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Is oxytocin involved in parturition?

Peripheral plasma levels of oxytocin were determined in women during pregnancy and labour. There was a significant increase in maternal plasma oxytocin with advancing gestation but no significant change in levels at any stage of labour. Oxytocin concentrations in umbilical cord plasma were measured after spontaneous vaginal delivery and at elective caesarean section. A significant arteriovenous difference, with higher arterial levels, was found in both groups and the values after labour were significantly higher tha at elective caesarean section. These findings suggest that the fetus is able to produce oxytocin which may play a role in human parturition.

Female↗

Maternal serum total activin A and follistatin in pregnancy and parturition.

OBJECTIVE: To examine changes in maternal serum levels of activin A and follistatin during pregnancy and labour. DESIGN: In three cross sectional and three longitudinal studies venous blood was collected from women during pregnancy, spontaneous labour, labour induction and prior to elective caesarean section for the measurement of activin A and follistatin. SETTING: Monash Medical Centre, Clayton, Victoria, Australia. POPULATION: One hundred and twenty-three women participated in a cross sectional study in pregnancy, 18 women in two longitudinal pregnancy studies, 36 women in a cross sectional labour study, nine women in a longitudinal study of labour induction. Ten women undergoing elective caesarean section were also studied. METHODS: Activin A and follistatin were measured using two sensitive and specific enzyme-linked immunosorbent assays. RESULTS: In the cross sectional study of pregnancy, mean (SEM) maternal serum activin A and follistatin levels increased towards term (2.4 ng/mL (0.3) and 1.8 ng/mL (0.3) in first trimester to 18.9 ng/mL (3.8) and 5.3 ng/mL (0.9) at term, respectively), but the longitudinal study revealed that levels plateau in the last three weeks of pregnancy (16.0 ng/mL (2.6) and 6.2 ng/mL (1.4) at 37 weeks and 16.6 ng/mL (3.5) and 6.2 ng/mL (0.5) before labour for activin A and follistatin, respectively). There was no difference in levels of activin A and follistatin between women delivered by caesarean section and labouring women at term (14.9 ng/mL (2.8) vs 11.0 ng/mL (0.93) and 5.95 ng/mL (0.67) vs 5.71 ng/mL (0.63), respectively) and levels of both proteins did not alter throughout spontaneous or induced labour. CONCLUSIONS: We believe that these data argue against activin A playing an acute role in the initiation or regulation of human parturition.

Activins↗

Another look at initiation of human parturition.

Despite our moderate understanding of the physiology of the initiation of labour in various animal species, notably ruminants and rodents, the mechanism in man remains enigmatic. In the initiation process in the human the major role is apparently taken by the placental and fetal membranes, while the fetus may modulate the timing of labour. This review sets out to examine current knowledge of the process of initiating and maintaining parturition in the human.

Adrenal Cortex Hormones↗

Plasma levels of immunoreactive melatonin, estradiol, progesterone, follicle stimulating hormone, and beta-human chorionic gonadotropin during pregnancy and shortly after parturition in humans.

Plasma concentrations of immunoreactive melatonin, estradiol, progesterone, follicle stimulating hormone (FSH), and beta-human chorionic gonadotropin (beta hCG) were studied between 1000 and 1230 h in 105 Chinese females during six periods of normal pregnancy and 1-5 min after normal delivery. We have also examined the midday levels of immunoreactive melatonin in the cord blood of fetuses and plasma collected 1-5 min after and 24 h after delivery from their mothers. Concentrations of hormone immunoreactivities were determined by radioimmunoassay, and distinct fluctuations of all hormones were recorded during pregnancy. In the pregnant females, there were significant negative correlations between melatonin and estradiol, melatonin and progesterone, beta hCG and progesterone, and beta hCG and estradiol, and positive correlations between melatonin and FSH and progesterone and estradiol. Furthermore, plasma melatonin levels in the cord blood demonstrated no sex difference and were significantly lower than and correlated positively with the levels in their mothers. Our results suggest that sex steroids may inhibit and FSH may potentiate circulating melatonin levels in gravid women; changes in the levels of melatonin during pregnancy may affect the in utero development of the human embryo; and circulating melatonin in the mother may be the major source of blood melatonin in the fetus before parturition.

Chorionic Gonadotropin↗

Maternal and fetal circulating levels of thymosin alpha 1 during parturition.

The thymus directs T-lymphocyte development and contributes to the maintenance of immune homeostasis, in part, through its production of peptides known as thymosins. In pregnancy, maternal serum levels of thymosin alpha 1 have been reported to be low at midgestation and to increase by term, suggesting that maternal levels represent fetal levels. To evaluate this further, we obtained maternal venous and newborn mixed cord blood from 90 pregnancies between 20 and 42 weeks of gestation at delivery. An ELISA was used for thymosin alpha 1 assay, and analysis was by paired t test and regression. Maternal and newborn levels were independent of gestational age, but an apparent association (r = 0.51) between the two was inconclusive. Maternal levels (1,207 +/- 947 pg/ml) tended to be higher than those of healthy adults (1,043 +/- 576 pg/ml). Mixed umbilical cord serum levels (1,466 +/- 940 pg/ml) were higher than maternal levels (P less than or equal to 0.005). Although maternal thymosin alpha 1 levels may reflect fetal levels, immunological perturbations related to parturition appear to influence both.

Adolescent↗

Interleukin-1 alpha and interleukin-1 beta in preterm and term human parturition.

Interleukin-1 (IL-1) has been implicated in the mechanism of human parturition in the setting of infection. The purpose of this study was to determine the effect of labor (term and preterm) and microbial invasion of the amniotic cavity on amniotic fluid (AF) concentrations IL-1 alpha and IL-1 beta. AF was retrieved by transabdominal amniocentesis from the following groups of women: midtrimester genetic amniocentesis (16 to 18 wk) (N = 15), preterm labor with intact membranes (21 to 36 wk) with or without infection (N = 72), preterm premature rupture of membranes (PROM) (N = 88), and term not in labor or in active labor with or without infection (N = 58). AF was cultured for aerobic and anaerobic bacteria as well as Mycoplasmas. IL-1 was measured with a commercially available immunoassay validated for AF (sensitivity: IL-1 alpha, 157 pg/ml; IL-1 beta, 50 pg/ml). All women at midtrimester had undetectable AF IL-1 alpha and IL-1 beta. Among women in preterm labor with positive AF cultures, IL-1 alpha and IL-1 beta were detectable in the AF in 86.6% (13/15) and 100% (15/15), respectively. In contrast, all women with negative AF cultures without labor (N = 36) had undetectable AF IL-1 alpha concentrations and 52.7% (19/36) had undetectable AF IL-1 beta concentrations. Histopathological chorioamnionitis was present in 92.8% (13/14) of patients who had positive AF cultures and detectable IL-1 in the AF. IL-1 was significantly higher in patients with preterm PROM, labor, and positive AF cultures than in the other subgroups of patients with preterm PROM.(ABSTRACT TRUNCATED AT 250 WORDS)

Amniotic Fluid↗

Macrophage inflammatory protein-1 alpha in term and preterm parturition: effect of microbial invasion of the amniotic cavity.

PROBLEM: This study was conducted to determine whether: (1) gestational age, parturition, and microbial invasion of the amniotic cavity (MIAC) are associated with changes in amniotic fluid concentrations of immunoreactive macrophage inflammatory protein-1 alpha; (2) amniotic fluid concentrations of macrophage inflammatory protein-1 alpha are correlated with the white blood cell count and the concentrations of interleukin-8 in amniotic fluid. METHOD: Amniotic fluid was retrieved by amniocentesis from 126 patients; 54 women with preterm labor and intact membranes (no MIAC-delivery at term, N = 21; no MIAC-preterm delivery, N = 16; MIAC-preterm delivery, N = 17); 62 patients at term (no labor, N = 19; labor-no MIAC, N = 20; labor-MIAC, N = 23); and 10 patients in the midtrimester of pregnancy. Amniotic fluid was cultured for aerobic, anaerobic and Mycoplasma species. Determinations of amniotic fluid macrophage inflammatory protein-1 alpha and interleukin-8 were performed with immunoassays validated for amniotic fluid (sensitivity: 14.2 pg/ml and 0.3 ng/ml, respectively). Kruskal-Wallis analysis of variance (ANOVA) for censored data, Mann-Whitney U test and Spearman's rank correlation were performed for analysis. RESULTS: 1) Amniotic fluid macrophage inflammatory protein-1 alpha was present in only 31.0% (9/29) of patients not in labor (midtrimester and term). 2) Patients with preterm labor and MIAC had higher amniotic fluid concentrations of macrophage inflammatory protein-1 alpha than those without MIAC (no MIAC-delivery at term: median 0.0 pg/ml, range 0.0-221.2; no MIAC-preterm delivery: median 37.4 pg/ml, range 0.0-494.6; MIAC-preterm delivery: median 7171.0 pg/ml, range 402.5-37994.0; P < 0.00001). 3) Among patients at term, MIAC was associated with higher concentrations of amniotic fluid macrophage inflammatory protein-1 alpha than patients without MIAC (no labor: median 0.0 pg/ml, range 0.0-25.6; labor-no MIAC: median 16.7 pg/ml, range 0.0-161.6; labor-MIAC: median 103.8 pg/ml, range 0.0-4349.0, P < 0.001). 4) Among patients in preterm labor, a strong correlation was found between amniotic fluid concentrations of macrophage inflammatory protein-1 alpha and interleukin-8 (r = 0.9, P < 0.00001) and between amniotic fluid macrophage inflammatory protein-1 alpha concentrations and amniotic fluid white blood cell count (r = 0.6, P < 0.0001). CONCLUSIONS: (1) Macrophage inflammatory protein-1 alpha is undetectable in most amniotic fluid samples from patients in the midtrimester of pregnancy and at term not in labor. (2) Microbial invasion of the amniotic cavity is associated with increased concentrations of immunoreactive amniotic fluid macrophage inflammatory protein-1 alpha in both term and preterm gestations. (3) Amniotic fluid macrophage inflammatory protein-1 alpha concentrations significantly correlate with interleukin-8 levels and white blood cell count in amniotic fluid. Our data strongly suggest a role for macrophage inflammatory protein-1 alpha in the mechanisms responsible for the recruitment of leukocytes into the amniotic cavity during the course of intrauterine infection.

Amnion↗

Changes in human and rat uterine phosphoethanolamine and taurine with pregnancy and parturition.

Phosphoethanolamine and taurine have been identified in uterine extracts from rat and, for the first time, human tissue. The concentration of phosphoethanolamine [PEtn] determined by HPLC and 31P NMR spectroscopy, increased markedly (40%) within the first 6-12 h following parturition in rats, suggesting a role in involution. It appears that changes in [PEtn] account for the changes in the NMR phosphomonoester peak previously reported. A significant fall in [PEtn] was found in the human myometrium with pregnancy. Taurine was found in high concentrations in the rat and human uterus but decreased with pregnancy. The possible functional significance of these changes is discussed.

Adult↗

Independent release of oxytocin and vasopressin during parturition in the rabbit.

1. Oxytocin and vasopressin were assayed in samples of blood collected from seven conscious rabbits during parturition.2. Oxytocin was detected in the blood in ten out of fourteen samples collected during the expulsion of one or more foetuses. Four samples contained 6-100 muu./ml., three 100-200 muu./ml. and three 200-500 muu./ml.3. Vasopressin was detected in six blood samples collected during the delivery of foetuses but in only one experiment did the amount exceed that found in the corresponding control sample collected before or after delivery.4. When both hormones were detected in the same blood sample, the ratio of oxytocin to vasopressin varied from 5:1 to at least 26:1.5. It is concluded that, while oxytocin may not be essential for parturition in the rabbit, stretching of the birth canal during the expulsion of foetuses normally acts as a stimulus for the reflex release of oxytocin from the neurohypophysis and that oxytocin is released independently of vasopressin.

Animals↗

Respiration and parturition affected by conditional overexpression of the Ca2+-activated K+ channel subunit, SK3.

In excitable cells, small-conductance Ca2+-activated potassium channels (SK channels) are responsible for the slow after-hyperpolarization that often follows an action potential. Three SK channel subunits have been molecularly characterized. The SK3 gene was targeted by homologous recombination for the insertion of a gene switch that permitted experimental regulation of SK3 expression while retaining normal SK3 promoter function. An absence of SK3 did not present overt phenotypic consequences. However, SK3 overexpression induced abnormal respiratory responses to hypoxia and compromised parturition. Both conditions were corrected by silencing the gene. The results implicate SK3 channels as potential therapeutic targets for disorders such as sleep apnea or sudden infant death syndrome and for regulating uterine contractions during labor.

5' Untranslated Regions↗

Oxytocin receptors and human parturition: a dual role for oxytocin in the initiation of labor.

The concentration of oxytocin receptors increased in the myometrium of pregnant women and reached maximum levels in early labor. Concentrations of oxytocin receptors were also high in the decidua and reached a maximum at parturition. In vitro, prostaglandin production by the decidua, but not by the myometrium, was increased by the addition of oxytocin. Oxytocin may therefore stimulate uterine contractions by acting both directly on the myometrium and indirectly on decidual prostaglandin production. Oxytocin receptors are probably crucial for the onset of human labor, and the stimulus for the increase in uterine prostaglandins may be oxytocin originating from the fetus.

Decidua↗

Stimulation of prostaglandin biosynthesis by urine of the human fetus may serve as a trigger for parturition.

Urine of the human fetus stimulated prostaglandin biosynthesis in vitro by increasing the conversion of arachidonic acid into prostaglandins. The stimulatory activity in urine from fetuses delivered at term after labor of spontaneous onset was greater than that in urine from fetuses delivered by cesarean section at term before the onset of labor. Such stimulation of prostaglandin biosynthesis by the fetal membranes, by way of a substance released into the urine and thence into amniotic fluid, could serve as a signal for the initiation of parturition.

Adult↗

Gap junctions: their presence and necessity in myometrium during parturition.

Thin sections of longitudinal and circular muscle of myometrium obtained from rats during pregnancy, at term, during delivery, and postpartum were quantitatively examined in the electron microscope. Gap junctions (low resistance pathways) were only present during or immediately prior to delivery and immediately postpartum. The absence of gap junctions during gestation may be necessary for maintenance of pregnancy, while their occurrence during parturition may lead to effective termination of pregnancy.

Animals↗

Ceftriaxone distribution between maternal blood and fetal blood and tissues at parturition and between blood and milk postpartum.

The penetration of ceftriaxone into the fetus at parturition was studied in 17 subjects. Despite its high protein binding, ceftriaxone quickly reached the umbilical cord blood, amniotic fluid, and placenta, achieving substantial concentrations, which then disappeared, with elimination half-lives of approximately 6 h, identical to that of the mother. The elimination half-life of ceftriaxone of 5 to 6 h in these mothers was somewhat shorter than that reported for normal subjects. The concentrations of ceftriaxone achieved in fetal tissues were sufficient for therapeutic effects. The penetration of ceftriaxone into milk was studied 3 days postpartum in 20 other patients. This antimicrobial agent entered breast milk rapidly and disappeared with a half-life of 12 to 17 h. The concentrations achieved were only 3 to 4% of those in maternal serum and were most likely of little clinical relevance.

Adult↗

Changes in breast sensitivity at puberty, during the menstrual cycle, and at parturition.

Sensitivity to pain and touch was measured in the nipple, areola, and cutaneous breast tissue of prepubertal boys and girls, postpubertal men and nuliparous women before and after delivery. Before puberty there were no differences between the sexes, but after puberty the tactile sensitivity of all areas of the women's breast was significantly greater than the men's. Tactil sensitivity of all areas also varied during the menstrual cycle, with maximal sensitivity at midcycle and at menstruation; the mid-cycle peak was absent when the women were taking oral contraceptives. But the most dramatic changes occured within 24 hours of parturition, when there was a great increase in breast sensitivity. This may be the key event for activating the suckling-induced discharge of oxytocin and prolactin and inhibiting ovulation during lactation.

Adult↗

Milk fever controls: comparison of 1-alpha and vitamin D3 in conjunction with induced parturition.

The efficacies of vitamin D3 and its 1-alpha hydroxyl derivative (1-alpha) in controlling clinical milk fever, hypocalcaemia and hypophosphataemia in parturient cows have been compared. A corticosteroid was used in some cases to optimise and control the interval between prophylactic treatment and parturition. Our observations suggest that the combination of 1-alpha and corticosteroid was particularly valuable and could be used in the development of a successful prophylactic regime. This conclusion is supported by both clinical and biochemical measurements.

Animals↗