 days pregnant. Thirteen pregnant mares were treated with a nonsteroidal anti-inflammatory drug, flunixin meglumine, to inhibit the synthesis of PGF2 alpha caused by Salmonella typhimurium endotoxin given IV. Flunixin meglumine was administered either before injection of the endotoxin (group 1, -10 min; n = 7), or after endotoxin injection into the mares (group 2, 1 hour, n = 3; group 3, 2 hours, n = 3); 12 pregnant mares (group 4) were given only S typhimurium endotoxin. In group 4, the secretion of PGF2 alpha, as determined by plasma 15-keto-13,14-dihydro-PGF2 alpha concentrations, was biphasic, initially peaking at 30 minutes followed by a second, larger peak approximately 105 minutes after the endotoxin was given IV. When flunixin meglumine was administered at -10 minutes, synthesis of PGF2 alpha was inhibited for several hours, after administration of flunixin meglumine at 1 hour, the second secretory surge of PGF2 alpha was blocked, and administration of the drug at 2 hours did not substantially modify the secretion of PGF2 alpha. Plasma progesterone concentrations were unchanged after endotoxin injections were given in group 1. In group 2, progesterone values decreased less than 2 ng/ml and remained low for several days. In group 3 and group 4, progesterone concentrations decreased to values less than 0.5 ng/ml by 48 hours after endotoxin injections were given.(ABSTRACT TRUNCATED AT 250 WORDS)     

Termination of pseudopregnancy by administration of prostaglandin F2alpha and termination of early pregnancy by administration of prostaglandin F2alpha or colchicine or by removal of embryo in mares.

At day 24 of gestation, pregnant mares were allotted to 1 of 5 treatment groups (3 to 5 mares/group): group A--nontreated controls; group B--intraembryonic injection of 4 mg of colchicine on day 24; group C--removal of embryo on day 24; group D--subcutaneous injection of 1.25 mg of prostaglandin F2alpha (PGF2alpha) on day 32; and group E--removal of embryo on day 24 and subcutaneous injection of PGF2alpha on day 32. In all mares treated with colchicine (group B), the fetal bulge was absent within 2 days. The interval from injection of colchicine to onset of estrus was very short (mean, 4 days). These results indicated that treatment with colchicine was lethal to the 24-day embryo, and pseudopregnancy did not occur. Surgical removal of the embryo (group C) resulted in pseudopregnancy characterized by a prolonged interval from treatment to return to estrus (mean, greater than 31 days), prolonged production of progesterone, and prolonged maintenance of tense uterine and cervical tone. The interval from treatment to ovulatory estrus was longer (P less than 0.05) for group C mares than for group B mares. The mean interval from treatment to complete loss of tense tubular uterine tone was not significantly different between group A pregnant controls (28.3 days) and group C pseudopregnant mares (30 days). Treatment of pregnant mares (group D) with a single injection of PGF2alpha on day 32 resulted in loss of pregnancy in 4 of 4 mares within 2 to 5 days, and in all group D mares a large decrease in progesterone concentration occurred on day 33, 34, or 35. Although subsequent reproductive activity was variable, all group D mares rapidly lost the tense uterine and cervical tone characteristic of early pregnancy. These results indicated that a single subcutaneous injection of 1.25 mg of PGF2alpha caused loss of pregnancy, and pseudopregnancy did not occur. Treatment of group E mares, which had been made pseudopregnant by removal of embryo, with 1.25 mg of PGF2alpha resulted in termination of pseudopregnancy in 5 of 5 mares. All group E mares returned to estrus within 2 to 5 days after treatment, and progesterone concentration decreased (P less than 0.05) within 2 days after treatment. There was no significant difference in loss of tense tubular uterine or cervical tone between pregnant (group D) and pseudopregnant (group E) mares after PGF2alpha treatment.     

Induced abortion with two Prostaglandin F2α analogues in mares: Plasma progesterone changes

Three experiments were conducted to test the abortifacient effects of PGF2α analogues on mares during midgestation (average gestation length 141.5 days). The progesterone concentration was measured by radioimmunoassay. In experiment I, five mares recieved an injection of PGF2α analogue (fluprostenol: 500 μg intramuscularly) and a second injection either at 24, 48, of 72 h. Although the progesterone concentration decreased (P < 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 I, the same five mares were given PGF2α analogue as follows: 250 μg intravaginally and 500 μg intramuscularly. The treatment was repeated 48 h later. Progesterone concentrations had not increased since experiment 1 and dit 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 PGF2α analogue (cloprostenol: 375 μg) 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 PGF2α treatment, decreased (P<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.     

Prolactin and progesterone concentrations during early pregnancy and relationship to pregnancy loss prior to day 45

Eleven multiparous Quarter Horse and Thoroughbred mares were used to determine the plasma concentrations of progesterone and prolactin during early pregnancy and to examine the relationship of plasma progesterone and prolactin to pregnancy loss prior to d 45 of gestation. Plasma samples were collected at two day intervals beginning on d 14 of pregnancy (d 0 = ovulation) and countinued to d 80. Ovulation and pregnancy status were determined by ultrasonography. Four mares experienced pregnancy loss between d 28 and 44 and plasma samples were collected for 10 days beyond the detected loss. Seven mares had successful pregnancies (Term group).Plasma progesterone concentrations peaked by d 28 in the Term group, with individual peak values ranging from 14.9 to 31.9 ng/ml. Values then declined until d 36, followed by a rise until d 80. Prior to d 45 of gestation 5 of the 7 mares had a peak in excess of 15 ng/ml and 3 of these had brief periods, ranging fron 1 to 8 days when progesterone dropped to less than 2 ng/ml. The other 2 mares had peak plasma progesterone concentrations of less than 7 ng/ml, but maintained concentrations in excess of 2 ng/ml during this period.Within the mares experiencing pregnancy loss, 2 mares had a decline in plasma progesterone concentrations prior to pregnancy loss, while the other 2 had typical progesterone patterns beyond the detected loss. Differences in individual patterns of plasma progesterone concentration were observed in both groups (P<.01).Plasma prolactin concentrations ranged from less than .32 to 4.58 ng/ml in the Term group and from .31 to 1.9 ng/ml in the mares experiencing pregnancy loss. Differences in the individual patterns of prolactin secretion were observed in both groups (P<.01).A correlation between progesterone and prolactin was observed in the Term group between day 14 and 37 (P<.01, r²=.88).     

Effect of a Nonsurgical Embryo Transfer Procedure and/or Altrenogest Therapy on Endogenous Progesterone Concentration in Mares

Endogenous progesterone levels may decline after transcervical embryo transfer in some mares. Progestogen therapy is commonly used to support endogenous progesterone levels in embryo transfer recipient mares or those carrying their own pregnancy. The goal of this study was to determine the effects of the transcervical transfer procedure and/or altrenogest therapy on luteal function in mares. Mares were assigned to one of six treatment groups: group 1 (untreated control; n = 7 cycles), group 2 (sham transfer, no altrenogest; n = 8 cycles), group 3 (sham transfer plus altrenogest; n = 8 cycles), group 4 (pregnant, no altrenogest; n = 9 mares), group 5 (pregnant plus altrenogest; n = 9 mares), and group 6 (nonpregnant plus altrenogest; n = 10 cycles). Mares in groups 4-6 were bred and allowed an opportunity to carry their own pregnancy. Blood samples were collected for 22 days beginning on the day of ovulation. Sham embryo transfer (groups 2 and 3, combined) did not result in a decline in endogenous progesterone levels compared with control mares (group 6). However, sham embryo transfer did result in luteolysis and an abrupt decline in endogenous progesterone levels in one of the 16 (6.2%) sham-transferred mares. Altrenogest therapy in sham-transferred mares (group 3) was associated with lower endogenous progesterone levels on days 10, 12, and 13 postovulation when compared with sham-transferred mares that did not receive altrenogest (group 2). Administration of altrenogest to pregnant mares (group 5) was associated with lower concentrations of endogenous progesterone from days 14 to 18 and on day 21 compared with endogenous progesterone levels in pregnant mares not administered altrenogest (group 4). In conclusion, a transcervical embryo transfer procedure can cause luteolysis in a low percentage of mares. Altrenogest therapy may be associated with a reduction in endogenous progesterone secretion, presumably mediated by a reduction in pituitary luteinizing hormone (LH) release and a decrease in luteotropic support.     

Effect of surgical manipulation, placental fluid, and flunixin meglumine on fetal viability and prostaglandin F2 alpha release in the gravid uterus of mares

Twenty-one pregnant mares with single or twin conceptuses between 41 and 65 days of gestational age were allotted to 5 treatment groups. A ventral median celiotomy was performed in all mares. In group-1 mares (3 mares, single conceptus), the uterus and fetus were palpated for 5 minutes. In group-2 mares (3 mares, single conceptus, flunixin meglumine), 250 ml of sterile placental fluid was injected into the nongravid uterine horn. In group-3 mares (4 mares, unicornuate twin conceptuses), group-4 mares (3 mares, unicornuate twin conceptuses, flunixin meglumine), and group-5 mares (8 mares, bicornuate twin conceptuses, flunixin meglumine), 1 conceptus was removed from the uterus via hysterotomy. All mares received progesterone prophylactically until day 100 of gestation or until the fetus died. The 3 mares in group 1 delivered clinically normal, live foals. The mean prostaglandin F2 alpha metabolite (PGFM) plasma concentration peaked at 180 +/- 5.2 pg/ml during uterine manipulation and fetal palpation, then declined to baseline by 1 hour. Free placental fluid (group 2) undermined the chorioallantois ventrally and resulted in fetal death within 3 hours after surgery. The mean PGFM plasma concentration peaked at 39 +/- 4 pg/ml following injection of placental fluid. None of the remaining fetuses in the 7 mares with unicornuate twin conceptuses (groups 3 and 4) survived. Five mares with unicornuate twin conceptuses (group 5) delivered single viable foals. In another mare in group 5, the fetus was alive 4 days after surgery, when the mare was euthanatized for a fractured femur.(ABSTRACT TRUNCATED AT 250 WORDS)     

Progestins in Mid- to Late-Pregnant Mares

Two experiments were conducted to determine when a placental source of progestin was sufficient for maintaining pregnancy in the mare. In the first study, embryos were transferred into ovariectomized mares and pregnancy was maintained with altrenogest^a Altrenogest treatment was terminated at either day 100 (n=6) or day 150 (n=6). Twelve ovarian-intact mares were assigned to a second experiment on day 100 of gestation. On day 160 of gesta- tion, these mares were assigned to one of three treatments: 1) ovariectomy on day 160 and given altrenogest to day 200 (n=4); 2) ovariectomy on day 180 and given altrenogest to day 250 (n=4); or 3) ovariectomy on day 200 and given altrenogest to day 300 (n=4). Blood samples were collected every 2 weeks from all mares in both experiments from day 100 to parturition and assayed for concentrations of pro- gestins. Pregnancy loss from day 100 to parturition was not different among groups in either experiment. Serum con- centrations ofprogestins in ovary-intact mares were greater (P<0.05) than those in ovariectomized pregnant mares until day 130, after which they were similar. Serum con- centrations of progestins in the ovariectomized pregnant mares rose gradually from day 100 until near parturition. Serum concentrations of progestins in the ovary-intact pregnant mares declined from day 100 to day 157, did not vary significantly from day 157 to day 245, then rose until near parturition. Serum concentrations ofprogestins tended to decrease the sixth day prior to parturition. From these     

Effect of altrenogest‐treatment of mares in late gestation on adrenocortical function,blood count and plasma electrolytes in their foals

Reasons for performing study: Mares with compromised pregnancies are often treated with altrenogest to prevent abortion. However, there is only limited information about effects on the foal when altrenogest treatment is continued during final maturation of the fetus. Objectives: To determine effects of altrenogest treatment during late gestation in mares on maturity, haematology changes, adrenocortical function and serum electrolytes in their newborn foals. Methods: Six mares were treated with altrenogest (0.088 mg/kg bwt) once daily from Day 280 of pregnancy until foaling and 7 mares served as controls. Results: Foals born to altrenogest‐treated mares had a significantly lower neutrophil/lymphocyte ratio on the first day after birth than control foals (P<0.05). Basal plasma cortisol concentrations immediately after birth were higher in foals of altrenogest‐treated mares than in control foals (P<0.05). Cortisol release in response to exogenous adrenocorticotropic hormone (ACTH) ‐ except for higher values 15 min after ACTH injection in foals of altrenogest‐treated mares on Day 1 ‐ revealed no differences in adrenocortical function between the groups of foals. Plasma potassium concentration in foals from altrenogest‐treated mares compared to control foals was significantly lower immediately after birth (P<0.05) and plasma ionised calcium concentration was significantly lower 3 h after birth (P = 0.01). Conclusions and potential relevance: Altrenogest treatment of pregnant mares prolonged labour had no major effects on adrenocortical function in foals. A reduced neutrophil/ lymphocyte ratio in these foals may suggest either immunomodulatory effects of altrenogest or dysmaturity of the foals.     

Estradiol and progesterone concentrations resulting from the administration of an exogenous hormone regimen in diestrous embryo transfer recipients

Estradiol and progesterone concentrations were evaluated from diestrous embryo transfer recipient mares (5 to 14 days post-ovulation) which were treated with an exogenous hormone regimen. Upon detection of the donor mare's ovulation (0 hours), 10 mg PGF_2α was given to the recipient mare; at 12, 24 and 36 hours 20 mg estradiol cypionate; at 48 hours, 500 mg progesterone in oil and then 22 mg altrenogest at 60, 72 and 96 hours. Altrenogest (22 mg/day) was continued until end of the trial (detection of a fetal heart beat). Embryos were transferred non-surgically 6 or 7 days after the start of treatment.Plasma samples were evaluated over three periods; period 1-between recipient mare ovulation and prior to PGF_2α period 2-between PGF and embryo transfer and period 3-post-transfer. During periods 2 and 3, estradiol was higher (P<.05) for mares which were 10 to 14 days post-ovulation (late diestrous) as compared to mares which were 5 to 9 days post ovulation (mid-diestrous) when treatment began. Progesterone concentrations were higher (P<.05) for the mid-diestrous mares in the same periods. The pregnancy rate was higher for the late diestrous mares than the mid-diestrous mares (58% (7/12) vs 10% (1/10)). However, no difference (P>.05) was detected in estradiol or progesterone in the late diestrous mares which were pregnant or open. During period 2, estradiol was higher (P<.05) in the pregnant than open mares. Whereas, during period 3, progesterone was higher (P<.05) in the open mares.These data suggest that estradiol is important for the establishment of pregnancy in the mare. Furthermore, hormone treatment developed in this study appears to have some potential in synchronization of diestrus mares to be used as embryo recipients.     

A cooperative action of endothelin-1 with prostaglandin F(2alpha) on luteal function in the cow

Prostaglandin F(2alpha) (PGF(2alpha)) is the primary luteolysin in the cow, and luteal endothelin-1 (ET-1) interacts with PGF(2alpha) during the process of luteolysis. In contrast, a developing corpus luteum (CL) is refractory to exogenous administration of PGF(2alpha). Thus, the present study was aimed to investigate the functional relationship between ET-1 and PGF(2alpha) in the mid-CL (PGF(2alpha)-sensitive) and early-CL (PGF(2alpha)-refractory). In the mid-CL model, cows (n = 6/treatment) were assigned to receive one of five types of treatments on day 10 of the estrous cycle: (1) an injection of saline; control, (2) a 500 microg of PGF(2alpha) analogue (sufficient dose to induce luteolytis); full-PG, (3) an intraluteal injection of 0.25 mg ET-1; ET-1, (4) a 125 micro g of PGF(2alpha) (insufficient dose to induce luteolytis); 1/4PG or (5) an intraluteal injection of 0.25 mg ET-1 after administration of a insufficient dose of PGF(2alpha) analogue; 1/4PG/ET. In the early-CL model, cows were assigned to receive one of two types of treatments on day 5 of the estrous cycle: (1) a sufficient dose of PGF(2alpha) analogue; PG (n = 5) or (2) an intraluteal injection ET-1 after a sufficient dose of PGF(2alpha); PG/ET (n = 7). In the mid-CL model, 1/4PG/ET resulted in a rapid reduction of progesterone (P) concentrations similar to that in full-PG from the next day. However, the levels of P in 1/4PG/ET (1.5-2.5 ng/ml) kept significantly higher than that in full-PG (< 0.5 ng/ml). ET-1 or 1/4PG did not decrease plasma P concentrations (4-6 ng/ml). The plasma ET-1 levels increased with the full-PG administration. In the early-CL model, both treatments had no effect on plasma P increase and ET-1 levels. The overall results indicate that the intraluteal ET-1 injection after administration of insufficient dose of PGF(2alpha) induces the depression of P secretion in vivo during the mid luteal phase in the cow, supporting the concept that ET-1 is one of a local mediator of functional luteolysis in the cow. The result further indicates that the early-CL is not only PG-refractory but also ET-1-refractory.     

Effectiveness of a two-dose regimen of prostaglandin administration in inducing luteolysis without adverse side effects in mares

Our objectives were to determine whether repeated administration of prostaglandin F2alpha (PGF2alpha) to simulate the endogenous mode of secretion would be more effective than a single injection in inducing luteolysis and enable use of smaller doses less likely to cause adverse side effects. The main study comprised 43 dioestrous mares, who were given im. either a single 10 mg dose of natural PGF2alpha (n = 22) or 2 doses of 0.5 mg PGF2, 24 h apart (n = 21). The intensity of side effects was assessed in 8 dioestrous mares given 5, 1.5, 0.5 or 0 mg PGF2alpha in consecutive cycles. Two doses of 0.5 mg PGF2alpha 24 h apart caused lysis of the corpus luteum in all mares, whether this was determined from a fall in plasma progesterone concentrations or reproductive tract/behavioural changes; and when 10 mg PGF2, was given, the corpus luteum was lysed in 17 of 22 mares i.e. a lower proportion (P = 0.0485). A single dose of 0.5 mg PGF2a was no more effective than saline in inducing luteolysis.The intensity of side effects of PGF2alpha increased with dose. Although the 0.5 mg dose was no more likely than saline to cause sweating or muscle spasms, it raised plasma cortisol concentrations and prevented the decline in heart rate seen after saline. We conclude that a 2 dose regimen of administration increases the luteolytic efficacy of PGF2alpha and thereby provides a way to minimise adverse side effects.     

Hormonal changes in sows after induced porcine parvovirus infection in early pregnancy

Hormonal changes, lesions, and virus isolation studies were determined in sows after uterine artery inoculation with porcine parvovirus [( PPV], strain NADL-8) in early pregnancy. Two sows were given PPV on days 14 or 16 and were euthanatized and necropsied on day 35 after twice daily plasma collection for hormone measurement. Parvovirus was given to 4 sows on day 14 and to 4 sows on day 21 with 5 times daily plasma samples collected for 1 week. Sows were examined on days 21 and 28, respectively. Four control sows in each group on days 14 and 21 were given a placebo injection and were similarly studied. All embryos in all but 1 sow given PPV were in various stages of resorption at necropsy. Normal embryos were present in all control sows. Estrone sulfate values increased logarithmically, progesterone values remained stable, and concentrations of 13, 14-dihydro-15-keto-prostaglandin (PG) F2 alpha (PGFM), a PGF2 alpha metabolite, were less than 200 ng/ml for sows given a placebo. In contrast, sows with resorbing embryos did not have an increase in estrone sulfate values. A decrease in plasma progesterone values occurred in 9 of 10 sows inoculated with PPV; this decrease was accompanied by greater than or equal to 1 marked increase in PGFM concentrations. Quantitative assessment of the uterus revealed significantly greater cytoplasmic density in endometrial and glandular cell (P less than 0.01), a greater glandular epithelium height (P less than 0.05), and twice the number of glands (P less than 0.05) in control sows, compared with values in sows inoculated with PPV.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of Injectable Sustained Release Progestin Formulations for Suppression of Estrus and Ovulation in Mares

Thirty-one mares were used in an experiment to evaluate the effectiveness of three sustained-release injectable formulations of altrenogest and one formulation of medroxyprogesterone acetate (MPA) for long-term suppression of estrus and ovulation. Luteolysis was induced by injection of prostaglandin-F_2α (Lutalyse) on day 0 (6th day after the previous ovulation) and was immediately followed by treatment with 1) no injection (controls; n = 7), 2) 1.5 mL of an altrenogest solution in sustained-release vehicle (LA 150, 1.5 mL; 225 mg altrenogest; n = 6), 3) 3 mL (450 mg altrenogest) of the same solution (n = 6), 4) 500 mg altrenogest in lactide-glycolide microparticles suspended in 7-mL vehicle (MP 500; n = 6), or 5) 1.0 g MPA as a 5-mL suspension. Mares were checked for estrus daily, and their ovaries scanned every other day until a 25-mm or greater follicle was detected, after which they were scanned daily. Control mares returned to estrus an average of 3.9 days after Lutalyse administration; all the single-injection altrenogest formulations increased (P < .05) the days to return to estrus, with the greatest increase occurring in mares receiving MP 500. Return to estrus was not affected by MPA treatment. Time of ovulation was determined by serial ultrasound scans and confirmed by daily plasma luteinizing hormone (LH) and progesterone concentrations. Control mares ovulated an average of 8.8 days after Lutalyse administration. Treatment with 1.5 or 3 mL of LA 150 increased (P < .05) the mean days to ovulation to 16.5 and 21.2 days, respectively; MP 500 increased (P < .05) the days to ovulation to 33.5 days. Administration of MPA did not affect (P > .1) days to ovulation relative to control mares. The MP 500 treatment provided long-term suppression of estrus and ovulation and could prove useful for that purpose. Treatment with the LA 150 solutions provided shorter-term suppression, and a relatively tight grouping of the individual mares around the mean days to ovulation; these one-shot formulations could be useful for synchronizing ovulation in cyclic mares and inducing normal estrous cyclicity in vernal transitional mares exhibiting erratic, anovulatory estrous periods.     

Use of a Compounded Long-Acting Progesterone Formulation for Equine Pregnancy Maintenance

The objective of this study was to test the efficacy of a compounded long-acting progesterone formulation (BioRelease P4 LA 150; BETPHARM, Lexington, KY) containing 150 mg progesterone/ml for pregnancy maintenance in mares after prostaglandin (PG) F_2α-induced luteolysis. On day 18 of gestation, mares were randomly assigned to one of four groups (n = 7/group): (1) saline-treated control (Saline); (2) PGF_2α-treated control (PGF); (3) PGF_2α- and Regu-Mate-treated (Regu-Mate); and (4) PGF_2α- and BioRelease P4 LA 150-treated (BioRelease). On day 18, Saline mares received 1 ml sterile saline IM, whereas PGF, Regu-Mate, and BioRelease mares received 250 μg cloprostenol IM. Beginning on day 18, Regu-Mate mares received 10 ml Regu-Mate orally once daily and BioRelease mares received 10 ml BioRelease P4 LA 150 containing 150 mg/ml progesterone IM once every 7 days; treatments were continued until day 45 or until pregnancy loss occurred. Pregnancy diagnosis was performed every 3 days between days 18 and 45 (or until pregnancy loss). Pregnancy loss was defined as complete absence of a discernible embryonic vesicle as determined with transrectal ultrasonography. Pregnancy loss rates between days 18 and 45 were: Saline, 1/7; PGF, 7/7; Regu-Mate, 1/7; and BioRelease, 0/7. The pregnancy loss rate was higher (P < .01) in PGF_2α-treated control mares compared with the other groups. There were no differences (P > .1) in pregnancy loss rates among the saline-treated control, Regu-Mate-treated, and BioRelease P4 LA 150-treated mares. These results indicate that intramuscular administration of BioRelease P4 LA 150 containing a total of 1.5 g progesterone every 7 days provided a sufficient level of progesterone to maintain pregnancy between days 18 and 45 of gestation in mares that lacked an endogenous source of progesterone; therefore, this long-acting formulation of progesterone appears to be an efficacious and suitable alternative to currently available progesterone formulations that require daily administration.     

Duration of anestrus in Pramenka and Romanov ewes in Yugoslavia.

Jugular plasma progesterone was determined for two groups of native Yugoslavian ewes (Pramenka, Groups 1 and 2) and for a group of Romanov ewes (Group 3) from the end of January to late October in 1988. Ewes were pregnant until the end of March (pregnancy progesterone concentrations, 2.84 to 33 ng/mL). From the end of March to the beginning of July, progesterone concentration decreased (0 to .15 ng/mL). From early July to late October, progesterone concentrations increased. Progesterone concentrations were at their nadir near the summer solstice and increased significantly by early July in all three groups. The duration of anestrus was similar in Pramenka and Romanov ewes. In nonpregnant Pramenka ewes, the pattern of changes in plasma progesterone was similar to those seen in pregnant ewes except for an earlier decline with very low concentrations observed after mid-March.     

Safety of altrenogest in pregnant mares and on health and development of offspring

Fifty-one light-horse mares were utilized to evaluate the safety of an oral progestin, altrenogest, administered throughout gestation on: gestation length, embryonic and fetal loss, periparturient events, health and development of offspring, and future reproductive capabilities of the mares. Pregnancies were established by inseminating mares with 250 × 10⁶ progressively motile spermatozoa from the same stallion every other day throughout estrus or by non-surgical transfer of embryos. Mares were randomly assigned to 1 of 2 treatments upon confirmation of pregnancy on day 20: 1) controls, 2 ml of neobee oil orally per 44.5 kg of body weight; and 2) treated, 2 ml of altrenogest dissolved in neobee oil at a concentration of 2.2 mg/ml orally per 44.5 kg of body weight. Treatments were administered daily from day 20 to 320 of gestation.There were no significant differences between treatment groups for duration of gestation, placental weight, time to placental expulsion and incidence of retained placental membranes. Number of female foals born from altrenogest treated mares (14 of 23) was greater (P<.05) than the number from untreated control mares (4 of 16). Female foals born from altrenogest treated mares had larger clitori (P<.05) than those from control mares. Times to sternal recumbency, standing and nursing were similar for the 2 groups (P>.05). Body weight and height at withers, heart girth circumference and length and width of cannon were measured at time of birth and at 2, 4, 6, 8, 12 and 16 weeks of age. Measurements did not differ (P>05) between treated and control foals for any development parameters.Beginning on day 20 postpartum, mares were teased daily. During estrus, mares were inseminated every other day with 250 × 10⁶ motile spermatozoa. Teasing and/or insemination was continued for 2 cycles or until mares were 35 days pregnant. The number of mares pregnant after 1 cycle and after 2 cycles of insemination was similar (P>.05) for treated and control mares. Nineteen of 21 treated mares and 15 of 16 control mares were pregnant after 2 cycles of insemination. Number of cycles per pregnancy was similar (P>.05) for treated and control mares (1.37 vs 1.13) as was number of days mares exhibited estrus (6.30 vs 6.13). Number of inseminations per cycle did not differ (P>.05) between treated and control mares (2.92 vs 3.00). In summary, there was no effect of treatment with altrenogest from day 20 to 320 of gestation on periparturient events, viability and growth of offspring and subsequent reproductive performance of mares.     

Effects of oral supplementation with β-carotene on concentrations of β-carotene, vitamin A and α-tocopherol in plasma, colostrum and milk of mares and plasma of their foals and on fertility in mares

In this study, effects of oral β-carotene supplementation to mares (β-carotene group: 1000 mg/day, n = 15; control group: n = 15) from 2 weeks before foaling until 6 weeks thereafter on concentrations of β-carotene, vitamin A and α-tocopherol in plasma, colostrum and milk and plasma of their foals were determined. In addition, effects on fertility were studied. Beta-carotene concentrations increased in plasma and colostrum of β-carotene-supplemented mares compared to control mares (p < 0.05). In mares of both groups, β-carotene concentrations were higher in colostrum than in milk (p < 0.05). In foals, β-carotene concentrations increased with colostrum uptake and were higher in foals born to supplemented mares (p < 0.05; control group: 0.0003 ± 0.0002 μg/ml on day 0, 0.008 ± 0.0023 μg/ml on day 1; β-carotene group: 0.0005 ± 0.0003 μg/ml on day 0, 0.048 ± 0.018 μg/ml on day 1). Concentrations of vitamin A and α-tocopherol were higher in colostrum than in milk (p < 0.05) but did not differ between groups. Concentration of α-tocopherol in plasma of mares decreased over time and in foals, increased markedly within 4 days after birth. All but one mare (control group) showed oestrus within 2 weeks post-partum. Occurrence of oestrus did not differ between groups. More mares of the control group (7/7 vs. 5/12 in the β-carotene group) became pregnant after being bred in first post-partum oestrus (p < 0.05). In conclusion, β-carotene supplementation to mares increased β-carotene concentrations in plasma, colostrum and milk of mares and plasma of their foals but had no positive effects on fertility.     

A preliminary study of the efficacy of fluphenazine as a treatment for fescue toxicosis in gravid pony mares

This study was designed to determine the efficacy of a single injection of the long-acting D₂-dopamine receptor antagonist, fluphenazine deconoate, on the clinical symptoms and plasma prolactin concentrations of mares grazing endophyte-infected tall fescue. Twelve mares were maintained on an 80% endophyte-infected tall fescue pasture. Group T (n=6) received 25 mg of fluphenazine deconoate i.m. on day 320 of gestation, while group C (n=6) served as untreated controls. Daily plasma samples were obtained and analyzed for prolactin using a homologous equine radioimmunassay. The prolactin data were then grouped according to week after treatment (day 320 to 327=Week 1; day 328 to 335=Week 2) and to week prior to parturition (day 0 to −7=Week −1; day −8 to −14=Week −2). A single injection of fluphenazine had no effect on experiment-wide plasma prolactin concentrations or on prolactin concentrations relative to week of treatment or parturition. However, a treatment by time period interaction was observed. Plasma prolactin concentrations were higher (p<.05) in treated mares (35.6±29.1 ng/ml) on week 2 compared to control mares (14.9±14.2 ng/ml). In addition, there was a trend (p=.09) for fluphenazine treated mares (68.1±64.2 ng/ml) to exhibit higher prolactin concentrations one week prior to parturition when compared to control animals (27.8±27.4 ng/ml). Peak prolactin was higher (p<.05) in fluphenazine treated mares and in mares which foaled normally. Gestation lengths were shorter (p<.05) in group T (330±2.9 days) compared to group C (341±3.2 days). It appeared that treated mares exhibited fewer clinical signs of fescue toxicosis than mares in group C. Four out of six of the untreated mares exhibited at least one of the clinical signs of fescue toxicosis (agalactia, stillbirth, thickened placenta, retained placenta) while only one treated mare showed obvious clinical symptoms. These data indicate that a single injection of a long-acting dopamine receptor antagonist may be beneficial in reducing the effects of fescue toxicosis in pregnant mares grazing endophyte-infected tall fescue pastures. However, additional research is needed to determine the most effective dosage and administration times.     

Plasma progesterone in mares showing oestrus during early pregnancy (author's transl)]

Sixtyfour mares were examined 3 and 6 weeks after mating. Progesterone was measured in 22 mares 3 weeks after mating in order to see if this could be of any help in the oestrous diagnosis. None of the pregnant mares had plasma progesterone below 2 ng/ml. Pregnant mares that did not show oestrus had higher levels of plasma progesterone than pregnant mares showing signs of oestrus 3 weeks after mating. Clinical findings in pregnant and nonpregnant mares 3 weeks after mating is compared, and oestrus in pregnant mares is discussed.     

Plasma luteinizing hormone and progesterone concentrations in goats with estrous cycles of normal or short duration after prostaglandin F2 alpha administration during diestrus or pregnancy

Plasma luteinizing hormone (LH) and progesterone concentrations were compared in does experiencing short-duration estrous cycles and in does with estrous cycles of normal duration. The short-duration estrous cycles were observed immediately after induction of abortion in pregnant does by use of prostaglandin (PG) F2 alpha. Intramuscular administration of 5 mg of PGF2 alpha was accomplished in 8 does that were 52 to 63 days into gestation and in 9 cycling does at 7 to 10 days after estrus. In both groups, the mean plasma concentration of progesterone decreased from a luteal phase concentration immediately before to less than 1 ng/ml by 24 hours after PGF2 alpha administration. Of the 8 does that aborted, 6 experienced short-duration estrous cycles, and 4 of these 6 had an LH surge during the time of blood sample collection. The mean time from PGF2 alpha administration to the LH surge was significantly (P less than 0.05) longer in does with short-duration estrous cycles (71 hours) than that in does with estrous cycles of normal duration (58 hours). The mean area under the LH concentration curve was significantly (P less than 0.005) less for does with short-duration estrous cycles. Short-duration estrous cycles were associated with delayed preovulatory LH surges of reduced magnitude.