Prostaglandin F2 Alpha Metabolite Research Articles

Can Non-invasive Hormone Profiling in Female Tigers (Panthera tigris) could Differentiate True Pregnancy and Pseudopregnancy

Background: The tigers (Panthera tigris) being the world’s largest cat are one of the critically endangered species which are at the verge of extinction. The pseudopregnancy or false pregnancy or pseudocyesis is a syndrome which is characterized by the presence of signs of pregnancy in a non-pregnant animal. False lactation or nervous lactation are the terms which are used to refer pseudopregnancy as there is very low quantities of milk production is seen. This condition can be differentiated with true pregnancy by using hormones and by correlation of behavioral symptoms of pregnancy with hormonal profiles for confirmation of pregnancy in female tigers. Methods: Total seven animals were used in the experiment and was divided into three groups (G I, G II and G III). Group G I consist of 03 non-bred animals of less than 9 years of age, G II consisted of 03 non-bred animals of more than 9 years of age and G III was consisted of 03 animals after mating irrespective of their age. Faecal samples were collected non-invasively from enclosures weekly up to 14 weeks. Only fresh samples (deposited within 24 h) was chosen, urine puddles were aspirated from the floor. The extracted samples were then analysed for estimation of relaxin, progesterone and prostaglandin F2 alpha metabolite (PGFM) by enzyme linked immunosorbent assay (ELISA). Result: Relaxin the hormone for early detection of pregnancy in felines gives elevated concentration from 49 days after mating and attains a peak during parturition, whereas, no elevation or peak was observed in pseudopregnant animals. Progesterone, in true pregnancy remains elevated from 7th week onwards after mating, it gets dropped after 7th week with wide fluctuation in pseudopregnant animals. PGFM elevation observed after nine weeks of gestation in true pregnancy whereas, no elevation will be observed in pseudopregnant tigress.

Processes involved in prostaglandin F2alpha autoamplification in heifers.

Endometrial and luteal synthesis of prostaglandin F2alpha (PGF2A) occurs before and during luteolysis and is critical for luteal regression. This study demonstrates that PGF2A stimulates further PGF2A synthesis (autoamplification) apparently from the corpus luteum. Understanding the endocrine profile of prostaglandin F2alpha (PGF2A) autoamplification is fundamental to comprehend luteal and endometrial responses to PGF2A. On day 10 of postovulation (preluteolysis), heifers (n = 6/group) were treated intrauterine with saline or PGF2A (0.5 mg; hour 0). A third group received flunixin meglumine + PGF (FM+PGF) to prevent endogenous synthesis of PGF2A. Exogenous PGF2A was metabolized at hour 2 as measured by PGF2A metabolite (PGFM). From hours 5 to 48, concentrations of PGFM were greatest in the PGF group, smallest in the FM+PGF, and intermediate in the control suggesting endogenous synthesis of PGF2A only in PGF group. Progesterone (P4) concentrations decreased transiently between hours 0 and 1 in PGF and FM+PGF groups but rebounded to pretreatment concentrations by hours 6 and 4, respectively. No control or FM+PGF heifers underwent luteolysis during the experimental period. Conversely, in the PGF group, one heifer had complete luteolysis (P4 < 1 ng/mL), two heifers had partial luteolysis followed by P4 and CL resurgence by hour 48, and three heifers did not undergo luteolysis. Endogenous PGF2A appears to be of luteal origin due to the lack of pulsatile pattern of PGFM and lack of endometrial upregulation of oxytocin receptor (typical of endometrial synthesis of PGF2A), whereas luteal downregulation of PGF receptor and HPGD indicates a classic luteal response to PGF2A signaling although other specific mechanisms were not investigated. The hypothesis was supported that a single PGF2A treatment simulating the peak of a natural luteolytic pulse and the uteroovarian transport of PGF2A stimulates measurable endogenous PGF2A production.

Meloxicam and Dexamethasone Administration as Anti-Inflammatory Compounds to Sows Prior to Farrowing Does Not Improve Lactation Performance.

Simple SummarySows may experience pain and discomfort whilst giving birth. Additionally, the birthing process is accompanied by an inflammation response. Administering anti-inflammatory compounds prior to birth may provide an opportunity to improve piglet survival and growth. The aim of this experiment was to assess the efficacy of both a non-steroidal (NSAID; meloxicam) and steroidal (SAID; dexamethasone) anti-inflammatory drug for improving farrowing house performance of sows. In younger sows, there was no impact of treatment; however, older sows from the NSAID treatment gave birth to fewer live piglets. Postnatal mortality was unaffected by treatment and no improvement in piglet growth was observed. Feed intake of both NSAID and SAID sows was improved when compared with the control group; however, there was a tendency for a delayed oestrus in the NSAID group. Administering NSAID to sows prior to farrowing is not recommended as it reduces piglet survival and subsequent reproduction.The aim of this experiment was to determine whether administration of an anti-inflammatory compound to sows prior to farrowing would, via reduced pain and inflammation, increase piglet survival and growth. At day 114 of gestation, multiparous sows were randomly allocated to one of the following treatments: Control (n = 43), which received 10 mL saline, NSAID (n = 55) which received 0.4 mg/kg meloxicam and SAID (n = 54) which received 0.1 mg/kg dexamethasone. Treatments were applied again on day 116 if farrowing had not occurred. There was no treatment effect on piglets born alive or dead from parity two to four sows but in those of parity five and older, NSAID administration reduced the number of piglets born alive and increased the number of piglets born dead (p < 0.05). Sow rectal temperature and incidence of mastitis were unaffected by treatment (p > 0.05). Lactation day two plasma concentrations of cortisol, prostaglandin F2 alpha metabolite and haptoglobin did not differ among treatments (p > 0.05). Treatment effects were not observed in liveborn piglet mortality at any age, or litter weight at day 21 (p > 0.05). Average feed intake during lactation was increased by both NSAID and SAID treatments (p = 0.001). The use of meloxicam prior to farrowing should be avoided as it reduced the number of piglets born alive and did not improve piglet survival and growth.

Effect of natural pre-luteolytic prostaglandin F2α pulses on the bovine luteal transcriptome during spontaneous luteal regression†.

The pulsatile pattern of prostaglandin F2alpha (PGF) secretion during spontaneous luteolysis is well documented, with multiple pulses of exogenous PGF necessary to induce regression using physiologic concentrations of PGF. However, during spontaneous regression, the earliest pulses of PGF are small and not associated with detectable changes in circulating progesterone (P4), bringing into question what, if any, role these early, subluteolytic PGF pulses have during physiologic regression. To investigate the effect of small PGF pulses, luteal biopsies were collected throughout natural luteolysis in conjunction with bihourly blood samples to determine circulating P4 and PGF metabolite to retrospectively assign biopsies to early and later regression. Whole transcriptome analysis was conducted on CL biopsies. Early PGF pulses altered the luteal transcriptome, inducing differential expression of 210 genes (Q < 0.05) during early regression, compared with 4615 differentially expressed genes during later regression. In early regression, few of these differentially expressed genes were directly associated with luteolysis, rather there were changes in local steroid and glutathione metabolism. Most (94%) differentially expressed genes from early regression were also differentially expressed during later regression, with 98% of these continuing to be altered in the same direction compared with CL at a similar stage of the cycle that had not yet been exposed to PGF. Thus, early, subluteolytic PGF pulses impact the luteal transcriptome, though not by altering steroidogenesis or causing direct inhibition of cellular function. Rather, small pulses alter pathways resulting in the removal of cellular support systems, which may sensitize the CL to later pulses of PGF.

Altrenogest affects the development and endocrine milieu of ovarian follicles in prepubertal and mature gilts†.

Altrenogest with gonadotropins is commonly used to synchronize the estrous cycle, but it can also lead to follicular cyst formation, especially in prepubertal gilts. Here, we aimed to investigate how maturity and altrenogest treatment affect the development, endocrine milieu, and molecular control of ovarian follicles. Crossbred prepubertal and mature gilts were challenged or not (control) with altrenogest, and ovaries were collected in the morning on the first day of behavioral estrus. In prepubertal gilts, altrenogest decreased the percentage of primordial and atretic small follicles, but increased large antral follicles when compared with controls. In mature gilts, altrenogest reduced the percentage of primary follicles and elevated the total number of antral follicles. Maturity affected the estradiol level in the follicular fluid of preovulatory follicles, luteinizing hormone (LH)-stimulated cyclic adenosine monophosphate (cAMP) generation, and LH receptor messenger RNA (mRNA) expression in granulosa. Moreover, cytochrome P45017A1 (CYP17A1) mRNA levels in the theca layer were affected and correlated with follicular androstendione and estradiol concentration. Altrenogest negatively affected follicular fluid progesterone concentration and decreased levels of prostaglandin (PG) E2 in prepubertal gilts and PGF2alpha metabolite in mature gilts. LH-stimulated cAMP release in granulosa cells of mature gilts as well as human chorionic gonadotropin- and forskolin-induced cAMP were also affected. In addition, altrenogest downregulated CYP17A1 mRNA in the prepubertal theca layer and PGF2alpha synthase expression in the granulosa and theca layer of mature gilts. To the best of our knowledge, this is the first study to report multiple effects of maturity and altrenogest on the endocrine milieu and molecular regulations governing ovarian follicle development in gilts.

Characteristics and causes of the inadequate corpus luteum

An inadequate luteal phase occurs in domestic ruminants in several physiological situations (e.g. puberty, post partum), and also following the induction of ovulation in anoestrous ewes with GnRH treatment. The induced corpora lutea (CL) initially developed, but then regressed rapidly after Day 4, unless the animals had been primed with progesterone before GnRH therapy or hysterectomized. Significant increases in prostaglandin F-2 alpha metabolite (PGFM) secretion and coincident peaks of oxytocin and PGFM occurred around the time of premature regression. Endometrial oxytocin receptors were also detectable at this time in ewes which had abnormal luteal phases, but not in ewes which had been progesterone primed and thus had normal luteal phases. This suggests that the presence or otherwise of the oxytocin receptor during the early luteal phase may be crucial in determining whether the CL has a short or normal lifespan. These results show that an inadequate luteal phase is often caused by the premature induction of luteolysis and the presence of the endometrial oxytocin receptor in necessary for this occurrence. This receptor in turn is controlled by the steroid environment to which the uterus has previously been exposed.

Pulsatility and Interrelationships of 13,14-Dihydro-15-Keto-PGF2alpha (PGFM), Luteinizing Hormone, Progesterone, and Estradiol in Heifers1

Temporality among episodes of a prostaglandin F2alpha metabolite (PGFM), progesterone (P4), luteinizing hormone (LH), and estradiol (E2) were studied during preluteolysis and luteolysis. A vehicle group (n = 10) and a group with an E2-induced PGFM pulse (n = 10) were used. Blood sampling was done every 0.25 h for 8 h. An episode was identified by comparing its coefficient of variation (CV) with the intra-assay CV. Pulsatility of PGFM, P4, LH, and E2 in individual heifers was inferred if the autocorrelation functions were different (P < 0.05) from zero. About four nonrhythmic fluctuations of PGFM/8 h were superimposed on PGFM pulses. Pulsatility was detected for LH but not for P4 and E2. A transient increase in P4 was not detected during the ascending portion of a PGFM pulse. Progesterone decreased (P < 0.003) during Hours -1.25 to -0.50 of the PGFM pulse (Hour 0 = peak) and ceased to decrease temporally with an increase (P < 0.05) in LH. Maximum P4 concentration occurred 0.25 h after an LH pulse peak, and an increase (P < 0.005) in E2 began at the LH peak. Nadirs of LH pulses were greater (P < 0.05) and the nadir-to-nadir interval was shorter (P < 0.003) in the E2 group, which is consistent with reported characteristics during luteolysis. The results did not support the hypothesis of a transient P4 increase early in a PGFM pulse and indicated a balance between a luteolytic effect of PGF and a luteotropic effect of LH within the hours of a PGFM pulse.

Expression of COX-1 and COX-2 in the endometrium of cyclic, pregnant and in a model of pseudopregnant rats and their regulation by sex steroids

BackgroundCyclooxygenases (COXs) are the rate limiting enzymes in the process of prostaglandins (PGs) synthesis, which are critical regulators of a number of reproductive processes, including ovulation, implantation, decidualization and parturition. The aim of the present study was to investigate the expression and regulation of COX-1 and COX-2 and levels of prostaglandins during rat pregnancy, in a model of pseudopregnancy and estrous cycle.MethodsUteri were collected from the cyclic rats on each day of estrous cycle, after every two days for pregnant (days 2 to 22) and pseudopregnant rats (days 1 to 9). In vitro primary endometrial stromal cells were cultured in the presence of steroid hormones and their respective inhibitors for the possible modulation of COX-1 and COX-2. Endometrial protein extracts were used for western blot analysis and tissue sections were prepared for protein localization using immunofluorescence. Measurements of PGF2alpha and PGE2 metabolites in serum were performed by enzyme immunoassay (EIA).ResultsCOX-1 expression was found to be elevated during implantation and parturition, however, the levels of COX-1 decreased during decidualization periods. COX-2 was detected during early pregnancy from day 2 to 5, increased during decidual regression, and was also expressed at the time of parturition. COX-2 protein expression was found to be increased at estrus phase in cyclic rats. Both enzymes were found to be modulated in the endometrium of pseudopregnant rats, suggesting that they are regulated by 17beta-estradiol and progesterone. A significant increase in PGE2 metabolite levels was observed on day 10, 12 and 14 of pregnancy. However, an increase in PGF2alpha metabolite levels was observed only on day 14. The concentration of both these metabolites changed during pseudopregnancy and maximum levels were observed at day 7. Significant increase in PGE2 metabolite was observed at proestrus phase, on the other hand, PGF2alpha metabolite was significantly increased at proestrus and metestrus phase. COX-2 protein was regulated by 17beta-estradiol in cultured endometrial stromal cells which was blocked in the presence of ICI-182,780.ConclusionsTaken together, these results suggest that COX-1 and COX-2 could be differentially regulated by steroid hormones and might be the key factors involved in embryo implantation, decidualization, decidua basalis regression and parturition in rats.

Characteristics of Pulses of 13,14-Dihydro-15-Keto-Prostaglandin F2alpha Before, During, and after Spontaneous Luteolysis and Temporal Intrapulse Relationships with Progesterone Concentrations in Cattle1

Pulses of the prostaglandin F2alpha (PGF) metabolite 13,14-dihydro-15-keto-PGF (PGFM) were compared among heifers that were in the preluteolytic, luteolytic, and postluteolytic periods (n = 7 or 8 heifers/period). Hourly blood sampling was done in 18-h sessions 15, 16, or 17 days after ovulation. Hourly sampling and statistical identification of a PGFM pulse allowed novel comparisons of PGFM pulses among the three periods. Each period had a similar number of PGFM pulses (2.3 +/- 0.2). The pulses were more prominent during the luteolytic period than during the other periods, as indicated by significantly greater concentration for the peak and amplitude between nadir and peak. Significantly more fluctuations that did not meet the definition of a pulse occurred at the beginning of the preluteolytic period and end of the postluteolytic period than during the luteolytic period. The same nadir ended a pulse and began the next pulse in 85% of adjacent pulses. Seven heifers were selected objectively, based on a progesterone concentration >5 ng/ml at Hour -3 (Hour 0 = peak of PGFM pulse) and a progressive decrease in progesterone from Hours -3 to 0. Progesterone increased (P < 0.03) between Hours 0 and 1, remained at a mean plateau at Hours 1 and 2, and then decreased. Results support the hypothesis of a transient intrapulse rebound in progesterone during an individual PGFM pulse, but only during the first portion of luteolysis. These findings should be considered in future proposals on the mechanisms involved in the effects of PGF on progesterone concentrations.

Hormonal factors influencing fractional excretion of filtered sodium in normal children.

Fractional excretion of filtered sodium (FENa), plasma renin activity (PRA), urinary kallikrein excretion and main urinary metabolite of prostaglandin F2 alpha (PGF MUM) excretion were measured to evaluate the relationship between FENa and these hormonal factors in 33 healthy children aged 8 to 15 years. FENa showed a significant negative correlation with PRA and PGF MUM excretion (P less than 0.001, P less than 0.01, respectively), suggesting that PRA and PGF MUM are useful investigations in evaluating FENa. Especially PRA is often measured routinely and should be measured first, which may provide useful pathophysiological information on the genesis of abnormal FENa.

Nutritional regulation of uteroplacental prostaglandin production and metabolism in pregnant ewes and mares during late gestation.

Prostaglandins (PGs) are produced by a variety of uteroplacental tissues during pregnancy and are released into the fetal fluid sacs and both the uterine and umbilical circulations. Uterine PG output increases towards term and is enhanced by maternal undernutrition in pregnant ewes and mares. In both species, withdrawal of food but not water for 30-48 h increases uterine venous PG levels and the uterine venous arterial concentration differences in PGE and 13, 14, dihydro-15-keto-prostaglandin F2 alpha (PGFM), the stable metabolite of PGF2 alpha. The increments in uterine V-A concentration differences in PGE and PGFM increase towards term and are associated with raised plasma PG levels in the fetal circulation. The PG changes observed during fasting are closely related to the fall in plasma glucose and the rise in plasma FFA in peripheral plasma. When normal metabolite levels are restored either by refeeding or glucose infusion, there is a rapid fall in PG levels with a narrowing of the uterine V-A concentration differences in the ewe and mare. When the data from all the animals are combined, there is an inverse correlation between uterine glucose uptake and PGFM output in both the pregnant ewe and mare. The availability of glucose and FFA to the gravid uterus therefore has an important role in controlling uteroplacental PG production and metabolism in late gestation although the specific steps in biochemical pathways regulated by these metabolites remain unclear. In the ewe, fasting increases uterine contractility and leads to early delivery of viable lambs in animals close to term (> 95% gestation), whereas in the mare it causes premature delivery of non-viable foals in most animals in late gestation (> 80% gestation). Nutritionally induced changes in uteroplacental PG production and metabolism therefore have important consequences for the outcome of pregnancy and may have a pivotal role in the induction of labour both before and at normal term.

Effective Oxytocin Treatment on Placental Expulsion after Foaling in Heavy Draft Mares

The aim of this study was to establish the effectiveness of administration of oxytocin (OT) on placental expulsion after foaling. Four foaling mares with the placentas retained for up 1 hr after foaling received OT (50 IU) administration at 1 hr intervals before expulsion of the placenta. The changes in the plasma concentrations of OT and the PGF2alpha metabolite (PGFM) were investigated, and the influence of OT administration was considered. The results were as follows. The placenta was expelled after one to three OT administrations in all four mares that received OT. In two mares, which expelled the placenta within 30 min after OT administration, the OT concentration increased and remained high. Expulsion of the placenta was delayed in two mares, and one of these mares, which received three doses of OT beginning 1 hr after foaling, showed only a small increase in the OT concentration after the first administration; the other mare did not receive OT until 3 hr after foaling. The OT concentration was increased before placental expulsion in all the mares, and the PGFM concentration also increased in the two mares with retained placentas. In conclusion, we suggest that intramuscular administration of 50 IU of OT at 1-hr intervals beginning 1 hr after foaling is effective for inducing placental expulsion.

The influence of tumor necrosis factor α (TNF) on the secretory function of bovine corpus luteum: TNF and its receptors expression during the estrous cycle

Tumor necrosis factor alpha (TNF) inversely regulates the function of bovine corpus luteum (CL). Whereas the low doses of TNF induce luteolysis, the high doses prolong CL lifespan and prevent luteolysis in vivo. We suggest that the varying effects of TNF may be caused by its action exerted on CL via multiple signaling pathways involving two distinct receptors: TNFR-I (responsible for induction of the cell death) and TNFR-II (implicated in cell proliferation). In the study, we determined CL expressions of TNF, TNFR-I and TNFR-II mRNAs during the bovine estrous cycle using semi-quantitative RT-PCR. Specific transcripts for TNF, TNFR-I and TNFR-II were found in the CL with the highest (p<0.05) expression in the regressed CL. We also examined the TNF influence on the bovine CL function in vivo. On Day 15 of the estrous cycle, cows were infused (via aorta abdominalis) with saline, TNF (1 or 10 microg) or analogue of prostaglandin (PG)F(2alpha) (aPGF(2alpha) , 500 microg; a positive control). Four hours after infusions, CLs were collected by colpotomy and luteal contents of progesterone (P(4)), stable metabolites of nitric oxide (NO; nitrite/nitrate), leukotriene (LT)C(4), luteolytic PGF(2alpha),and luteotropic PGE(2) were determined. Moreover, caspase-3 activity was measured in the CLs as an indicator of apoptosis induction. The luteal content of P(4) decreased (p<0.05) after infusion of 1 microg of TNF. TNF inversely affected PGs content in CL: the low dose increased (p<0.01) the PGF(2alpha) level and the high dose increased (p<0.05) PGE(2) level. Contents of LTC(4) and nitrite/nitrate increased (p<0.01) after the low dose of TNF. Moreover, 1 microg of TNF induced apoptosis and increased (p<0.05) caspase-3 activity in the CLs collected during the late luteal phase. In conclusion, the high expressions of TNF and TNF receptors mRNAs were observed during or just after the luteolysis. A low concentration of TNF stimulated in vivo luteolytic factors such as PGF(2alpha), LTC(4) and NO as well as induced apoptosis; whereas the high concentration of TNF stimulated a survival pathway in the bovine CL increasing luteal content of P(4) and PGE(2).

Relationship between Peripartal Plasma Oxytocin and Prostaglandin F2.ALPHA. Metabolite and Placental Expulsion Time in Heavy Draft Mares

The aim of this study was to clarify the relationship between circulating oxytocin (OT) and PGF(2alpha) metabolite (PGFM) in mares at the third stage of labor and placental expulsion time in order to investigate a cause of retained placenta of which the incidence increase in a heavy draft mare. Blood was sampled every 5 min from foaling to expulsion of the placenta in 18 heavy draft mares to evaluate circulating OT and PGFM. The relationships between OT and PGFM concentration and recorded placental expulsion times were investigated. The results were as follows (1) The highest level of OT concentration was observed close to foaling in 15 mares. (2) The OT concentrations close to foaling were variable with a large difference from the lowest concentration, 22.1 pg/ml, to the highest concentration, 209.3 pg/ml. (3) The highest level of PGFM was observed close to foaling in 17 mares. (4) During the 60 min following foaling, the OT concentrations of the mares (n=11) that had a shorter placental expulsion time (i.e., <1 h), were significantly higher than those of the mares (n=7) that had a longer placental expulsion time (i.e., >1 h; P<0.05). Collectively, the OT concentration immediately after foaling is negatively related to the placental expulsion time. Deficiency of OT secretion at foaling have should be considered as one of the causes of retained placenta in heavy draft mares.

Fatty acid composition of plasma, medial basal hypothalamus, and uterine tissue in primiparous beef cows fed high-linoleate safflower seeds1

The experimental objectives were to evaluate the influence of supplemental high-linoleate safflower seeds on fatty acid concentrations in plasma, medial basal hypothalamus, uterine tissues, and serum 13,14-dihydro-15-keto PGF(2)alpha metabolite (PGFM) in primiparous beef cows during early lactation. Beginning 1 d postpartum, 18 primiparous, crossbred beef cows (411 +/- 24.3 kg of BW) were fed foxtail millet hay at 1.68% of BW (DM basis) and either a low-fat supplement (control: 63.7% cracked corn; 33.4% safflower seed meal; and 2.9% liquid molasses; DM basis) at 0.35% of BW (n = 9) or a supplement (linoleate) containing 95.3% cracked high-linoleate (79% 18:2n-6) safflower seeds and 4.7% liquid molasses (DM basis) at 0.23% of BW (n = 9). Diets were formulated to be isonitrogenous and isocaloric. The linoleate diet contained 5.4% of DMI as fat vs. 1.2% for control. Beginning 1 d postpartum, cattle were bled every 3 d for collection of serum and plasma. Cattle were slaughtered at 37 +/- 3 d postpartum for collection of the medial basal hypothalamus, myometrium, endometrium, caruncular tissue, intercaruncular tissue, and oviduct. Feeding linoleate increased (P = 0.001) plasma concentrations of 18:2n-6, 18:2cis-9 trans-11 and total unsaturated fatty acids; however, 18:1trans-11 did not differ (P = 0.19) between treatments. Concentrations of 20:5n-3 in the medial basal hypothalamus tended (P = 0.10) to be greater for cattle fed linoleate. Concentrations of fatty acids in the oviduct were greater (P < 0.05) than in other uterine tissues. Cows fed linoleate had greater (P = 0.05) concentrations of 18:3n-3 in the endometrium and less (P = 0.06) 18:2cis-9 trans-11 in the myometrium than cows fed the control. Supplemental fat increased (dietary treatment x day postpartum, P = 0.01) concentrations of PGFM in serum more in linoleate than control cows from d 3 to 9 postpartum. Lipid supplementation early in the postpartum period altered the fatty acid composition of medial basal hypothalamus, uterine tissue, and serum concentrations of PGFM. The most novel observation was that the oviduct appeared to be the most sensitive tissue to additional dietary linoleic acid, which could potentially influence fertility.

Novel cyclooxygenase‐catalyzed bioactive prostaglandin F2α from physiology to new principles in inflammation

Prostaglandin F2alpha (PGF2alpha), a foremost stable vasoactive cyclooxygenase (COX)-catalyzed prostaglandin, regulates a number of key physiological functions such as luteolysis, ovarian function, luteal maintenance of pregnancy, and parturition as a constitutive part of ongoing reproductive processes of the body. It has recently been implicated in the regulation of intricate pathophysiological processes, such as acute and chronic inflammation, cardiovascular and rheumatic diseases. Since the discovery of a second isoform of COXs, it has been shown that PGF2alpha can be formed in vivo from arachidonic acid through both isoforms of COXs, namely cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Being synthesized in various parts of the body, it metabolizes instantly to a number of rather inactive metabolites mainly in the lungs, liver, kidney, and efficiently excretes into the urine. 15-Keto-dihydro-PGF2alpha, a major stable metabolite of PGF2alpha that reflects in vivo PGF2alpha biosynthesis, is found in larger quantities than its parent compound in the circulation and urine in basal physiological conditions, with short-lived pulses during luteolysis, induced termination of pregnancy and parturition, and is increased in tissues and various body fluids during acute, sub-chronic, and severe chronic inflammation. Further, the close relationship of PGF2alpha with a number of risk factors for atherosclerosis indicates its major role in inflammation pathology. This review addresses multiple aspects of PGF2alpha in addition to its emerging role in physiology to inflammation.

Pyometra in Bitches Induces Elevated Plasma Endotoxin and Prostaglandin F2α Metabolite Levels

Endotoxemia in bitches with pyometra can cause severe systemic effects directly or via the release of inflammatory mediators. Plasma endotoxin concentrations were measured in ten bitches suffering from pyometra with moderately to severely deteriorated general condition, and in nine bitches admitted to surgery for non-infectious reasons. Endotoxin samples were taken on five occasions before, during and after surgery. In addition, urine and uterine bacteriology was performed and hematological, blood biochemical parameters, prostaglandin F2α metabolite 15-ketodihydro-PGF2α (PG-metabolite), progesterone and oestradiol (E2-17β) levels were analysed.The results confirm significantly increased plasma levels of endotoxin in bitches with pyometra and support previous reports of endotoxin involvement in the pathogenesis of the disease. Plasma concentrations of PG-metabolite were elevated in pyometra bitches and provide a good indicator of endotoxin release since the concentrations were significantly correlated to the endotoxin levels and many other hematological and chemistry parameters. The γ-globulin serum protein electrophoresis fraction and analysis of PG-metabolite can be valuable in the diagnosis of endotoxin involvement if a reliable, rapid and cost-effective test for PG-metabolite analysis becomes readily available in the future. Treatment inhibiting prostaglandin biosynthesis and related compounds could be beneficial for bitches suffering from pyometra.

Dietary supplementation with safflower seeds differing in fatty acid composition differentially influences serum concentrations of prostaglandin F metabolite in postpartum beef cows

Synthesis and secretion of prostaglandin F2alpha (PGF2alpha) is elevated following parturition and exerts divergent effects on the re-establishment of fertile estrous cycles in cows. The objective of these experiments was to determine if oil seed supplements differing in fatty acid composition differentially influence serum concentrations of the specific PGF2alpha metabolite, PGFM. Safflower seed supplements were formulated to provide 5% of dry-matter intake as fat. In Trial 1, 24 multiparous beef cows were individually fed control (beet pulp-soybean meal) or cracked high-linoleate safflower seed (78% 18:2n-6) supplements for 80 d postpartum. Linoleate supplemented cows had greater (P < 0.001) serum concentrations of PGFM than control cows. In Trial 2, primiparous beef cows (n = 36) were individually fed control (cracked corn-soybean meal), cracked high-linoleate (76% 18:2n-6) or -oleate (72% 18:1n-9) safflower seed supplements for 92 d postpartum. As in Trial 1, serum concentrations of PGFM were greater (P < or = 0.04) in linoleate than control or oleate supplemented cows. Serum concentrations of PGFM, however, did not differ (P = 0.40) among oleate and control supplemented cows. Although potential impacts on reproductive performance remain to be proven, dietary oil supplements high in linoleate, but not oleate, increased serum concentrations of PGFM compared to control supplements.

Fish meal supplementation alters uterine prostaglandin F2α synthesis in beef heifers with low luteal-phase progesterone1,2

The objective of the current study was to evaluate the effect of omega-3 fatty acids in fish meal on mitigating uterine PGF2alpha synthesis in heifers with low luteal-phase concentrations of progesterone. Animals were individually fed a corn silage-based diet supplemented with fish meal (5% of DMI; n = 12) or corn gluten meal (6% of DMI; n = 13). Estrous cycles were synchronized using PGF2alpha beginning on d 25 of supplementation. Random heifers from each supplement group (n = 6 fish meal, and n = 7 corn gluten meal) were given three additional i.m. injections of PGF2alpha (25 mg) at 12-h intervals beginning at 0600 on d 3 after estrus to induce formation of corpora lutea that secrete lower concentrations of progesterone. Jugular blood samples were collected daily commencing on d 1 and continuing through d 16 of the estrous cycle to determine serum progesterone concentrations. Oxytocin was administered i.v. (100 IU) to heifers on d 16 after estrus to stimulate uterine PGF2alpha synthesis. Before statistical analyses, heifers were sorted to either normal or low luteal-phase progesterone as determined from serum progesterone on d 9 of the estrous cycle. After sorting, treatment groups consisted of 1) normal luteal progesterone + fish meal (n = 6); 2) low luteal progesterone + fish meal (n = 6); 3) normal luteal progesterone + corn gluten meal (n = 6); and 4) low luteal progesterone + corn gluten meal (n = 7). Serum concentrations of the PGF2alpha metabolite following oxytocin stimulation tended (P = 0.09) to be greater in heifers with low luteal-phase progesterone compared with heifers with normal luteal-phase progesterone. Fish meal supplementation mitigated this response in heifers with low luteal-phase progesterone (P < 0.05), but had no effect on heifers with normal luteal-phase progesterone. In conclusion, the omega-3 fatty acids in fish meal seem to decrease uterine PGF2alpha synthesis in heifers with low luteal-phase serum concentrations of progesterone.

Delay of preterm birth in sheep by THG113.31, a prostaglandin F 2α receptor antagonist

A novel prostaglandin F2alpha receptor antagonist, THG113.31, was tested for the suppression of uterine contractility and delay of preterm labor in sheep. We determined the tocolytic effectiveness of THG113.31 on contractions that were stimulated in vitro by prostaglandin F2alpha and E2 in longitudinal and circular myometrial strips. We also tested the ability of THG113.31 in vivo to lower uterine electromyographic activity that was induced by the progesterone receptor blocker, RU486, and to delay preterm birth. THG113.31 suppressed the amplitude of prostaglandin F2alpha, but not prostaglandin E2-induced contractions of both circular and longitudinal myometrium (P<.01). The times to delivery after RU486 were 34.8+/-1.1 hours (saline solution) and 41.9+/-0.5 hours (THG113.31; P<.001) or an average delay of 7.1 hours. There were no changes in fetal blood gases (PaO2 , PaCO2 , pH, or SaO2) because of THG113.31. Fetal cortisol levels rose in each group, and fetal and maternal prostaglandin E2 and F2alpha metabolite concentrations rose similarly in both groups. THG113.31 specifically suppresses prostaglandin F2alpha-induced myometrial contractility and delays delivery.