Secretion rate of prostaglandin F during induced labor in goats.

Relationships between plasma flow and plasma concentrations of prostaglandin F were examined in the utero-ovarian veins of three pregnant goats. Plasma flow, measured by veno-arterial dilution of para-Aminohippurate in two goats, was unchanged or increased slightly when PGF concentrations were elvated by short-term infusions of PGF2alpha into a uterine vein. Utero-ovarian plasma flow was measured during labor in two goats. Flow doubled during advanced labor and then decreased sharply to very low rates during the terminal expulsive phase of stage II labor. A total of 8.3 and 9.5 mg PGF was released into the utero-ovarian vein of two goats during the last 6 hours before fetal delivery and maximal release rates of approximately 100 ug. min-1 were obtained some 5-10 minutes before delivery was completed. The highest plasma concentrations of PGF were detected immediately after completion of fetal delivery when utero-ovarian plasma flows were lowest.     

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.     

F prostaglandin levels in amniotic fluid during balloon-induced cervical softening and labor at term

Mechanical stretching of the uterus was applied to seven term patients not in labor with unripe cervix by means of intra-uterine application of a rubber balloon. Significant cervical softening, and initiation and progress of labor was achieved in all cases. Serial analyses of the F prostaglandins (PGF) in amniotic fluid were performed before and at given intervals of cervical dilatation. Before the application of stretch, the level of PGF varied greatly; the values in 5 cases were measureable but low (less than 645 pg/ml) and in two cases the levels were below the sensitivity of the assay (less than 50 pg/ml). Large fluctuations of the levels were noted in many cases during the treatment. However, the rise of the PGF values was significantly with the progress of cervical dilatation compared to the pre-treatment values (P<0.05 at both 3–4 and 5–6 cm, and P<0.01 at 9–10 cm). It was concluded that the increased release of PGF in amniotic fluid is mediated by uterine stretching, and that upon being released PGF is probably involved in the cervical softening and progress of labor.     

Peripheral plasma levels of progesterone in pregnant goats and in pregnant goats treated with prostaglandin F2a

Prostaglandin or prostaglandin analogues have been shown to be luteolytic in the pregnant goat. In this study the temporal changes in the plasma concentrations of progesterone during pregnancy and after administration of PGF2a to pregnant goats are described. PGF2a administration to pregnant goats at 30 and 65 days after breeding induced abortion within 34 to 75 hours. These abortions were accompanied by estrus and profuse muco-hemorrhagic discharges. When PGF2a was administered to pregnant goats 140 or 142 days after breeding, premature parturition occurred within 42 to 76 hours. Live kids were delivered in all cases. The plasma levels of progesterone in all pregnant goats showed dramatic decreases within 24 hours after the prostaglandin injections and continued to decrease gradually until abortions or premature parturition. Thereafter, the progesterone levels remained low for several days.     

Secretion of unconjugated estrone during pregnancy and around parturition in goats

The secretion of unconjugated estrone and its production site in pregnant goats were investigated in vivo. The mean estrone concentration (n = 15) in the peripheral plasma increased gradually, being 83 pg/ml on Day 40 and 483 pg/ml on Day 140 after mating. The estrone concentration increased rapidly after Day 2 before partum, reaching a peak at parturition (2370 pg/ml), and falling to 171 pg/ml at Day 1 post partum. The concentrations of estrone from the umbilical vein and umbilical artery did not differ from that found in the maternal jugular vein, suggesting that the fetus does not take part in estrogen production. The estrone concentration from the uterine vein after the fetus was removed was higher than the concentrations found in the maternal jugular vein and umbilical artery. In the placental tissue, a high concentration of estrone (18157 pg per gram of wet tissue) was detected. These findings suggest that the main production site of unconjugated estrone is the placenta.     

F2-isoprostane induced prostaglandin formation in the rabbit

F(2)-isoprostanes, non-enzymatic free radical mediated products of arachidonic acid, have shown to form during various oxidant stress status and have potent biological effects. This study investigates to what extent 8-iso-PGF(2alpha) (a major F(2)-isoprostane), a bioactive product of lipid peroxidation can modify endogenous prostaglandin F(2alpha) (PGF(2alpha)) formation since prostaglandins are inflammatory as well as potent vasoregulatory substances that modulate diverse important physiological functions, and also form during acute and chronic inflammation. An immediate appearance and disappearance of 8-iso-PGF(2alpha) was seen in both plasma and urine within a short interval after i.v. administration of 43 microg/kg of 8-iso-PGF(2alpha) to the rabbits. A successive but differential formation of PGF(2alpha) resulted in a rapid and pulsatile increase of plasma 15-keto-dihydro-PGF(2alpha), a major metabolite of primary PGF(2alpha). Later, this compound was excreted efficiently as intact compound into the urine during the 3 h of experiment. A 8-fold increase of PGF(2alpha) metabolite in plasma at 10 min and 12-fold increase in the urine at 30-60 after the i.v. administration of 8-iso-PGF(2alpha) was observed which continued throughout the 3 h of experiment. This observation suggests that pharmacologically administered or endogenously produced 8-iso-PGF(2alpha) during oxidant stress induces prostaglandin formation presumably through the classical cyclooxygenase-catalysed arachidonic acid oxidation which might be inflammatory itself to the cells and exerts further vasoconstrictive effects.     

The effect of prostaglandin F2 alpha on third stage labor.

The effects of intramyometrially injected PGF2 alpha intravenous Ergometrin and no treatment were compared during 3rd stage labor in 140 patients. In comparison with Ergometrin or no treatment, PGF2 alpha significantly reduced the duration of 3rd stage labor, blood loss, incidence of subinvolution and subfebrility.     

Estrus synchronization and controlled breeding in goats using prostaglandin F(2)alpha

Estrus synchronization in the goat employing the double injection regimen of 7.5 mg of prostaglandin F(2)alpha (Lutalyse) at each injection, resulted in 64% and 84% synchronization at first and second injections, respectively. Breeding at estrus induced by the second injection resulted in 90% conception. Kidding at the end of the gestation period was spread over a 17-day period. The first and the last does had 141 and 158 days of gestation, respectively. The findings of this study indicate that two injections of prostaglandin F(2)alpha 10 days apart is superior to a single injection for estrus synchronization in the goat. Breeding following the second injection resulted in high conception rate. Due to individual differences in gestational lengths, estrus synchronization with prostaglandin F(2)alpha cannot be depended upon for synchrony of kidding.     

Doses of prostaglandin F(2)alpha effective for induction of estrus in goats

A total of 11 cycling does weighing between 24 and 50 kg were injected with varying dosages of prostaglandin F(2)alpha (PGF(2)alpha) between 7 and 10 days into each estrous cycle. Five injections each of 1.25, 2.5, 5.0, or 7.5 mg PGF(2)alpha were alternated with five injections of 1.0 ml saline. Saline treated does served as controls. All does were teased twice daily with a buck and observed for signs of estrus for 5 days post-injection. Daily systemic concentrations of progesterone (P(4)) were determined by radioimmunoassay. The mean (+/- S.E.) hours from injection to estrus was 47 +/- 3.3, 42 +/- 4.3, 44 +/- 8.5, and 43 +/- 5.5 for does receiving 1.25, 2.5, 5.0, and 7.5 mg PGF(2)alpha, respectively. None of the does receiving saline exhibited estrus in the 5-day post-injection observation period. Mean (+/- S.E.) concentrations of systemic P(4) in all does on the day of injection was 4.22 +/- 0.45 ng/ml. Concentrations 24 hours post-injection were 0.21 +/- 0.02, 0.15 +/- 0.05, 0.17 +/- 0.04, 0.16 +/- 0.04, and 4.5 +/- 1.36 ng/ml for does receiving 1.25, 2.5, 5.0, and 7.5 mg PGF(2)alpha, and 1.0 ml saline, respectively. The results suggested that 1.25 mg PGF(2)alpha was effective for induction of estrus in the cycling goat.     

Sequential administration of cronolone and prostaglandin F2alpha for estrus synchronization in goats.

Fifteen does received intravaginal pessaries impregnated with 20 mg fluorogestone acetate (Cronolone) at various times after the end of estrus for a period of fourteen days. The does were then treated on days 2, 4, 5, 12, or 16 after onset of estrus following the progestin treatment, with 15 mg of prostaglandin F2_α (Lutalyse) injected intramuscularly. Seventy three percent of the does showed estrus within 2 days after withdrawal of progestin treatment. Ten out of 11 does treated with prostaglandins 4 to 16 days after the end of estrus exhibited estrus within 44 to 72 hours after treatment. Breeding following the use of prostaglandin in these does resulted in a high pregnancy rate. It is concluded that a sequential use of progestin and prostaglandin may be a useful method for achieving estrus synchronization associated with high fertility in does.     

Lipid metabolism and production of progesterone and prostaglandin F during induced regression of porcine corpora lutea

Patterns of luteal lipid and arachidonic acid accumulation were examined in relation to luteal progesterone and prostaglandin F synthesis in 30 sows and gilts between days 8 and 18 of the estrous cycle. Net release of progesterone from luteal tissue declined from 722 ng/100 mg tissue at day 8 to 81 ng/100 mg tissue at day 18. Although statistical significance was not present, net prostaglandin F release increased slightly from 8.6 to 13.9 ng/100 mg tissue. Luteal free cholesterol, esterified cholesterol, and free fatty acid contents did not change between days 8 and 18 whereas triglycerides accumulated rapidly between days 14 and 18 of the estrous cycle. Phospholipids increased between days 8 and 12, plateaued at 20.2 mg/g between days 14 and 16, and decreased to 15.4 mg/g on day 18. Between days 12 and 18, arachidonic acid increased from 19.4 to 34.8% in cholesterol esters, from 10.1 to 22.5% in triglycerides, and from 12.3 to 27.2% in luteal free fatty acids. Arachidonic acid in luteal phospholipids increased from 21.3 to 25.1% between days 14 and 16 of the estrous cycle. Luteal regression was associated with conservation of arachidonic acid. Based on blood plasma lipid fatty acid compositions, the corpus luteum elongated and desaturated essential fatty acids. Within porcine corpora lutea, calculated free arachidonic acid content was adequate for maintenance of prostaglandin synthesis.     

Decrease of utero-placental blood flow during prostaglandin F2α induced abortion

Pregnancy had been terminated in 6 normal midtrimester pregnant patients by the extraovular injection of 10 mg prostaglandin F2α (PGF2α). In these 6 Experimental and 3 Control patients utero-placental blood flow had been measured, by changes in the density of radioactive Indium, distributed over the uterine area, as a function of time. In comparison with Controls utero-placental blood flow decreased in the Experimental patients already at 5 minutes after PG-treatment, long before advanced cyclic IUP evolved. This finding substantiates the conclusion (1–3), based on experiments in animal “models”, that decrease in utero-placental blood flow is an early step in the mechanism of PG action.     

The effect of prostaglandin F2∝ on third stage labor

The effects of intramyometrially injected PGF2∝ intravenous Ergometrin and no treatment were compared during 3rd stage labor in 140 patients. In comparison with Ergometrin or no treatment, PGF2∝ significantly reduced the duration of 3rd stage labor, blood loss, incidence of subinvolution and subfebrility.     

Observations on the use of prostaglandin F(2alpha) as an abortifacient and effect of gonadotrophin-releasing hormone on ovarian activity after induced abortion during the breeding season in goats

Results of two experiments are described. In the first experiment, forty-one mixed-breed goats (does) with unknown gestation lengths were given 10 mg prostaglandin F(2alpha) (PGF(2alpha)) (2 doses of 5 mg each, 24 h apart) i.m. Blood samples were obtained before each treatment with PGF(2alpha) by jugular venipuncture, and plasma progesterone (P(4)) concentrations were determined by a nonextraction solid-phase radioimmunoassay. P(4) concentrations (ng/ml) were significantly decreased (15.47 vs 1.55, P<0.005) 24 h after the first injection of PGF(2alpha). A total of 63 fetuses was collected within 46.5 h following the first injection. Mean (+/- SE) crownrump lengths and body weights of 62 fetuses were 21.46 +/- 0.29 centimeters (cm) and 575.00 +/- 20.60 g, respectively. Based on these findings, the mean gestation length of these does was estimated to be 86.96 +/- 0.74 d. Thirty-one does retained their placenta for 12 to 72 h and were treated with a single injection of 5 mg PGF(2alpha) and 800 mg oxytetracycline i.m. Placental expulsion in all does occurred within 24 h posttreatment. The results of this study suggest that two doses of 5 mg PGF(2alpha) intramuscularly (i.m.) 24 h apart is an effective abortifacient at about 3 mo of pregnancy in does. In the second experiment, 38 does from the first experiment were divided in two groups of 19 each on Day 13 postabortion. Group A (treated) was given 50 ug GnRH i.m. while Group B (control) received 1 ml 0.9% saline i.m. Blood samples were obtained prior to treatment and on Day 23 postabortion and assayed for P(4) concentrations. There was no significant difference (P>0.10) in P(4) concentrations of samples obtained pre- and post-GnRH treatment. However, 14 of 19 and 12 of 19 in Groups A and B, respectively, exhibited estrus within 52 days following abortion. Twenty-six does were bred naturally and 17 became pregnant.