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Oxytocin receptors in the human uterus during pregnancy and parturition.

We have determined the concentration and distribution of oxytocin receptors in myometrial and decidual tissues obtained at cesarean section or hysterectomy during pregnancy. Myometrial receptor concentration was low at 13 to 17 weeks but had risen about twelvefold by 37 to 41 weeks. After the onset of labor, either preterm or term, the receptor levels were maximal and significantly higher than before the onset of labor. In cases of failed induction of labor with oxytocin and in postterm pregnancies (43 to 46 weeks), the receptor concentration was significantly lower than in spontaneous labor. Myometrial receptor concentrations in the fundus and the corpus were similar and significantly higher than in the lower part of the uterine segment, and the cervix had the lowest concentration. The parietal decidua had oxytocin receptor concentrations of the same magnitude as the myometrium. These results are consistent with a functional role of endogenous oxytocin in the activation of the human uterus during pregnancy and parturition.

Binding, Competitive↗

Increased inorganic sulfate in mother and fetus at parturition: evidence for a fetal-to-maternal gradient.

Inorganic sulfate is a cosubstrate for numerous sulfoconjugation reactions, including sulfation of estrogen steroids in the fetoplacental unit. It is known that the availability of inorganic sulfate can be the rate-limiting factor in these reactions, but fluxes of inorganic sulfate across the maternal-placental barrier have not been well characterized. Therefore, we measured serum inorganic sulfate in matched samples from 46 mothers and fetuses at parturition to identify any maternal-fetal gradient and explore clinical correlations. The concentration of inorganic sulfate, measured by controlled-flow anion chromatography, was significantly higher (p = 0.006) in fetal cord blood [458 +/- 10 microM; mean +/- SE] than in the maternal circulation [431 +/- 19 microM]. That a gradient was not observed for chloride ion rules out sampling artifact as a source of the difference. Maternal and fetal concentrations of inorganic sulfate were highly correlated (r = 0.84, p less than 0.001). No influence was observed for gestational history, newborn weight, sex, or Apgar scores, but values were significantly higher in those with relatively shorter (less than 36 weeks) or longer (greater than 41 weeks) gestations. We demonstrated that a small but significant fetal-to-maternal inorganic sulfate gradient exists at birth, but the origin of this gradient is not known.

Adolescent↗

Infection and labor. III. Interleukin-1: a signal for the onset of parturition.

The regulatory signals responsible for the increased biosynthesis of prostaglandins during parturition have not been established. Because interleukin-1 is capable of stimulating prostaglandin production by intrauterine tissues and is an inflammatory mediator, we propose that interleukin-1 may act as a signal for the onset of human labor in the setting of intrauterine infection. The purpose of these studies was to determine interleukin-1 activity in amniotic fluid and to establish its relationship with the onset of term and preterm labor. Amniotic fluid from 182 patients was assayed for interleukin-1 activity. Cell-associated interleukin-1 activity was detected in fluid obtained in the third trimester but not in fluid obtained in the second trimester of pregnancy, suggesting a maturational event in interleukin-1 production. The factor responsible for interleukin-1 activity had biochemical characteristics of interleukin-1 alpha (estimated molecular weight of 14 kilodaltons, isoelectric point = 4.9), and its activity was blocked with an anti-interleukin-1 alpha antisera. Women in spontaneous labor at term were likely to have fluid phase interleukin-1 activity in amniotic fluid than women who were not in labor at term. Preterm labor in the setting of intraamniotic infections was associated with significant interleukin-1 activity in amniotic fluid. This bioactivity was predominantly attributable to interleukin-1 beta. A strong correlation between interleukin-1 and amniotic fluid concentrations of prostaglandin E2 and prostaglandin F2 alpha was found in women in preterm labor. These findings support the hypothesis that interleukin-1 may play a role in the initiation of preterm labor associated with intraamniotic infection.

Amniotic Fluid↗

Fetal intermediate lobe is stimulated by parturition.

The fetal pituitary gland secretes beta-endorphin in blood in response to delivery. However, other forms of endorphin have recently been observed in the fetal pituitary, such as N-acetyl-beta-endorphin, which is devoid of opiate activity, and a desacetylated form of alpha-melanocyte-stimulating hormone. Both endorphins originate in the pituitary intermediate lobe. The sensitivity of this lobe to labor stress was assessed by the evaluation of beta-endorphin, N-acetyl-beta-endorphin, melanocyte-stimulating hormone, and desacetylated alpha-melanocyte-stimulating hormone in maternal plasma and cord blood in 11 cases of vaginal delivery and 10 cases of elective cesarean section without labor. Plasma peptide levels were determined by specific radioimmunoassays after extraction on Sep-Pak C-18 cartridges and high-performance liquid chromatography fractionation. Cord blood samples of infants delivered vaginally showed higher beta-endorphin (8.5 +/- 1.6 pmol/L, mean +/- SE) and desacetylated alpha-melanocyte-stimulating hormone (13.6 +/- 3.2 pmol/L) levels than those delivered by elective cesarean section (3.7 +/- 0.8 and 4.2 +/- 1.1 pmol/L, for beta-endorphin and desacetylated alpha-melanocyte-stimulating hormone, respectively). N-acetyl-beta-endorphin and alpha-melanocyte-stimulating hormone levels do not differ in relation to the mode of delivery. In maternal circulation beta-endorphin levels were higher in those delivered vaginally (5.2 pm 1) than in women who had cesarean sections (2.5 +/- 0.5 pmol/L), whereas no changes were found for the other peptides. In vaginal deliveries, the level of desacetylated alpha-melanocyte-stimulating hormone was higher in cord blood (13.6 +/- 3.2 pmol/L) than in maternal plasma (6.5 +/- 3 pmol/L); there were no significant differences with regard to the other peptides. Fetal and maternal levels of all the peptides were similar in cases of cesarean section. We conclude that parturition activates proopiomelanocortin peptide release from both the anterior and the intermediate pituitary lobe and that the fetus secretes the appropriate beta-endorphin molecule, that is, the peptide able to bind opiate receptors. Concomitant secretion of desacetylated alpha-melanocyte-stimulating hormone may occur with adrenal androgen activation at birth.

Cesarean Section↗

Origin of cervical collagenase during parturition.

Cervical biopsy specimens were obtained under standard conditions from the posterior lip of the uterine cervix in 105 patients. A significant increase of collagenase activity was observed during parturition as determined with an assay with iodine 125-labeled native triple-helical collagen type I as the substrate. The collagenase was not likely to originate from cervical fibroblasts because in situ hybridization failed to detect synthesis of the specific procollagenase messenger ribonucleic acid. However, migration of polymorphonuclear leukocytes into the cervical stroma occurred on onset of labor, and an antibody specific for human leukocyte collagenase that did not cross react with fibroblast collagenase revealed the presence of the enzyme in the granules of polymorphonuclear leukocytes and subsequently in the extracellular matrix of the cervix. Therefore it is likely that the cells critically involved in collagen degradation during cervical dilatation are not resident fibroblasts but rather polymorphonuclear leukocytes emigrating from blood vessels.

Blotting, Northern↗

Premature parturition is characterized by in utero activation of the fetal immune system.

OBJECTIVE: At birth the fetus emerges from a sterile environment into a nonsterile one. This process is associated with activation of the fetal immune system which protects the fetus against infection in the newborn period. We conducted this study to determine whether activation of the monocyte-neutrophil system occurs in fetuses before premature birth. STUDY DESIGN: Forty patients in premature labor with intact membranes underwent cordocentesis for research purposes. Fetal blood was analyzed with the use of flow cytometry to measure the cell surface markers CD11c, CD13, CD15, and CD67, which are associated with monocyte and neutrophil activation, and CD14 and CD63, which were used as controls. RESULTS: Twenty-eight percent (11/40) of the infants were delivered prematurely within 72 hours of entering the study while the remainder were delivered at term. Our data clearly indicate that premature infants delivered within 72 hours had a higher percentage of CD11c, CD13, CD15, and CD67 than those delivered at term. In contrast, there were no significant differences in the percentages of CD14 and CD63. CONCLUSION: Activation of the monocyte-neutrophil system exists in fetuses destined for premature delivery. These findings indicate that premature parturition is associated with in utero immune system activation.

Adolescent↗

Progesterone-binding globulin and progesterone in guinea-pigs after ovariectomy, abortion and parturition.

The level of progesterone in the serum of pregnant guinea-pigs which continued their pregnancies after ovariectomy on Day 30 fell and then rose again. In contrast, progesterone-binding globulin (PBG) was apparently not affected. PBG did however fall in guinea-pigs which aborted and also after parturition. It is apparent therefore that high PBG levels were associated with continued pregnancy. The half life of PBG was found to be approximately 2 days.

Abortion, Spontaneous↗

Progesterone withdrawal without parturition.

It has been demonstrated that administration of 100 mg of trilostane (an inhibitor of 3 beta-hydroxysteroid dehydrogenase) to late pregnant sheep will rapidly lower circulating levels of progesterone and that delivery ensues. Our intention was to reduce the dose of trilostane in order to separate the latter two sequelae and thereby obtain insight into the relationship between progesterone and prostaglandin biosynthesis. At the dose chosen (10 mg) the treatment did not induce parturition in 4 chronically catheterized sheep during late pregnancy. Circulating progesterone concentrations declined precipitously in all ewes but recovered to near basal values by 24 h after administration of trilostane. Circulating concentrations of 13,14-dihydro-15-keto-prostaglandin F2 alpha rose slightly but significantly at 4-5 h after administration of trilostane but never reached values normally associated with labor. Plasma estradiol levels were unchanged by treatment. These results are consistent with the view that progesterone withdrawal must be of a critical magnitude and duration for prostaglandin biosynthesis to be sufficiently stimulated to induce labor in sheep during late gestation.

Animals↗

A potential role for epidermal growth factor/alpha-transforming growth factor in human parturition.

Epidermal growth factor (EGF)/alpha-transforming growth factor (alpha-TGF) concentrations were measured in amniotic fluid by radioreceptor assay in non-laboring and laboring patients at term. The median concentrations of EGF/alpha-TGF were 1.28 ng/ml and 5.0 ng/ml in non-laboring and laboring patients respectively (p less than 0.05, Wilcoxon test). EGF was then incubated with amnion cells in monolayer culture to ascertain the effect of this hormone on the release of prostaglandin E2. Experiments were carried out in quadruplicate in 11 separate primary amnion-cell cultures (EGF was used at 1 ng/ml and 5 ng/ml, respectively). An increased release of prostaglandin E2 into the media was found. The response was concentration-dependent (p less than 0.01). We suggest that there may be a role for EGF in the mechanism of human parturition.

Amniocentesis↗

Effects of reducing dietary [(Na+ + K+) - (Cl- + SO4=)] on the rate of calcium mobilisation by dairy cows at parturition.

The effects of feeding diets with different milliequivalents (meq) of dietary [(Na+ + K+) - (Cl- + SO4=)] to dairy cows during the last seven weeks of pregnancy on their acid-base status and calcium mobilisation rate around parturition were studied. Ten monozygotic twin pairs of pregnant cows (five pairs of parity 1 or 2, and five pairs of parity 3 or more) were allocated to two diets which were formulated to provide either -4 meq (anion diet) or +572.5 meq (cation diet) of [(Na+ + K+) - (Cl- + SO4=)] kg-1 dietary dry matter (DM). The daily rations consisted of 4 kg grass hay and 7 kg concentrates. Changes in meq of dietary [(Na+ + K+) - (Cl- + SO4=)] were achieved by adding KCl, K2SO4 and (NH4)2SO4 (anion diet) or K2CO3 (cation diet) to basal concentrates. Plasma calcium concentration and blood acid-base parameters were not affected by dietary treatment. However, urinary calcium excretion was markedly higher and urinary pH and bicarbonate excretion significantly lower in cows fed the anion diet than in cows fed the cation diet. The responses to hypocalcaemia induced by an intravenous infusion of EDTA solution were similar in the cows fed either diet.

Animal Nutritional Physiological Phenomena↗

A comparison of maternal and foetal folacin and cobalamin activities at parturition in relation to Plasmodium falciparum infection.

Folacin deficiency in malaria endemic areas is not reported other than in severely malnourished children. This is surprising in view of the high incidence in these areas of malaria in pregnancy, with its complications of prematurity and low birth weight, all of which can predispose to folacin deficiency. This paper reports results of folacin and cobalamin activities of blood samples collected from women at parturition and their newborns in a holoendemic area in West Kenya. Evidence is given that Plasmodium falciparum infection has little influence on cord plasma or red cell folacin activities. Mean values for folacin and cobalamin are not low when compared with reported values from neonates from temperate climates.

Erythrocytes↗

Lead and cadmium in maternal blood, umbilical cord blood, amniotic fluid and placenta of cows and buffaloes after foetal death (abortion) and after normal parturition.

The cause of abortion in dairy animals is not yet exactly known. Concentrations of lead and cadmium in maternal blood, umbilical cord blood, amniotic fluid and placenta under foetal death (abortion) conditions and after normal parturition has demonstrated that these tissues in aborting cows and buffaloes accumulate much more lead and cadmium as compared to the normally delivering cows and buffaloes. It is believed that the toxic metals cause damage to the placenta and thus foetal death.

Abortion, Spontaneous↗

Possible role for prostacyclin in human parturition.

Human amnion, chorion, decidua and placenta produced 6-oxo-PGF1alpha when superfused in vitro. Furthermore amnion, an avascular tissue, produced more 6-oxo-PGF1alpha after labour than all other tissues investigated and its production of 6-oxo-PGF1alpha was significantly greater after labour than before the onset of labour. These findings suggest that prostacyclin production by foetal membranes may have a role in the mechanisms controlling human parturition. Moreover, this is the first evidence for the production of prostacyclin by an avascular tissue.

Epoprostenol↗

Specific changes in the in vitro production of prostanoids by the ovine cervix at parturition.

A method of tissue superfusion has been used to measure in vitro prostanoid production by the ovine cervix during late pregnancy and at parturition. In late pregnancy (105-135 days of gestation) cervical tissue produced relatively large amounts of prostaglandin E (PGE); in comparison, the production rates of prostaglandin F (PGF), 13, 14-dihydro-15-oxo-prostaglandin F (PGFM) and 6-oxo-prostaglandin F1 alpha were generally low. Thromboxane B2 (TXB2) production was minimal and often unmeasurable. There were significant increases in the production rates of PGE and 6-oxo-PGF1 alpha by cervical tissue taken immediately after delivery, when compared to late pregnancy. Mean production rates of PGE increased from 19.8 +/- 4.1 to 43.8 +/- 7.4 ng/g. dry wt./min; 6-oxo-PGF1 alpha production rates increased more than three-fold from 10.0 +/- 2.7 to 34.6 +/- 9.8 ng/g. dry wt./min (means +/- S.E.M.). There were no significant differences in the rates of production of PGF, PGFM and TXB2 by the two groups.

Animals↗

Estradiol-17 beta and 2-hydroxyestradiol-17 beta-induced differential production of prostaglandins by cells dispersed from human intrauterine tissues at parturition.

Prostaglandin (PGE, 6-keto PGF1 alpha) output by cells dispersed from human amnion and decidua in the presence of increasing levels (0-5000 ng/ml) of estradiol-17 beta (E2) or 2-hydroxyestradiol-17 beta (2-OH E2) was studied in relation to parturition. Tissues were obtained from women at term either before (CS) or after (SL) spontaneous labor and vaginal delivery. In the absence of estrogens, the output of both PGs from amnion increased significantly with labor. No significant increase in decidua PG output occurred with labor. Neither estrogen influenced CS amnion PG output. However, both E2 and 2-OH E2 stimulated SL amnion PGE output (2-OH E2 greater than E2) while having no affect on 6-keto PGF1 alpha output. Only the highest dose of 2-OH E2 stimulated PGE output in CS decidua, but both estrogens significantly inhibited 6-keto PGF1 alpha output in this tissue. In SL decidua only 2-OH E2 significantly stimulated PGE, and neither estrogen affected 6-keto PGF1 alpha output. These results might suggest that estrogens modulate PG biosynthesis at the level of endoperoxide to primary PG conversion.

6-Ketoprostaglandin F1 alpha↗

Identification and changes in concentrations of prostaglandin H synthase (PGHS) isoforms in rat myometrium at parturition.

The isoform(s) of prostaglandin H synthase (PGHS) present in pregnant rat myometrium have been identified and the ontogeny of their expression studied during late gestation and parturition. Concentrations of PGHS have been related to changes in concentration of nuclear and cytosolic estrogen (ER) and progesterone receptors (PR) occurring at this time. Nuclear PR concentrations were maximal on days 16-18 of pregnancy, decreased from days 18 to 22 (delivery) and fell 24 hours postpartum. Nuclear ER concentrations increased significantly from days 20 to 22 of pregnancy and fell postpartum. Whereas the ratio of nuclear ER/PR was firmly in favour of progesterone action on days 16-20 it increased on day 22 corresponding to increased estrogen action. Western immunoblotting with specific antibodies revealed a single 72 kDa PGHS-1 isoform in myometrium at each timepoint. There was no evidence for the inducible PGHS-2 isoform in myometrium. Densitometric analysis showed the concentration of PGHS-1 increased significantly from day 16 to a maximum at the time of delivery on day 22 and decreased immediately afterwards. Expression of the constitutive PGHS-1 isoform is associated with the changing ratio of nuclear ER/PR and may therefore be hormonally regulated.

Animals↗

Signal for term parturition is of trophoblast and therefore of fetal origin.

Up to now we know, that cytokines are key intermediates in the mechanisms, responsible for intrauterine activation in case of intra amniotic infection. The aim of our study was to investigate the role of cytokine- and prostaglandin production in normal term labor. Release of Il-6, Il-1 beta, TNF-alpha, PGE2, PGF2 alpha, was monitored in vaginal secretions originating from uterine cavity, cervix and vagina during normal course of labor. Cells from fetal membranes, decidua and villous trophoblast, obtained from placentas of patients after spontaneous delivery (n = 12), or without labor, after elective cesarean section (n = 12), were cultured, in order to identify cytokine and prostaglandin producing cells. In all cases, term labor and parturition was associated with strongly elevated cytokine- and prostaglandin concentrations in cervical secretions. Cell culture experiments clearly demonstrated, that cells from villous trophoblast, cultured after spontaneous delivery produced significantly more cytokines and prostaglandins than cells form villous trophoblast, cultured after elective cesarean section. Cells from fetal membranes also produced more Il-6 and PGE2 after labor. In contrast to that, cells from decidua produced similar amounts of cytokines and prostaglandins before and after spontaneous term labor. Therefore we conclude, that the signal for term labor and delivery is of trophoblast and so of fetal origin.

Amniotic Fluid↗

The use of dimenhydrinate in conjunction with dexamethasone for induction of parturition in beef cattle.

Forty-eight crossbred Chianina cows (3 to 5 years of age), with an expected gestation length of 288 days, were randomly divided into four treatment groups to evaluate the use of dimenhydrinate (an antihistamine agent) in conjunction with dexamethasone (DEX) for inducing parturition in beef cattle. Group (A) received a 20 mg dose of DEX (im) on day 282 of gestation and a carrier vehicle (iv) 24 hours later (day 283); Group (B) was given a carrier vehicle (im) on day 282 and 500 mg of dimenhy-drinate (DMH) diluted in 200 ml of 2.5% dextrose-0.9% saline solution given (iv) on day 283 and Group (C) received 20 mg of DEX (im) on day 282 and 500 mg of DMH in solution (iv) on day 283 of gestation. The remaining 12 cows assigned to Group (D) were not handled and were allowed to calve under natural conditions. The number of cows calving and percent calving within 60 hours after the first injection were: 10(91%), none(0%) and 12(100%) for the DEX, DMH and DEX plus DMH groups, respectively. The mean gestation length of the control cows in Group (D) was 288.6 days. Frequency of dystocia was: 18.2, 8.3, 0 and 0% and retained placentae (>/=24 hours) was: 72.8, 16.6, 33.3 and 0% for DEX, DMH, DEX plus DMH and control groups, respectively. In this study, a 20 mg dose of DEX (im) followed 24 hours later with 500 mg of DMH (iv) was more successful for calving induction than when DEX or DMH was used alone. The combination DEX and DMH treatment induced calving in a shorter interval from treatment (P<.05) and decreased the incidence of retained placentae (P<.01) when compared with those induced following DEX treatment.

Journal Article↗