Uterine prostaglandin concentrations following fetal death in sheep

Concentrations of prostaglandin E (PGE), PGF and 6-oxo-PGF_1α (the hydrolytic product of PGI₂) were measured by radioimmunoassay (RIA) in myometrium, endometrium, cotyledons, amnion and chorioallantois taken from different uterine areas from chronically catheterized sheep bearing fetuses which had died 12–26 h previously (n=4) or 34–72 h previously (n=4). These two groups of animals were designated fetuses dead <30 h and >30 h respectively. The time of fetal death was assessed on the basis of fetal heart rate and blood gases. At the time of the tissue collection the ewes were between 123 and 130 days after mating. For comparative purposes, tissues also were collected from four sheep bearing live chronically catheterized fetuses at 130 days of gestation.For myometrium, concentration of PGF, PGE and 6-oxo-PGF_1α were significantly higher in sheep bearing dead fetuses, compared to those bearing live fetuses. Analysis of variance also showed a significant effect of uterine area on myometrial PGE concentrations, concentrations being higher in tubal areas than elsewhere. Concentrations of PGE, PGF and 6-oxo-PGF_1α were higher in endometrium taken from uteri containing dead fetuses. In cotyledons, concentrations of PGF and 6-oxo-PGF_1α but not PGE, were significant elevated following fetal death. Concentrations of 6-oxo-PGF_1α, but not PGE or PGF, were elevated in both chorioallantois and amnion of sheep bearing dead fetuses, compared to those bearing live fetuses. In association with elevated PG concentrations, there was a progressive increase in the frequency and maximum amplitude of uterine contractions. These results show that PG concetrations are elevated following fetal death in sheep, and suggest an association between elevated PG concentrations and delivery of the dead fetus.     

Prostaglandin production by porcine allantochorion in vitro: effect of cortisol infusion in vivo.

The effect of cortisol infusion into the porcine fetus on subsequent prostaglandin (PG) production in vitro by the fetal placenta (the allantochorion) was studied. Also, the possible in vitro effects of glucocorticoids and other steroids on PG production by dispersed cells were examined. Two fetuses in each of 6 sows were catheterized on day 100 or 101 of gestation (normal gestation is 114-116 days); one was infused with cortisol (6 mg/day) and one with saline for 5 days beginning on day 103. On day 108, fetal allantochorionic tissue was aseptically collected from the infused fetuses and 2 uninfused litter mates (controls). Pieces of tissues were cut from the allantochorion (4 sows) and dispersed cell preparations were made from each fetus (4 sows). Each preparation was cultured for 24 h, and the production of PGE2, PGF2 alpha, and 6-keto-PFG1 alpha (prostacyclin metabolite) measured. In vivo cortisol infusion had no significant effect on the in vitro production of PGE2 or PGF2 alpha by tissues or dispersed cell preparations. However, tissue from the fetuses infused with cortisol produced significantly less 6-keto-PGF1 alpha than uninfused controls (54% of control, p < 0.05). The dispersed cells from uninfused fetuses and 2 cortisol-infused animals were also incubated for 24 h with 10(-7) and 10(-9) M concentrations of estrone, estradiol, progesterone, cortisol, and dexamethasone, and the production of PGE2, PGF2 alpha, and 6-keto-PFG1 alpha was measured. No significant effect of any of these steroids in vitro on prostanoid production was observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of beta-adrenergic agonist infusions on myometrial activity and plasma prostaglandin levels in the nonpregnant sheep

Recent studies have reported that beta-adrenergic agonists stimulate the production of stimulatory prostaglandins (PGs) by intrauterine tissues in vitro. These drugs are used clinically to inhibit uterine contractions; consequently an increase in stimulatory PGs in vivo might have potentially adverse effects. We have, therefore, investigated whether beta-adrenergic agonists increase plasma PG concentrations in vivo. Samples of peripheral (aorta) and uterine venous enriched (vena cava) blood from nonpregnant sheep were collected at 15-min intervals for 1 h before, 3 h during, and 1 h postinfusion of either (a) the beta-adrenergic agonist isoproterenol (Isop) at a dose of 0.16 microgram.kg-1.min-1; (b) Isop at a dose of 0.08 microgram.kg-1.min-1; or (c) saline, 1 mL/h via a jugular vein catheter. The sheep were also equipped with intrauterine recording balloons to record intrauterine pressure and myometrial electromyographic (EMG) electrodes to measure EMG activity. Infusion of Isop at 0.16 microgram.kg-1.min-1 produced a significant initial inhibition of uterine activity, although contractions returned (within 60 min) despite continued administration of Isop. Plasma PGE2 (but not PGF2 alpha or 13,14-dihydro-15-keto-PGF2 alpha (PGFM] concentrations were significantly elevated during the Isop infusion. Administration of Isop at 0.08 microgram.kg-1.min-1 produced no effects on uterine contractile activity but was associated with a significant elevation in plasma PGE2 (but not PGF2 alpha or PGFM) concentrations. No changes in plasma PGE2, PGF2 alpha, or PGFM occurred during saline infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of in vitro heat shock upon the synthesis and secretion of prostaglandins and protein by uterine and placental tissues of the sheep

The objectives of this study were to determine the secretion patterns of prostaglandins (PG) and protein during mid- (Day 100) and late- (Day 140) pregnancy in the ewe and to ascertain whether that pattern is altered by in vitro heat shock. Explant cultures were prepared from intercaruncular endometrium, caruncular endometrium, fetal cotyledon and interplacentomal placenta. Cultures were incubated at 39 or 42 degrees C for 18 h in the presence of arachidonic acid or L-[4,5(3)H]leucine. There were no effects of day of gestation or consistent effects of temperature upon de novo synthesis of tissue and secretory protein. Elevated temperature generally depressed PGE(2) secretion by maternal tissues and PGF secretion by caruncular endometrium but had little effect on PGE(2) release by fetal tissues or on PGF release by intercaruncular endometrium or fetal tissues. Day of gestation by tissue type interactions were found for PGF and PGE(2) release. At Day 100, maternal tissues secreted more PGF and PGE(2) than fetal tissues; at Day 140, PG secretion from fetal tissues was greater than at Day 100, and fetal PGE(2) release exceeded release from maternal tissues. Tissue proteins resolved by SDS-PAGE revealed the appearance in heat-shocked tissue of 93 and 72 kDa heat-shock proteins. In conclusion, elevated temperature depressed PGE(2) release, particularly from maternal tissues. Changes in PGE(2) suggest that the increase in utero-placental PGE(2) with increasing gestational age is due to changes in secretion of the fetal placenta.     

Prostaglandins in the circulation of the fetal lamb

Prostaglandin E and PGF have been measured in the plasma of chronically catheterized fetal lambs throughout the last 20–35 days (0.73 onwards) of gestation. The mean concentration of PGE was higher than that of PGF. There was a significant increase in the concentration of PGE but little change in the concentration of PGF in samples of fetal plasma taken within 24 h of parturition. In contrast, at this time in maternal utero-ovarian venous plasma, there was a large increase in PGF, but relatively little change in PGE. There was a significant decrease in the concentration of PGE and PGF in the plasma of lambs within 12 h after birth compared to the levels found in the same animals as fetuses a few hours previously. The physiological importance of these changes is discussed.     

Nutritional control of respiratory and other muscular activities in relation to plasma prostaglandin E in the fetal sheep

The effects of nutrient availability on fetal plasma prostaglandin E (PGE) concentrations, on fetal breathing movements and electromyographic (EMG) activities of fetal nuchal and forelimb muscles were investigated in pregnant ewes by varying dietary intake and by manipulation of fetal plasma glucose concentration. The incidence of fetal breathing movements (06.00-10.00 h) decreased with increasing gestational age while fetal arterial concentrations of plasma PGE increased significantly over the same period of gestation. Maternal fasting for 48 h reduced the incidence of fetal breathing movements and the amount of nuchal EMG activity (06.00-10.00 h) in animals older than 130 days but had no effect earlier in gestation. No changes in forelimb EMG activity were observed during fasting at any gestational age. Plasma PGE levels increased significantly during fasts begun both before and after 130 days of gestation. When data from fed and fasted states were combined for all fetuses, irrespective of gestational age, there was a significant inverse correlation between fetal breathing movements incidence and plasma PGE concentration in utero. This relationship was even more pronounced when the fetuses were considered individually. Insulin infusions induced hypoglycaemia, an increase in fetal plasma PGE concentration and a significant reduction in the incidence of fetal breathing movements at all ages. Glucose infusions of fetal breathing movements only after 130 days and had no effect on plasma PGE levels in utero at any gestational age. Neither insulin nor glucose infusions altered the EMG activities of the nuchal and forelimb muscles. The results show that glucose availability is an important factor in determining the incidence of fetal breathing movements in utero and indicate that nutritionally induced changes in fetal breathing movements are mediated in part by PGE. They also suggest that PGE is a physiological regulator of fetal breathing movements in the sheep during late gestation.     

The effect of dietary supplementation with linoleic acid to late gestation ewes on the fatty acid composition of maternal and fetal plasma and tissues and the synthetic capacity of the placenta for 2-series prostaglandins

Linoleic acid (18:2n-6) is metabolised to arachidonic acid (20:4n-6), the precursor for 2-series prostaglandins (PGs). Increased consumption of 18:2n-6 during pregnancy may thus modify PG synthesis during labour. We have investigated whether increased 18:2n-6 composition during gestation altered the fatty acid consumption and PG synthesis of maternal and fetal tissues in the sheep. Ewes were fed a control diet or a diet providing 40% more 18:2n-6 from 96 days gestation. Half of each group received dexamethasone on day 136 to up-regulate the PG synthetic pathways promoting parturition. Maternal and fetal tissues were collected at 138 days. The 18:2n-6 diet significantly increased the 20:4n-6 content of maternal plasma, fetal plasma and allantochorion (51-81%) phosphatidylcholine, and fetal liver (40%) and maternal caruncular endometrium (57%) phosphatidylethanolamine. Increased 18:2n-6 intake increased production of PGF(2alpha) and PGE(2) in all placental tissues (maternal caruncular and intercaruncular endometrium and fetal allantochorion) by 23-98%, whereas dexamethasone increased it by 32-142%. This suggests that consumption of an 18:2n-6-enriched diet in late pregnancy enhanced placental PG production by increasing the supply of 20:4n-6. Variations in the extent to which the diet altered the polyunsaturated fatty acid (PUFA) content of the different tissues indicated complex interactions between nutrient availability and metabolic adaptation.     

Bovine placental prostaglandin synthesis in vitro as it relates to placental separation

Bovine placentomes were collected during late gestation, prepartum and immediately postpartum. Postpartum tissues were collected prior to fetal membrane separation. Maternal and fetal placentomal components each were examined for their ability to synthesize prostaglandins (PG's) from arachidonic acid (AA) and metabolize PGF2 alpha and PGE2 in vitro. Maternal placental PG synthesis was lower (P less than .05) than that for fetal placental tissue and was primarily PGF's. Fetal placental PG synthesis increased (P less than .05) prepartum and was primarily PGE's. Fetal placental PGE production predominated (P less than .05) postpartum if the fetal membranes were retained, while PGF production predominated (P less than .05) if the membranes were released. Maternal and fetal placental tissues were unable to convert PGE2 to PGF2 alpha (P greater than .05). Postpartum fetal placental tissue was able to convert PGF2 alpha to PGE2 (P less than .05) if the fetal membranes were retained but not if the membranes were released (P greater than .05). These results indicate that fetal placental synthesis of PGF's may be related to placental membrane separation. The shift in fetal placental PG production from PGE's to PGF's may be due to a cessation of the ability of released fetal tissue to convert PGF2 alpha to PGE2.     

The effect of intrauterine infusions of prostaglandin E2 on luteal function in nonpregnant gilts

Two trials were conducted to study the effects of intrauterine infusions of prostaglandin E(2) (PGE(2)) on luteal function in nonpregnant gilts. Cannulae were surgically implanted on day 9 postestrus into the lumen of each horn with a cephalic vein cannula inserted for collection of peripheral blood. Intrauterine infusions of 0, 25, 75 or 200 mug of PGE(2) were initiated at 0900 h on day 12 and administered thereafter every 12 hr until estrus or day 22 in the first trial. The second trial protocol included an increase in the dose of PGE(2) administered as well as the frequency of infusion. Infusion of 0, 200, 300 or 400 mug PGE(2) was begun at 0300 h on day 12 and continued every 6 hr until estrus or day 22. Cephalic plasma samples for progesterone analysis were collected every six hours from 0300 h on day 11 to 2100 h on day 26 in both trials. In Trial 1 mean plasma progesterone concentrations for all treatments were not different (P>0.05) from the controls on any given day of the estrous cycle. Interestrous interval was unaffected by intrauterine infusion of PGE(2). The mean plasma progesterone concentrations for all treatments were not different (P>0.05) from the controls on days 11-18 of the estrous cycle in Trial 2. However, plasma progesterone concentrations for the 200-mug and 300-mug PGE(2) groups appeared to be greater than the controls on days 14 and 15, indicating a possible delay in the decline of progesterone for these groups. The mean plasma progesterone concentrations for the treatment groups were lower (P<0.05) than the controls on days 20-26 of the cycle. treatment cycle length did not differ (P>0.05) from previous cycle length; thus treatment with PGE(2) had no effect on interestrous interval. PGE(2) may have retarded the decline of progesterone secretion by the corpus luteum in some cases, but at these dosages and frequencies of administration PGE(2) was ineffective in prolonging luteal maintenance.     

Regulation of breathing movements in fetal sheep by prostaglandin E2

In fetal sheep, plasma prostaglandin (PG) E2 concentrations are high, and fetal breathing movements (FBM) occur intermittently, primarily during low-voltage fast electrocortical activity (LVFA). There is evidence suggesting that prostaglandins, specifically PGE2, may regulate FBM. To define the physiological role of PGE2 in regulation of FBM, we infused meclofenamate (0.9 mg X kg-1 X h-1), a prostaglandin synthetase inhibitor, into six fetal sheep to suppress endogenous prostaglandin production. Afterward, PGE2 was added in mean doses of 9, 18, 36, and 90 ng X kg-1 X min-1. Meclofenamate decreased PGE2 concentrations and increased FBM, especially during high-voltage slow electrocortical activity (HVSA). Addition of PGE2 reversed the effects of meclofenamate, increasing PGE2 concentrations and decreasing FBM, especially during HVSA. The response to PGE2 was dose dependent; the overall incidence of FBM and incidences of FBM during HVSA and LVFA were inversely correlated with both the infused PGE2 dose and the mean PGE2 concentration. At higher doses of PGE2, FBM occurred intermittently and only during LVFA; thus PGE2 infusion restored the physiological pattern of FBM. These results indicate that PGE2 regulates FBM by inhibiting FBM during HVSA.     

Exogenous progesterone reduces follicular prostaglandin E and 6-keto prostaglandin F-1 alpha in the cyclic hamster

In cyclic hamsters, exogenous progesterone (100 micrograms) administered s.c. at 09:00 h on the day of dioestrus II reduced prostaglandin (PG) E and 6-keto PGF-1 alpha but not PGF concentrations in preovulatory follicles measured at 09:00 h of pro-oestrus. The injection of 10 micrograms ovine LH (NIADDK-oLH-25) concurrently with 100 micrograms progesterone on dioestrus II prevented the decline in follicular PGE and 6-keto PGF-1 alpha values. Administration of LH alone did not significantly alter follicular PG concentrations. Inhibition of follicular PGE accumulation by progesterone was due to a decline in granulosa PGE concentration and not thecal PGE. Progesterone administration also reduced follicular oestradiol concentrations. Administration of oestradiol-17-cyclopentanepropionate (ECP) (10 micrograms) with progesterone did not prevent the decline in follicular PGE and 6-keto PGF-1 alpha but did increase follicular PGF concentrations. However, ECP given alone on dioestrus II reduced follicular PGE and increased PGF concentrations in preovulatory follicles on pro-oestrus. It is concluded that exogenous progesterone administered on dioestrus II inhibits granulosa PGE and 6-keto PGF-1 alpha accumulation in preovulatory follicles, probably by reducing serum LH concentrations, and that the granulosa cells, which are LH-dependent, are a major source of follicular PGE.     

Role of progesterone in regulating uteroovarian venous concentrations of PGF2 alpha and PGE2 during the estrous cycle and early pregnancy in ewes

The role of progesterone in regulation of uteroovarian venous concentrations of prostaglandins F2 alpha(PGF2 alpha) and E2 (PGE2) during days 13 to 16 of the ovine estrous cycle or early pregnancy was examined. At estrus, ewes were either mated to a fertile ram or unmated. On day 12 postestrus, ewes were laparotomized and a catheter was inserted into a uteroovarian vein. Six mated and 7 unmated ewes received no further treatment. Fifteen mated and 13 unmated ewes were ovariectomized on day 12 and of these, 7 mated and 5 unmated ewes were given 10 mg progesterone sc and an intravaginal pessary containing 30 mg of progesterone. Uteroovarian venous samples were collected every 15 min for 3 h on days 13 to 16 postestrus. Mating resulted in higher mean daily concentrations of PGE2 in the uteroovarian vein than in unmated ewes. Ovariectomy prevented the rise in PGE2 with day in mated ewes but had no effect in unmated ewes. Progesterone treatment restored PGE2 in ovariectomized, mated ewes with intact embryos. Mating had no effect on mean daily concentrations of PGE2 alpha or the patterns of the natural logarithm (1n) of the variance of PGF2 alpha. Ovariectomy resulted in higher mean concentrations and 1n variances of PGF2 alpha on day 13 and lower mean concentrations and 1n variances of PGF2 alpha on days 15 and 16. Replacement with progesterone prevented these changes in patterns of mean concentrations and 1n variances of PGF2 alpha following ovariectomy. It is concluded that progesterone regulates the release of PGF2 alpha from the uterus, maintaining high concentrations while also preventing the occurrence of the final peaks of PGF2 alpha which are seen with falling concentrations of progesterone. This occurs in both pregnant and non-pregnant ewes. Progesterone is also needed to maintain increasing concentrations of PGE2 in mated ewes.     

The urinary excretion of prostaglandins and thromboxane B2 in healthy volunteers: a study in males and females, and on the influence of seminal fluid contamination

Radioimmunoassay measurements of prostaglandins (PGs) E2, F2 alpha, 6-keto-PGF1 alpha and thromboxane (Tx) B2 in 24 h urine specimens from a male and a female healthy volunteer on several consecutive days revealed a dramatic increase of PGE2, PGF2 alpha, 6-keto-PGF1 alpha on days, upon which they had sexual intercourse; only TxB2 remained stable. Furthermore, the PGE2/PGF2 alpha ratio rose to values greater than 0.5 on days with sexual intercourse. This was found to be due to contamination of the urine samples by seminal fluid. Two 24 h urine samples from each of 26 healthy male and female volunteers (HV) revealed higher (p less than 0.01) mean PGE2 and PGF2 alpha values in males than in females. The results show that the interpretation of the urinary PG excretion as a measure of renal PG synthesis should be considered carefully, and that a PGE2/PGF2 alpha ratio greater than 0.5 indicates probable seminal contamination of urine.     

Effects of meclofenamate on breathing movements in fetal sheep before delivery

There is evidence that prostaglandins (PG), specifically PGE2, participate in the regulation of fetal breathing movements (FBM). During late gestation, when FBM occur intermittently and primarily during low-voltage electrocortical activity, the concentration of PGE2 in fetal plasma ([PGE2]) is high. During the days before delivery [PGE2] increases and FBM decrease. To determine whether the increase in [PGE2] is responsible for the concurrent decrease in FBM, we infused the prostaglandin synthase inhibitor, meclofenamate (0.7 mg.kg-1.h-1), into eight fetal sheep continuously for 5-13 days before delivery; five control fetuses received a continuous infusion of the solvent for 5-11 days before delivery. Compared with control infusion, meclofenamate caused a significant decrease in [PGE 2] until the day of delivery and a significant increase in FBM [overall and during high-voltage electrocortical activity (HVA)] until 2 days before delivery. Although there were significant correlations between [PGE2] and FBM (overall and during HVA), both groups showed similar decreases in FBM during the 2 days before delivery. We conclude that the decrease in FBM before delivery is not dependent on the concurrent increase in [PGE2].     

Prostaglandin F and E levels in the conceptus, uterus and plasma during early pregnancy in the ewe

Concentrations of prostaglandins E and F (PGE and PGF) were measured in the embryo or fetus, extra embryonic or fetal membranes (membranes), intercaruncular and caruncular endometrium and plasma collected from uterine and ovarian arterial and venous vessels from separate groups of ewes laparotomized at 5 day intervals from day 10 to day 55 of pregnancy. Our purpose was to investigate the role of prostaglandins E and F in the maternal recognition of pregnancy, implantation and early placental function. Our data suggest that the initial maintenance of the corpus luteum in the pregnant ewe does not involve a reduction in PGF production, compared to pregnant ewes; but a change in the pattern of PGF secretion. This is accompanied by an elevation in PGE production of similar magnitude to that observed in non pregnant ewes. The extra embryonic/fetal membranes appear to be the major source of elevated PGF levels in the maternal circulation prior to day 30 of pregnancy. Between days 35 and 55 of gestation the rising PGF levels in maternal serum probably come from the fetus. Over the same period PGE levels rise in the fetus and intercaruncular endometrium, but PGE secretion into the maternal circulation is not enhanced. A role for PGF and PGE in fetal, placental and uterine growth is suggested; placental and uterine endocrine function may also be targets.     

Prostaglandin F and E levels in the conceptus, uterus and plasma during early pregnancy in the ewe

Concentrations of prostaglandins E and F (PGE and PGF) were measured in the embryo or fetus, extra embryonic or fetal membranes (membranes), intercaruncular and caruncular endometrium and plasma collected from uterine and ovarian arterial and venous vessels from separate groups of ewes laparotomized at 5 day intervals from day 10 to day 55 of pregnancy. Our purpose was to investigate the role of prostaglandins E and F in the maternal recognition of pregnancy, implantation and early placental function. Our data suggest that the initial maintenance of the corpus luteum in the pregnant ewe does not involve a reduction in PGF production, compared to pregnant ewes; but a change in the pattern of PGF secretion. This is accompanied by an elevation in PGE production of similar magnitude to that observed in non pregnant ewes. The extra embryonic/fetal membranes appear to be the major source of elevated PGF levels in the maternal circulation prior to day 30 of pregnancy. Between days 35 and 55 of gestation the rising PGF levels in maternal serum probably come from the fetus. Over the same period PGE levels rise in the fetus and intercaruncular endometrium, but PGE secretion into the maternal circulation is not enhanced. A role for PGF and PGE in fetal, placental and uterine growth is suggested; placental and uterine endocrine function may also be targets.     

The effect of progesterone and human interferon alpha-2 on the release of PGF2 alpha and PGE from epithelial cells of human proliferative endometrium.

Progesterone and interferon-like trophoblastic proteins modulate prostaglandin (PG) synthesis from endometrium in early ovine and bovine pregnancy. Enriched epithelial cells were prepared from human endometrium removed in the proliferative phase of menstrual cycle (n = 8). Progesterone at a concentration of 1 microM suppressed PGE release from the cells during the first 24 hours in culture. After 48 hours in culture progesterone at a dose of 100 nM and 1 microM suppressed both the release of PGF2 alpha and PGE from the cells and this suppression was maintained for a further two days. Addition of exogenous 30 microM arachidonic acid (AA) abolished this effect of progesterone on both PGF2 alpha and PGE release. Interferon alpha-2 did not suppress the basal release of PGF2 alpha nor PGE. In the presence of progesterone, interferon alpha-2 attenuated the progesterone mediated suppression of PGF2 alpha but not PGE release from endometrial cells. These findings suggest that progesterone suppresses the basal release of PGs from human endometrium, but unlike the sheep, interferon alpha-2 does not exert this action on human endometrium.     

Meclofenamate does not affect lung development in fetal sheep

Prostaglandins may be involved in some aspects of fetal lung development, including surfactant metabolism, tracheal fluid production, and possibly lung growth. In the fetus, during the days before delivery, plasma PGE2 concentration increases and concurrently, tracheal fluid production decreases and surfactant production increases. To determine whether the increase in PGE2, specifically plasma PGE2 concentration, is responsible for these changes, we continuously infused the prostaglandin synthetase inhibitor, meclofenamate (0.7 mg/h per kg), into 8 fetal sheep for 5-13 days before delivery; 5 control fetuses received a continuous infusion of solvent for 5-11 days before delivery. Meclofenamate infusion significantly decreased plasma PGE2 concentrations until the day of delivery. However, meclofenamate did not affect tracheal fluid production or its decrease before delivery, fetal plasma cortisol concentration, surfactant content of tracheal fluid and lung tissue, organ weights, lung weights, or lung DNA and protein content. We conclude that the changes in lung development during the days before delivery are not dependent on the usual high fetal plasma concentration of PGE2 or its increase before delivery.     

Temporal response of uterine prostaglandins to estradiol treatment in the ovariectomized-pregnant rat

Previous studies in our laboratory have shown that 24 hours of estradiol treatment significantly enhanced uterine prostaglandin (PG)F, PGE and thromboxane B2 (TxB2) levels but had no effect on 6-Keto-PGF1 alpha (6KF) concentrations in ovariectomized-pregnant rats. One explanation for the lack of an augmentation in 6KF was a temporal difference in response (i.e. 6KF increased and decreased within the 24 hour period). To test this possibility rats were ovariectomized on day 19 of pregnancy and sacrificed 0, 4, 8, 12, 16, 20 and 24 hours after estradiol treatment. Uterine tissue and venous plasma were analyzed for PGs by radioimmunoassay. No significant (p greater than .05) alterations were detected for any of the uterine PGs at 0, 4, 8 and 12 hours. However, at 16 hours PGF, TxB2 and PGE all showed significant (p less than .05) increases (2.4, 3.4 and 2.1 fold, respectively) compared to 12 hours. In contrast, no significant augmentation in 6KF levels (p greater than .05, 1.3 fold) was detected at 16 compared to 12 hours although it was enhanced relative to 0 and 4 hours. In addition, PGF, TxB2 and PGE, but not 6KF, showed further increases 24 hours after estradiol administration. No alterations were found (p greater than .05) for any of the PGs in uterine venous plasma at the time points studied. In summary, uterine PGF, PGE and TxB2 net production appears to be more enhanced by estradiol treatment than 6KF at the time points studied. In addition, there is a slight, but significant, difference in the temporal response characteristics of 6KF compared to the other PGs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Production of prostaglandin by late-gestation porcine placental cells in vitro.

Fifteen sows were assigned to three groups of five each, according to gestational age (109 days, 114 days or labour). Two fetuses per sow were chosen at random, and amnion, allantochorion, amniochorion, amniotic fluid and fetal urine were collected. Tissues were enzymatically dispersed and incubated for 1, 2, 3 or 4 h and the prostaglandin (PG) content of the supernatant medium was measured by radioimmunoassay. In general, all placental cell types produced at least three times more prostaglandin E (PGE) and 6-keto-PGF1 alpha than PGF. Production did not vary across gestational age, except that production of 6-keto-PGF1 alpha was lower in cells collected during labour, resulting in a relative increase in PGF and PGE. Aminochorion cells had a lower de novo capacity to synthesize PG than did allantochorion or amniochorion, whereas treatment of allantochorion with preterm amniotic fluid, preterm or term fetal urine resulted in increased PG output. These results demonstrate that porcine placental cells can synthesize and metabolize prostaglandin in late gestation but suggest that their capacity to produce PGI2 (as measured by 6-keto-PGF1 alpha) is lower than for other prostaglandins during labour.