Prostaglandin F2α Metabolite Concentrations Research Articles

Induced prostaglandin release alters steroid concentrations but not pregnancy survival in cows

Embryonic mortality (EM) is a major factor limiting reproductive efficiency in cattle, and despite negative connotations related to reproductive performance, prostaglandin F2α (PGF2α) is capable of being released by the uterus by Day 30 of gestation. Therefore, the objective was to evaluate differences in PGF2α release after an oxytocin challenge between cows with high circulating concentrations of pregnancy-associated glycoproteins (PAGs) vs low PAG because of the association of increased PAG concentrations with pregnancy success. At Day 30 of gestation, pregnant cows were divided into oxytocin treatment (OT; n = 13) and control (CON; n = 12) groups. Treatment cows were further subdivided by circulating PAG concentration (high PAG, n = 7; and low PAG, n = 6). Blood samples were collected every 30 min beginning 1 h before oxytocin administration and continuing for 4 h. Prostaglandin F2α metabolite (PGFM), progesterone, estradiol-17β (E2), and PAG concentrations were quantified. The peak concentration of PGFM occurred 2 h after oxytocin injection in treatment animals and returned to baseline levels by 4 h. No correlations were observed between PAG and PGFM, progesterone, or E2 concentrations (P > 0.05). There was no difference in initial or final PGFM concentrations between groups (P > 0.05). Progesterone and E2 concentrations decreased in cows after treatment of oxytocin (P < 0.05); however, only progesterone returned to basal concentrations by the end of the sampling period. In summary, cows with high vs low PAG concentrations at Day 30 of gestation have a similar PGFM response to oxytocin challenge.

PSII-33 Differences in prostaglandin release in cows with high vs low circulating concentrations of pregnancy associated glycoproteins

Abstract Embryonic mortality (EM) is a major factor limiting pregnancy rates in cattle and occurs early (&amp;lt; day 28) or late (≥ day 28) during gestation. However, causes and mechanisms associated with late EM remain unknown. Despite negative connotations related to pregnancy, prostaglandin F2α (PGF) is capable of being released by the bovine uterus between days 28 and 32 of gestation. Therefore, the objective was to evaluate differences in PGF release between cows with high circulating concentrations of pregnancy associated glycoproteins (PAG) vs low PAG following an oxytocin (OT) challenge. Increased concentrations of PAG are associated with pregnancy success. At day 29 of gestation, pregnant cows were divided into high (n = 10) and low (n = 10) PAG groups and received either 100 I. U. of oxytocin intramuscularly (OT) or saline (control). Blood samples were collected every 30 minutes beginning 1 hour before and continuing for 4 hours after treatment. Prostaglandin F2α metabolite (PGFM), progesterone (P4), estradiol (E2) and PAG concentrations were determined. Peak concentration of PGFM occurred 2 hours after OT injection (average high PAG group peak: 345.6 ± 73.6 pg/mL; low PAG group peak: 326.4 ± 61.4 pg/mL, P &amp;gt; 0.05) and returned to baseline levels by 4 hours. No correlations were observed between PAG and PGFM concentrations (P &amp;gt; 0.05). There was no difference in initial or final PGFM concentrations between high or low PAG groups and control animals (P &amp;gt; 0.05). Furthermore, there was no difference in P4 or E2 concentration between treatment and control animals (P &amp;gt; 0.05) despite a luteolytic release of PGF2α. In summary, cows with high vs low PAG concentrations at day 30 of gestation have a similar PGFM response to OT challenge. This project supported by Agriculture and Food Research Initiative Competitive Grant no. 2017-67015-26457 from USDA-NIFA.

Oxytocin-induced prostaglandin F2-alpha release is low in early bovine pregnancy but increases during the second month of pregnancy†.

Circulating prostaglandin F2α metabolite (PGFM) after an oxytocin challenge was evaluated throughout the first 2months of pregnancy in lactating Holstein cows. On day 11, 18, and 25 after artificial insemination (AI), and on days 32, 39, 46, 53, and 60 of pregnancy, cows were challenged with 50IU oxytocin, i.m. Blood was collected before (0min), 30, 60, 90, and 120min after oxytocin for plasma PGFM concentrations. Ultrasound evaluations were performed for pregnancy diagnosis on day 32-60 post-AI. Nonpregnant (NP) cows on day 18 were designated by a lack of interferon-stimulated genes in peripheral blood leukocytes and Pregnant (P) based on day 32 ultrasound. On day 11, P and NP were similar with low PGFM and no effect of oxytocin on PGFM. On day 18, oxytocin increased PGFM (3-fold) in NP with little change in P cows. Comparing only P cows from day 11 to 60, basal circulating PGFM increased as pregnancy progressed, with day 11 and 18, lower than all days from day 25 to 60 of pregnancy. Oxytocin-induced PGFM in P cows on day 25 was greater than P cows on day 18 (2.9-fold). However, oxytocin-induced PGFM was lower on day 25 compared to day 53 and 60, with intermediate values on day 32, 39, and 46 of pregnancy. Thus, the corpus luteum (CL) of early pregnancy (day 11, 18) is maintained by suppression of PGF, as reflected by suppressed PGFM in this study. However, during the second month of pregnancy, uterine PGF secretion was not suppressed since basal PGFM and oxytocin-induced PGFM secretion were elevated. Apparently, mechanisms other than suppression of oxytocin receptors maintain CL after day 25 of pregnancy.

Effect of dietary supplementation with long-chain n-3 fatty acids during late gestation and early lactation on mare and foal plasma fatty acid composition, milk fatty acid composition, and mare reproductive variables

The effects of dietary marine-derived n-3 fatty acids (FA) on mare milk and mare and foal plasma FA, postpartum ovarian follicular growth and prostaglandin concentrations were evaluated. Sixty days prior to expected foaling dates, mares were assigned to one of three diets: corn oil (CORN, n = 6), docosahexaenoic acid (DHA) diet (D; 12.64 g/d, n = 7), or eicosapentaenoic acid (EPA) and DHA (ED; 8.84 g EPA, 10.43 g DHA/d, n = 7). Milk and plasma were collected for FA analysis. Follicular data were recorded through the first postpartum ovulation. Post-ovulation serial blood samples were evaluated for prostaglandin F2α metabolite (PGFM). Supplementation with DHA, or DHA plus EPA resulted in lower linoleic acid and greater EPA and DHA in mare plasma (P < 0.05), greater arachidonic acid and DHA, or EPA and DHA in milk (P < 0.05), and greater DHA, or EPA and DHA in foal plasma (P < 0.05). Days to the first postpartum ovulation was greater (P < 0.01) in ED (22.5 ± 2.1) compared to CORN (12.5 ± 2.3) and D (13.3 ± 2.3) groups. Follicular retention (≥35 mm) prior to ovulation was longer (P < 0.05) for ED (12.7 ± 1.9 d) compared to CORN (6.3 ± 2.0 d) or D (6.0 ± 2.0 d) groups. Treatment did not affect PGFM concentrations. Maternal EPA and DHA supplementation beginning in late gestation altered the FA profile of milk and mare and foal plasma, and may result in delayed ovulation in the early postpartum period.

Endocrine changes, fetal growth, and uterine artery hemodynamics after chronic estrogen suppression during the last trimester of equine pregnancy.

Equine pregnancy is characterized by very high circulating concentrations of estrogens. The physiological roles of estrogens during equine gestation are largely unknown, although some studies suggest a role in the regulation of uterine artery hemodynamics and a relationship between low circulating estrogen concentrations and late pregnancy loss. The objectives of this experiment were to evaluate the effects of estrogen suppression on uterine artery hemodynamics and on pregnancy outcome. Estrogen synthesis was suppressed using letrozole, a potent aromatase inhibitor. Twelve pregnant mares were randomly assigned to a control (n = 6) or treatment (n = 6; 500 mg letrozole orally every 4 days) group with treatment starting at 240 days of gestation and continuing until parturition. Weekly serum samples were analyzed to determine testosterone, dehydroepiandrosterone sulfate, estradiol, estrone sulfate, progestins, and prostaglandin F2α metabolite concentrations. Ultrasonographic examinations were performed biweekly and measurements included uterine artery hemodynamics (diameter, pulsatility, and resistance indices), fetal growth using the diameter of the fetal eye, and placental evaluation using the combined thickness of the uterus and placenta. At parturition, gestational length, foal weight, and neonatal viability were determined. Letrozole suppressed estrogen synthesis during gestation by approximately 90% compared to control values. This large reduction in circulating estrogens had no effect on uterine artery hemodynamics, normal placental development, maintenance of pregnancy, or neonatal viability. However, neonates from letrozole-treated mares had lower (P < 0.05) birth weights than controls, suggesting that estrogens may play a role in fetal growth that is not mediated through regulation of uterine blood flow.

Measurement of C-reactive protein and prostaglandin F2α metabolite concentrations in differentiation of canine pyometra and cystic endometrial hyperplasia/mucometra.

Canine pyometra is a dioestrus period disease in which systemic inflammatory response syndrome (SIRS) is a common outcome due to the response of the body to the bacterial infection. The purpose of this study was i) to differentiate canine pyometra and cystic endometrial hyperplasia (CEH)/mucometra by measuring serum C-reactive protein (CRP) and prostaglandin F2α metabolite (PGFM) concentrations in blood and ii) to compare serum concentrations of CRP and PGFM in bitches with a pathological uterus (pyometra or CEH/mucometra) to concentrations in bitches with a healthy uterus. Mean CRP concentrations were found significantly higher (p < 0.001) in dogs with pyometra compared to those with CEH/mucometra or healthy uterus. However, no statistical difference could be detected between the groups for mean PGFM concentrations. Mean white blood cell count (WBC), alkaline phosphatase (ALP) and total protein concentrations were found significantly higher (p < 0.001) in dogs with pyometra. Escherichia coli was the most frequently isolated microorganism from dogs with pyometra (64.3%). Edwardsiella spp. was detected in a single case of pyometra for the first time. In conclusion, our results demonstrate that serum CRP concentrations were increased in dogs with pyometra and thus we conclude that serum CRP concentration but not PGFM might be useful as a marker to differentiate a case of CEH/mucometra from pyometra in female dogs. To the authors' knowledge, this is the first report in which Edwardsiella spp. has been isolated in the canine uterus.

Increased concentrations of C-reactive protein but not high-mobility group box 1 in dogs with naturally occurring sepsis

Sepsis is difficult to diagnose and remains a common mortality cause worldwide in both humans and animals. The uterine infection pyometra causes sepsis in more than half of affected dogs and therefore allows the natural physiological development of sepsis to be studied. To find a sepsis-specific biochemical marker that could be combined with conventional clinical criteria for a more robust and quick diagnosis of sepsis, we measured systemic concentrations of high-mobility group box 1 (HMGB1) in 23 healthy control dogs and in 27 dogs with pyometra, 74% of which had sepsis. We also measured concentrations of the major acute phase protein C-reactive protein (CRP) and an indicator for endotoxaemia, prostaglandin F2α metabolite (PGM) to assess the relative contribution of HMGB1 to the detection of systemic inflammation and endotoxaemia. We found that HMGB1 concentrations, in line with concentrations of CRP and PGM, were significantly increased in dogs with pyometra, and that concentrations of CRP, but not HMGB1, were significantly higher in dogs with sepsis compared to dogs without sepsis. Although serum HMGB1 did not differ between dogs with or without sepsis and was not correlated with either CRP or PGM concentrations, HMGB1 was correlated with the total white blood cell counts, suggesting an independent regulation and involvement in inflammation.

Circulating hormone concentrations within a pulse of a metabolite of prostaglandin F2α during preluteolysis and early luteolysis in heifers

Plasma from hourly blood samples from two previous studies in heifers was assayed for hormones that were not considered in the previous reports. The objective was to determine the intrapulse temporal relationships between a prostaglandin F2α metabolite (PGFM) pulse and various hormones during preluteolysis and luteolysis. Hormone concentrations were centralized to the peak of a PGFM pulse (Hour 0) and evaluated from Hours −3 to 3. Experiment 1 ( n = 6) was done during early luteolysis. Progesterone decreased during Hours −3 to 0 and then rebounded, but did not return to prepulse concentrations, and concentration of LH increased between Hours −1 and 2. In Experiment 2 ( n = 7), comparisons were made between the last PGFM pulse of preluteolysis and the first pulse of luteolysis. Intrapulse concentrations of LH increased rapidly between Hours 0 and 1 during preluteolysis and gradually between Hours −2 and 2 during luteolysis. Intrapulse differences in cortisol among hours were not significant for preluteolysis and approached significance ( P < 0.06) during luteolysis, owing primarily to an apparent increase between Hours −2 and 1. Oxytocin concentrations showed only an hour effect ( P < 0.0003) from to an increase between Hours −2 and 0 and a decrease between Hours 0 and 2. Results indicated that oxytocin and PGFM concentrations increased and decreased concomitantly and supported the hypothesis that the reported more prominent rebound in progesterone during the descending portion of a PGFM pulse during preluteolysis than during luteolysis involves a greater transient increase in LH.

Effects of flunixin meglumine and transportation on establishment of pregnancy in beef cows1

Objectives of these studies were to determine the effects of flunixin meglumine (FM) administration on early embryonic mortality and circulating PG and cortisol concentrations in transported and non-transported cows. Cows (n = 483) from 3 locations were used to evaluate the effects of transportation and FM approximately 14 d after AI on the establishment of pregnancy and serum concentrations of progesterone, PGF metabolite (PGFM), and cortisol. Treatments were transport (n = 129), transport + FM (n = 128), no transport (n = 130), and no transport + FM (n = 96). Multiparous cows (n = 224) were used at 2 locations, and nulliparous cows (n = 259) were used at 1 location. The no transport + FM treatment was used at only 2 locations. Flunixin meglumine (approximately 1.1 mg/kg of BW; i.m.) was administered before the cows were separated into transportation groups. Transportation included 4 to 6 h of transportation, without calves, via semitractor trailer. Nontransported cows remained penned, with their calves in adjacent pens, during the same period as the transported cows. Blood samples were collected from all cows before and after treatment and, at 2 locations, approximately 3 h after the onset of treatment. Location affected AI pregnancy rate (P < 0.01). Treatment effects, although not significant (P = 0.16), were of a magnitude to be considered practically important. Cows that received transportation + FM tended (P = 0.07) to have greater AI pregnancy rates (74%) than those that did not receive FM (66%), irrespective of transportation. Cortisol concentration was greater (P < 0.05) for transported cows than for nontransported cows. Cows receiving FM had greater (P < 0.05) AI pregnancy rates than non-FM cows (71 vs. 61%, respectively). Cows receiving transportation had lower (P < 0.01) mean PGFM concentrations than nontransported cows (45.4 vs. 54.6 pg/mL, respectively), and cows receiving FM had lower (P < 0.01) mean PGFM concentrations than non-FM cows (39.4 vs. 60.6, respectively). We conclude that transportation of cows approximately 14 d after AI increased serum cortisol concentrations but did not affect AI pregnancy rates. However, treatment of cows with FM increased AI pregnancy rates, irrespective of whether they were transported.

Effect of estrogen formulation and its site of deposition on serum PGFM concentrations, uterine contractility, and time of ovulation in artificially inseminated weaned sows

At the time of artificial insemination, 48 mixed parity sows were assigned by parity to receive 25 μg estradiol-17β either in oil deposited onto the vaginal mucosa (E-oil), or dissolved in extended semen (E-semen), or received no estrogen and served as controls. All sows were inseminated transcervically 24 h after detection of estrus. The time of ovulation was determined in 15 sows per treatment by transrectal ultrasonography. Concentrations of prostaglandin F2α metabolite (PGFM) were determined in blood samples obtained from eight sows per treatment at 1 h intervals from 1 h pre-treatment until 7 h post-treatment. The remaining eight sows per treatment were fitted with a transducer to allow determination of intrauterine pressure changes during 1 h pre-treatment until 5 h post-treatment. There were no differences among treatments for wean to estrus interval, size of ovarian follicles at the time of treatment or the estrus detection to ovulation interval. In all treatments, plasma PGFM concentrations were increased from 1 h after treatment. However, the increase was greater and of longer duration in the E-oil sows ( P=0.03) supporting the suggestion that this formulation and route of administration enhanced uterine PGF2α release. Compared to controls, both estradiol treatments were associated with myometrial contractions of increased amplitude and duration, supporting a causal link between estradiol treatment, increased uterine PGF2α release, and enhanced myometrial contractility.

Effect of oral administration of flunixin meglumine on the inflammatory response to endotoxin in heifers

Abstract Objective To compare the effect of oral and IV administrations of flunixin meglumine on the endotoxin-induced inflammatory response in heifers. Design The study was conducted in 2 experimental sets in which heifers were exposed to low IV doses of Escherichia coli endotoxin. Within each set, heifers were allocated to 3 treatment groups; pretreatment with flunixin meglumine orally and IV prior to endotoxin administration, or endotoxin administration only. The dose of flunixin used was the recommended therapeutic dose in cattle. Animals 11 clinically normal heifers weighing from 400 to 640 kg. Procedure A permanent cannula was inserted into the jugular vein on the day prior to the experiment. Blood samples were collected regularly during the experiment and analyzed for the content of prostaglandin F2α metabolite, Cortisol, blood mononuclear cells, and polymorphonuclear neutrophilic leukocytes and rectal temperature was measured. Results Endotoxin administration caused clinical signs and hematologic changes characteristic of endotoxemia in cattle. Flunixin administered orally prior to experimentally induced endotoxemia exerted an effect equal to that after its IV administration. Significant increases in rectal temperature and prostaglandin F2α metabolite concentrations after administration of endotoxin were abrogated when the heifers were pretreated with flunixin, irrespective of route of administration. Cortisol concentrations were lower after pretreatment with flunixin. However, flunixin did not prevent the decrease in blood mononuclear cells and polymorphonuclear neutrophilic leukocytes seen after endotoxin administration. Conclusion Owing to no major difference in the inflammatory response between oral and IV flunixin dosing, flunixin granules may be an alternative to parenteral use in bovine practice.

Effect of intrauterine bacterial infusions and subsequent endometritis on prostaglandin F2 alpha metabolite concentrations in postpartum beef cows.

Multiparous Angus and crossbred Angus cows were used to determine the effect of induced endometritis on plasma concentrations of 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) and progesterone (P4) and on duration of the estrous cycle of treatment. Beginning on the day of calving (d 0), blood samples were collected on alternate days. On three consecutive days, ranging from d 8 to 14 of the first postpartum estrous cycle, uterine horns were inoculated transcervically with either 3 x 10(9) colony forming units (cfu) of Actinomyces pyogenes and 1.5 x 10(9) cfu of beta-hemolytic Escherichia coli (treated; n = 9) in sterile PBS or with sterile PBS alone (control; n = 9). Samples of uterine fluid were collected by transcervical aspiration twice weekly from just before the start of each series of inoculations until the end of the experiment. Endometrial biopsies were collected transcervically between d 4 to 6 and 11 to 13 after inoculation. Based on clinical observations and results of bacterial cultures, all treated cows developed acute uterine infections. Controls did not develop uterine infections. Endometrial biopsies indicated that there were no significant diffuse or focal cellular reactions in response to the infection. The interestrous interval was greater (P less than .0003) for treated (27.7 +/- 1.0 d) than for control (20.6 +/- 1.0 d) cows, but P4 concentrations were similar between the two groups. Mean PGFM concentration and PGFM profiles were similar (P greater than .10) between treated and control cows before bacterial infusions. Bacterial infusions increased mean PGFM concentration (P less than .0001) and changed the shape of the PGFM profile (P less than .02).(ABSTRACT TRUNCATED AT 250 WORDS)

The physiological and clinical effects of progesterone inhibition with mifepristone (RU 486) in the second trimester

A double-blind placebo-controlled trial was performed in 20 primigravidae to assess the physiological and clinical effects of oral mifepristone on myometrial contractility and sensitivity in the second trimester. Ten women received 600 mg of oral mifepristone and 10 women a placebo 24 h before abortion was induced in both groups, with extra-amniotic PGE2 instillation. Intrauterine pressure recordings demonstrated increased spontaneous uterine activity and increased sensitivity to PGE2 and ergometrine, but no change in oxytocin sensitivity after mifepristone treatment. There were no significant differences in PGE or PGF metabolite concentrations in peripheral maternal plasma over the 24-h study period after treatment between the mifepristone and placebo groups. The mean induction abortion interval in the mifepristone group was 512 (SD 321) min compared with 1128 (SD 606) min in the placebo group (P less than or equal to 0.02). The mechanism whereby mifepristone provokes enhanced uterine contractility and sensitivity to prostaglandins, with a reduction in abortion times, does not appear to be through endogenous production of PGE or PGF.

Peripartal endocrine changes associated with retained placenta in dairy cows

Peripheral serum concentrations of prostaglandin F 2α metabolite (PGFM), cortisol, and progesterone (P 4) were determined in cows that retained placentae (RP; n = 18) and cows that did not retain placentae after parturition (NRP; n = 28). Blood samples collected from Day 15 before until Day 15 after parturition were assayed. Significant increases (P < 0.05) in PGFM concentrations occurred in RP cows between Days 7 and 6 before parturition compared with NRP cows. There were no differences in the interval required to attain peak concentrations of PGFM and the interval required to reach basal concentrations after parturition in both groups. However, the amount of PGFM secreted during the peripartum period was significantly higher in RP cows (P < 0.01). Starting from Day 6 before parturition, serum cortisol concentrations in RP cows increased significantly to peak levels 3 d before parturition (P < 0.05). Cortisol levels decreased to basal concentrations in RP cows on Day 1 postpartum. The peripartal serum P 4 concentrations in RP and NRP cows did not differ. The results indicate that prepartal PGFM and cortisol increases may constitute reliable indicators of retained placenta in dairy cows.

Effects of intrauterine infection on the function of the corpora lutea formed after first postpartum ovulations in dairy cows

This study was carried out to determine the relationship between postpartum intrauterine infections, endocrine patterns and the function of corpora lutea formed following the first postpartum ovulations in dairy cows. Blood samples were collected daily starting from the day of parturition until 30 d after parturition or until the second postpartum estrus, whichever occurred first. Sera were assayed for progesterone (P 4), prostaglandin F 2α metabolite (PGFM), and luteinizing hormone (LH) concentrations. Palpations per rectum and real-time ultrasound scanning of the reproductive tracts were carried out in all cows once every 4 d for 1 mo, starting from Day 4 after parturition. In addition, endometrial swabs were collected aseptically from each cow once every 4 d during the first month postpartum. The swabs were cultured for aerobic and anaerobic bacteria. Twelve cows (60%) exhibited short estrous cycles (SC; 6 to 14 d long) following first postpartum ovulations. The mean preovulatory LH surges and LH patterns during the first postpartum cycles were similar in both groups, leading us to believe that lack of luteotrophic stimulation was not a factor in the occurrence of SC. Bacterial isolations were frequent in SC cows. The occurrence of moderate to heavy bacterial growth patterns and the repeated isolations of the similar organisms during postpartum suggests the persistence of uterine infections in SC cows. Increases in PGFM concentrations prior to luteolysis in SC cows were associated with moderate to heavy infection. Thus, postpartum uterine infections do not appear to affect ovulations, but prostaglandin (PGF 2α) released in response to uterine infection may contribute to early demise of the corpus luteum formed after the first postpartum ovulation.