PGF2α Metabolite Research Articles

Effects of calcium salts of fatty acids and calcium salt of methionine hydroxy analogue on plasma prostaglandin F2α metabolite and milk fatty acid profiles in late lactation Holstein–Friesian cows

Effects of a dietary lipid supplement containing calcium salts of fatty acids and methionine hydroxy analogue on plasma prostaglandin F2α (PGF2α) metabolite (PGFM) and milk fatty acid profiles were examined in 40 late lactation, nonpregnant, Holstein–Friesian cows for a period of 70 days. Effects on milk production, milk composition, and blood metabolites were also examined. Cows were paired on the basis of lactation number (first lactation, n=8; second lactation, n=32) and randomly assigned from within pairs to one of two dietary treatments: unsupplemented control (C) or 400g per cow per day of the lipid supplement (S). Cows receiving the supplement had higher (P<0.05) total milk production, total fat production (kg), and total lactose production (kg). Plasma cholesterol was significantly higher (P<0.01) after 30 days of treatment in cows receiving the supplement. Cows receiving the supplement had lower (P<0.01) concentrations of short chain milk fatty acids (C4:0 to C14:1) and higher concentrations of long chain fatty acids (C18:1 and C18:2; P<0.01) than control animals. Oxytocin-induced prostaglandin release on Day 16 postovulation was increased (P<0.01) in cows receiving the supplement. In conclusion, supplementation with calcium salts of fatty acids and methionine hydroxy analogue significantly increased milk yield and plasma PGFM.

Postovulatory effect of repeated administration of prostaglandin F 2α on the endocrine status, ova transport, binding of accessory spermatozoa to the zona pellucida and embryo development of recently ovulated sows

We investigated the postovulatory effect of repeated administration of prostaglandin F 2α (PGF 2α) on the endocrine status, ova transport, binding of accessory spermatozoa to the zona pellucida (ZP) and embryo development of recently ovulated sows. We used altogether 10 Swedish crossbred (Landrace×Yorkshire) multiparous sows. The treatment group (P-group) was administered 1 mg of PGF 2α intravenously every 6 h via an indwelling jugular cannula, commencing 4–8 h after ovulation was detected in the second estrus after weaning. All sows were inseminated once and blood was sampled until the end of the experimental period. After slaughter, we immediately recovered the reproductive tracts and divided them into three equal isthmic segments (IST1, IST2 and IST3) and a third of the uterine horn from the utero-tubal-junction (UTJ), and we flushed each one with PBS for ova recovery. We immediately stained the ova and examined them under epi-fluorescence illumination. We found the highest proportion of ova in the P-group in IST1 (41.5%), while we found the highest proportion in the C-group in the uterus (40.7%). A total of 68.7% of ova in the P-group had more than 50 accessory spermatozoa attached to the ZP, compared with 36.7% in the C-group sows. A total of 77% of ova had more than three blastomeres in the P-group, compared with 73% in the C-group. PGF 2α metabolite and cortisol levels were elevated ( P<0.05) following every PGF 2α administration. Despite peaks, we saw no changes ( P>0.05) in progesterone levels between the P-group and the C-group. We saw no differences ( P>0.05) in estradiol-17β levels between the P-group and the C-group. We concluded that PGF 2α stimulates the hypothalamus–pituitary–adrenal axis, as evidenced by the elevation of cortisol and progesterone but not estradiol-17β. Furthermore, repeated PGF 2α administration might be associated with a delayed ova transport and an increased number of accessory spermatozoa bound to the ZP. However, the effect of PGF 2α on embryo development is unclear.

Uterine, Ovarian, and Production Responses of Lactating Dairy Cows to Increasing Dietary Concentrations of Menhaden Fish Meal

The primary objective was to determine whether the dietary polyunsaturated fatty acids, eicosapentaenoic (EPA, C20:5, n-3) and docosahexaenoic (DHA, C22:6, n-3), present in fish meal (FM) can attenuate uterine secretion of PGF2α in response to a challenge with estradiol and oxytocin in lactating dairy cows. Cycling multiparous cows (n = 32) were fed diets containing 0 (0FM), 2.6 (2.6FM), 5.2 (5.2FM), or 7.8% menhaden FM (7.8FM). The diet consisting of 7.8FM also contained fish oil (0.28% of dietary dry matter) to increase intake of EPA and DHA. Average dry matter intake was 24.9 kg/d and unaffected by diet. Combined intakes of EPA and DHA averaged 0, 12.8, 24.1, and 54.0 g/d from the 0FM, 2.6FM, 5.2FM, and 7.8FM diets, respectively. At 30 to 34 d after initiation of dietary treatments, cows received an i.m. injection of 100μg of GnRH followed by i.m. administration of 25 and 15mg of PGF2α after 7 and 8 d, respectively. Synchronous ovulation was induced by an injection of 3000 IU of human chorionic gonadotropin (hCG) given 24h later on d 9. Subsequent luteal phase increases in plasma progesterone concentrations did not differ (0.88ng/ml per day). At 15 d after hCG injection, cows were injected with estradiol-17β (3mg, i.v.) at 0900h and oxytocin (100 IU, i.v.) at 1300h. Plasma PGF2α metabolite concentrations after oxytocin injection were reduced in cows fed diets containing FM compared with those fed 0FM. Milk production (39.1 kg/d) and concentrations of fat, protein, or urea nitrogen in milk were not affected by diet. Feeding fish meal and fish oil containing eicosapentaenoic acid and docosahexaenoic acid reduced the proportion of n-6 fatty acids and increased that of n-3 fatty acids in milk in a dose-responsive manner.

Role of PGF2alpha and oxytocin in parturition in the brushtail possum (Trichosurus vulpecula).

Maturation of the fetal pituitary and adrenal glands allows the secretion of cortisol, which in turn leads to an increase in prostaglandin and mesotocin production. The production of prostaglandin and mesotocin results in an increase in uterine contractions and initiates birth in marsupials. The major metabolite of PGF(2alpha), 13,14-dihydro-15-keto-prostaglandin F(2alpha) (PGFM), has been found in the plasma of the possum at the time of birth and administration of PGF(2alpha) to female possums induced the adoption of the birth position. Evidence that mesotocin is an integral hormone of birth in the tammar wallaby indicates that both PGF(2alpha) and mesotocin or oxytocin are required for marsupial birth. The presence of PGF(2alpha) receptors in the uterus and corpus luteum of the possum, and the in vitro uterine responsiveness to PGF(2alpha) or oxytocin, were examined. PGF(2alpha) receptors were not observed in possum uteri and the inability of PGF(2alpha) to cause contractions indicates that PGF(2alpha) is not involved directly in contraction of the uterus at parturition. The presence of oxytocin and mesotocin receptors in the uterus of possoms and the ability of oxytocin to induce uterine contraction in vitro supports the view that mesotocin is required for expulsion of the young from the uterus. Low numbers of PGF(2alpha) receptors were found in the possum corpus luteum at birth, indicating an involvement of PGF(2alpha) in regression of the corpus luteum.

Role of PGF2alpha and oxytocin in parturition in the brushtail possum (Trichosurus vulpecula)

Maturation of the fetal pituitary and adrenal glands allows the secretion of cortisol, which in turn leads to an increase in prostaglandin and mesotocin production. The production of prostaglandin and mesotocin results in an increase in uterine contractions and initiates birth in marsupials. The major metabolite of PGF(2alpha), 13,14-dihydro-15-keto-prostaglandin F(2alpha) (PGFM), has been found in the plasma of the possum at the time of birth and administration of PGF(2alpha) to female possums induced the adoption of the birth position. Evidence that mesotocin is an integral hormone of birth in the tammar wallaby indicates that both PGF(2alpha) and mesotocin or oxytocin are required for marsupial birth. The presence of PGF(2alpha) receptors in the uterus and corpus luteum of the possum, and the in vitro uterine responsiveness to PGF(2alpha) or oxytocin, were examined. PGF(2alpha) receptors were not observed in possum uteri and the inability of PGF(2alpha) to cause contractions indicates that PGF(2alpha) is not involved directly in contraction of the uterus at parturition. The presence of oxytocin and mesotocin receptors in the uterus of possoms and the ability of oxytocin to induce uterine contraction in vitro supports the view that mesotocin is required for expulsion of the young from the uterus. Low numbers of PGF(2alpha) receptors were found in the possum corpus luteum at birth, indicating an involvement of PGF(2alpha) in regression of the corpus luteum.

Prostaglandin F2α metabolite and F2-isoprostane excretion rates in migraine

The pathophysiology theory of migraine postulates a local, neurogenic inflammation and the possible involvement of oxidative stress. We analysed the levels of 15-oxo-dihydro-prostaglandin F(2alpha) (a metabolite of prostaglandin F(2alpha)) and 8-iso-prostaglandin F(2alpha) (a major isoprostane), which are biomarkers for inflammation and oxidative stress respectively, in urine from 21 patients with migraine, with and without aura. Urine samples from migraine patients were collected during a migraine attack, and control samples were collected from the same subjects on a migraine-free morning. The mean basal levels of 15-oxo-dihydro-prostaglandin F(2alpha) and 8-iso-prostaglandin F(2alpha) in the morning control urine samples were 0.54+/-0.11 and 0.31+/-0.13 nmol/mmol of creatinine respectively. The mean levels of 15-oxo-dihydro-prostaglandin F(2alpha) and 8-iso-prostaglandin F(2alpha) in the urine samples collected during the migraine attack in the 21 patients were 0.53+/-0.13 and 0.32+/-0.11 nmol/mmol of creatinine respectively. Thus there were no differences in the 15-oxo-dihydro-prostaglandin F(2alpha) and 8-iso-prostaglandin F(2alpha) excretion rates during the migraine attack compared with on the migraine-free day. However, the basal 8-iso-prostaglandin F(2alpha) excretion levels on the migraine-free day were significantly lower in pre-menopausal women (0.24+/-0.08 nmol/mmol of creatinine, n=11) compared with post-menopausal women (0.39+/-0.14 nmol/mmol of creatinine; n=7; P=0.009). In conclusion, in this study we found no support for the involvement of inflammation and oxidative stress in migraine pathophysiology. Our results indicate, however, a lower level of oxidative stress in pre-menopausal compared with post-menopausal women.

Pre-parturition profile of steroids and prostaglandin in cows with or without foetal membrane retention

Retained foetal membranes in cattle is one of the most common complications associated to the reduction in milk yield and impaired fertility in dairy cattle. In order to determine some endocrine mechanisms controlling parturition and delivery of foetal membranes, plasma concentrations of steroids and prostanoids were determined in 20 healthy Holstein cows. Samples were taken within the interval of 5 days pre-parturition to 12 h after calving. Progesterone (P 4) levels were similar in cows with (PR) and without (NPR) placental retention. While the estradiol-17β (E 2) peak at parturition was lower in PR than in NPR cows, cortisol levels were greater in PR cows 12 and 24 h pre-parturition. The Prostaglandin F 2α metabolite (PGFM) levels were higher at parturition in NPR compared with the PR group, but 12 h later, these levels in the PR group increased so that concentrations were greater as compared with NPR cows. The Prostaglandin E 2 metabolite (PGEM), 24, 48 and 72 h pre-parturition, were higher in PR cows. However, the PGFM:PGEM ratio was greater in cows up NPR at all time when included, indicating the importance of higher levels of Prostaglandin F 2α (PGF 2α) than Prostaglandin E 2 (PGE 2) for normal placental delivery. In conclusion, placental retention was related to both estrogen and PGF 2α deficiency, which may be a consequence of metabolic stress leading to PGE 2 and maternal cortisol synthesis before parturition.

Effect of an implant containing the GNRH agonist deslorelin on secretion of LH, ovarian activity and milk yield of postpartum dairy cows

Prevention of high plasma progesterone concentrations in the early postpartum period may improve fertility. Our objective was to determine whether a Deslorelin implant (DESL; 2100 μg, SC) would reduce secretion of LH and alter follicle dynamics, plasma concentrations of progesterone, estradiol and PGF 2α metabolite (PGFM) in postpartum dairy cows. Cows received DESL on Day 7 postpartum (Day 7, n=8) or were untreated (Control, n=9). All cows were injected with GnRH (100 μg, im) on Day 14 to assess LH response. A protocol for synchronization of ovulation with timed AI was initiated on Day 60 (GnRH [Day 60], CIDR [Day 60 to Day 67], PGF 2α [Day 67, 25 mg and Day 68, 15 mg], GnRH [Day 69], AI [Day 70]). The LH response to injection of GnRH on Day 14 was blocked in animals treated with DESL. Numbers of Class 1 (<6 mm) follicles were unaffected (P > 0.05) whereas numbers of Class 2 (6 to 9 mm) (P < 0.01) and Class 3 (9 mm) follicles were less (P < 0.01) in DESL cows between Day 7 and Day 21. From Day 22 to Day 60, DESL-treated cows had more of Class 1 follicles and less Class 2 (P < 0.01) and Class 3 (P < 0.01) follicles, and lower plasma concentrations of progesterone and estradiol (P < 0.01). Concentrations of PGFM between Day 7 and Day 42 were not affected by treatment (P > 0.05). All cows ovulated in response to GnRH on Day 69. Subsequent luteal phase increases in plasma progesterone concentrations (Day 70 to Day 84) did not differ. The use of the DESL implant associated with PGF 2α given 14 days later suppressed ovarian activity and caused plasma progesterone concentrations to remain < 1 ng/mL between Day 22 and Day 51. The DESL implant did not affect milk production.

Plasma concentrations of estradiol 17β and PGF2α metabolite and placental fatty acid composition and antioxidant enzyme activity in cows with and without retained fetal membranes

Fetal membrane retention is one of the most common problems in Holstein cattle after parturition. To investigate mechanisms involved, the following parameters were studied in the peri-parturition period: plasmatic concentrations of estradiol-17β (E 2) and PGFM (PGF2α metabolite), activity of antioxidant enzymes (superoxide dismutase-SOD, catalase-CAT and glutathione peroxidase-GSH-Px), thiobarbituric acid reagent substances (TBAR) concentrations and fatty acid composition of the placentae. E 2 at parturition in the NPR group (control cows, n = 10) was higher than in PR cows (placental retention, n = 10) (P < 0.05). Activity of SOD in fetal tissue of NPR animals was higher than that of the PR group. In contrast, there was no difference between the two groups in activity of GSH-Px and CAT and the TBAR content of placental tissues. PR maternal tissues had proportionally more arachidonic and linoleic acid than tissues from NPR cows. Therefore, a complex of sequential events may cause placenta retention, starting with an unbalance of antioxidant capacity of the placenta, followed by a decrease in production of estrogen, which leads to the accumulation of arachidonic and linoleic acid in placental tissues.

Feto-Placental Hypoxemia Regulates the Release of Fetal Activin A and Prostaglandin E2

The evaluation of the role of critical hypoxia in unexplained fetal death in utero has been hampered by the lack of a physiological marker. Here we report the novel observation that feto-placental hypoxemia is an acute trigger for increased activin secretion from the feto-placental unit in late pregnancy. Hypoxemia was induced in chronically cannulated late pregnant fetal sheep by restricting blood flow through the maternal uterine arteries. Using maternal and fetal blood samples and amniotic fluid obtained via chronically implanted catheters, fetal blood gas parameters, plasma and amniotic fluid concentrations of activin A, prostaglandin (PG) E2 and PGFM, the circulating metabolite of PGF2α, were determined before, during and after a ten hour period of fetal hypoxemia. Hypoxemia acutely increased activin A and PGE2 levels in both amniotic fluid and the fetal circulation with values rapidly returning to baseline with normoxemia. PGFM also increased in both compartments with a relatively delayed time frame compared to that of activin A and PGE2. The increase in activin A and PGE2 induced by hypoxemia may be a mechanism to regulate feto-placental blood flow during fetal compromise and also offers the possibility that activin A represents a useful marker of feto-placental hypoxemia.

Feto-placental hypoxemia regulates the release of fetal activin A and prostaglandin E(2).

The evaluation of the role of critical hypoxia in unexplained fetal death in utero has been hampered by the lack of a physiological marker. Here we report the novel observation that feto-placental hypoxemia is an acute trigger for increased activin secretion from the feto-placental unit in late pregnancy. Hypoxemia was induced in chronically cannulated late pregnant fetal sheep by restricting blood flow through the maternal uterine arteries. Using maternal and fetal blood samples and amniotic fluid obtained via chronically implanted catheters, fetal blood gas parameters, plasma and amniotic fluid concentrations of activin A, prostaglandin (PG) E(2) and PGFM, the circulating metabolite of PGF(2alpha), were determined before, during and after a ten hour period of fetal hypoxemia. Hypoxemia acutely increased activin A and PGE(2) levels in both amniotic fluid and the fetal circulation with values rapidly returning to baseline with normoxemia. PGFM also increased in both compartments with a relatively delayed time frame compared to that of activin A and PGE(2). The increase in activin A and PGE(2) induced by hypoxemia may be a mechanism to regulate feto-placental blood flow during fetal compromise and also offers the possibility that activin A represents a useful marker of feto-placental hypoxemia.

Asthma and sex hormones.

A chronic in ammatory state of the airways is considered the hallmark of asthma (1). However, the incidence, severity, and prognosis of asthma can be affected by a number of factors, including the patient's sex and age. The sex of the fetus seems to in uence the development of the respiratory apparatus. In fact, between weeks 28 and 40 of gestation, the lungs are in a more advanced state in females than in males (2), a fact which could explain, at least in part, the higher incidence of respiratory distress in male infants (3). Clinical observations and epidemiologic studies agree that childhood asthma is more frequent in boys than in girls (4). Moreover, in some children, usually boys, asthmatic symptoms that started in infancy disappear around puberty (5), while many girls have the disease only during adolescence (6). Age has been implicated in the severity of asthma. Asthma beginning during adulthood is generally more severe than childhood-onset asthma (7). Asthma that starts around the menopause or in old age is generally quite severe (5). According to two recent epidemiologic investigations, the patient's sex and age affect the hospitalization rate for asthma (8, 9), which is a marker of severity. In the ®rst study (a retrospective study of 33 269 patients), the admission rate of boys in the 0±10-year age group was almost twice that of girls. In the next decade, sex differences in the hospitalization rate were irrelevant, although there was a small, but signi®cant prevalence of females. At all ages above 20 years, hospital admission rates were higher in women than men, with a female/ male ratio ranging from 3:1 in subjects aged 20±50 years to 2.5:1 in those over 50 years of age (8). Similar data were reported by Elliasson (9). Both studies found a relationship between the age and sex of the patient and the severity of the asthma attack as indicated by duration of hospitalization. In fact, the duration of hospitalization increased with age in both sexes; moreover, hospital stays were longer in women over 30 years of age than in men of the same age (8, 9). Abbreviations. FSH: follicle-stimulating hormone; LH: luteinizing hormone; NK cell: natural killer cell; IL-1, -4, -5, -6: interleukin-1, -4, -5, -6; TGF-b: tumor growth factor-beta; PEFR: peak expiratory ow rate. Allergy 2001: 56: 13±20 Printed in UK. All rights reserved Copyright # Munksgaard 2001

15-Ketodihydro-PGF2α, Progesterone and Cortisol Profiles in Heifers after Induction of Parturition by Injection of Dexamethasone

In order to study rapid changes in 15-ketodihydro-PGF2α, cortisol and progesterone in the period preceding parturition in cattle, pre-term parturition was induced in 4 late pregnant heifers. Parturitions were induced by 2 intramuscular injections of 20 mg dexamethasone with a 24-h interval. The first injection was made on days 254, 258, 264 and 265 in gestation, respectively. Twenty-four h before the first injection an intravenous polyurethane cannula was inserted. Blood samples were collected at least every hour until 12 h after parturition and during the second stage of labour at least 6 times per hour. Plasma was analysed for 15-ketodihydro-PGF2α and progesterone by radioimmunoassays, and for cortisol by an ELISA. The average time from injection to parturition was 7.7 (6.6–8.9) days (mean (range)). Two of the heifers had retained foetal membranes (RFM). At the start of the experiment the levels of PGF2α metabolite were low (< 300 pmol/L) and increased slowly to levels between 1000 and 2000 pmol/L at one day before parturition. During the last day, however, the levels increased rapidly and the highest levels (>10000 pmol/L) were reached at the time of delivery. No pulsatile release was seen. Immediately after foetal expulsion the PG-metabolite levels decreased rapidly in all animals. In the 2 animals with RFM, however, this decline ceased within a few h. The PG-metabolite levels in these animals then started to increase and reached levels as high as during parturition. Luteolysis occurred between 1.6 and 0.4 days before parturition in all animals. The cortisol profile showed a distinct peak at the time of parturition in the RFM heifers. This peak was absent in the non-RFM heifers. This study shows that the PGF2α release at prepartal luteolysis and parturition is not pulsatile in cattle and that cortisol profiles in heifers with retained foetal membranes might differ from the profiles in non-RFM heifers at the time of parturition.

The role of sub-optimal preovulatory oestradiol secretion in the aetiology of premature luteolysis during the short oestrous cycle in the cow

Premature regression of the corpus luteum, following the first post partum ovulation, is often preceded by sub-optimal preovulatory oestradiol secretion and accompanied by elevated levels of oxytocin receptors early in the luteal phase. We have investigated the role of preovulatory oestradiol in the control of subsequent oxytocin receptor concentration and activity by treating ovariectomised cows, over a simulated 48 h follicular phase, with high (600 μg per day) medium (300 μg per day) or low (150 μg per day) levels of oestradiol. These doses of oestradiol generated mean±S.E.M. plasma oestradiol concentrations of 12.1±1.0, 4.9±0.5 and 2.9±0.4 pg ml −1, respectively. In Study 1 ( n=4 per group), we found that by day 4 following oestrus there was a significant ( P<0.05) effect of the level of oestradiol on the inhibition of oxytocin binding activity measured in endometrial biopsy samples. This had fallen to mean±S.E.M. concentrations of 25±2 fmol per mg protein in the high group, 47±8 fmol per mg protein in the medium group and 65±12 fmol per mg protein in the low group. In Study 2, cows ( n=3 per group) were treated with the same three levels of oestradiol followed by treatment with increasing levels of progesterone from days 3 to 6 following oestrus, generating mean±S.E.M. plasma concentrations of 2.17±0.18 ng ml −1 by day 6. On day 6, there was a significant ( P<0.01) effect of the level of oestradiol on PGF 2α release in response to oxytocin challenge. High, medium and low oestradiol groups exhibiting mean±S.E.M., increase plasma PGF 2α metabolite concentrations of 10.0±2.2, 21.3±4.3 and 41.3±1.2 pg ml −1, respectively, during the hour after oxytocin administration. From these results, we postulate that at the first post partum ovulation a low level of preovulatory oestradiol can result in the early generation of a luteolytic mechanism during the subsequent luteal phase due to impaired inhibition of oxytocin receptors allowing increased PGF 2α release.

Changes in ocular surface caused by antiglaucomatous eyedrops: prospective, randomised study for the comparison of 0.5% timololv 0.12% unoprostone

AIMTo study changes induced in ocular surface epithelia and the tear film by antiglaucomatous eyedrops. A β blocker (0.5% timolol) and a novel prostaglandin F2α metabolite related drug (0.12% unoprostone)...

Postovulatory effect of repeated intravenous administration of ACTH on the contractile activity of the oviduct, ova transport and endocrine status of recently ovulated and unrestrained sows

The effect of repeated intravenous administration of ACTH (Synacthen® depot) on the contractile activity of the oviduct, ova transport and endocrine status was studied in 11 Swedish crossbred (Landrace × Yorkshire) multiparous sows. In the second estrus after weaning, the ACTH group (Group A, n=6) sows were administered 0.01 mg/kg body weight of ACTH every 6 h commencing 4 to 8 h after ovulation, whereas the control group (Group C, n=5) sows were administered saline solution. Immediately after standing estrus, a Millar® pressure transducer was placed about 3 cm into the isthmus via a laparotomy. Blood samples for hormonal analyses and pressure recordings of the oviduct were collected from all sows until slaughter. After slaughter, the genital tract opposite to the side with the transducer was retrieved, and 3 equal isthmic segments and the first third of the uterine horn portion adjacent to the UTJ were flushed separately for ova recovery. Cortisol levels were significantly (P<0.05) elevated after ACTH administration. Progesterone and PGF 2α metabolite levels were significantly (P<0.05) elevated only after the first ACTH administration. No significant differences (P>0.05) were seen in the mean pressure and frequencies of phasic pressure fluctuations either before or after every ACTH administration between Groups A and C. No significant difference (P>0.05) was seen in the proportion of ova recovered in the different segments between Groups A and C. It can be concluded from the present study that the administration of ACTH (0.01 mg/kg body weight) to sows at 4 to 8 h after ovulation, and after each subsequent ACTH administration, elevates cortisol levels, whereas progesterone and PGF 2α metabolite levels are elevated only after the first treatment, and that this has no effect on the mean isthmic pressure, the frequency of phasic pressure fluctuations or ova transport.

Intrauterine endotoxin infusion in rat pregnancy induces preterm delivery and increases placental prostaglandin F2α metabolite levels

Objective: This study was designed to examine the effects of intrauterine endotoxin (lipopolysaccharide) on rat pregnancy. Study Design: Pregnant Sprague-Dawley rats (N = 26) were implanted with uterine catheters on day 15 or 16 of a 22-day gestation. Animals were randomly assigned to receive either lipopolysaccharide (25 or 50 μg) or sodium chloride solution (1 mL) on day 17 and then were either sacrificed on day 19 or observed until delivery. Placentas were harvested at the time of death, homogenates were prepared, and prostaglandin F2α metabolite levels were determined by means of radioimmunoassay. Data were analyzed by analysis of variance, Student-Newman-Keuls, and Mann-Whitney tests. Results: Lipopolysaccharide-treated groups (25 and 50 μg) displayed a shorter interval to delivery (mean ± SE, 82 ± 13 and 63 ± 8 hours, respectively) than control animals (117 ± 3 hours). Pups of lipopolysaccharide-treated (25 and 50 μg) female animals had lower live birth weights (4.92 ± 0.01 and 5.12 ± 0.24 g, respectively) compared with control animals (6.04 ± 0.07 g). Placental homogenates from lipopolysaccharide-treated female animals contained higher levels of prostaglandin F2α metabolite (1567 ± 64 and 1475 ± 59 pg/mL) than those from sodium chloride solution–infused control animals (804 ± 68 pg/mL). Conclusion: Bacterial products induce the preterm delivery of low-birth-weight pups in rats, possibly by increasing local prostaglandin biosynthesis. (Am J Obstet Gynecol 2000;182:1496-501.)

Oviductal isthmic motility in relation to ovulation and endocrine changes in unrestrained sows

This study was designed to characterize changes in the motility of the oviductal isthmus in relation to endocrine changes around ovulation in unrestrained sows in their normal environment. Oviductal isthmic motility was monitored on Poly view ™ from 11 h prior to and up to 36 h after ovulation in 13 unrestrained multiparous sows during their second estrus after weaning, using a pressure microtransducer implanted 3 cm into the isthmus. Both the maximum, minimum and mean pressures and the frequency of phasic pressure fluctuations were high prior to ovulation but declined significantly (P<0.05) at 9 to 12 h, 13 to 16 h, 13 to 16 h and 5 to 8 h after ovulation, respectively. Plasma estradiol-17β and prostaglandin F 2α metabolite levels declined significantly (P<0.05) at 4 to 7 h prior to ovulation while progesterone levels increased significantly (P<0.01) at 5 to 8 h after ovulation. The decrease in the plasma estradiol-17β levels was correlated to the decrease in maximum and mean pressures and the frequency of phasic pressure fluctuations (n=113; r=0.30, 0.25, 0.25, respectively; P<0.01) but not to the decrease in minimum pressure (n=l 13; r=0.17, P>0.05). Similarly, the decrease in PGF 2α metabolite levels was correlated to the decrease in minimum, maximum and mean pressures and the frequency of phasic pressure fluctuations (n=112; r=0.43, 0.35, 0.38, 0.32, respectively; P<0.001). Conversely, the increase in plasma progesterone levels was correlated to the decrease in minimum, maximum and mean pressures and the frequency of phasic pressure fluctuations (n=113; r=−0.56, −0.70, −0.68, −0.60, respectively; P<.0001). Therefore, the pressure parameters seem to be influenced by changes in the levels of estradiol-17β, prostaglandin F 2α and progesterone with respect to ovulation.

The influence of inhibited prostaglandin biosynthesis on post-ovulatory oviductal ova transport in sows

Changes in prostaglandin and progesterone concentrations after ovulation seem to affect reproductive functions in the sow. The influence of lowered prostaglandin levels on ova transport velocity through the isthmus part of the oviduct, and on progesterone concentrations, was studied during the second estrus after weaning in thirteen purebred Yorkshire multiparous sows. To determine the time of ovulation transrectal ultrasonographic examination was performed. In the second estrus, six sows were given intravenous injections of flunixin meglumine (2.2 mg/kg body weight) every sixth hour from 4 to 8 h after time of ovulation until about 48 h after ovulation, at which time the sows were slaughtered. Blood samples were collected every second hour from about 12 h before ovulation until slaughter. Progesterone and prostaglandin F 2α (PGF 2α) metabolite levels were determined. Immediately after slaughter the isthmus part of the oviducts were cut into 3 equally long segments and the number of ova in each segment, and in the upper part of the uterine horns, was determined. Before start of treatment, PGF 2α metabolite levels were similar in the 2 groups (P = 0.84). In the treatment group, PGF 2α values dropped to below the detection limit immediately after start of treatment, whereas in the control group the concentrations were quite stable throughout the sampling period (P = 0.005). Ova recovery rate was 94 % in the treatment group and 95 % in the control group. At time of slaughter, in the treatment group ova had on average passed 2.1 segments whereas in the control group the ova had passed 2.5 segments (P = 0.57). The progesterone levels increased continuously in both groups after ovulation but there was no difference in the mean progesterone concentrations between the two groups before (P = 0.96) or after (P = 0.58) ovulation. It can be concluded that the transport of ova through the isthmus part of the oviduct is unaffected by an inhibition of prostaglandin synthesis immediately after ovulation. Furthermore, the post-ovulatory progesterone profile seems unaffected by lowered PGF 2α levels.

Conjugated linoleic acid induces lipid peroxidation in humans

Conjugated linoleic acid (CLA) is shown to have chemoprotective properties in various experimental cancer models. CLA is easily oxidised and it has been suggested that an increased lipid oxidation may contribute to the antitumorigenic effects. This report investigates the urinary levels of 8-iso-PGF 2α, a major isoprostane and 15-keto-dihydro-PGF 2α, a major metabolite of PGF 2α, as indicators of non-enzymatic and enzymatic lipid peroxidation after dietary supplementation of CLA in healthy human subjects for 3 months. A significant increase of both 8-iso-PGF 2α and 15-keto-dihydro-PGF 2α in urine was observed after 3 months of daily CLA intake (4.2 g/day) as compared to the control group ( P<0.0001). Conjugated linoleic acid had no effect on the serum α-tocopherol levels. However, γ-tocopherol levels in the serum increased significantly ( P=0.015) in the CLA-treated group. Thus, CLA may induce both non-enzymatic and enzymatic lipid peroxidation in vivo. Further studies of the mechanism behind, and the possible consequences of, the increased lipid peroxidation after CLA supplementation are urgently needed.