Mg Of PGF2α Research Articles

The effects of ovariectomy and strech on the regulatory profile and activity of the uterus

Following ovariectomy of five New Zealand white rabbits at day 25 of pregnancy, the intrauterine pressure (IUP) and uterine progesterone (P) and prostaglandin (PG) levels were measured sequentially at days 25, 26 and 27. At day 25, when the uterine P and PGE and PGF were high, massive intrauterine treatment with 500 μg PGF2α provoked only a sustained contracture on which only low level oscillation in IUP was superimposed. At day 26, when the P levels had decreased significantly (P<0.001) and the PG levels had not changed significantly, 50 μg PGF2α significantly increased cyclic IUP as compared with the day 25 value (P<0.001). At day 27, when the P levels decreased further, as little as 5 μg PGF2α provoked still higher cyclic IUP, in spite of a significant reduction in PG levels (P<0.05). Stretching the uterus of six post partum and six 26 days pregnant rabbits (after removing the uterine contents) significantly increased the uterine PGF levels (P<0.001). However, stretch increased only cyclic IUP of the post partum uterus and was without effect on the pregnant uterus, which still had high P levels. These results indicate that the myometrium is activated by exogenous PG or stretch, regardless of whether the uterine PG levels increase, remain unchanged or even moderately decrease, provided that the uterine P levels are reduced to a critical value.

Effect of non-surgical intra-uterine insemination on fertility at first estrus synchronized with prostaglandin F2.ALPHA..

An experiment was conducted to investigate the synchronization of estrus with Prostaglandin F2α (PGF2α) in Australian Merino ewes at unknown stages of the estrous cycle and the aspects of non-surgical intra-uterine insemination with frozen-pelleted ram semen.One hundred and ninty-five out of 232 ewes (84.1%) treated intramuscularly with 16 mg of PGF2α showed estrus within five days after treatment. Ewes in estrus were inseminated once with either 0.1 ml of fresh-undiluted semen or 0.3 ml of frozen-thawed semen. Intra-uterine insemination without surgery was successful in 33 out of 78 ewes (43.0%). Non-return rates obtained on 21 days after the last insemination date were as follows: normal insemination with fresh-undiluted semen, 48.6% (17/35); normal insemination with frozen-thawed semen, 27.0% (10/37); deep-cervi-cal insemination with frozen-thawed semen, 37.8% (14/37); and intra-uterine insemina-tion with frozen-thawed semen, 54.5% (18/33). There was no significant difference in nonreturn rates between the normal insemination method with fresh-undiluted semen and intra-uterine insemination method with frozen-thawed semen. (Japan. J. Anim. Reprod. 23 (3), 11620, 1977).

Corpus luteum function in the guinea pig: Effect of PGF 2α and inhibitors of prostaglandin and progesterone biosynthesis

Exogenous PGF 2α failed to consistently alter estrous cycle length of the guinea pig. A wide range of dose levels were administered with varying frequency, at different stages of the estrous cycle, in different vehicles and by various routes. Massive doses of PGF 2α (5.0–10.0 mg) produced a significant (p<.05), although transient, lowering of plasma progesterone levels. Smaller doses were ineffectual. An i.p. injection of 25 mg of PGF 2α was toxic in four of five treated animals. It would appear that the intact guinea pig is extremely resistant to the luteolytic effects of parenterally administered PGF 2α. Estradiol-17β, administered s.c. on days 3 to 10 of the estrous cycle, significantly (p<.05) reduced corpus luteum diameter and plasma progesterone levels. Estrous cycle length was unaffected. Clomiphene, in the same experiment, caused premature vaginal opening in some treated animals, but corpus luteum size and plasma progesterone levels were unaffected and no ovulations occurred. The prolactin secretion inhibitor, CB-154, administered early in the estrous cycle, did not have any effect on estrous cycle length of the guinea pig alone or in combination with PGF 2α. The prostaglandin precursor, arachidonic acid, also failed to influence estrous cycle length when administered on days 8 and 9 of the cycle. Plasma progesterone levels remained unaltered. Oral administration of a prostaglandin synthetase inhibitor, (MK-715), caused a small, but non-significant (p>.05) prolongation of the estrous cycle. The progesterone biosynthesis inhibitors, aminoglutethimide and 6β-hydroxy-3α, 5α-cyclo-androstane-17-one did not effect estrous cycle length or plasma progesterone levels of the guinea pig.

Changes in pituitary hormone secretions and corpora lutea following PGF 2α administration to PMS/hCG-stimulated rats

Pseudopregnancy was induced in 26 day old female rats by giving 30 IU of PMS followed 56 hours later with 5 IU of hCG. Day 1 of pseudopregnancy was considered established 72 hours after PMS administration. Pseudopregnancy lasted 14 to 15 days. Ovarian weights increased from 4 to 8 times due to treatment. Histological examination of the corpora lutea (CL) of pseudopregnancy suggested luteolysis began on day 6 and extended to day 8. A “new” crop of CL appeared on day 9 suggesting the duration of pseudopregnancy was supported by more than one generation of CL or by CL maturing at different rates. Twice daily administration of 1 mg PGF 2α on days 5 to 8 prevented the appearance of the “new” CL on day 9, and increased signs of luteolysis in the initially formed CL. Lower doses (0.01 and 0.1 mg, b.i.d., × 4 days) delayed the appearance of “new” CL until day 10. Blood samples withdrawn between 0930 and 1100 hours were analysed for FSH, LH and prolactin. Animals treated with 0.01 and 0.1 mg of PGF 2α, b.i.d., × 4 days had increased LH values on day 8, thus the PG appeared luteotrophic. Rats treated with 1 mg of PGF 2α, b.i.d., × 4 days had decreased LH values on day 7 and the CL showed subsequent luteolysis. FSH levels were relatively constant during pseudopregnancy. However, all doses of PGF 2α reduced FSH levels on day 7. An associated decrease in uterine weight occurred, possibly due to reduced follicular development. Prolactin levels fell in response to PGF 2α treatment which undoubtedly contributed to the observed luteolysis. The signs of early cessation of pseudopregnancy were: increased serum FSH on days 9 and 10; increasing uterine weight; and the reappearance of follicular growth. These data suggest that PGF 2α reduced the duration of pseudopregnancy primarily by inhibiting the secretion of FSH, LH and prolactin.

Corpus luteum function in the ewe: Effect of PGF 2α and prostaglandin synthetase inhibitors

A series of experiments were conducted to evaluate the effects of mode and frequency of administration and estrous cycle stage on the response of the cycling ewe to PGF 2α. The effects of dexamethasone, arachadonic acid and prostaglandin synthetase inhibitors on estrous cycle length and plasma progesterone levels were also determined. Intramuscular administration of 5 or 10 mg of PGF 2α, on days 8 and 9 after estrus (5 ewes/group), significantly (p<.01) shortened the mean length of the estrous cycle and the interval from the end of treatment to estrus. Mean plasma progesterone levels, 24 hours after initial injection, were significantly (p<.01) lowered. When administered on day 8 only, these doses were considerably less effective in shortening estrous cycle length or lowering plasma progesterone levels. Intravaginal administration of PGF 2α, by polyurethane tampon, was also largely ineffective. Treatment of ewes with 10 mg of PGF 2α i.m., on days 3 and 4 of the estrous cycle, resulted in a return to estrus in 2 days in 25% of the treated animals. Plasma progesterone levels of PGF 2α-treated ewes were significantly lower than controls on the second, third and fourth days after the start of dosing. It would appear that PGF 2α exerts a retarding effect on developing CL functionality. The prostaglandin synthetase inhibitors, aspirin, flufenamic acid and 1-p-chlorobenzylidene-2-methyl-5-methoxy-3-indenylacetic acid, were administered orally or parenterally for 16 days beginning on day 8 of the estrous cycle. These compounds failed to prolong estrous cycle length. Parenteral administration of dexamethasone did not result in PGF 2α release in the cycling ewe, at least not in quantities sufficient to induce luteolysis. The prostaglandin precursor, arachadonic acid, also was not luteolytic when given parenterally to cycling ewes.

Inhibitory effect of prostaglandin F2 alpha on oxytocin release and on milk ejection in lactating rats.

The effect of prostaglandin F2 alpha (PGF2alpha) on milk ejection and on oxytocin release during suckling for one or two periods of 30 min was studied in lactating rats. Doses of PGF2 alpha (20 or 40 phi g) were injected i.p. 15 min before the suckling period. Control rats were injected with physiological saline. An inhibition of milk ejection proportional to the dose of drug administered was obtained. A normal milk ejection response was induced with a small dose of oxytocin injected immediately before nursing to mothers treated with PGF2 alpha, indicating that the blocking effect was not due to a lack of mammary gland response. Two groups of mothers were injected with 40 phi g PGF2 alpha 2 and 4 h respectively before suckling. In both groups milk ejection was partially but significantly inhibited. In rats pre-treated with sodium pentobarbitone (3-5 mg/100 g body wt) to prevent the release of oxytocin induced by suckling, PGF2 alpha (10 or 20 phi g) did not modify the inhibition of milk ejection indicating that PGF2 alpha does not have milk-ejecting activity. The administration of oxytocin to anaesthetized rats, immediately before a second suckling period, induced a normal milk-ejection response while in the rats treated with PGF2 alpha, oxytocin was less effective. The results indicate that PGF2 alpha inhibited milk ejection by a central block on oxytocin release and that the lipid is not able to mimic peripherally the milk-ejecting activity of oxytocin.

Influence of prostaglandin F 2α on the development of the chick embryo: morphological and biochemical aspects

Summary Fertile eggs were incubated for 48, 72 or 96 hours. Experimental eggs were treated with 10, 40 or 100 μg PGF 2α in 10 μl of saline while controls received either the saline alone or were left unopened. All embryos were recovered at day 9 of incubation. The number of dead embryos were noted, and all living embryos were staged for growth and examined for external malformations. Treatment of the embryos with the prostaglandin did not significantly affect their development. A small number of embryos incubated for 96 hours and treated with 40 μg PGF 2α , received 50 μd of 3 H-thymidine or 3 H-proline at periods of 3, 6 or 24 hours following exposure to the prostaglandin. The uptake of the radiolabelled precursors, as well as the total protein content, was significantly reduced in the treated embryos compared to the corresponding controls.

Influence of the estrous cycle and prostaglandins on utero-ovarian vein blood flow in the rat

The blood flow rate in the utero-ovarian vein (UOV) has been measured in adult female rats during the different phases of the estrous cycle. It was observed that the blood flow rate in the UOV is high at proestrus and at estrus and low during diestrus days 1 and 2. The intravenous injection of 10 μg PGF 2α or PGE 2 diminishes the blood flow rate in the UOV. The efficacy of the two PGs in reducing blood flow is different in the various phases of the estrous cycle, being maximal during the day of estrus.

Onset of oestrus and fertility of dairy heifers and suckled beef cows treated with prostaglandin F2α

SUMMARYSuckled cows (average 70 days post partum) and British Friesian dairy heifers (13 to 24 months of age) were injected intramuscularly with prostaglandin F2α (PGF2α) on two occasions 12 days apart, to synchronize oestrus and ovulation. The cattle were inseminated twice, 70 and 88 hr after the second injection.Injections of 20, 30 or 40 mg of PGF2α were equally effective in 59 heifers; after the first injection, 11 failed to show oestrus during the following 10 days and 10 began oestrus within 36 hr. The majority of the heifers (59%) began oestrus during the 3rd or 4th day after the first injection of PGF2α. After the second injection of PGF2α, all but two heifers showed oestrus and the majority (88%) began oestrus in 3 to 6 days.Injections of 30 or 60 mg of PGF2α were equally effective in 66 suckled cows; after the second injection of PGF2α, 68% of the cows began oestrus from the 3rd to the 6th day but 10 (15%) cows failed to show oestrus.Fertility was highest among heifers and cows which began oestrus during 3 to 5 days after the second injection of PFG2α, 54% of the treated heifers and 42% of the treated cows calving during the expected intervals. Nineteen of the 20 control heifers were mated and 25 of 33 control cows were observed in oestrus and inseminated during 3-week or 25-day breeding periods. Eleven (55%) control heifers and 14 (42%) control cows calved during the expected intervals. Thus, fertility of the treated cattle inseminated at predetermined intervals after PGF2α was equivalent to that in the controls.

Estrous synchronization and fertility in gilts treated with estradiol-benzoate and prostaglandin F 2α

Experiment 1 was designed to determine the amount of estradiol-benzoate (EB) and the number of days of EB treatment required to delay luteal regression for 20 days. Thirty-six gilts were injected with 5 or 10 mg of EB once daily on Days 14, 13 and 14 or 11 through 14 of the estrous cycle. Estrus occurred 2 to 3 days after EB treatment in six gilts in which EB treatment on Days 14 or 13 and 14 failed to prevent luteal regression. Luteal regression and the return to estrus were delayed in the other 30 gilts. Twenty-three gilts exhibited estrus 11 to 20 days after the last day of EB treatment. Only seven gilts had functional corpora lutea (CL) by 20 days after EB. The best response was in the group given 10 mg of EB daily on Days 11 through 14 in which 5 of 6 gilts had maintained CL. Experiment 2 was designed to evaluate fertility after EB and prostaglandin F 2α (PGF 2α) treatment. Twenty-eight gilts were given injections of 10 mg of EB on Days 10 through 14 of the cycle. The EB was followed by two injections, four hours apart, of 5 mg of PGF 2α, 1, 5, 10 or 20 days after the end of EB treatment. Twenty-two gilts exhibited a synchronized estrus 4 to 6 days after PGF 2α treatment. Twenty-one were inseminated twice during the 16 to 32 hr interval after the detection of estrus with 6×10 9 spermatozoa in the Beltsville L-1 extender. Seventeen gilts had normal appearing embryos at autopsy. A total of 118 ova (93.7% of the CL number) were collected from eight gilts on Days 4 to 6 of pregnancy, and 106 (89.9%) were fertilized and developing normally. Embryo recovery from nine gilts on Days 24 to 26 was 91.5% (118 embryos), and 98.4% of the embryos appeared to have been normal. These results show that estrous synchronization and conception can be obtained by PGF 2α injections started 5 to 20 days after EB treatment.

Induction of temporary sterility in female hamsters by an intraperitoneal Silastic-PVP-PGF 2α tube

In the female hamster, temporary sterility for a period of 10 or 15 days was induced by an intraperitoneal Silastic-PVP-tube containing 0.5 or 1.0 mg of PGF 2α, respectively. All Silastic-PVP-PGF 2α tube bearing animals regained fertility and delivered normal litters at various times after the placement of the tube. The release rate of 3H-PGF 2α from the Silastic-PVP tube was described and their potential use as a drug delivery system discussed.

Action of prostaglandin F 2α on pregnancy in hamsters: Luteolytic and extra-ovarian effects

Pregnancies in hamsters may be terminated with 10 μg PGF 2α administered b.i.d. on days 4, 5 and 6 of gestation. Small (250 μg and above) daily injections of progesterone on the same days will reverse this PG effect; in contradistinction, 10 mg of progesterone per day failed to maintain normal pregnancies in hamsters spayed on day 5. Daily administration of 3 mg of progesterone and 1 μg of estrone essentially normalized the gestation; administration of PGF 2α at 10 mg on days 5, 6 and 7 of pregnancy in steroid-maintained rats, resulted in pregnancy termination in all animals, while 1 mg was partly effective. These data demonstrate an extra-ovarian site of action of prostaglandin F 2α on pregnancy in hamsters.

Induction of midterm abortion in rabbits and hamsters with Silastic-PVP tubes containing prostaglandins E 2 and F 2α

Treatment with a combination of prostaglandins E 2 and F 2α in a Silastic-PVP tube improved the induction of midterm abortion in rabbits and hamsters. In the rabbit, intravaginal deposition of 2 mg PGE 2 and 1 mg PGF 2α caused 100% abortion whereas in the hamster the same effect was obtained after intrauterine insertion of 250 μg PGE 2 and 75 μg PGF 2α. It is suggested that PGE 2 and PGF 2α cause luteal regression and fetal death followed by enhanced uterine contraction and fetal expulsion. A mild diarrhea was associated with PGE 2 treatment in the rabbit but this side effect was not observed in the PGE 2 treated hamster.

The effect of locally administered PGF 2α on the contractility of the nonpregnant human uterus in vivo

The effect of locally administered prostaglandin F 2α on the sensitivity and reactivity of the nonpregnant human uterus during the menstrual cycle was studied. An increase in uterine contractility in response to as little as 1.0 μg PGF 2α could be observed in all patients during both the early and late portions of the menstrual cycle, but at the time of ovulation a marked decrease in sensitivity was noted. Endogenous prostaglandin normally occurs in the secretory endometrium in levels compatible with the amount of exogenous prostaglandin which elicited increased uterine activity. These findings support the hypothesis that PGF 2α plays an important physiological role in the cyclical regulation of uterine motility during the human menstrual cycle.

Intermittent low-dose administration of prostaglandins intraamniotically in pathological pregnancies: A comparison with oxytocin and ergometrine

The effects of prostaglandin F 2α on uterine contractility were compared with the effects of oxytocin and ergometrine. All patients had an intrauterine death. 5 patients were induced with prostaglandin F 2α, given intraamniotically in low doses, starting with 125 μg. Doses were increased in relation to uterine activity. 5 other patients were induced by intravenous administration of oxytocin and ergometrine. Uterine pressure was monitored by a transabdominal open-tip catheter system. Results were quantitated in tonus (mm Hg), amplitude (mm Hg), frequency (number of contractions per 10 min), Montevideo units, active and total pressure areas per 20 min. Possible biochemical and coagulation changes were controlled before, during and after induction. Changes did not occur. Intermittent increasing small doses of PGF 2α increased uterine activity exponentially. Hypertonia persisting longer than 5 min was seldom seen with oxytocin or with PGF 2α. Ergometrine increased frequency of uterine contractions, without influencing tonus, probably due to a specific effect on the ‘archemyometrium’. The induction-delivery interval was shorter in the PGF 2α group (range: 6–15 h) than in the oxytocin group (range: 7–24 h). In the latter group more inductions were necessary to complete delivery. Using PGF 2α in these small doses did not cause any side effects. With the intraamniotic injections, starting with 125 μg PGF 2α, clinical results are the same as those reported in the literature for high doses.

Influence of the estrous cycle and prostaglandins on utero-ovarian vein blood flow in the rat

The blood flow rate in the utero-ovarian vein (UOV) has been measured in adult female rats during the different phases of the estrous cycle. It was observed that the blood flow rate in the UOV is high at proestrus and at estrus and low during diestrus days 1 and 2. The intravenous injection of 10 μg PGF 2α or PGE 2 diminishes the blood flow rate in the UOV. The efficacy of the two PGs in reducing blood flow is different in the various phases of the estrous cycle, being maximal during the day of estrus.

Decreased blood flow through rat testis after intratesticular injection of PGF 2α

The blood flow through the testes was calculated for 26 rats after measurements of the clearance rate of intratesticularly injected 133Xenon dissolved in saline. The testicular blood flow in the rats was measured immediately after injection of 1 or 10 μg PGF 2α into each testis, as well as one and four weeks later. The range of group mean flows in the contral groups was 27.5–37.0 ml/100 g/min. The injection of 1 or 10 μg PGF 2α immediately decreased (p < 0.025 and p < 0.0005) the flow to 12.0 and 4.3 ml/100 g/min, respectively. One and four weeks later, no difference was found between the control and experimental groups. At autopsy during the fourth week, no difference was found between the control and PGF 2α - treated groups with regard to the weight of the adrenals, testes, prostate gland and seminal vesicles, or in the histological appearance of the testes. Unilateral injection of 10 μg PGF 2α decreased the flow through the injected testis and tended to decrease the flow through the non-injected testis.

Intrauterine injection of prostaglandin F 2α for termination of early pregnancy in out-patient

Prostaglandin F 2α administered as single intrauterine injection was used for termination of very early pregnancy in 34 out-patients. Twelve patients were induced with 1.0 mg, 18 patients with 2.0 mg and 4 patients with 4.0 mg of PGF 2α. After 2 weeks, abortion was complete in 58% induced with 1.0 mg, in 78% induced with 2.0 mg, and in all 4 patients induced with 4.0 mg. After 3 weeks, abortion was complete in 83% induced with 1.0 mg and in 100% induced with 2.0 mg. There was one failure, which occurred in the group treated by using 1.0 mg PGF 2α. Immediate side-effects were kept at an acceptable level with a very mild premedication. No serious complications occurred but curettage was performed on 2 patients because of bleeding. Spontaneous menstruation started in the 1.0 mg group within an average of 33 days (range 23–60), in the 2.0 mg group within an average of 36 days (range 25–61). The use of 2.0 mg PGF 2α for the routine termination of very early pregnancy is recommended.

On the mechanism of prostaglandin F 2α-induced abortion in hamsters

The mechanisms by which prostaglandins (PGs) induce abortion in hamsters remain poorly understood. PGs may effect one or more of these factors: a) corpus luteum (CL) structure and/or function; b) ovarian blood supply; c) pituitary function; and d) uterine motility. A minimum s.c. dose of 12.5 μg of PGF 2α is required to abort hamsters on day 5 of pregnancy. Radioimmunoassays revealed a drop of 71% in serum progesterone (P) levels 3 hours after dosing. Pregnancy was maintained indefinitely in hamsters receiving PGF 2α on day 5 by injections of progesterone on days 4, 5, and 6. In a related experiment, pregnancy was maintained with 5 mg doses of 17α-ethyl-19-nortestosterone (ENT) before and after PGF 2α injection, thereby permitting assessment of endogenous P levels (ENT does not cross-react with antiprogesterone antisera). Serum P levels were depressed by PGF 2α in both ENT and control hamsters. Finally, PGF 2α was injected on day 6 in hypophysectomized hamsters in which pregnancy was maintained with ovine prolactin (1 mg) and ovine FSH (5 μg). Serum P levels were decreased 70% 3 hours post-injection, although pregnancy was maintained in 37% of the animals. PGF 2α thus interferes directly with P secretion by the ovary in the absence of the pituitary and in the presence of injected luteotrophic complex. A sustained drop of 85–90% in serum P levels appears to be required for PGF 2α to induce abortion in 100% of the hamsters. We conclude that PGF 2α does not permanently damage CL when pregnancy is maintained by exogenous hormones, and the involution observed by others is most likely a consequence rather than a cause of pregnancy loss.

INTRAUTERINEINJECTION OF PROSTAGLANDIN F2α FOR TERMINATION OF EARLY PREGNANCY IN OUT‐PATIENT

Abstract. Prostaglandin F2α administered as single intrauterine injection was used for termination of very early pregnancy in 34 outpatients. Twelve patients were induced with 1.0 mg, 18 patients with 2.0 mg and 4 patients with 4.0 mg of PGF2α. After 2 weeks, abortion was complete in 58 % induced with 1.0 mg, in 78 % induced with 2.0 mg, and in all 4 patients induced with 4.0 mg. After 3 weeks, abortion was complete in 83 % induced with 1.0 mg and in 100% induced with 2.0 mg. There was one failure, which occurred in the group treated by using 1.0 mg PGF2α. Immediate sideeffects were kept at an acceptable level with a very mild premedication. No serious complications occurred but curettage was performed on 2 patients because of bleeding. Spontaneous menstruation started in the 1.0 mg group within an average of 33 days (range 23‐60), in the 2.0 mg group within an average of 36 days (range 25‐61). The use of 2.0 mg PGF2α for the routine termination of very early pregnancy is recommended.