Prostaglandin 15-hydroxy dehydrogenase and Δ reductase levels in the lungs of maternal, fetal and neonatal rabbits

The levels of prostaglandin 15-hydroxy dehydrogenase and reductase have been studied in the lungs of maternal, fetal and neonatal rabbits. Fetal lungs obtained at gestational age of 28–30 days (full term 31 days) had the same levels of prostaglandin dehydrogenase as the adults, while the reductase levels in the fetal lungs were only one fourth that in the adults. The lungs of maternal rabbits at near term possessed very high levels of prostaglandin dehydrogenase — approximately twenty-fold higher than in the adult non-pregnant female controls. The Δ¹³ reductase appeared slightly elevated during pregnancy. Neonatal animals at different ages showed the same levels of both enzymes as the near term fetus and/or the non-pregnant adults, which suggests that the development of the ability for prostaglandin metabolism is completed at least several days before birth. The high dehydrogenase levels in the near term maternal lungs indicated the requirement for extra protection against prostaglandin release during late pregnancy.     

Prostaglandin 15-hydroxy dehydrogenase and Δ13 reductase levels in the lungs of maternal,fetal and neonatal rabbits

The levels of prostaglandin 15-hydroxy dehydrogenase and reductase have been studied in the lungs of maternal, fetal and neonatal rabbits. Fetal lungs obtained at gestational age of 28–30 days (full term 31 days) had the same levels of prostaglandin dehydrogenase as the adults, while the reductase levels in the fetal lungs were only one fourth that in the adults. The lungs of maternal rabbits at near term possessed very high levels of prostaglandin dehydrogenase — approximately twenty-fold higher than in the adult non-pregnant female controls. The Δ¹³ reductase appeared slightly elevated during pregnancy. Neonatal animals at different ages showed the same levels of both enzymes as the near term fetus and/or the non-pregnant adults, which suggests that the development of the ability for prostaglandin metabolism is completed at least several days before birth. The high dehydrogenase levels in the near term maternal lungs indicated the requirement for extra protection against prostaglandin release during late pregnancy.     

Blood concentrations of gonadotrophins, prolactin and gonadal steroids in males and in non-pregnant and pregnant female African elephants (Loxodonta africana)

No seasonal variation in any of the hormones measured was apparent in males or females. Testosterone levels in males increased around puberty (10-11 years) and remained significantly higher in adult than prepubertal males. This was not accompanied by any significant change in levels of LH, FSH or prolactin. In non-pregnant females there was no apparent difference in levels of LH, FSH or prolactin with age. There was a significant increase in progesterone around puberty (12 years) but there was considerable overlap in values between prepubertal and adult females. During pregnancy, progesterone levels were significantly higher than in non-pregnant females with maximum levels occurring at mid-pregnancy (9-12 months). However, there was considerable overlap in values between non-pregnancy and pregnancy. Concentrations of LH and FSH decreased significantly during mid-pregnancy while prolactin levels increased dramatically during pregnancy; after 7 months of gestation until term levels were always at least 8 ng/ml greater than in any non-pregnant female. It is suggested that this consistent increase in plasma/serum levels of prolactin can be used to diagnose pregnancy in the elephant.     

Stimulated cytokine production correlates in umbilical arterial and venous blood at delivery

BACKGROUND: Umbilical venous blood is easy to obtain after delivery, and thus has been commonly used in many studies for cytokine analysis. Our aim was to evaluate whether or not induced cytokine production differs after stimulation in umbilical artery and vein whole blood samples, using two different stimulation protocols. The effect of such stimulation on fetal and maternal blood was also evaluated. METHODS: Blood samples from umbilical artery (UA) and vein (UV), and from the mother were collected from 23 women after delivery at term. Concentrations of cytokines (IL-4, IFN-gamma, IL-6 and TNF-alpha) were measured in plasma and whole blood after PMA/ConA and PMA/ionomycin stimulation. RESULTS: Both in maternal and in fetal samples, cytokine concentrations in unstimulated plasma samples were lower than in stimulated samples, except for IL-4 after PMA/ConA stimulation. UA and UV showed similar, average cytokine levels after stimulation and the correlations were high (r=0.68-0.95). Cytokine concentrations were clearly higher in umbilical blood than in maternal blood after stimulation, but not in plasma. Correlations between maternal and umbilical samples after stimulation were generally low (r<0.41). IFN-gamma was not detectable in unstimulated plasma samples. The production of IL-4 and IFN-gamma was more intense after PMA/ionomycin stimulation than after PMA/ConA stimulation. INTERPRETATION OF THE RESULTS: Concentrations of the cytokines examined are similar in blood from the UA and UV. For IL-4 and IFN-gamma, the stimulant used has a significant effect on the level of cytokine expression, and interestingly, the effect is more pronounced on the fetal than on the maternal side.     

Concentrations of progesterone in arterial and venous plasma of fetal pigs and their dams in late gestation

Blood samples were drawn from uterine arteries and veins of pregnant gilts and from the umbilical artery and vein of each of their fetuses during laparotomy at Day 80. Concentrations of progesterone (P) were greater in fetal than maternal plasma. Uptake of P from the placenta by the fetal blood was evident but was not equivalent to the maternal uterine arterial-venous difference in P concentration. No correlation between plasma P and fetal weight was noted. Concentrations of P in both umbilical vessels of female fetuses were higher than in male fetuses. These data indicate that fetal sex affects the rate of transport and/or synthesis of P in the utero/placental compartment and/or the rate of metabolism of P in the fetus. The relative importance of de novo synthesis and transplacental transport of P in establishing concentrations of P in fetal blood remains to be elucidated.     

Iron deficiency in the rat: biochemical studies of fetal metabolism

The effects of dietary-induced iron deficiency on fetal and maternal metabolism were studied in the rat. Concentrations of phenylalanine, but not tyrosine, were significantly elevated in plasma from iron-deficient maternal and fetal rats at day 20 of gestation with individual fetal plasma levels of phenylalanine as high as 10 mg per 100 ml. Concentrations of total 5-hydroxyindole compounds were significantly decreased in brain tissue from iron-deficient fetuses (day 20 of gestation), suggesting that synthesis of the compounds may be inhibited by iron deficiency. Mitochondrial NADH oxidase activity was markedly decreased (60%) in homogenates of fetuses at day 14 of gestation and may account for the high fetal resorption rate and small fetal size observed in the rat in iron deficiency.     

Prostaglandin induced early abortions in the bovine. Clinical outcome and endogenous release of prostaglandin F2α and progesterone

Peripheral blood plasma levels of progesterone and the main blood plasma metabolite of prostaglandin F_2α (15-keto-13, 14-dihydro-PGF_2α) were analysed in 12 heifers in which abortions were induced with a prostaglandin analogue (cloprostenol) at pregnancy stages from 39–146 days. All animals except one (treated on day 75 of pregnancy) aborted within 4 days following treatment.The peripheral plasma levels of progesterone decreased rapidly following the injection of cloprostenol. All heifers had shortlasting peaks of the prostaglandin metabolite in connection with luteal regression. In animals pregnant for less than 80 days this release ceased at the time of delivery of the fetuses, which were expelled within unruptured fetal membranes. Standing estrus was observed in connection with the expulsion of the fetuses. Two of the animals were mated at this estrus and became pregnant. In contrast, animals pregnant for more than 100 days released massive amounts of prostaglandin F_2α during a 2–5-days period post partum and had retained fetal membranes. No heat was observed in connection with these abortions. The animal that failed to abort showed no change in the prostaglandin metabolite levels.     

Absence of Antidiuresis during Administration of Prostaglandin F2α

Water diuresis was induced in six patients in mid-pregnancy. Three were then given oxytocin and the remainder prostaglandin F₂α (PGF₂α), both drugs being infused intravenously in doses used to induce labour at term. Pronounced antidiuresis occurred with oxytocin, whereas PGF₂α showed no such effect. The probable absence of any risk of water intoxication when using PGF₂α in inducing labour may be of particular value when maternal pre-eclampsia or renal disease is present.     

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.     

Plasma F2-isoprostanes are elevated in newborns and inversely correlated to gestational age

F(2)-isoprostanes, prostaglandin F(2)-like compounds formed by free radical-catalyzed lipid peroxidation, are considered the most reliable markers of oxidative stress. It has been repeatedly suggested that newborns are exposed to conditions of oxidative stress resulting from the change from a low oxygen pressure in utero to a high oxygen pressure at birth. We measured the levels of F(2)-isoprostanes in plasma of newborns by gas chromatography/mass spectrometry and we found that F(2)-isoprostanes are significantly higher in term newborns compared to healthy adults. The greatest values were found in preterm newborns in whom F(2)-isoprostanes are even higher than in term babies. Moreover a significant inverse correlation was found between the plasma levels of isoprostanes and the gestational age. A quite normal level of isoprostanes was found in the mothers both at delivery and during pregnancy. Placental total F(2)-isoprostanes (sum of free plus esterified) were significantly higher in preterm compared to term deliveries and such a difference might account for the difference in plasma isoprostanes. Plasma non-protein-bound iron is higher in preterm than in term newborns, even if no correlation was found with plasma F(2)-isoprostanes. Erythrocyte desferrioxamine-chelatable iron content (0 time) and release (24 h of aerobic incubation) are higher in newborns than in adults and in preterm than in term newborns, but again no correlation was found with plasma F(2)-isoprostanes. The marked increase in plasma isoprostanes suggests that oxidative stress is a feature of the physiopathological changes seen in the perinatal period.     

Thromboxane B-2 in the plasma and amniotic fluid of late pregnant and periparturient sheep.

The concentration of thromboxane (TX) B-2 was similar in plasma from all sources but was significantly greater (P less than 0.01) in amniotic fluid. Fetal hypophysectomy was without effect on maternal or fetal levels of TXB-2 (P greater than 0.1). Neither normal parturition at term nor prematurely induced delivery was associated with any significant trend in TXB-2 levels. During late pregnancy (105--145 days of gestation) the concentrations of TXB-2 and 13, 14-dihydro-15-keto-prostaglandin F (PGFM) in maternal and fetal plasma were significantly correlated (P less than 0.001). There was, however, no correlation between TXB-2 and PGFM levels in samples taken during the 36 h before delivery. These data suggest that thromboxanes play little part in the mechanism of parturition in sheep.     

Radioimmunoassay of 13,14-dihydro-15-keto prostaglandin F in bovine peripheral plasma

A radioimmunoassay has been developed for 13,14-dihydro-15-keto-prostaglandin F in bovine peripheral plasma. Acidified plasma samples were extracted with diethyl ether and the dried extracts assayed for 13,14-dihydro-15-keto-prostaglandin F using antiserum raised against a 13,14-dihydro-15-keto-prostaglandin F_2α-albumin complex. The tracer used for the assay was prepared enzymatically from tritiated prostaglandin F_1α. Polyethylene glycol was employed to separate free and bound 13,14-dihydro-15-keto-prostaglandin F. The inter-assay coefficient of variation based on 9 determinations of control plasma was 13.8%. The detection limit of the assay was 25 pg 13,14-dihydro-15-keto-prostaglandin F/ml plasma.In 3 cows around estrus there was a complex series of peaks of 13,14-dihydro-15-keto-prostaglandin F concentrations coincident with luteolysis and declining progesterone concentrations. Changes in peripheral plasma concentrations of 13,14-dihydro-15-keto-prostaglandin F in the pregnant cow near term showed a close correlation with prostaglandin F levels in utero-ovarian venous plasma. The concentration of 13,14-dihydro-15-keto-prostaglandin F in 12 men was 114±20 pg/ml plasma. It is concluded that the measurement of peripheral 13,14-dihydro-15-keto-prostaglandin F concentrations may offer a simple and convenient method for monitoring uterine prostaglandin F production in the cow.     

Radioimmunoassay of 13,14-dihydro-15-keto prostaglandin F in bovine peripheral plasma

A radioimmunoassay has been developed for 13,14-dihydro-15-keto-prostaglandin F in bovine peripheral plasma. Acidified plasma samples were extracted with diethyl ether and the dried extracts assayed for 13,14-dihydro-15-keto-prostaglandin F using antiserum raised against a 13,14-dihydro-15-keto-prostaglandin F_2α-albumin complex. The tracer used for the assay was prepared enzymatically from tritiated prostaglandin F_1α. Polyethylene glycol was employed to separate free and bound 13,14-dihydro-15-keto-prostaglandin F. The inter-assay coefficient of variation based on 9 determinations of control plasma was 13.8%. The detection limit of the assay was 25 pg 13,14-dihydro-15-keto-prostaglandin F/ml plasma.In 3 cows around estrus there was a complex series of peaks of 13,14-dihydro-15-keto-prostaglandin F concentrations coincident with luteolysis and declining progesterone concentrations. Changes in peripheral plasma concentrations of 13,14-dihydro-15-keto-prostaglandin F in the pregnant cow near term showed a close correlation with prostaglandin F levels in utero-ovarian venous plasma. The concentration of 13,14-dihydro-15-keto-prostaglandin F in 12 men was 114±20 pg/ml plasma. It is concluded that the measurement of peripheral 13,14-dihydro-15-keto-prostaglandin F concentrations may offer a simple and convenient method for monitoring uterine prostaglandin F production in the cow.     

Prostaglandin concentrations in intra-uterine tissues from late-pregnant sheep before and after labour

Prostaglandin E (PGE), prostaglandin F (PGF) and 13,14-dihydro-15-keto-prostaglandin F (PGFM) have been measured in cotyledons and myometrium from sheep before and after labour. Fetal cotyledons contained more PGE than maternal cotyledons which in turn contained more than myometriu. The maternal cotyledon contained the highest concentrations of PGF, but the fetal cotyledon was the only tissue exhibiting a statistically significant rise in the concentration of PGF following labour. Concentrations of PGFM were closely correlated with (although usually lower than) those of PGF.     

Prostaglandins in fetal tracheal and amniotic fluid from late pregnant sheep

Concentrations of prostaglandin E (PGE), prostaglandin F (PGF) and 13,14-dihydro-15-keto-prostaglandin F (PGFM) have been measured in fetal tracheal and amniotic fluid from chronically catheterized sheep during late pregnancy. Amniotic fluid contained significantly greater concentrations of these prostaglandins than tracheal fluid (p less than 0.01); there was no correlation between the level of prostaglandins found in each fluid. In tracheal fluid concentrations of PGE and PGFM exceeded those of PGF (P less than 0.01) whereas no significant differences were found in amniotic fluid. The levels of prostaglandins in these fluids were similar in ewes bearing hypophysectomized fetuses.     

Maternal selenium deficiency increases hydrogen peroxide and total lipid peroxides in porcine fetal liver

To investigate the role of selenium (Se) in the developing porcine fetus, prepubertal gilts (n=42) were randomly assigned to either Se-adequate (0.39 ppm Se) or Se-deficient (0.05 ppm Se) gestation diets 6 wk prior to breeding. Maternal and fetal liver was collected at d 30, 45, 70, 90, and 114 of pregnancy. Concentrations of Se in maternal liver decreased during gestation in gilts fed the low-Se diet. The activity of cellular glutathione peroxidase (GPx) was decreased at d 30 and 45 of gestation in liver of gilts fed the low-Se diet. Concentrations of malondialdehyde (MDA) and hydrogen peroxide (H₂O₂) were greater in liver homogenates from gilts fed the low-Se diet. Within the fetuses, liver Se decreased in those fetuses of gilts fed the low-Se diet. Although the activity of GPx in fetal liver was not affected by the maternal diet, concentrations of H₂O₂ and MDA in fetal liver were greater in fetuses from gilts fed the low-Se diet. Maternal liver GPx activity was approx 12-fold greater than fetal liver GPx activity regardless of dietary treatment. These results indicate that maternal dietary Se intake affects fetal liver Se concentration and feeding a low-Se diet during gestation increases oxidative stress to the fetus, as measured by fetal liver H₂O₂ and MDA.     

Rabbit corticosteroid-binding globulin: primary structure and biosynthesis during pregnancy

The cDNA-deduced primary structure of rabbit corticosteroid-binding globulin (CBG) contains 383 amino acids (mol wt, 42,326), including three cysteine residues and four sites for N-glycosylation. It is primarily the product of a 1.68-kilobase hepatic mRNA, but small amounts of CBG mRNA were also found in maternal lung, spleen, and ovary and fetal kidney. In the fetus, hepatic CBG mRNA concentrations increase markedly after day 11 and were 2- to 5-fold higher than those in maternal liver during days 17-23. They then declined to very low levels at term (31 days). By contrast, maternal hepatic CBG mRNA levels did not increase until day 23; reached a peak at about day 27, and then declined to prepregnancy values by 3 days after delivery. In general, fetal and maternal hepatic CBG mRNA concentrations reflect the corresponding serum CBG levels. Our data, therefore, indicate that the marked changes in fetal and maternal plasma CBG levels during pregnancy reflect changes in the biosynthesis of the protein rather than alterations in compartmentalization or clearance.     

Distribution of bovine fetuin and albumin in plasma, allantoic and amniotic fluids during development

A radioimmunoassay for bovine fetuin was developed and its specificity and validity established. Albumin was measured by radial-immunodiffusion assay. Fetuin levels in fetal plasma increased from 10 to 15 mg/ml between 4 and 8 months of gestation; albumin levels remained higher than fetuin. Neonatal plasma fetuin levels rapidly declined during the first 14 days post partum, coincident with a marked reciprocal increase in albumin levels. In allantoic fluid fetuin and albumin concentrations reached a peak at 7 months but fetuin values were always higher. In amniotic fluid both proteins peaked at 8 months; albumin levels were similar to those in allantoic fluid but fetuin values remained consistently lower than those in allantoic fluid throughout gestation. Fetuin levels in maternal plasma declined from 0.7 to 0.4 mg/ml between 1 month and term. We conclude that (1) at term there is an abrupt change from fetuin synthesis to increased albumin synthesis by the neonatal liver; (2) fetuin appears to be preferentially accumulated in the allantois whereas albumin is equally concentrated in the allantois and amnion.