Increase In PGFM Research Articles

Use of serum progesterone and prostaglandin F2α metabolite levels to predict onset of parturition in the bitch.

The prediction of time to onset of parturition in a preparturient bitch is of great clinical value, particularly for bitches at high risk of dystocia and those lacking relevant clinical data from the time of breeding. In a previous study, four cut-offs for plasma progesterone levels, measured by radioimmunoassay, were shown to be useful for predicting the likelihood of a bitch entering stage one of parturition within defined time intervals. The first aim of the current study was to evaluate these cut-offs in a clinical setting, using serum progesterone samples drawn from preparturient bitches 12-hourly instead of 6-hourly and assessed using chemiluminescence immunoassay. Furthermore, the use of 13,14-dihydro-15-keto-prostaglandin F2α, (PGFM), a metabolite of prostaglandin F2α , in predicting the time to onset of parturition was evaluated. Forty bitches carrying two or more foetuses were admitted to a specialist veterinary reproduction hospital 53 d after the onset of cytological dioestrus when that date was known, or 57 d after the last mating. Vaginal speculum examinations were performed every 6hr until cervical dilatation was visualized (time of cervical dilatation; TCD). Serum samples were collected at 08h00 and 18h00 daily until TCD. All bitches underwent elective caesarean section at TCD. Results of this study show that approximately 5% and 10% of preparturient bitches will reach TCD within 12hr despite a serum progesterone level of at least 15.8nmol/L and 8.7nmol/L respectively. In addition, there is a 95% probability that a preparturient bitch will reach TCD within 48hr if her serum progesterone level is below 8.7nmol/L, and a 91% probability of her reaching TCD within 24hr if her serum progesterone level is below 3.18nmol/L. Approximately 90% of bitches that demonstrate a 20% increase in PGFM over a 12-hr period are likely to be within 36hr of TCD. These results provide useful benchmarks for the management of canine parturition.

Concentrations of progesterone and a PGF2α metabolite during the interovulatory interval compared to the corresponding days of pregnancy in mares

The concentrations of progesterone (P4) and a metabolite of PGF2α (PGFM) in mares were compared between the interovulatory interval (IOI; n = 8) and the corresponding days of pregnancy (n = 9). In daily blood samples, P4 increased between the day of ovulation (Day 0) and ∼Day 6 and then gradually decreased until the beginning of luteolysis in the IOI group. Before the beginning of luteolysis, there were no significant differences in P4 concentrations between the IOI and early pregnancy. In the IOI, PGFM concentration on the day before the beginning of luteolysis began to increase (P < 0.04) and reached a maximum mean (42.9 ± 11.6 pg/mL) on Day 14. In pregnancy, a novel increase in PGFM occurred from Day 12 to a maximum mean on Day 15 (16.7 ± 3.1 pg/mL). Daily PGFM concentrations were not different between the two groups until the increase just before luteolysis in the IOI. During 8-h sessions of hourly blood sampling, the mean and maximum PGFM concentrations were significantly greater in IOI than in pregnancy for each 8-h session on Days 13, 14, and 15. The minimum was not different between groups on any day. Pulses of PGFM were identified by coefficient of variation during the hourly 8-h sessions on day-sets of Days 4–7, 9–11, and 13–16. Despite the PGFM increase in daily samples between Days 12 and 15 of pregnancy, the amplitude and peaks of CV-identified pulses did not differ in the pregnant mares among the three day-sets. The pulses were similarly small for day-sets 4–7 and 9–11 in the IOI and for all day-sets in pregnancy (eg, amplitude on Days 13–16: 43.4 ± 15.6 pg/mL vs 5.4 ± 1.1 pg/mL for IOI vs pregnancy). Hypothesis 1 was not supported that daily PGFM concentrations in an IOI increase at the intersection between the end of the rapid P4 increase and the gradual P4 decrease. Hypothesis 2 was supported that pregnant mares have low amplitude PGFM pulses during the days of the high amplitude pulses at luteolysis in the IOI.

Use of urinary 13,14, dihydro-15-keto-prostaglandin F2α (PGFM) concentrations to diagnose pregnancy and predict parturition in the giant panda (Ailuropoda melanolecua).

Pregnancy determination is difficult in the giant panda (Ailuropoda melanolecua), representing a challenge for ex situ conservation efforts. Research in other species experiencing pseudopregnancy indicates that urinary/fecal concentrations of 13,14, dihydro-15-keto-prostaglandin F2α (PGFM) can accurately determine pregnancy status. Our objective was to determine if urinary PGFM concentrations are associated with pregnancy status in the giant panda. Urinary PGFM concentrations were measured in female giant pandas (n = 4) throughout gestation (n = 6) and pseudopregnancy (n = 4) using a commercial enzyme immunoassay. Regardless of pregnancy status, PGFM excretion followed a predictable pattern: 1) baseline concentrations for 11–19 weeks following ovulation; 2) a modest, initial peak 14–36 days after the start of the secondary urinary progestagen rise; 3) a subsequent period of relatively low concentrations; and 4) a large, terminal peak at the end of the luteal phase. Pregnant profiles were distinguished by an earlier initial peak (P = 0.024), higher inter-peak concentrations (P < 0.001), and a larger terminal peak (P = 0.003) compared to pseudopregnancy profiles. Parturition occurred 23 to 25 days from the initial PGFM surge and within 24 hours of the start of the terminal increase. These pattern differences indicate that urinary PGFM monitoring can be used to predict pregnancy status and time parturition in the giant panda. Furthermore, this is the only species known to exhibit a significant PGFM increase during pseudopregnancy, suggesting a unique physiological mechanism for regulating the end of the luteal phase in the giant panda.

Different prostaglandin F2 α secretion in response to oxytocin injection between pregnant and non-pregnant cows: effect of the day of oxytocin challenge test for determining the difference.

The present study was conducted to determine the difference in plasma prostaglandin F2 α metabolite concentrations following oxytocin (OT) challenge between pregnant and non-pregnant cows. Experiment 1: cows were subjected to the OT challenge test on days 12, 14 or 16 (day of estrus=day 0) with or without prior insemination and plasma 13,14-dihydro-15-keto prostaglandin F2 α (PGFM) concentrations were measured from -30 to 180min after OT injection. On day 16, the increment of plasma PGFM concentrations in response to OT injection was significantly smaller in pregnant than that in cyclic cows. On days 12 and 14, there was little OT-induced PGFM secretion and no difference in PGFM increase between the pregnant and cyclic cows. Experiment 2: cows were inseminated on day 0 and subjected to the OT challenge test on day 16. Cows were classified into non-pregnant/early embryonic death (NP/EED), late embryonic death (LED) and pregnant (PREG) groups. The increment of PGFM concentrations in response to OT injection was less in both PREG and LED groups than that in the NP/EED group. In conclusion, plasma PGFM secretion induced by OT is suggested as the base of pregnancy diagnosis prior to returning estrus in cows.

Defective secretion of Prostaglandin F2α during development of idiopathic persistent corpus luteum in mares

Five mares that developed idiopathic persistent corpus luteum (PCL) were compared with 5 mares with apparently normal interovulatory intervals (IOIs). Progesterone (P4) and a metabolite of prostaglandin F2α (PGFM) were assayed daily beginning on the day of ovulation (Day 0). Transition between the end of an initial progressive P4 increase and the beginning of a gradual decrease in P4 occurred on mean Day 6. The gradual decrease in P4 between Days 6 and 12 was less (approached significance, P < 0.06) in the PCL group than in the IOI group. The P4 concentration on Day 12 (before luteolysis in IOI group) was greater (P < 0.05) in the PCL group than in the IOI group. In a post hoc comparison, an interaction (P < 0.04) of group by day for Days 4 to 7 indicated that the end of the progressive increase in P4 was temporally associated with a transient increase in concentration of PGFM in IOI mares but not in PCL mares. Complete luteolysis (P4 < 1 ng/mL) occurred in the IOI mares on Days 13 to 15. Partial luteolysis (mean P4 decrease, 62%) occurred in 3 of the 5 PCL mares. Normalization to the day at the end of the most pronounced P4 decrease in the IOI mares and in the 3 PCL mares with partial luteolysis resulted in a day-by-group interaction (P < 0.05) for PGFM concentration. The interaction was partly from lower PGFM concentration on the day at the end of the pronounced P4 decrease in the 3 PCL mares than in the IOI mares. The peak of a transient PGFM increase and the day at the end of the most pronounced decrease in P4 were synchronized in each IOI mare but not in any of the 3 PCL mares. In the other 2 PCL mares, partial luteolysis did not occur, and a transient increase in PGFM was not apparent. Results tentatively indicated that the relationship between P4 and PGFM may be altered as early as Day 6 in PCL mares and supported the hypothesis that prostaglandin F2α secretion is defective in mares with idiopathic PCL.

Interrelationships among progesterone, LH, and luteal blood flow during a pulse of a PGF2α metabolite and functional role of LH in the progesterone rebound in heifers

On Day 16 (Day 0 = ovulation) or before the expected transition into the luteolytic period, heifers were not treated (control group, N = 7) or were treated with a single 0.1-mg dose of estradiol (E2) (E2 group, N = 6) or E2 combined with the GnRH antagonist acyline (E2/Ac group, N = 5). Hourly blood samples were collected from hour of treatment (Hour 0) to Hour 20. Estradiol induced a pulse of PGFM, but the peak of the pulse occurred 2 hours later (P < 0.05) and mean PGFM concentrations during the descending portion of the pulse were lower (P < 0.05) in the E2/Ac group than in the E2 group. In the E2 group, concentration of progesterone (P4) decreased (P < 0.05) during the ascending portion of the PGFM pulse, and increased (rebounded; P < 0.05) along with an LH increase during the descending portion. In the E2/Ac group, a rebound in P4 and an increase in LH were not detected during the descending portion of the PGFM pulse. The percentage of CL with color Doppler signals of blood flow increased (P < 0.04) concurrently with the PGFM increase during Hours 0 to 5 and during the ascending portion of the PGFM pulse. Blood flow and PGFM decreased concurrently. The following hypotheses were supported: (1) LH has a positive effect on PGFM pulses; (2) the rebound in P4 and the increase in LH during the descending portion of a PGFM pulse are functionally related; and (3) the increase in luteal blood flow in association with a PGFM pulse represents a direct effect of PGF2α rather than an effect of P4 or LH.

Influence of Trueperella pyogenes in uterus on corpus luteum lifespan in cycling cows

To study ovarian responses to long-term intrauterine infusions of Trueperella pyogenes (T. pyogenes), 12 nonlacting Holstein cows were transcervically infused with 10 mL of a bacterial solution (8–19 × 108 colony-forming units/mL), and the uteri of another four cows (control) were similarly infused with sterile physiological saline. Infusions were done six times, every 3 days from Days 3 to 18 (Day 0 = day of spontaneous ovulation). Development of ovarian follicles and the CL were monitored with transrectal, real-time ultrasonography. In five of the experimentally infected cows (group A), the CL, which developed after Day 0, regressed without maturing, and the first dominant follicle (DF) ovulated (mean ± SEM interovulatory interval, 8.6 ± 0.5 days). In group A, plasma 13,14-dihydro-15-keto-PGF2α (PGFM) concentrations rose sharply on Day 6, but plasma progesterone concentrations did not increase substantially (as in the control) and were maintained at approximately 2.5 ng/mL after the first DF ovulated. In seven of the 12 infected cows (group B), the developing CL which formed after Day 0 matured and the second DF ovulated. However, the CL lifespan was shorter (P < 0.01) and the second DF ovulated earlier than in control (interovulatory interval, 16.0 ± 0.4 days and 22.3 ± 1.9 days; P < 0.01). Although there was no sharp increase in PGFM in group B, it tended to be high between Days 11 and 18. In conclusion, long-term, intrauterine infusions of T. pyogenes caused the CL to regress prematurely or to have a somewhat shorter lifespan because of release of endogenous PGF2α.

Canine placenta: a source of prepartal prostaglandins during normal and antiprogestin-induced parturition

Expression of cyclooxygenase 2 (COX2, now known as PTGS2), prostaglandin E2 synthase (PTGES, PGES), and prostaglandin F2alpha synthase (PGFS), of the respective receptors PTGFR (FP), PTGER2 (EP2), and PTGER4 (EP4) and of the progesterone receptor (PGR, PR) was assessed by real-time PCR, immunohistochemistry (IHC), or in situ hybridization (ISH) in utero/placental tissue samples collected from three to five bitches on days 8-12 (pre-implantation), 18-25 (post-implantation), and 35-40 (mid-gestation) of pregnancy and during the prepartal luteolysis. Additionally, ten mid-pregnant bitches were treated with the antiprogestin aglepristone (10 mg/kg bw (2x/24 h)); ovariohysterectomy was 24 and 72 h after the second treatment. Plasma progesterone and 15-ketodihydro-PGF2alpha (PGFM) concentrations were determined by RIA. Expression of the PGR was highest before implantation and primarily located to the endometrium; expression in the placenta was restricted to the decidual cells. PTGS2 was constantly low expressed until mid-gestation; a strong upregulation occurred at prepartal luteolysis concomitant with an increase in PGFM. PGFS was upregulated after implantation and significantly elevated through early and mid-gestation. PTGES showed a gradual increase and a strong prepartal upregulation. PTGFR, PTGER2, and PTGER4 were downregulated after implantation; a gradual upregulation of PTGFR and PTGER2 occurred towards parturition. ISH and IHC co-localized PGFS, PTGFR, PTGES, and PTGS2 in the trophoblast and endometrium. The changes following application of aglepristone were in the same direction as those observed from mid-gestation to prepartal luteolysis. These data suggest that the prepartal increase of PGF2alpha results from a strong upregulation of PTGS2 in the fetal trophoblast with the withdrawal of progesterone having a signalling function and the decidual cells playing a key role in the underlying cell-to-cell crosstalk.

Influence of Experimental Intrauterine Infusion of Arcanobacterium pyogenes Solution on Ovarian Activity in Cycling Cows

To examine the ovarian response to Arcanobacterium pyogenes (A. pyogenes) in uterus, bacterial solution was infused into the uteri of cows, and the follicle and corpus luteum (CL) development were monitored with a real-time ultrasound instrument. In addition, the plasma concentrations of progesterone (P(4)) and 13, 14-dihydro-15-keto-PGF(2alpha) (PGFM) were determined. A 10 ml bacterial solution that contained A. pyogenes (8 to 15 x 10(8) CFU/ml) was infused into the uterus of eight cows transcervically three days after natural ovulation. As a control, sterile physiological saline was infused into 4 other cows. The dominant follicle developed normally in 8 cows after bacteria inoculation. In 4 of these 8 cows, the developing CL regressed, and the first wave dominant follicles, which normally become atretic, ovulated after the inoculation. In the remaining 4 cows, the CL did not regress. The PGFM concentration increased transiently in all 8 cows after the infusion. The mean PGFM concentration of the cows with a regressed CL was significantly lower (P<0.01) than that of the cows whose CLs did not regress. In the control cows, there was no regression of developing CLs, no ovulation of first wave dominant follicles and no transient increase in PGFM after the infusion of sterile physiological saline. These results show that infusion of A. pyogenes into the uterus did not affect folliculogenesis and might have induced PGF(2alpha) production from the uterus.

Plasma concentrations of 13,14-dihydro-15-keto prostaglandin F 2-alpha (PGFM), progesterone and estradiol in pregnant and nonpregnant diestrus cross-bred bitches

The canine corpus luteum (CL) typically sustains elevated plasma progesterone concentrations for 2 months or more, with a peak approximately 15–25 days after ovulation, followed by a slow decline. The processes involved in the slow, protracted regression of the CL over the remaining 1.5–2-month period in nonpregnant bitches and until shortly prepartum in pregnant bitches are not well characterized. The rapid luteolysis that occurs immediately prepartum appears to be a result of a prepartum rise in peripheral PGF. The potential role of PGF in the slow regression process in the several weeks preceding parturition and in nonpregnant bitches after 15–25 days after ovulation is not known. Therefore, plasma concentrations of 13,14-dihydro-15-keto-prostaglandin F 2-alpha (PGFM), progesterone (P 4) and estradiol (E 2) were determined and compared in bitches during nonpregnant diestrus ( n = 9) or pregnancy ( n = 8). During the gradual decrease in plasma concentrations of progesterone in both groups, the P 4 pattern appeared unrelated to changes in either E 2 or PGFM concentrations. The PGFM pattern was different between diestrus and pregnant bitches ( P > 0.01); there was an apparent progressive but slow increase in PGFM in pregnant bitches from Days 30 to 60, followed by a large increase prior to parturition; concentrations declined immediately postpartum. However, there were no increases in PGFM during the same interval in nonpregnant bitches. Mean estradiol concentrations were sporadically elevated during the last third of pregnancy and less so in nonpregnant diestrus; there was no acute prepartum increase in estradiol associated with the PGFM increase. In summary, although there were no apparent changes in peripheral PGF 2α concentration involved in regulating the slow protracted phase of luteal regression in nonpregnant bitches, modest increases in PGFM may play a role in ovarian function after mid-gestation in pregnant bitches. Furthermore, the acute prepartum rise in PGFM was not dependent on any concomitant increase in estradiol concentrations.

Quantitative control of oxytocin-induced PGF2 alpha release by progesterone and oestradiol in ewes.

The effect of oestradiol and progesterone concentrations on the uterine PGF2 alpha response to oxytocin was investigated by measuring 13,14-dihydro-15-keto PGF2 alpha (PGFM) secretion. One week after ovariectomy, 27 ewes were administered progestagen for 10 days followed by oestradiol for 2 days. Day 0 was designated as the time of the last 'oestrous' oestradiol injection. Six groups of ewes (n = 4) were then treated for 12 days with a high or low dose of progesterone (36 or 12 mg day-1) either alone or with a high or low dose of oestradiol (36 or 12 micrograms day-1) administered (in 1 ml of corn oil by i.m. injection, at intervals of 8 h) in a pattern designed to simulate a natural oestrous cycle profile. A control group (n = 3) was given corn oil alone. Ewes were treated with 1 microgram oxytocin (i.v.) on days 4, 8 and 12 of the simulated cycle and plasma was collected for assay of PGFM. An oxytocin-induced PGFM response occurred only on day 12, when the response was suppressed by high doses of progesterone and stimulated by high oestradiol doses. There was a significant effect of progesterone (P < 0.05) and a highly significant effect of oestradiol (P < 0.01) on the pattern of PGFM release in response to oxytocin. Low progesterone/high oestradiol stimulated the largest and most sustained increase in PGFM following oxytocin. There was a significant relationship between the oestradiol:progesterone ratio and the mean PGFM response on day 12 (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma prostaglandin metabolite concentrations in normal and dysfunctional labour

To determine the concentrations of the metabolites of prostaglandin E2 (PGEM) and of prostaglandin F2 alpha (PGFM) prior to the onset of labour and during spontaneous labour, and to correlate the changes in concentrations of these metabolites with labour outcome. Longitudinal study throughout labour. Labour ward of a large maternity unit. Seven primigravid and 11 parous women in the late third trimester with no signs of labour, and 17 primigravid and 11 parous women in spontaneous labour. Six of the primigravid women required augmentation with oxytocin because of dysfunctional labour. Before labour, parous women had significantly higher concentrations of both PGEM (P < 0.007) and PGFM (P < 0.006) compared with primigravid women. During labour, PGFM concentrations were significantly higher in both primigravid (P < 0.0002) and parous (P < 0.0001) women compared with the concentrations of these metabolites in women not in labour; the same was true for PGEM in primigravid (P < 0.003) but not in parous (P = 0.1) women. There was a small but significant increase (P < 0.02) in PGEM as labour progressed in both the normal groups. Amniotomy was associated with a significant increase in PGFM in primigravid and parous women (P < 0.002 and P < 0.009, respectively). The concentration of PGFM one hour following amniotomy correlated inversely with the amniotomy to delivery interval in both the normal primigravid (r = -0.624; P = 0.04) and the parous (r = 0.745; P = 0.021) groups. Women with dysfunctional labour showed no significant rise in PGEM or PGFM. Their PGFM concentrations were significantly lower than those seen in normal labour (P < 0.05). The concentration of PGFM in cord blood was significantly higher (P < 0.0001) in the parous women who laboured than in women delivered by elective caesarean section. There was no difference in the corresponding concentrations of PGEM (P = 0.9). These data show that spontaneous labour is associated with increased concentrations of prostaglandin metabolites in the maternal plasma, and are consistent with PGF2 alpha being an important stimulator of uterine contractility, with a relative deficiency of PGF2 alpha being associated with dysfunctional labour.

Jugular plasma concentrations of 13,14-dihydro-15-keto-prostaglandin F 2α in prepubertal beef heifers treated with progestogen then challenged with oxytocin

Prepubertal Angus crossbred heifers (n=24) between 8 and 10 mo of age were used to determine if progestogen treatment would enhance jugular concentrations of 13,14-dihydro-15-keto-prostaglandin F 2α (PGFM) after oxytocin (OT) injections. Heifers were stratified by age and weight and allotted to randomized treatments in a 2 × 2 factorial arrangement. Heifers were treated with either a norgestomet (NOR) implant (6 mg) for 9 d or no implant (0 mg; BLK). On d 8 of NOR treatment, jugular veins were catheterized and, on d 9, blood samples were collected every 15 min for 165 min. The first four samples were used to determine basal PGFM concentrations (an indirect measure of uterine PGF 2α release). After collection of the fourth sample, either OT (100 IU) or saline (0 IU; SAL) was injected via the jugular catheter. After the 165-min sample was collected, NOR implants were removed. Beginning 48 h after implant removal, a second 165- min blood sampling period was initiated. Average progesterone concentrations were less than 1 ng/ml during both bleeding periods. Within treatment, PGFM concentrations were similar between the first and second sampling periods; therefore, data within treatment were combined. Basal PGFM concentrations were higher (P<.01) in NOR-treated than in BLK heifers. Oxytocin did not increase PGFM concentrations in BLK-OT heifers; however, a marked increase in PGFM was detected in the NOR-OT heifers in response to oxytocin. Average PGFM concentration was greatest (P<.0001) in NOR-OT heifers, and PGFM profiles differed (P<.0001) between NOR-OT and each of the other treatment groups. Results from this study indicate that NOR increases basal PGFM and may “condition” the uterus to respond to OT in prepubertal heifers.

Uterine Secretion of Prostaglandin F2α in Response to Oxytocin in Ewes: Changes during the Estrous Cycle and Early Pregnancy1

Experiment 1 was conducted to determine when the ovine uterus develops the ability to secrete prostaglandin F2 alpha (PGF2 alpha) in response to oxytocin and how development is affected by pregnancy. Pregnant and nonpregnant ewes received an injection of oxytocin (10 IU, i.v.) on Day 10, 13, or 16 postestrus. Jugular venous blood samples were collected for 2 h after injection for quantification of 13,14-dihydro-15-keto-PGF2 alpha (PGFM). In nonpregnant ewes, concentrations of PGFM increased following oxytocin on Day 16 but not on Day 10 or 13. Concentrations of PGFM did not increase following treatment on Day 10, 13, or 16 in pregnant ewes. Therefore, the ability of oxytocin to induce uterine secretion of PGF2 alpha develops after Day 13 in nonpregnant but not in pregnant ewes. Experiment 2 was conducted to precisely define when uterine secretory responsiveness to oxytocin develops. Pregnant and nonpregnant ewes received oxytocin on Day 12, 13, 14, or 15. In nonpregnant ewes, concentrations of PGFM increased following treatment on Days 14 and 15, but not earlier. Peripheral concentrations of progesterone showed that uterine secretory responsiveness to oxytocin developed prior to the onset of luteal regression. As in experiment 1, the increase in concentrations of PGFM following administration of oxytocin was much lower in pregnant than in nonpregnant ewes; however, some pregnant ewes did respond to oxytocin with an increase in PGFM. In experiment 3, pregnant ewes received an injection of oxytocin on Day 18, 24, or 30 postmating. Concentrations of PGFM increased following oxytocin on Days 18 and 24. The conceptus appears to delay and attenuate the development of uterine secretory responsiveness to oxytocin.

Associations among progesterone, estradiol-17β, oxytocin and prostaglandin in cattle treated with hCG during diestrus to extend corpus luteum function

Treatment of cattle during the middle of the middle of the luteal phase with appropriate doses of human chorionic gonadotropin (hCG) causes a 5 d extension of the estrous cycle. Three experiments were conducted to determine how treatment with hCG affected the pattern of secretion of prostaglandin F2α, as indicated by blood levels of 13,14- dihydro-15-keto-prostaglandin F2α (PGFM]). In experiment 1, Holstein cows were given saline (Sal) or hCG (10000 IU, im) on d 10 of the estrous cycle and blood samples were collected over a 6 h period on d 14 and 18 during which oxytocin (10 and 100 IU, iv) was given at 2 and 4 h. Concentrations of PGFM before and after oxytocin were similar between Sal and hCG-cycles, but PGFM was higher on d 18 than 5 14 (P < 0.05). In experiment 2, episodic PGFM was measured from 16 to 20 in cows given Sal or hCG on d 10. There was tendency for hCG to reduce PGFM baseline and pulse amplitude (P=0.22). In experiments 1 and 2, estradiol increased during d 16 to 20 of Sal-cycles, but did not change during this period of hCG-cycles. Therefore, in experiment 3, Holstein heifers were given Sal or hCG (5000 IU, im) on d 10, followed by corn oil (Oil) or estradiol benzoate (EB; 200 μg, im, 2X/day) on d 15 to 18. No difference in progesterone secretion was observed between Sal-Oil and Sal-EB heifers; however, EB hastened luteolysis in hCG-treated heifers (P < 0.05), without causing an increase in PGFM. Although subtle differences were seen in pulsatile PGFM, we conclude that hCG altered the pattern of estrogen secretion, and this led to delayed luteolysis.

Retained fetal membranes in cows: Manual removal versus nonremoval and its effect on reproductive performance

Sixteen primiparous Holstein cows with retained fetal membranes (RFM) were studied for postpartum prostaglandin release, uterine infection and resumption of estrous cyclicity after manual removal of RFM (eight cows) versus leaving the RFM untreated (eight cows). The RFM were results of induced parturition on Day 274 of gestation. Seventeen non-RFM primiparous cows were controls. The 15-keto-13, 14-dihydro-metabolite of prostaglandin F 2α (PGFM) was measured in daily blood samples. Aerobic and anaerobic bacteria were cultured from weekly uterine swabs from Week 3 until results were negative. Resumption of estrous cyclicity was determined by milk progesterone three times weekly. Manual removal caused an immediate and large but short-lived increase in PGFM, probably due to the physical damage of uterine tissue. No sustained difference in postpartum PGFM release between cows with RFM manually removed and cows with RFM left untreated was detected. Non-RFM controls had lowest PGFM concentrations. Uterine infections were more frequent and more severe after manual removal of RFM. Untreated RFM-cows and controls were similarly affected. Most infections involved Actinomyces (formerly Corynebacterium ) pyogenes and/or Fusobacterium necrophorum . Actinomyces pyogenes was isolated in the third week postpartum in 5 8 cows with RFM manually removed versus 2 8 cows with RFM left intact and in 2 17 controls. Manual removal prolonged the interval from calving to first functional corpus luteum by 20 d. This study, using RFM resulting from induced parturition, shows that manual removal of RFM can delay the postpartum return to normal reproductive status without altering PGFM profiles.

Effects of progesterone and oestradiol-17 beta on oxytocin-induced release of prostaglandin F-2 alpha in heifers.

Seven bilaterally ovariectomized heifers were used in 4 experiments and received: (1) saline injections, as control; (2) one injection of oestradiol (3 mg; i.v.); (3) two i.v. injections of oxytocin (100 i.u.) 6 h apart; or (4) one oestradiol injection 30 min after the first oxytocin injection and a second oxytocin injection 6 h later. All experiments were performed without progesterone and then after 7, 14 and 21 days of progesterone treatment. Frequent blood samples were taken for 1 h before and 7 h after the first injection of oxytocin or oestradiol for the measurement of 13,14-dihydro-15-keto-PGF-2 alpha (PGFM) by radioimmunoassay. After 7, 14 and 21 days of progesterone priming, oestradiol caused a significant increase (P less than 0.001) in plasma PGFM after 6 h but not before. After 7, 14 and 21 days of progesterone, there was a significant increase (P less than 0.005) in PGFM after the first oxytocin injection and a similar increase following the second. The oxytocin-induced increase in PGFM after 14 and 21 days of progesterone was significantly higher (P less than 0.001) 6 h after oestradiol injection than before the oestradiol injection. There was no significant effect of oestradiol on the response to oxytocin in animals that received no progesterone or in those animals that received progesterone for only 7 days. These results show that, under the influence of progesterone, oestradiol enhances the oxytocin-induced release of PGF-2 alpha, and suggest a possible synergistic action of these hormones for the induction of luteolysis in heifers.

Endocrine changes, with special emphasis on oestradiol-17 beta, prolactin and oxytocin, before and during labour and delivery in goats.

Jugular plasma concentrations of oestradiol-17 beta, prolactin, progesterone and 13,14-dihydro-15-keto-prostaglandin F-2 alpha (PGFM) were measured at 2-h intervals during the last 4 days of pregnancy in 6 goats. During advanced labour and delivery, samples were obtained more frequently and assayed for oxytocin. The animals were housed in a barn with continuous dim lighting. A distinct pattern of oscillation in prolactin concentrations, with peaks during the late afternoon, was apparent during the last 3 days. Geometric means of peak concentrations doubled each day and became of longer duration; night-time nadir values remained low except during the last night before parturition. A progressive increase in oestradiol-17 beta, with mean levels doubling every 36 h, was apparent during the last 3 days. There was no sharp pre-partum increase in oestradiol-17 beta. Correlated (r = 0.83) with the increase in oestradiol-17 beta was a gradual increase in PGFM and when the latter reached approximately 1000 pg/ml, the non-reversible decline in progesterone reflecting pre-partum luteolysis occurred. Subsequent changes in PGFM related closely to an approximately 20-fold increase in the ratio of oestradiol-17 beta to progesterone until maximal PGFM levels of 26.5 +/- 4.2 ng/ml were reached at delivery. Basal concentrations of oxytocin (8-15 microU/ml) were measured before the last 60 min and markedly higher, though erratic, concentrations were detected at various times before appearance of the allantochorion. Maximal oxytocin values (range 180-1570 microU/ml) occurred within minutes before or after delivery of the first fetus. The results suggest that increased pre-partum production of oestradiol-17 beta, in addition to provoking sufficient release of prostaglandins to cause luteolysis, may modulate either the sensitivity or set-points for an endogenous rhythm in prolactin secretion at the end of pregnancy. The nature of the oxytocin changes suggest that, after labour has evolved sufficiently, delivery is precipitated by an abrupt increase in oxytocin secretion.

Effect of estradiol-17β on peripheral plasma concentration of 15-keto,14-dihydro PGF 2α and luteolysis in cyclic cattle

Friesian heifers (n = 10) were assigned randomly to receive an intravenous injection of estradiol-17 β (E 2; 3 mg) or saline: ethanol vehicle solution (6 ml; 1:1) on day 13 of the estrous cycle. Blood was collected collected from the jugular vein by venipuncture into heparinized vacutainer tubes at 30 minute intervals for 2 hours (h) preinjection, 10.5 h postinjection and then at 3 h intervals until estrus. Repeated hormone measurements of 15-keto-13,14-dihydro-PGF 2α (PGFM) and progesterone (P 4) were evaluated by split-plot analysis of variance. Mean concentration of PGFM for the 12.5 h acute sampling phase was 164.1 ± .14 pg/ml. A treatment by time interaction was detected (P < .01). After treatment with E 2, PGFM concentrations began to increase at approximately 3.5 h, reached a mean peak of 330.4 ± 44.5 pg/ml (n = 5) at 5.5 ± .3 h, and returned to basal concentration by 9.0 ± .6 h. Vehicle treatment did not alter concentrations of PGFM. Injections of E 2 on day 13 of the estrous cycle caused luteolysis (P 4 concentration < 1 ng/ml) to occur earlier following injection (96.9 ± 10.6 h < 153.6 ±17.7 h; P, 0.05) than did the vehicle control treatment. During the chronic sampling phase of 3 h intervals, 39 of 606 samples (6.4%) were classified as PGFM spikes (323.0 ± 50.0 pg/ml); 21 (53%) of the spikes occurred at a mean interval of 18.9 ± 3.86 h before the time of completed luteolysis. Exogenous E 2 induced an acute increase in PGFM that may be indicative of uterine PGF 2α production. Peaks of PGFM in plasma were temporally associated with luteolysis on a within cow basis.

Interrelationships between endocrine changes in peripheral and uterine-venous blood and uterine activity at parturition in the pig

Relationships between endocrine changes and uterine activity were studied by analyses of samples taken at short intervals from sows during late gestation and labor. The initial reduction in peripheral progesterone concentrations occurred prior to the first significant increases in prostaglandin metabolite (PGFM) levels in peripheral blood which occurred 8–24 h prior to parturition. A more marked increase in PGFM occurred within 8–12 h of parturition and was closely associated with increased myometrial activity and higher concentrations of prostaglandin F (PGF) in peripheral and uterine-venous plasma. Prostaglandin E (PGE) was present at higher concentrations than PGF until the onset of labor when PGF concentrations were higher than PGE. Relaxin concentrations increased steadily during the last week of gestation. A relaxin peak coinciding with the increased PGFM levels was seen in all sows 24-12 h before delivery when progesterone levels had declined and before PGF concentrations and uterine activity increased. Other relaxin peaks, unassociated with altered prostaglandin concentrations, were seen at earlier times before term. Estrone concentrations were significantly higher in uterine-venous than in arterial plasma whereas the reverse relationship was found for estradiol-17β.