Changes in the plasma prostaglandin F2 alpha metabolite before and during spontaneous labor and labor induced by amniotomy, oxytocin and prostaglandin E2

To elucidate the role of endogenous prostaglandin F2 alpha in spontaneous and induced labor, plasma concentrations of 13, 14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) were determined before the onset of labor, at onset of labor, during active labor, at the crowning of the fetal head, and 1 and 2 hours after delivery. Patients in spontaneous labor and labor induced by amniotomy, oxytocin, and prostaglandin E2 were studied. The levels of plasma PGFM in patients who entered spontaneous labor fell 2 to 3 weeks before delivery, whereas those in the induced labor group did not change until the time of induction. Although the levels of PGFM rose gradually with the progress of labor in all cases, the levels in the spontaneous labor were significantly lower in each stage than in the corresponding stage of induced labor. These results suggest that endogenous prostaglandin F2 alpha (PGF2 alpha) production decreases 2-3 weeks prior to the spontaneous onset of labor and is increased again as labor progresses, that the patterns of PGF2 alpha production are similar to each other during spontaneous labor and labor induced by various methods. Therefore, it is felt that endogenous PGF2 alpha may participate in the progress of all kinds of labor.     

Peripartal changes in plasma progesterone and 15-keto-13,14-dihydro-prostaglandin F2α concentrations in Holstein cows with or without retained foetal membranes

Peripheral blood plasma concentrations of progesterone and the main metabolite of prostaglandin F_2α, (15-keto-13,14-dihydro-PGF_2α) PGFM, were determined in 10 Holstein cows with retained foetal membranes (RFM) and 12 Holstein cows without RFM (NRFM) during the peripartal period. The rate of uterine involution in the postpartum cows was monitored.There was no difference in the rate of uterine involution between cows with or without RFM. Cyclical ovarian activity was resumed within a month after parturition in both group. Increases in the mean peripheral plasma PGFM concentrations were evident in the RFM cows 6 days before parturition, compared to 48 h before parturition in the NRFM cows. A gradual decline in PGFM to prepartum concentrations occurred in both groups by Day 12 after parturition, although in the RFM cows, PGFM concentrations remained high until the placenta was shed.In both groups, the mean peripheral plasma concentrations of progesterone showed a marked decline beginning 48 h before partusition. The mean plasma progesterone concentrations were less than 1 ng/ml during the immediate postpartum period.     

Chronic stimulation of uterine prostaglandin synthesis during cervical ripening before the onset of labor

Concentrations of 13, 14-dihydro-15-keto-PGF2α (PGFM) were measured in plasma of six carefully selected primigravid women with an unripe cervix at term before and at various intervals after extra-amniotic insertion of a Foley catheter with or without methylhydroxyethylcellulose (Tylose^R) gel. The procedure caused an acute elevation of PGFM levels within 5 min (P < 0.025), which was maintained for at least 6 hours in the absence of uterine activation at 179 ± 32% of the initial values (P < 0.01). Extra-amniotic administration of Tylose gel caused an increase in PGFM levels which was both higher and more prolonged ( > 12 hours) than insertion of a Foley catheter alone.The observations indicate that cervical ripening without concomitant uterine activation is associated with an increase in PGFM levels. They also demonstrate that prolonged activation of (intra)uterine prostaglandin synthesis may occur several hours before the onset of labor-like uterine activity. A chance finding further suggests that spontaneous rupture of the membranes too may be preceeded by an increase in (intra)uterine prostaglandin synthesis. In their totality these observations lend strong support to the proposition that an increase in (intra)uterine prostaglandin production is a prerequisite to rather than a consequence of the initiation of labor.     

Peripartal endocrine changes associated with retained placenta in dairy cows

Peripheral serum concentrations of prostaglandin F(2)alpha 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.     

A dystocia and caesarean section model to characterize uteroplacental prostaglandin concentrations associated with retained placenta in dairy cattle

Plasma concentrations of prostaglandin F(2a) (PGF(2a), 13, 14-dihydro-15-keto-prostaglandin F(2a) (PGFM), prostaglandin E(2) (PGE(2)) and 13,14-dihydro-15-keto-prostaglandin E(2) (PGEM) were determined by RIA in blood samples taken from the jugular vein and the uteroplacental circulation (umbilical vein, umbilical artery and uterine vein) of 13 Holstein Friesian cows during caesarean section. According to discharge of placenta cows were divided in 2 groups. Group I (shedding of placenta within 12 hours, NRP, n=8) and Group II (retained placenta, RP, n=5). In blood samples taken from the jugular vein before surgery, no significant differences existed between groups regarding PGF(2a), PGFM, PGE(2) and PGEM. Concentrations of PGF(2a) and PGFM in the uteroplacental circulation of NRP cows were significantly higher than those of RP cows (except for PGFM in the umbilical vein). For all sampling sites except the jugular vein before surgery, PGE(2) and PGEM levels of NRP cows were significantly higher compared to RP cows.     

Hormonal changes in spontaneous and aglépristone-induced parturition in dogs

To increase our understanding of the endocrine changes associated with parturition in dogs, plasma concentrations of progesterone (P4), 15-ketodihydroprostaglandin F(2alpha) (PGFM), estradiol-17-beta (E2beta), cortisol, ACTH, prolactin (PRL), LH, and FSH were measured in six spontaneously whelping bitches and in six bitches in which parturition was induced with the progesterone-receptor blocker aglépristone on day 58 of pregnancy. Expulsion of pups in the induced group took place in the presence of P4 concentrations that were still elevated. PGFM concentrations increased before parturition in both groups, but levels were lower in the induced bitches. PGFM levels reached a maximum in both groups during parturition and quickly decreased in the spontaneously whelping group after parturition, but remained elevated in the induced group. In both groups, cortisol concentrations reached similar maximum levels during the last 30 h before the onset of expulsion. During the 3 days postpartum, cortisol concentrations were higher in the induced group. The highly variable ACTH concentrations did not differ significantly throughout the study within or between groups. In both groups, E2beta concentrations decreased and PRL concentrations increased between the late gestational period and the 30-h period before parturition. Concentrations of both LH (spontaneously whelping group) and FSH (both groups) decreased between late gestation and the postpartum period. The results of this study illustrate the hormonal changes around parturition in the bitch, and reveal that aglépristone-induced parturition is associated with still incomplete luteolysis, an altered PGFM profile, and elevated postpartum cortisol concentrations as compared with spontaneously whelping dogs.     

Validation of a 13,14-dihydro-15-keto-PGF(2alpha) enzymeimmunoassay and its application for reproductive health monitoring in postpartum buffaloes

The objective of the present study was to validate a simple, sensitive and direct enzymeimmunoassay (EIA) procedure for 13,14-dihydro-15-keto-PGF(2alpha) (PGFM) for use in buffaloes with postpartum reproductive disorders and determine the practicalities of using plasma concentrations of 13,14-dihydro-15-keto-PGF(2alpha) for monitoring their reproductive health. The EIA was used for determination of the circulating levels of PGFM associated with the retention of fetal membranes, postpartum endometritis and variable postpartum intervals. The concentrations of PGFM with retention of fetal membranes in the periparturient period were lower as compared to buffaloes that had uneventful parturitions. Concentrations of PGFM associated with postpartum endometritis were elevated as compared to those in buffaloes free of reproductive tract infections. Buffaloes having higher plasma concentrations of PGFM in early postpartum period had shorter postpartum intervals, indicating the association between PGFM concentrations postpartum and uterine involution as well as the resumption of estrous cycle in this species. The study presents the possibility of using circulating PGFM concentrations for monitoring the postpartum reproductive health of buffaloes.     

Incidence of retained placenta following induction of parturition with corticoids or prostaglandins

Three trials involving 214 cows were conducted to 1) compare the timing of events during normal parturition with parturition induced with a corticoid or a prostaglandin; 2) determine if synchrony could be improved by injection of steroids either concurrently or after injection of a corticoid or a prostaglandin; 3) determine if the incidence of retained placenta could be reduced; and 4) explore methods of treating retained placenta. The timing of events following induction of parturition was compared with that following a normal parturition in 76 heifers. The time from onset of labor to appearance of the placenta, abdominal press, appearance of feet and expulsion of the fetus did not differ between normal and induced parturition. The time from onset of labor to calf standing was increased from 2.3 +/- 2.0 hours in normal parturition to 5.8 +/- 5.5 hours in cows receiving 10 mg of flumethazone (P<0.05). The interval from onset of labor to calf nursing also tended to be longer (P>0.05<0.01). All control cows expelled fetal membranes by 48 hours after onset of labor, but the proportion expelled by the treatment groups varied from 24 to 76%. None of the treatments used in this study significantly increased placental expulsion over that noted when flumethazone or prostaglandins were used alone. No difference in placental expulsion time was noted in cows douched with nolvasan or injected with 30 cc oxytetracycline. None of the treatments used in the three trials reported in this study improved synchrony of parturition over that noted in the cows receiving only an injection of flumethazone or prostaglandins.     

The use of synthetic prostaglandin analogue (fluprostenol) to induce foaling.

The synthetic prostaglandin (PG) analogue fluprostenol was used to induce parturition in mares and its mode of action was investigated by measuring endocrine changes before and during the induction period. Progestagens and unconjugated oestrogens showed little change during the induction period, but two different patterns in plasma PGFM levels were observed. The first was seen when foaling occurred within 90 min of injection; PGFM levels rose soon after injection and peaked during the maximum expulsive stage of labour, thus resembling events during natural foaling. The second occurred when foaling took longer than 90 min, and in these mares PGFM levels rose at various times after injection and peaked well before the onset of the expulsive stage of labour. It is suggested that these differences reflect the hormonal readiness of the mares to foal. Other procedures, such as rupture of the allantochorion, and dilatation of the cervix and injection of fluprostenol into the allantois, produced no uterine activity and did not stimulate labour or PGFM release.     

Gestational changes in the progesterone and prostaglandin F levels of the guinea-pig

In 87 guinea-pigs the gestational changes were measured in the progesterone (P) and prostaglandin F (PGF) levels of the peripheral and uterine vein plasmas, ovaries, uterus, placenta, fetal membranes and amniotic fluid. In the ovaries, the peripheral and uterine vein plasma, placenta and uterus, P-concentrations increase during early pregnancy and after a plateau decrease significantly as term approaches. In contrast, the uterine-vein PGF-levels remain low throughout pregnancy and only increase near term. Thus, in the guinea-pig, as in the classic species of P-action, normal pregnancy is characterized by high P and low PGF levels and labor by low P and high PGF levels. Of special interest are the additional findings that in the guinea-pig the uterine tissue P-levels are only a fraction of the peripheral plasma levels and the placental PGF-levels far exceed those of the uterus and fetal membranes. To promote the biological interpretation of the endogenous changes in the regulatory profile of the pregnant guinea-pig, current studies examine the functional consequences of the experimentally induced changes in P and PGF-levels.     

Influence of linoleic/linolenic acid ratio in the diet of periparturient cattle on plasma concentrations of PGF2 alpha metabolite and placental expulsion rate

Forty-eight cows Holstein Friesian x Dutch Friesian (HF x DF) were randomly assigned to 2 groups fed 1 of 2 diets (isocaloric and isonitrogenous but different in linoleic/linolenic acid ratio) from 4 wk before expected parturition until 7 d after calving. Effects of the diet on plasma linoleic/linolenic acid ratio, plasma PGFM levels and placental explusion rate were studied. Dietary treatment resulted in significant differences in linoleic/linolenic acid ratio in blood plasma (1.00 +/- .22 vs 4.41 +/- .53). The placental expulsion rate was not significantly different between the 2 treatment groups. Plasma PGFM levels, as analyzed for 28 cows from 30 d before parturition until 1.5 d after parturition, were similar for the diets. Cows with a longer placental expulsion rate had lower PGFM levels at parturition (for instance, placental expulsion rate shorter (n = 11) and longer (n = 17) than 6 h, 1248 vs 2965 pg/ml, residual standard deviation 1185 pg/ml, P < 0.01). The results show that the dietary linoleic/linolenic acid ratio can influence the plasma linoleic/linolenic acid ratio without affecting the placental expulsion rate or plasma PGFM levels around parturition.     

Changes in plasma levels of PGF2 alpha and PGI2 metabolites at and after delivery at term

Plasma levels of 6-keto-PGF1 alpha and 13,14-dihydro-15-keto-PGF2 alpha (PGFM) were measured by high pressure liquid chromatography and radioimmunoassay during and up to 48 hours after term labor. PGFM levels increased during labor to reach values which at full dilatation, at delivery of the fetal head and at placental separation were each time higher than levels obtained earlier. In all women (n = 10) PGFM levels reached their maximum and started to decline within 10 min. after placental separation. Levels decreased to prelabor values within 2 to 3 hours after delivery and no temporary increases were observed within the first 2 days. Levels of 6-keto-PGF1 alpha on the other hand, showed no consistent trends throughout labor and the early puerperium. The observed changes are believed to be of relevance for ensuring adequate hemostasis after birth.     

Cervical ripening and plasma prostaglandin levels. Comparison of endocervical and extra-amniotic PGE2

Two modes of cervical application of a gel containing PGE2 have been compared in a total of 30 patients with indication for induction of labor and unripe cervix. Fifteen patients had gel injected endocervically; in 10 patients the gel contained 400 micrograms PGE2, in 5 controls the gel was inactive. Fifteen subjects had a 15 ml Foley catheter passed through the cervix and placed extra-amniotically; in 10 of them 3 ml gel with 400 or 800 micrograms PGE2 was injected, while 5 controls received inactive gel. Plasma levels of 13,14-dihydro-15-keto-PGE2 alpha (PGFM) were measured in blood samples drawn before and 1/2, 1, 2, 4, 6, and 8 hours after gel application. Neither the Foley catheter nor the application of inactive gel caused significant changes in the cervical scores or the PGFM levels. PGE2 in the endocervix increased cervical scores without altering plasma PGFM levels. Extra-amniotic PGE2 caused a more rapid increase of the cervical scores and a progressive rise in PGFM levels. The plasma (PGFM) levels were found to be related to the degree and to the rate of cervical dilatation. The correlation with cervical dilatation was highly significant. Labor began spontaneously or after artificial rupture of the membranes in 80% of the extra-amniotic, and 50% of the endocervical PGE2-group, but in none of the controls. These data indicate that increased uterine PGF2 alpha production is not necessary for the early stages of cervical ripening, whereas dilatation beyond 4 cm does not proceed without such increase.     

低频神经和肌肉电刺激对产程、分娩方式、母婴结局的影响分析

目的:观察低频神经和肌肉刺激仪用于分娩镇痛对产程、分娩方式、产后出血、会阴完整度、母婴结局的影响.方法:随机选择2019年8月～2020年3月在我院分娩的足月妊娠产妇220名,根据第一产程是否应用低频神经和肌肉刺激仪分为观察组112例及对照组108例,两组均接受常规分娩护理,观察组为自愿接受低频神经和肌肉电刺激镇痛的产...     

Effects of calving-related disorders on prostaglandin, calcium, ovarian activity and uterine involution in postrartum dairy cows

Postpartum ovarian activity, uterine involution and plasma concentrations of calcium and 15-keto-13, 14 dihydro-prostaglandin F2alpha (PGFM) were assessed in dairy cows with retained fetal membranes (n=10) and milk fever (n=10) at parturition. In addition, calcium and PGFM were evaluated in dairy cows affected with uterine prolapse (n=10) and pyometra (n=14). Cows with retained fetal membrane averaged 24.2+/-3.7 d until their first postpartum ovulation, while controls averaged 29.0+/-3.7 d (P>0.10). In cows with retained fetal membranes, the difference in follicular activity between the contralateral and ipsilateral ovaries in relation to the previously gravid uterine horn was appreciably greater post partum when compared with that of the controls. Cows with milk fever had an average of 30.8+/-3.1 d until their first postpartum ovulation, while control cows had an average of 20.4+/-3.3 d (P<0.05). The mean diameter of the uterine horns in cows with milk fever was greater (P<0.05) compared with that of the controls between Days 15-32 post partum. Concentrations of plasma calcium were lower in cows with retained fetal membranes within 24 h after parturition and during the first week post partum than in the controls (6.27+/-0.18 vs 7.40+/-0.18 mg/100ml, P<0.05). Concentration of calcium was lower (P<0.05) in cows with milk fever on Day 1 prior to treatment (4.68+/-0.40 < 5.8+/-0.45 mg/100ml) than in control cows; however, the calcium (Ca) level was not different during the subsequent 7 d post partum after treatment. Cows with uterine prolapse had lower concentrations of Ca during the first 7 d post partum than the controls (6.10+/-0.15 vs 7.33+/-0.12mg/100ml; P<0.01). Cows with pyometra had higher (P<0.05) concentrations of plasma PGFM than the controls (208.+/-13.2 > 138.1+/-15.2).     

Plasma levels of 13,14-dihydro-15-keto prostaglandin F2 alpha, estrogens, and progesterone during stretch-induced labor at term

The uterus of six healthy multiparous women at term was mechanically stretched by a rubber catheter and balloon. Apparent labor was inaugurated in all cases within 5 hours and increased progressively with time. Advanced cervical softening and dilatation were also evident after the stretch treatment. Significant increases in the levels of 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) were observed with the progress of treatment (P less than 0.01). Plasma estrogens and progesterone levels did not change significantly during the treatment (P greater than 0.05). Stretching and/or resulting uterine contractions appear to induce the secretion of prostaglandin F2 alpha (PGF) from the organ, which in turn seems to be involved in both cervical softening, and the onset and progress of labor, under stable conditions of plasma estrogens and progesterone.     

Plasma levels of 13,14-dihydro-15-keto prostaglandin F2α, estrogens, and progesterone during stretch-induced labor at term

The uterus of six healthy multiparous women at term was mechanically stretched by a rubber catheter and balloon. Apparent labor was inaugurated in all cases within 5 hours and increased progressively with time. Advanced cervical softening and dilatation were also evident after the stretch treatment. Significant increases in the levels of 13,14-dihydro-15-keto-prostaglandin F_2α (PGFM) were observed with the progress of treatment (P < 0.01). Plasma estrogens and progesterone levels did not change significantly during the treatment (P > 0.05). Stretching and/or resulting uterine contractions appear to induce the secretion of prostaglandin F_2α (PGF) from the organ, which in turn seems to be involved in both cervical softening, and the onset and progress of labor, under stable conditions of plasma estrogens and progesterone.     

Cervical ripening and plasma prostaglandin levels. Comparison of endocervical and extra-amniotic PGE2

Two modes of cervical application of a gel containing PGE₂ have been compared in a total of 30 patients with indication for induction of labor and unripe cervix. Fifteen patients had gel injected endocervically; in 10 patients the gel contained 400μg PGE₂, in 5 controls the gel was inactive. Fifteen subjects had a 15 ml Foley catheter passed through the cervix and placed extra-amniotically; in 10 of them 3 ml gel with 400 or 800μg PGE₂ was injected, while 5 controls received inactive gel. Plasma levels of 13,14-dihydro-15-keto-PGF_2α (PGFM) were measured in blood samples drawn before and , 1, 2, 4, 6, and 8 hours after gel application. Neither the Foley catheter nor the application of inactive gel caused significant changes in the cervical scores or the PGFM levels. PGE₂ in the endocervix increased cervical scores without altering plasma PGFM levels. Extra-amniotic PGE₂ caused a more rapid increase of the cervical scores and a progressive rise in PGFM levels. The plasma (PGFM) levels were found to be related to the degree and to the rate of cervical dilatation. The correlation with cervical dilatation was highly significant. Labor began spontaneously or after artificial rupture of the membranes in 80% of the extra-amniotic, and 50% of the endocervical PGE₂-group, but in none of the controls. These data indicate that the increased uterine PGF_2α production is not necessary for the early stages of cervical ripening, whereas dilatation beyond 4 cm does not proceed without such increase.     

Altered fetal pituitary-adrenal function in the ovine fetus treated with RU486 and meloxicam, an inhibitor of prostaglandin synthase-II

Term and preterm labor are associated with increased fetal hypothalamic-pituitary-adrenal (HPA) activation and synthesis of prostaglandins (PGs) generated through the increased expression of prostaglandin H synthase-II (PGHS-II) in the placenta. Inhibition of PGHS-II has been advocated as a means of producing uterine tocolysis, but the effects of such treatment on fetal endocrine functions have not been thoroughly examined. Because PGE(2) is known to activate the fetal HPA axis, we hypothesized that administration of meloxicam, a PGHS-II inhibitor, to sheep in induced labor would suppress fetal HPA function. Chronically catheterized pregnant ewes were treated with RU486, a progesterone receptor antagonist, to produce active labor, and then treated with either high-maintenance-dose meloxicam, graded-maintenance-dose meloxicam, or a saline infusion. Maternal uterine contraction frequency increased 24 h after the RU486 injection and the animals were in active labor by 48 +/- 4 h. RU486 injection led to increased concentrations of PGE(2), ACTH, and cortisol in the fetal circulation, and increased concentrations of 13,14 dihydro 15-ketoprostaglandin F(2 alpha) (PGFM) in the maternal circulation. Uterine activity was inhibited within 12 h of beginning meloxicam infusion at both infusion regimes. During meloxicam infusion there were significant decreases in fetal plasma PGE(2), ACTH, and cortisol concentrations, and PGFM concentrations in maternal plasma. In control animals, frequency of uterine contractions, maternal plasma PGFM, fetal plasma PGE(2), ACTH, and cortisol concentrations increased after RU486 administration, and continued to rise during saline infusion until delivery occurred. We conclude that RU486-provoked labor in sheep is associated with activation of fetal HPA function, and that this is attenuated during meloxicam treatment to a level considered compatible with pregnancy maintenance.     

Uterine activity and prostaglandin production following intraamniotic hyperosmolar urea

The relationship between endogenous prostaglandin (PG) production and uterine activity was studied in hyperosmolar urea induced abortion patients. Polygraphic recordings of intraamniotic pressure were obtained at periodic intervals following intraamniotic injection of 80 gm urea. At 0, 0.25, 1, 4 and 8 hours amniotic fluid and blood samples were obtained for PGE, PGF and 13,14-dihydro-15-keto-prostaglandin F_2α (PGFM) analysis by radioimmunoassay. Blood was also sampled at time of absorption. In eight patients studies, uterine tone was elevated by 0.25 hour although no rhythmic contractions were observed by 1 hour. At 4 hours, amniotic fluid PGF concentration increased significantly (P < .01) over the pre-injection value and continued to increase at 8 hours. Amniotic fluid PGE, PGFM and all plasma PG's showed no change during the 8 hour period following urea administration. At time of abortion the plasma PGFM concentration was significantly greater than at the time of injection (238 ± 54.4 vs. 86.7 ± 7.3 pg/ml). There was no significant differences between pre-injection and absorption plasma PGF or PGE concentrations. In the present study, there is no evidence that increased prostaglandin production precedes urea induced contractions. The possible role of PG's in uterine contractions is discussed.