A simple pharmacokinetic model linking plasma progesterone concentrations with the hormone released from bovine intravaginal inserts

On the basis of pharmacokinetic modeling, this study provides some insights into predicting in vivo plasma progesterone concentrations when using bovine intravaginal inserts for systemic progesterone delivery. More significantly, this contribution is the first attempt to build a simple pharmacokinetic model that links plasma progesterone concentrations with the hormone released from bovine intravaginal inserts. After evaluating three rival pharmacokinetic models and considering some phenomena involved in the intravaginal administration of progesterone, a primary pharmacokinetic model having a good data fitting capability with only two adjustable parameters is proposed to the above mentioned task. Kinetic parameters are given for lactating Holstein dairy cows with two levels of daily milk yields; and non-pregnant, non-lactating Holstein-Friesian cattle. Model predictions indicate the occurrence of a preferential distribution of the intravaginally administered progesterone dose through a first uterine pass effect.     

Efficacy of intravaginal progesterone administration combined with prostaglandin f(2alpha) for cystic ovarian disease in Japanese Black cows

The objective of this study was to investigate cystic ovarian disease (COD) in commercial Japanese Black cows and to evaluate the efficacy of 7-day insertion of an intravaginal progesterone insert (CIDR) combined with prostaglandin F(2alpha) (PGF(2alpha)) at CIDR removal. Experiment 1 was conducted to group cysts into 4 patterns based on alteration of plasma progesterone (P(4)) concentrations on d -7 and d 0 (=CIDR insertion) with 1.0 ng/ml as the cut-off level by ultrasonographic examination of 28 cows with COD that were >or=40 days postpartum and anoestrous after calving. In Experiment 2, a total of 55 cows under the same conditions as in Experiment 1 were utilized, and the same regimen as in Experiment 1 was performed without 7 days of pre-observation before treatment. As a result, 92.9% of CLs on d 21 were highly formed in Experiment 1 and 83.6% were highly formed in Experiment 2. The conception rates within 60 days after CIDR removal were also satisfactory high and were 71.4% and 54.5%, respectively. There were no differences in any overall reproductive parameters between Experiments 1 and 2 (P>0.05). The average days between CIDR removal and conception were 24.4 +/- 5.3 and 24.0 +/- 6.5 days, respectively (P>0.05); therefore, the conception dates of the cows in Experiment 2 were at least 7 days earlier compared with Experiment 1. In conclusion, treatment with a CIDR and PGF(2alpha) against COD could minimize the risk of incorrect treatment and provide sufficient reproductive performance in Japanese Black cows.     

The effects of duration and concentration of plasma progesterone on the fertility of post-partum cows treated with pregnant mare serum gonadotrophin and intravaginal progesterone

The effects of duration of insertion of progesterone releasing devices (PRIDs) on the concentrations of plasma progesterone (plasma P4) and the relationship of these with fertility were examined respectively in ovariectomised and intact Bos taurus cattle. In experiment 1, ovariectomised cows (n = 14) were treated with PRIDs to produce high and low plasma P4 for 7 or 14 days giving 4 treatment groups designated H7, H14, L7 or L14. Mean plasma P4 in the H14 and L14 groups were 6.6 and 6.0 ng/ml respectively, during the first week and 5.4 and 3.8 ng/ml respectively, during the second. Mean plasma P4 of 6.3 and 4.2 ng/ml were observed in H7 and L7. In experiment 2, suckled cows (n = 171) received the same PRID treatments as cows in experiment 1, plus either 375 or 750 iu pregnant mare serum gonadotrophin, and subsequent calving rates were recorded. These were significantly lower after L7 than the other treatments (12% v 38%, P less than 0.025). These results showed that fertility after oestrus was closely related to plasma P4 observed before oestrus and indicated that treatment with progesterone for as little as 1 week can produce normal fertility providing plasma P4 attain a critical threshold during treatment.     

Effects of plasma progesterone concentrations on LH release and ovulation in beef cattle given GnRH

The effects of plasma progesterone concentrations on LH release and ovulation in beef cattle given 100 microg of GnRH im were determined in three experiments. In Experiment 1, heifers were given GnRH 3, 6 or 9 days after ovulation; 8/9, 5/9 and 2/9 ovulated (P<0.02). Mean plasma concentrations of progesterone were lowest (P<0.01) and of LH were highest (P<0.03) in heifers treated 3 days after ovulation. In Experiment 2, heifers received no treatment (Control) or one or two previously used CIDR inserts (Low-P4 and High-P4 groups, respectively) on Day 4 (estrus=Day 0). On Day 5, the Low-P4 group received prostaglandin F(2alpha) (PGF) twice, 12 h apart and on Day 6, all heifers received GnRH. Compared to heifers in the Control and Low-P4 groups, heifers in the High-P4 group had higher (P<0.01) plasma progesterone concentrations on Day 6 (3.0+/-0.3, 3.0+/-0.3 and 5.7+/-0.4 ng/ml, respectively; mean+/-S.E.M.) and a lower (P<0.01) incidence of GnRH-induced ovulation (10/10, 9/10 and 3/10). In Experiment 3, 4-6 days after ovulation, 20 beef heifers and 20 suckled beef cows were given a once-used CIDR, the two largest follicles were ablated, and the cattle were allocated to receive either PGF (repeated 12h later) or no additional treatment (Low-P4 and High-P4, respectively). All cattle received GnRH 6-8 days after follicular ablation. There was no difference between heifers and cows for ovulatory response (77.7 and 78.9%, P<0.9) or the GnRH-induced LH surge (P<0.3). However, the Low-P4 group had a higher (P<0.01) ovulatory response (94.7% versus 61.1%) and a greater LH surge of longer duration (P<0.001). In conclusion, although high plasma progesterone concentrations reduced both GnRH-induced increases in plasma LH concentrations and ovulatory responses in beef cattle, the hypothesis that heifers were more sensitive than cows to the suppressive effects of progesterone was not supported.     

Measurement of Faecal Progesterone Metabolites and its Application for Early Screening of Open Cows Post-insemination

The present study investigated the changes of serum progesterone (P4) and its faecal metabolites in pregnant and non-pregnant cows (Expt 1) and the feasibilty of using faecal P4 metabolites for early screening of open cows post-insemination (Expt 2). In Expt 1, seven crossbred Holstein-Friesian (HF) cows were studied. Serum and faecal samples were collected once daily from the day of artificial insemination (AI) until 25 days after AI. In Expt 2, 27 crossbred HF inseminated cows were employed. Serum and faecal samples were obtained on the day of AI (day 0) and on days 19-22 post-insemination. Enzyme immunoassay measurements of serum P4 and faecal P4 metabolites were established. The low detection limit of the assay was 0.01 ng/ml and the amount of P4, resulting in a 50% reduction in the initial binding value, was 1.07 ng/ml. The intra- and inter-assay coefficients of variation were <8% and <14%, respectively. A positive correlation between the levels of serum P4 and faecal P4 metabolites was found in every single cow (r = 0.73-0.88, p < 0.001) and pooled data (r = 0.78, p < 0.001). The estimated value of faecal P4 metabolites at 100 ng/g of faeces was equal to the serum P4 levels of 1 ng/ml. The accuracies of pregnancy and non-pregnancy diagnosis based on the analyses of faecal P4 metabolites between day 0 and days 19-22 post-insemination, were 67% and 100%, respectively. In conclusion, the measurement of faecal P4 metabolites can be a potentially alternative method for early screening of open cows post-insemination with the same accuracy and precision, as measured by serum P4 assay.     

Supra-basal progesterone concentrations during the follicular phase are associated with development of cystic follicles in dairy cows

The objective of this study was to test the hypothesis that supra-basal concentrations of progesterone during the follicular phase are associated with the development of follicular cysts. Twenty-five non-lactating dairy cows were used in the study, which was performed over five identical replicate trials. Luteolysis was induced during the mid-luteal phase. Transrectal ultrasonography was performed daily to determine the occurrence/timing of ovulation. Plasma samples were collected for progesterone, oestradiol and luteinizing hormone (LH) analysis. Three cows failed to ovulate (cystic anovulatory) but did ovulate in a subsequent replicate (cystic ovulatory). Eight cows from the appropriate replicates were used as control cows (normal group). Follicular growth patterns and plasma oestradiol concentrations were similar between the three groups. However, the plasma progesterone concentrations during the follicular phase were twofold higher in the cystic anovulatory group (P < 0.01). Furthermore, no LH surge was detected in these animals. While LH pulse amplitude was similar between groups, LH pulse frequency in the cystic anovulatory group was attenuated (P < 0.05). In conclusion, the formation of follicular cysts were preceded by elevated plasma progesterone concentrations and the suppression of the LH surge.     

Effect of exogenous progesterone administration on luteal sensitivity to PGF during the early development of the corpus luteum in mares and cows

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

Effects of time of progesterone supplementation on embryo development and interferon-tau production in the cow

We have investigated the effects of the timing of progesterone supplementation on early embryo development in mature, non-lactating Holstein-Friesian cows. Animals were inseminated 72 h (day 1) and 96 h following prostaglandin injection and were either left as untreated controls (n=6) or received progesterone supplementation from either days 5 to 9 (early; n=6) or from days 12 to 16 (late; n=6). Daily plasma samples were collected until day 16, when cows were slaughtered and reproductive tracts recovered and flushed to collect embryos and to measure interferon-tau activity. Both early and later progesterone supplementation resulted in marked increases in plasma progesterone (P<0.01). Early, but not late, progesterone supplementation resulted in a fourfold increase in trophoblast length (P<0.01) and a sixfold increase in uterine concentration of interferon-tau (P<0.05). The results demonstrate that progesterone supplementation during the postovulatory rise, but not later in the luteal phase, increases embryo development and interferon-tau production.     

Effects of suckling on oestradiol benzoate induced LH release in post-partum, ovariectomised cows

Twelve suckling and 12 non-lactating post-partum cows were treated with a progesterone-releasing pessary for 7 or 14 d followed by an injection of 500 micrograms oestradiol benzoate (ODB) 24 h after pessary removal or no injection. Suckling had no significant effect on plasma progesterone concentrations (plasma P4) or plasma luteinising hormone concentrations (plasma LH) during pessary insertion. After pessary removal plasma LH rose in response to ODB. The extent of the rise was similar in suckling and non-lactating cows treated with progesterone for 14 d but was significantly lower in non-lactating than suckling cows (P less than 0.025) treated for 7 d. These findings indicate that suckling increases the responsiveness of plasma LH in post-partum cows following progesterone and oestrogen treatment compared to non-lactating cows and that extended treatment with progesterone can remove this difference.     

Effect of prostaglandin F2 alpha-induced luteolysis on in vivo and in vitro progesterone production by individual placentomes of cows

This study investigated placental progesterone production by bovine placentomes. Catheters were placed in the femoral artery (FA) and in the caruncular artery (CA), caruncular vein (CV) and lymphatic vessel of a prominent placentome of 13 cows at 200 d of gestation. Four of the 13 cows were given prostaglandin F2 alpha (PGF2 alpha) after surgery, and blood and lymph were collected for progesterone determination. After 24 h, progesterone was higher (P less than .01) in FA and CA plasma from control cows that FA and CA plasma from PGF2 alpha-treated cows (5.11 +/- .29 and 5.17 +/- .64 vs 1.41 +/- .08 and 1.15 +/- .08 ng/ml, respectively), but CV concentrations were similar (3.38 +/- .30 vs 2.56 +/- .24, respectively). There was a net uptake of progesterone by placentomes from control cows (P less than .01) but a net secretion in PGF2 alpha-treated cows (P less than .05). Lymph contained low progesterone concentrations regardless of treatment. Cows were slaughtered at 240 d of gestation. Placentomes were removed and perfused with pregnenolone through the maternal and fetal arteries. Fetal venous effluent contained more progesterone than maternal venous effluent (P less than .001) in both groups, and fetal venous effluent of placentomes from PGF2 alpha-treated cows contained more progesterone than that from control cows (P less than .05). Maternal and fetal components of other placentomes were cultured alone or in co-culture along with pregnenolone and (or) epostane. Fetal tissue produced more progesterone (P less than .001) than maternal tissue when each was cultured alone, but fetal tissue production declined when co-cultured with maternal tissue.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reproductive performance of dairy cows not detected in oestrus but with a detectable corpus luteum, in response to treatment with progesterone, oestradiol benzoate and prostaglandin F2alpha

AIM: To determine if the reproductive performance of dairy cows not previously detected in oestrus but with a detectable corpus luteum before the planned start of mating (PSM), could be improved by treatment with progesterone, oestradiol benzoate (ODB) and prostaglandin F2alpha (PGF). METHODS: Cows in 18 herds which had not been detected in oestrus, but which had a detectable corpus luteum present at veterinary examination 7 days prior to the PSM (Day -7), were allocated to 1 of 2 groups. Treated cows (n=232) received an injection of 2 mg ODB and an intravaginal progesterone releasing device (CIDR insert) on Day -7, and an injection of PGF on the day of insert removal 7 days later (Treated group). The Control group (n=243) remained untreated. Cows were mated to detected oestrus from Day 0, and conception dates confirmed by manual palpation or transrectal ultrasonography. RESULTS: During the first 7 days of mating, 37.4% of Control cows and 65.9% of Treated cows were inseminated on detection of oestrus (p<0.001). Pregnancy rates for this period were 20.4% and 36.3%, respectively (p=0.001). Conception rates to first insemination, pregnancy rates after 21 days of mating and at the end of the mating period were similar between groups (p>0.1). Median interval from the PSM to conception did not differ between treatment groups (24 and 23 days for Control and Treated, respectively, p>0.1). CONCLUSION: Treating postpartum dairy cows which had not previously been detected in oestrus but which had a detectable corpus luteum, with progesterone, ODB and PGF did not significantly improve their reproductive performance compared with no hormonal intervention. KEY WORDS: dairy cattle, postpartum, anoestrous, reproduction, progesterone treatment.     

Age‐related changes in the bovine corpus luteum function and progesterone secretion

Decreased fertility associated with maternal ageing is a well‐known critical problem, and progesterone (P4) concentration decreases during the menopause transition in women. The corpus luteum (CL) secretes P4, thereby supporting the implantation and maintenance of pregnancy. It is proposed that a bovine model is suitable for studying age‐associated decline of fertility in women because the physiology of cows is similar to that of women and cows have a greater longevity compared with other animal models. Thus, we investigated the age‐dependent qualitative changes and inflammatory responses in the bovine CL. In vivo experiment: Cows were divided into three groups, namely, young (mean age: 34.8 months), middle (80.1 months) and aged (188.9 months). Blood samples were collected on days 7 and 12 during the estrous cycle. In vitro experiments: Cows were divided into young (mean age: 27.6 months) and aged (183.1 months). The CL tissues of these groups were collected from a local slaughterhouse and used for tissue culture experiments. An in vivo experiment, plasma P4 concentration in aged cows was significantly lower than that in young cows, whereas no difference was found regarding the area of CL. An in vitro examination in the bovine CL tissues showed that the luteal P4 concentration, P4 secretion, and mRNA expression of StAR and 3β‐HSD were lower in aged cows compared with young cows, especially in the early luteal phase. However, no differences were detected in the mRNA expression of inflammation‐ and senescence‐related factors and inflammatory responses to lipopolysaccharides between the CL tissues from young and aged cows, indicating that an age‐dependent increase in inflammation is not involved in the luteal function. P4 production and secretion from the bovine CL diminish in old cows, especially during the early luteal phase, suggesting that senescence may affect the luteal function in cows.     

Effect of ovulatory follicle size and expression of estrus on progesterone secretion in beef cows

Induced ovulation of small dominant follicles (SF, < 12 mm; CO-Synch protocol) in postpartum beef cows resulted in formation of corpora lutea (CL) that exhibited a delayed rise in progesterone (P4) compared with CL from large dominant follicles (LF, > 12 mm). Experiment 1 characterized P4 concentrations from ovulation to subsequent estrus among GnRH-induced or spontaneously ovulated SF (or= 12 mm) to determine if P4 secretion by CL formed from GnRH-induced SF remains lower postovulation in nonlactating beef cows. Nonlactating beef cows were induced to ovulate 48 h after PGF(2alpha) (CO-Synch; GnRH on d - 9, PGF(2alpha) on d - 2, and GnRH on d 0) or exhibited estrus and spontaneously ovulated after PGF(2alpha). Follicle size was measured at the second GnRH in cows induced to ovulate or approximately 3 h after the onset of estrus for cows that ovulated spontaneously. Cows were classified into 1 of 4 groups: 1) GnRH-induced ovulation-SF (or= 12 mm; Ind-LF; n = 16); 3) spontaneous ovulation-SF (or= 12 mm; Spon-LF; n = 22). Serum concentrations of P4 from d 3 to 15 were reduced in the Ind-SF compared with the Ind-LF (P = 0.05), Spon-SF (P = 0.07), and Spon-LF (P = 0.03). Experiment 2 characterized P4 concentrations (0 to 60 d postAI) among GnRH-induced or spontaneously ovulated SF (or= 13 mm) to determine if P4 secretion by CL formed from GnRH-induced SF remained lower during early gestation. Ovulation was induced with GnRH 48 h after PGF(2) (CO-Synch) or occurred spontaneously, and ovulatory follicle size was measured at AI. Lactating cows were classified into 1 of 3 groups: 1) GnRH-induced ovulation-SF (or= 13 mm; Ind-LF; n = 43); or 3) spontaneous ovulation-LF (>or= 13 mm; Spon-LF; n = 27). The increase in P4 concentrations was greater (P = 0.06) in pregnant (d 2 to 12) compared with nonpregnant cows. Also, the increase in P4 from d 2 to 12 was greater (P = 0.01) in the Ind-LF compared with the Ind-SF groups, but there was no difference (P = 0.94) among groups in P4 from d 14 to 60 in pregnant cows. Follicle size at AI influenced the increase in P4 in cows that failed to conceive (P = 0.007), but not among cows that became pregnant (P = 0.32) to AI. In summary, P4 secretion after GnRH-induced ovulation of SF was decreased from d 2 to 12 compared with that of LF, but was similar among pregnant cows from d 14 to 60 postAI (d 0).     

Intravaginal progesterone devices in synchronization protocols for artificial insemination in beef heifers

Two experiments were designed to investigate the administration of intravaginal progesterone in protocols for oestrus and ovulation synchronization in beef heifers. In Experiment 1, cyclic Black Angus heifers (n = 20) received an Ovsynch protocol and were randomly assigned to receive (CIDR‐Ovsynch) or not (Ovsynch) a progesterone device between Days 0 and 7. Treatment with a controlled internal drug release (CIDR) device significantly increased the size of the dominant follicle prior to ovulation (12.8 ± 0.4 CIDR‐Ovsynch vs 11.4 ± 0.4 Ovsynch) (p < 0.02). Plasma progesterone concentrations throughout the experiment were affected by the interaction between group and day effects (p < 0.004). In Experiment 2, cyclic Polled Hereford heifers (n = 382) were randomly assigned to one of the six treatment groups (3 × 2 factorial design) to receive a CIDR, a used bovine intravaginal device (DIB), or a medroxiprogesterone acetate (MAP) sponge and GnRH analogues (lecirelin or buserelin). All heifers received oestradiol benzoate plus one of the devices on Day 0 and PGF on Day 7 pm (device withdrawal). Heifers were detected in oestrus 36 h after PGF and inseminated 8–12 h later, while the remainder received GnRH 48 h after PGF and were inseminated on Day 10 (60 h). The number of heifers detected in oestrus on Day 8 and conception rate to AI on Day 9 were higher (p < 0.01) in the used‐DIB than in the CIDR or MAP groups, while the opposite occurred with the pregnancy rate to FTAI on Day 10 (p < 0.01). There was no effect of progesterone source, GnRH analogue or their interaction on overall pregnancy rates (64.9%). Progesterone treatment of heifers during an Ovsynch protocol resulted in a larger pre‐ovulatory follicle in beef heifers. Progesterone content of intravaginal devices in synchronization protocols is important for the timing of AI, as the use of low‐progesterone devices can shorten the interval to oestrus.     

Effects of Estradiol and Progesterone on the Numbers and Distribution of Mastocytes in the Uterus of Ovariectomized Rats

The purpose of this study was to investigate the effects of estradiol(E)and progesterone(P)on mastocyte distribution in the uterus of ovariectomized rats.Thirty-five adult female rats were divided randomly into seven groups:one sham operated control group(SHAM);one ovariectomized group(OVX);three ovariectomized plus E treatment groups(OVX+E 20,100,or 500 μg/kg body weight·d);and two ovariectomized plus P groups(OVX+P 2 or 10 mg/kg body weight·d).Seven days after treatment,the contents of estradiol and progesterone in serum were detected by radioimmunoassay,and mastocytes in the uterus were stained by toluidine blue staining.Results were as following:① Compared to ovariectomized rat,the concent ration of estradiol in serum increased by 97.13 % in OVX+E 20(P0.05),204.84 % in OVX+E 100(P0.05),and 936.45 % in OVX + E 500 group(P0.05);the progesterone concent ration increased by 77.25 % in OVX+P 2(P0.05)and 235.25 %in OVX+P 10 group(P0.05).② Compared to ovariectomized rat,the number of mast cells in uteri decreased by 32.65% in OVX+E 20,64.50 % in OVX+E 100(P0.05),74.49 % in OVX+E 500(P0.05)and 70.67 % in OVX+P 10 groups(P0.05).However,the number of mast cells increased by 66.73% in OVX+P 2 group(P0.05)compared with OVX.The trend of mast cells number in the rat uterus was decreased gradually with the increase of estrogen or progesterone concent ration.The number of mast cells in ovariectomized rat uterus was affected by estrogen or progesterone.These results demonstrated that estrogen or progesterone directly affected the number of mast cells in the uterus of rat.     

Conception rates to fixed-time artificial insemination of two oestrus synchronisation programmes in dairy heifers

AIM: To evaluate the conception rate to fixed-time artificial insemination (FTAI) of two oestrus synchronisation programmes in dairy heifers on eight farms over 2 years.

METHODS: The study was conducted in 2008 and 2010 on eight farms near Palmerston North, New Zealand. Nulliparous Friesian and Friesian×Jersey heifers (13–15 months of age) were randomly allocated to one of two oestrus synchronisation programmes. Group 1 (GPG+P4; n=330), received gonadotrophin-releasing hormone (GnRH) I/M on Day 0, a progesterone (P4)-releasing intravaginal device from Days 0–7, prostaglandin F_2α (PGF) I/M on Day 7 and a second dose of GnRH at the time of FTAI on Day 9. The second group (P4+PGF; n=343) received a P4-releasing intravaginal device from Days 0–7, PGF on Day 6 and FTAI on Day 9. Pregnancy was diagnosed from Days 42–52 by transrectal ultrasonography.

RESULTS: The overall conception rate was 52.4% and 54.8% for the GPG+P4 and P4+PGF groups, respectively. The odds of conception for the two treatments were not different (OR=0.90; 95% CI=0.67–1.23), nor was there any difference between groups in different years (p=0.58). Farm affected conception rate (p=0.002), but there was no interaction with treatment (p=0.92) .

CONCLUSIONS: This study has shown that an alternative synchronisation programme can produce similar results in terms of conception rate to the GPG+P4 treatment, currently commonly used in heifers. More research is required to establish whether other modifications to the GPG+P4 programme can produce similar results at lower costs, and to identify and quantify farm factors which affect the economic benefit of heifer synchronisation.

CLINICAL RELEVANCE: This study indicated that synchronising heifers with P4 and PGF resulted in conception rates equivalent to those resulting from a GPG+P4 treatment, but with reduced drug costs. However, because heifers in the GPG+P4 group received the second GnRH injection at the time of AI, they needed only three yardings as opposed to the four required for the heifers treated with P4 and PGF. Thus, the choice of programme for an individual farm will depend on that farm's circumstances, in particular the cost of yarding the heifers.     

Relationship of maternal plasma progesterone and estrone sulfate to dystocia in Holstein-Friesian heifers and cows.

Thirteen primiparous and 41 multiparous Holstein-Friesian cattle were used to study the relationship between maternal plasma progesterone (P4) and estrone sulfate (E1S) concentrations and the prevalence of dystocia. The calvings in 4 heifers and 30 cows were normal (eutocia), while the calvings in 9 heifers and 11 cows were difficult (dystocia). Neither the concentrations of P4 nor E1S were different between the groups with eutocia and dystocia from days 90 to 270 of pregnancy. However, a few days prior to parturition, eutocial cows and heifers showed a sharp decline of plasma P4, while dystocial cattle did not show such a remarkable decline of P4 concentration. Plasma P4 levels in dystocial cows a few days antepartum were significantly higher than in eutocial animals (P<0.05 or P<0.01). Prepartum E1S concentrations were significantly lower (P<0.05) in dystocial than eutocial cattle during the prepartum period from days 6 to 1 in heifers and from days 3 to 1 in cows. These results suggest that insufficient production of E1S and delayed regression of the corpora lutea are possible causes of dystocia in cattle.     

Effects of GnRH or progesterone treatment on day 5 post-AI on plasma progesterone, luteal blood flow and leucocyte counts during the luteal phase in dairy cows

This study was designed to test the effects of progesterone or GnRH treatment on day 5 post-AI on fertility and luteal function in dairy cows and heifers. Five days after AI, 32 animals were randomly assigned to a control, intravaginal progesterone for 14 days progesterone releasing intravaginal device (PRID) or GnRH treatment group. On days 5, 7, 12, 14, 17 and 19 post-AI, each animal underwent colour Doppler ultrasonography of the corpus luteum and blood samples were collected for cell counts and plasma progesterone determination. Through general linear model repeated measures analysis of variance, significant effects were observed of treatment, parity, inseminating bull, reduced vascularization of the CL and pregnancy on plasma progesterone concentrations, whereas mean plasma progesterone and time luteal phase day, and treatment and plasma progesterone concentration on day 5 post-AI were found to, respectively, affect neutrophil and lymphocyte counts throughout the luteal phase. Moreover, two binary logistic regression analyses were performed. Based on the odds ratio, the likelihood of pregnancy by days 26-32 post-AI was 23.4 times higher in animals with high mean progesterone levels throughout the study period, compared with animals with low mean progesterone. The likelihood of reduced CL vascularization was 14 times higher in animals treated with PRID, compared with control and GnRH-treated animals. In conclusion, our results indicate that treatment on day 5 post-AI with PRID reduced subsequent CL vascularization, whereas GnRH treatment increased plasma progesterone concentrations on day 12 post-AI, although an effect was identified of the inseminating bull on plasma progesterone levels. Pregnant animals showed higher mean plasma progesterone concentrations than in nonpregnant ones and heifers higher than in lactating cows, whereas blood cell counts differed depending on the treatment and on the mean plasma progesterone concentration on day 5 post-AI.     

Oxytocin-induced secretion of prostaglandin F2alpha in postpartum beef cows: effects of progesterone and estradiol-17beta treatment

The purpose of the present study was to determine the effect of progesterone or progesterone + estradiol-17beta on oxytocin-induced prostaglandin F2alpha (PGF2alpha) secretion in postpartum beef cows. Thirty-four anestrous postpartum beef cows were ovariectomized (d 32 [Groups 1 to 3] or d 23 [Groups 4 to 6] postpartum [d 0 = parturition]) and allotted to six treatments (Group 1; negative control) to simulate short (Groups 2 through 5) or normal (Group 6) length estrous cycles. Steroid treatments for the respective groups were as follows: Group 1) no estradiol-17beta or progesterone treatment (n = 8; negative control); Group 2) progesterone (d 34 to 40; n = 6); Group 3) estradiol-17beta (d 32 to 33) and progesterone (d 34 to 40; n = 6); Group 4) progesterone (d 23 to 29), no estradiol-17beta (d 32 to 33), and progesterone (d 34 to 40; n = 5); Group 5) progesterone (d 23 to 29), estradiol-17beta (d 32 to 33), and progesterone (d 34 to 40; n = 5); and Group 6) progesterone (d 23 to 29), estradiol-17beta (d 32 to 33), and progesterone (d 34 to 50; n = 4; positive control). Oxytocin (100 IU) was injected (i.v.) at the end of each treatment to test the ability of the postpartum uterus to secrete PGF2alpha as measured by a stable metabolite of PGF2alpha, 15keto-13,14 dihydro-PGF2alpha (PGFM). Peak concentrations ofPGFM (P < 0.08) and total PGFM secreted (area under the curve; P < 0.05) were increased on d 6 following first (Group 2) or second (Group 4) exposure to progesterone and were similar to peak concentrations and total PGFM secreted 16 d following a simulated normal estrous cycle (Group 6). Administration of estradiol-17beta before first progesterone exposure (Group 3) did not reduce peak concentrations of PGFM or total PGFM secreted relative to the preceding groups. Peak concentrations of PGFM (P < 0.08) and total PGFM secreted (P < 0.05) were reduced following a second progesterone exposure, provided that cows were pretreated with estradiol-17beta (Group 5). In summary, oxytocin-induced release of PGFM was inhibited on d 6 following second exposure to progesterone only when cows were pretreated with estradiol-17beta. Therefore, estradiol-17beta and progesterone were both associated with the timing of PGF2, secretion in postpartum cows.     

Supplemental norgestomet,progesterone, or melengestrol acetate increases pregnancy rates in suckled beef cows after timed inseminations

In Exp. 1, 187 lactating beef cows were treated with injections of GnRH 7 d before and 48 h after prostaglandin F2alpha (PGF2alpha; Cosynch) or with Cosynch plus a 7-d treatment with an intravaginal progesterone (P4)-releasing insert (CIDR-B; Cosynch + CIDR). In Exp. 2, 183 lactating beef cows were treated with the Cosynch protocol or with Cosynch plus a 7-d treatment with norgestomet (Cosynch + NORG). In Exp. 1 and 2, blood samples for later P4 analyses were collected on d -17, -7 (first GnRH injection), 0 (PGF2alpha injection), and at timed artificial insemination (TAI; 48 h after PGF2alpha). In Exp. 3, 609 lactating beef cows were treated with the Cosynch + CIDR protocol or were fed 0.5 mg of melengestrol acetate (MGA) per day for 14 d before initiating the Cosynch protocol 12 d after the 14th d of MGA feeding (MGA + Cosynch). Blood samples were collected as in Exp. 1 and 2, plus additional samples on d -33 and -19 before PGF2alpha. In Exp. 4, 360 lactating beef cows were treated with a Cosynch + CIDR protocol, with TAI occurring at either 48 or 60 h after PGF2alpha, while receiving either GnRH or saline to form four treatments. Blood samples were collected as in Exp. 1 and 2. In Exp. 1, addition of P4 reduced the ability of the first GnRH injection to induce ovulation in anestrous cows with low P4 before PGF2alpha but improved (P = 0.06) pregnancy rates (61 vs 66%). In Exp. 2, the addition of NORG mimicked P4 by likewise increasing (P < 0.01) pregnancy rates (31 vs 51%) beyond those after Cosynch. In Exp. 3, the Cosynch + CIDR protocol increased (P < 0.001) pregnancy rates from 46 to 55% compared to the MGA + Cosynch protocol. In Exp. 4, administration of GnRH at TAI improved (P < 0.05) pregnancy outcomes (50 vs 42%), whereas timing of TAI had limited effects. We conclude that a progestin treatment concurrent with the Cosynch protocol improved pregnancy outcomes in all experiments, but pretreatment of cows with MGA was not as effective as the CIDR insert or NORG implants in this Cosynch-TAI model. Most of the improvement in pregnancy rates was associated with the increase in pregnancy rates of anestrous cows, regardless of whether ovulation was successfully induced in response to GnRH 7 d before PGF2alpha. Injection of GnRH at TAI following the Cosynch + CIDR protocol increased pregnancy rates in cycling cows with high P4 before the PGF2alpha injection and in anestrous cows with low P4 before PGF2alpha injection.