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PubMed1978

Changes in the fetal thyroid axis after induction of premature parturition by low dose continuous intravascular cortisol infusion to the fetal sheep at 130 days of gestation.

The effect of cortisol infusion on plasma T4 and T3 concentrations has been investigated in the fetal lamb at 130-134 days of gestation. Infusion of cortisol at rates equivalent to one-third the quantity produced by the fetus at the time of parturition results in a significant fall in fetal plasma T4 concentration and a significant rise in fetal plasma T3 concentration. Delay in the initiation of labor as a result of progesterone administration to the ewe did not prevent the changes in the fetal thyroid axis. These modifications of thyroid function therefore appear to be caused by the infusion of cortisol rather than to be secondary to the induction of labor.

Animals↗
PubMed1980

Oxytocin receptors and parturition. I. Control of oxytocin receptor concentration in the rat myometrium at term.

Rat myometrium exhibited a marked rise in the concentration of oxytocin (OT) receptors during parturition. The elevation began several hours before labor, was maximal during labor, and declined several hours later. In the perinatal period, the change in OT receptor concentration was proportional to the ratio of plasma estradiol to progesterone levels. Several hours before the increase in OT receptor concentration, there was a proportional increase in estrogen receptor concentration in both the cytosol and nuclear fractions of the myometrium. In view of the known action of estrogens in increasing the concentration of OT receptors in rat uterus, we propose that the following sequence of events occurs in the initiation of labor in the rat. The decline in serum progesterone permits estradiol to stimulate the synthesis of estrogen receptors in the myometrium. This increased concentration of estrogen receptors and their occupancy by estradiol stimulates the appearance of more OT receptors, which then trigger labor by interacting with circulating OT.

Animals↗
PubMed1982

Time trend analysis of plasma unconjugated and sulfoconjugated estrone and 3 beta-delta 5-steroids in fetal and maternal sheep plasma in relation to spontaneous parturition at term.

Parturition in the sheep is preceded by a complex series of changes in both fetal and maternal plasma-steroid hormone concentrations. Using the chronically catheterized fetal sheep preparation, we measured unconjugated and sulfoconjugated pregnenolone, 17 alpha-hydroxypregnenolone, dehydroepiandrosterone, and estrone in fetal and maternal plasma over the final 20 days before spontaneous vaginal delivery at term. Where appropriate, third degree polynomial functions were fitted to the changing plasma hormone concentration profile. Fetal and maternal plasma pregnenolone and pregnenolone sulfate both fell from maximum values in the last 4 days of gestation. Fetal and maternal plasma estrone and estrone sulfate concentrations underwent a terminal rise over the last 4 days of gestation that was a mirror image of the fall in plasma pregnenolone and pregnenolone sulfate. Maternal 17 alpha-hydroxypregnenolone rose over the last 4 days of gestation. Fetal 17 alpha-hydroxypregnenolone, maternal and fetal plasma dehydroepiandrosterone sulfate, and fetal plasma dehydroepiandrosterone sulfate, and fetal plasma dehydroepiandrosterone showed no trend during the period of study. Maternal plasma dehydroepiandrosterone rose over the last 4 days of gestation. These results support the view that increased activity of placental 17 alpha-hydroxylase and 17-20-desmolase is responsible for the conversion of C-21 steroids to estrogens at term. delta 5-Steroids are present in very high plasma concentrations in fetal sheep plasma and may constitute a more important precursor pool for estrogen biosynthesis than does circulating plasma progesterone.

17-alpha-Hydroxypregnenolone↗
PubMed1975

On the role of prostaglandins in parturition in the rat.

Treatment of both intact and hypophysectomized pregnant rats on days 19 and 20 of pregnancy with PGF2alpha results in a rapid fall in plasma progesterone concentrations by day 20 followed by premature delivery on day 21. Administration of depoprovera did not prevent the PGF2alpha-induced fall in progesterone levels but premature littering was adverted. Indomethacin, an inhibitor of prostaglandin biosynthesis, postponed the onset of parturition by 20 h when administered in late pregnancy but rats treated with both indomethacin and PGF2alpha delivered at the normal time. Treatment of both intact and hypophysectomized animals with indomethacin delayed the fall in plasma progesterone concentrations which normally occurs between days 21 and 22 of pregnancy. Concomitant PGF2alpha treatment of rats receiving indomethacin caused plasma progesterone levels to fall in a pattern similar to controls. These findings indicate that endogenous PGF2alpha induces a fall in blood progesterone concentrations which is followed by increased myometrial activity.

Animals↗
PubMed1976

Mammary blood flow and endocrine changes during parturition in the ewe.

The temporal relationship between changes in mammary blood flow (MBF) and changes in the concentration of plasma prolactin, progesterone, estradiol-17beta, and cortisol, was examined in chronic sheep preparations undergoing spontaneous labor (Group I) or labor induced by an infusion of dexamethasone (1 mg/24 h) to the fetus (Group II). In Group I, an increase in prolactin (45 to 489 ng/ml), a decrease in progesterone (15 to 4 ng/ml), and an increase in MBF (97 to 365 ml/min) occurred at about the same time, whereas increases in estradiol-17beta (80 to 211 pg/ml) and cortisol (9 to 39 ng/ml) followed the change in MBF. A similar pattern of changes in MBF and hormonal concentrations occurred over a shorter period when premature labor was induced in the animals in Group II. These findings suggest that changes in plasma prolactin and progesterone concentrations play an important role in the regulation of MBF at the time of parturition.

Animals↗
PubMed1996

Changes in heat shock protein-90 and -70 messenger ribonucleic acid in uterine tissues of the ewe in relation to parturition and regulation by estradiol and progesterone.

Steroid receptors, including estrogen receptor (ER) and progesterone receptors (PR), form associations with heat shock proteins (Hsps). Dissociation of Hsps activates PR, whereas retention of Hsp90 in vitro stimulates ER. Progesterone and estrogen, interacting with their receptors, regulate myometrial contractility throughout pregnancy and during parturition. We hypothesize that uterine ER and PR changes concurrent with changes in Hsp90 and -70 abundance could alter uterine function. We quantified changes in Hsp90 and -70 messenger RNA (mRNA) abundance in pregnant sheep myometrium, endometrium, and fetal placenta during glucocorticoid-induced preterm and spontaneous labor. The effects pf estradiol and progesterone on Hsp90 and -70 mRNA in myometrium and endometrium were examined in ovariectomized nonpregnant ewes. Hsp90 and -70 mRNA distribution was evaluated by in situ hybridization in myometrium and endometrium. Dramatic tissue-specific increases in Hsp90 and -70 mRNA were observed in myometrium and endometrium (P < 0.05) during spontaneous and glucocorticoid-induced labor. Hsp90 and -70 mRNA localized in myometrial, arterial smooth muscle, and endometrial gland epithelial cells. Estradiol increased Hsp90 and -70 mRNA in myometrium and endometrium of nonpregnant ewes. Progesterone did not affect Hsp90 and -70 mRNA abundance, but inhibited the estradiol-stimulated increase. These data support our hypothesis that at term, increased abundance of Hsp90 and -70 may inhibit uterine PR and stimulate ER function in uterine tissues. Similar changes, if present, would be of importance in species showing no progesterone withdrawal before labor, such as primates, including pregnant women.

Animals↗
PubMed2001

Concomitant increase of G protein-coupled receptor kinase activity and uncoupling of beta-adrenergic receptors in rat myometrium at parturition.

The myometrial beta-adrenergic receptor (beta-AR)-adenylyl cyclase pathway is markedly desensitized at the end of pregnancy in the rat. We have investigated whether changes in the amount and/or the activity of G protein-coupled receptor kinase (GRK) occurred at the same period of pregnancy. Using Northern and Western blotting, we have identified GRK2, GRK5, GRK6, and a small amount of GRK3 in late pregnant rat myometrium. GRK activity, as measured by in vitro phosphorylation of rhodopsin, was detected in both cytosolic and plasma membrane fractions. Interestingly, in the 6-10 h preceding parturition, there was a substantial increase (+190%) of myometrial membrane-associated GRK activity. This was associated with an increase in membrane GRK2 immunoreactivity. Such alterations occurred concomitantly with uncoupling of beta-AR, as assessed by quantification of high-affinity binding receptors. These data suggest that GRK activity increase may be one of the mechanisms underlying alterations in the coupling between beta-AR and adenylyl cyclase and may thus contribute to the initiation of myometrial contractions at term.

Animals↗
PubMed2002

Coordinate regulation of prostaglandin metabolism for induction of parturition in mice.

Prostaglandins are essential for the initiation of parturition in mice. The peak in uterine prostaglandin F(2)(alpha) levels occurs at d 19.0 of gestation, just before the onset of labor. Our studies set out to determine the important regulatory step(s) involved in this increase of prostaglandin F(2)(alpha). We show that cytosolic phospholipase A(2) mRNA, protein, and activity do not significantly vary during mouse gestation. Rather, our studies demonstrate that cyclooxygenase-1 mRNA is abruptly induced at d 15.5 of gestation, but cyclooxygenase-1 protein levels only gradually increase throughout gestation. In contrast, cyclooxygenase-2 protein remains constant during gestation. We find that prostaglandin F synthase protein increases significantly during gestation reaching peak levels between d 15.5 and d 17.5 of gestation. We also find that the level of prostaglandin dehydrogenase, responsible for degradation of prostaglandins, decreases during late gestation. Taken together these results suggest that the regulation of prostaglandin F(2)(alpha) is a complex process involving the coordinate induction of synthetic enzymes along with a decrease in degradative enzymes involved in prostaglandin metabolism.

Animals↗
PubMed1977

Initiation of human parturition. VI. Identification and quantification of progesterone metabolites produced by the components of human fetal membranes.

The fetal membranes play a central role in the initiation of human parturition, a role that may be subserved in part by quantitative changes in progesterone metabolism. In order to identify and to quantify the metabolites of progesterone produced by the components of the human fetal membranes, amnion and chorion laeve tissues and homogenates were incubated with [3H]progesterone in the presence of added NADPH. The radioactive metabolites, 20alpha-hydroxy-4-pregnen-3-one, 5alpha-pregnane-3,20-dione and 3beta-hydroxy-5alpha-pregnan-20-one, were isolated and identified by derivative formation, a combination of chromatographic techniques, and by crystallization to constant specific activity after addition of authentic standards. A simplified technique of metabolite quantification was developed that involves one thin layer chromatographic procedure and liquid scintillation assay of radioactivity. The accuracy of this method was established by comparison with data obtained using classical techniques. This study demonstrates the presence of human fetal membranes 5alpha-reductase, 20alpha-hydroxysteroid oxidoreductase, and 3beta-hydroxy-steroid oxidoreductase, and a qualitative difference between amnion and chorion laeve.

20-alpha-Dihydroprogesterone↗
PubMed1983

Prostaglandin output in relation to parturition by cells dispersed from human intrauterine tissues.

Collagenase-dispersed cells from human amnion, chorion, decidua, and placenta have been maintained in short term cultures to study prostaglandin (PG) biosynthesis in relation to parturition. Cells retained metabolic function during the 6-h incubation period, as determined by the apparently linear utilization of radioactive glucose and the formation of tritiated water. All cells synthesized PGs (E, F, and 6-keto F1 alpha) from endogenous precursors. The output of all three PGs significantly increased in amnion and chorion, but not in decidua or placenta, obtained from women who had entered labor spontaneously at term and delivered vaginally (SL) when compared to women at term, but not in labor, delivered by elective cesarean section (CS). For example, PGE output (picograms per 10(5) cells/6 h) increased from 207 +/- 77 (n = 5) to 908 +/- 334 with labor (mean +/- SEM). The addition of indomethacin (10(-7)-10(-5) M) to SL amnion cells significantly decreased (P less than 0.001, by analysis of variance) PGE and PGF, but not 6-keto PGF1 alpha output. Comparison of PGF output with its metabolite, 13,14-dihydro-15-keto PGF2 alpha (PGFM); indicated that PGF values were similar to or higher than PGFM for all tissues other than CS chorion, where PGFM output was significantly greater (142 +/- 63 vs. 486 +/- 95; n = 5; P less than 0.05). PGFM levels in amnion increased with labor [104 +/- 51 (n = 5) to 341 +/- 96 (n = 5); P less than 0.05], suggesting that PG output increased with labor in the fetal membranes as a result of increased synthesis and not decreased metabolism.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

The dynamics of prostaglandin metabolism in human fetal membranes and decidua around the time of parturition.

To address whether prostaglandins (PGs) produced in the amnion can gain access to the myometrium, we used three in vitro systems to determine the characteristics of PG secretion, metabolism, and transfer in amnion, chorion, and decidua around the time of parturition. PG metabolism, measured in explant cultures or cytosol preparations, occurs predominantly by the enzyme PG dehydrogenase, which was highest in chorion and was 2- to 3-fold more active for PGE2 than PGF2 alpha. The activity increased significantly around the time of labor onset. The activity of PG-9-ketoreductase, which interconverts the E and F series of PGs, was 2-3 orders of magnitude less than that of PG dehydrogenase. Using a dual chamber perfusion apparatus, we demonstrated that similar amounts of PGE2 were secreted from the fetal (amnion) and maternal (chorio-decidua) surfaces, and this ratio did not change with labor. Using radiolabeled PGE2, radioactivity traversed full thickness membranes at the rate of 4%/h. Only approximately 12% of the transferred radioactivity remained as intact PGE2, and very little conversion to PGF2 alpha was detected. No changes in transfer were detected around the onset of labor. We conclude that it is unlikely that PGE2 produced in the amnion acts directly on the myometrium.

Amnion↗
PubMed1994

Human fetal membrane contribution to the prevention of parturition: uterotonin degradation.

This investigation was conducted to evaluate the potential capacity of the human fetal membranes-decidua parietalis, and in particular the chorion laeve, to degrade uterotonins that are produced in amnion, are present in amniotic fluid, or both. The four uterotonins that have been evaluated most frequently as myometrial contractants potentially involved in the initiation of human parturition are prostaglandins, oxytocin, endothelin-1, and platelet-activating factor. We assessed the levels of mRNA and the specific activities (SAs) of enkephalinase (the plasma membrane endopeptidase that degrades endothelins) and prostaglandin dehydrogenase (PGDH) in human fetal membranes, i.e. amnion and chorion leave, and in decidua parietalis. The SA of oxytocinase (which inactivates oxytocin) in these tissues also was determined. The SA of enkephalinase in chorion laeve from all anatomical sites (singleton and diamnionic-dichorionic twin placentae) in all pregnancies studied (mean +/- SEM, 95 +/- 7.9 ng/min.mg protein; n = 28) is similar to that in human fetal kidney (89.5 +/- 2.8; n = 6). Kidney tissue is believed to be one of the richest sources of enkephalinase. The SAs of enkephalinase in amnion (18.3 +/- 2.3 nmol/min.mg protein; n = 29) and in decidua parietalis (31.8 +/- 6.7; n = 20) also were high, but significantly less than that in chorion leave. The level of enkephalinase mRNA in chorion laeve in singleton pregnancies is high, as is the SA of enkephalinase (111.9 +/- 10.6 nmol/min.mg protein; n = 17). In paired chorion laeve tissues from five diamnionic-dichorionic twin placentae, the SAs of enkephalinase in reflected chorion laeve (74 +/- 12.8; P < 0.06 compared with singletons) and fused chorion laeve (64.8 +/- 6.5; P < 0.001 compared with singletons) were similar. The SA of PGDH in reflected chorion leave (46.3 +/- 6.9 nmol/min.mg protein; n = 19) was significantly greater than that in decidua (16 +/- 5.5; n = 15). There was a significant correlation between the levels of PGDH mRNA and PGDH enzyme SA. In fused chorion laeve of diamnionic-dichorionic twin placentae, the SA of PGDH (14.9 +/- 7.3; n = 4) was much less than that in reflected chorion laeve of the same twin pregnancy (70.5 +/- 14.7; n = 4). PGDH mRNA was not detectable in amnion tissue (n = 5) by northern analysis, and the SA of PGDH (< 1.2 +/- 1.0; n = 6) in amnion was undetectable or near the lower limit of assay detection.(ABSTRACT TRUNCATED AT 400 WORDS)

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2002

The in vivo control of prostaglandin H synthase-2 messenger ribonucleic acid expression in the human amnion at parturition.

Prostaglandin H synthase-2 (PGHS-2) activity and mRNA rise in the human amnion at late gestation, contributing to the increase in intrauterine PG production crucial for labor and delivery. In the present investigation we have determined the mechanism that controls amniotic PGHS-2 mRNA levels in vivo at term parturition. Amnion membranes were collected after elective cesarean section (n = 20), and after spontaneous labor (n = 20). PGHS-2 relative gene transcription rates were determined by transcriptional run-on, and PGHS-2 mRNA and heterogeneous nuclear RNA (hnRNA) relative abundance were measured by quantitative real-time RT-PCR. The PGHS-2 mRNA degradation rate was determined by incubating amnion in the presence of the transcription inhibitor 5,6-dichlorobenzimidazole riboside. The dynamics of PGHS-2 hnRNA and mRNA abundance were characterized in 0- to 24-h tissue incubations. The PGHS-2 relative gene transcription rate was a significant (P < 0.05) predictor of PGHS-2 hnRNA and mRNA abundance, and PGHS-2 hnRNA was also a predictor (P < 0.01) of PGHS-2 mRNA levels both before and after labor. Interestingly, even though PGHS-2 gene activity remained unchanged, PGHS-2 mRNA abundance increased with labor and displayed constitutive stability before and after labor. PGHS-2 mRNA levels spontaneously increased by 400% (P < 0.01) upon incubation for 24 h, whereas the transcription rate dropped by 95% during the first 2 h, then rebounded significantly between 6-24 h. Thus, PGHS-2 mRNA abundance is transcriptionally controlled in term amnion. Labor does not increase PGHS-2 gene activity or mRNA stability. The PGHS-2 gene is probably induced before labor by a factor(s) originating in the amnion membrane, and the resulting stable mRNA accumulates progressively in the tissue throughout labor and delivery.

Amnion↗
PubMed1994

Scanning electron microscopical observation of the intramitochondrial body in the bovine corpus luteum during pregnancy and after parturition.

Large luteal cells of the bovine pregnant luteum can be characterized as steroid-producing cells. Mitochondria of these cells contained intramitochondrial bodies (IMB). The three-dimensional structure of the IMB and the degenerative process of luteal cells were as follows: 1) The IMBs were globular or oval, 0.1 to 1.5 microns in diameter. Their outer surfaces were coarse but their cut surfaces were uniform. Their outer surfaces changed from rough to smooth during pregnancy. 2) At the late stage of pregnancy, the large luteal cells lost their cytoplasmic processes, showing the first sign of degeneration at the cell level in such a way that their mitochondrial cristae transformed from tubular to laminar, and that they contained accumulated lipid droplets. 3) After parturition, the IMBs came out from degenerating large luteal cells, and were conveyed by lymphatic capillaries.

Animals↗
PubMed2000

Genetic influences on premature parturition in an Australian twin sample.

We investigated possible genetic influences on women's liability to preterm birth, using data from a large sample of Australian female twin pairs. In a 1988-90 questionnaire survey, both members of 905 parous twin pairs (579 monozygotic and 326 dizygotic) reported on whether deliveries had been more than two weeks preterm. Tetrachoric twin pair correlations for first birth were rMZ = 0.20+/-0.11 and rDZ = -0.03+/-0.14, and for any birth were rMZ = 0.30+/-0.08 and rDZ = 0.03+/-0.11. Best-fitting models to data contained only additive genetic influences and individual environmental effects. Heritability was 17% for preterm delivery in first pregnancy, and 27% for preterm delivery in any pregnancy. In the former case, however, we could not reject a model without genetic influences. Although our data did not allow for differentiation of the varying aetiologies of premature parturition, results from this exploratory analysis suggest that further investigation of genetic influences on specific reasons for preterm birth is warranted.

Adult↗
PubMed1998

Bone metabolism after human parturition and the effect of lactation: longitudinal analysis of serum bone-related proteins and bone mineral content of the lumbar spine.

A prospective study was performed to investigate postpartum changes in human bone metabolism and the effects of lactation on them. The subjects consisted of two groups: 13 women who stopped breast-feeding within 3 months postpartum (short-term group) and 14 women who continued breast-feeding for more than 6 months postpartum (long-term group). Serum carboxyl-terminal propeptide of type I procollagen (PICP), carboxyl terminal cross-linked telopeptide of type I collagen (ICTP), and bone gla protein (BGP) were measured prepartum, and at 5 days, 1 month, 3 months and 9 months postpartum. Lumbar BMD was measured at 3-7 days, 3 months and 9 months postpartum. Between prepartum and 3 months postpartum, the values and variations in the markers were essentially the same in both groups. PICP was maintained at a constant and significantly higher level than the control value. In contrast, ICTP had increased markedly at 5 days postpartum, gradually decreasing thereafter. BGP was low prepartum and gradually increased. At 9 months postpartum, PICP and ICTP decreased to the control values in the short-term group. The postpartum time course of lumbar BMD showed a significant decrease in both groups at 3 months postpartum. Recovery to the puerperal level was seen at 9 months postpartum in the short-term group but not in the long-term group. In conclusion, bone resorption is stimulated by parturition as well as lactation resulting in postpartum loss of lumbar BMD.

Adult↗
PubMed1981

Experimental simulation of neuroendocrine dynamics at periparturient periods--a synthetic approach to pregnancy maintenance, parturition and lactation by programmed infusion of sex steroids in ovariectomized rats.

The blood levels of progesterone (P) and estradiol (E2) were artificially controlled in rats ovariectomized on days 19-20 of pregnancy (day 1: sperm in vaginal smears) by 48-168 h intravenous infusions according to 15 different temporally variable programs. The predominance of P infused in various curves for longer than 72 h, caused postmature deliveries on days 24-26 accompanying difficulties in labor and the lack of lactation, although changes in E2 levels antagonistically accelerated the timing of delivery. The most successful delivery and subsequent lactation were induced by an infusion of total amount of 1.5 mg P for 48 h (days 19-21) at a linearly decreasing rate in combination with an infusion of a total amount of 875 ng E2 for 72 h (days 19-22) at a slowly increasing rate, reaching a plateau in the morning of day 21 and rapidly decreasing to nil after that. Spontaneous delivery occurred on day 22 with a normal range of labor duration and no incidence of stillbirth. No further supply of sex steroids was required for the maintenance of lactation. Blood levels of prolactin shortly after delivery were much higher in these lactating ovariectomized rats than in non-lactating animals. The neuroendocrine dynamics at periparturient periods, which triggers the termination of pregnancy and then the induction of parturition and lactation, is discussed in relation to the results of these simulation experiments.

Animals↗
PubMed2003

Effect of maternal age on blood loss during parturition: a retrospective multivariate analysis of 10,053 cases.

OBJECTIVE: An extensive study as to whether maternal age itself is a risk factor for blood loss during parturition. METHOD: A total of 10,053 consecutive women who delivered a singleton infant were studied. The excess blood loss was defined separately for women with vaginal and cesarean deliveries as > or = 90th centile value for each delivery mode. The effects of 13 potential risk factors on blood loss were analyzed using multivariate analysis. RESULTS: The 90th centile value of blood loss was 615 ml and 1,531 ml for women with vaginal and cesarean deliveries, respectively. A low lying placenta (odds ratio [OR], 4.4), previous cesarean (3.1), operative delivery (2.6), leiomyoma (1.9), primiparity (1.6), and maternal age > or = 35 years (1.5) were significant independent risk factors for excess blood loss in women with vaginal delivery. Placenta previa (6.3), leiomyoma (3.6), low lying placenta (3.3), and maternal age > or = 35 years (1.8) were significant independent risk factors for excess blood loss in women with cesarean sections. CONCLUSION: A maternal age of > or = 35 years was an independent risk factor for excess blood loss irrespective of the mode of delivery, even after adjusting for age-related complications such as leiomyoma, placenta previa, and low lying placenta.

Adult↗