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Maternal and fetal plasma oxytocin levels during pregnancy and parturition in the sheep.

To assess fetal oxytocin release in relation to maternal oxytocin, serial paired maternal (femoral artery) and fetal (aorta) plasma oxytocin were determined by a specific and sensitive radioimmunoassay during pregnancy and parturition in the sheep. The maternal oxytocin level was 29.1 +/- 2.6 pg/ml (mean +/- SE) but was significantly lower than fetal oxytocin levels of 45.8 +/- 4.3 pg/ml (p less than 0.001). There was a significant correlation between paired maternal oxytocin and fetal oxytocin levels throughout late pregnancy (r = 0.2523, p less than 0.05). Maternal oxytocin levels calculated for every 5 days' gestation ranged from 15.8 +/- 2.7 to 32.7 +/- 5.6 pg/ml while the corresponding fetal oxytocin levels (21.6 +/- 3.5 to 62.5 +/- 21.6 pg/ml) were always higher (92 to 135 days) but not significantly different. However, at 136 to 142 days' gestation, fetal oxytocin levels (63.9 +/- 14.1 pg/ml) were significantly higher than maternal oxytocin levels (20.1 +/- 3.3 pg/ml) (p less than 0.01). Based on observations in two animals, fetal oxytocin levels appeared higher than maternal oxytocin levels at parturition with an increase a few days before labor. Our findings indicate that, in the sheep, fetal oxytocin levels were usually higher than but not significantly different from maternal oxytocin levels and that fetal oxytocin levels changed in relation to labor, suggestive of fetal release of oxytocin.

Animals↗

Enzymatic screening of human uterine cervical biopsies in nonpregnant and pregnant women at parturition.

Twelve enzymatic activities, involved in the metabolism of proteins, collagen, glycosaminoglycans, or in the energy metabolism, were studied in 72 cervical biopsies obtained after delivery of the placenta and in 12 cervices obtained by hysterectomy in nonpregnant patients. Although these activities display high interindividual variations, they are greatly and significantly increased at parturition as compared to the nonpregnant state, with the exception of creatine kinase, which is maximum in cervices obtained from nulliparous nonpregnant women. The activities are low in the group of women who are 35 to 40 years old. The other studied factors (blood group, parity, pregnancy duration, labor length, treatment, state of the cervix at the 9-month examination) have no clear influence on the enzymatic levels. The results are discussed in relation to the well-known structural changes of the cervix at parturition.

Adult↗

Changes in active and latent collagenase in human placenta around the time of parturition.

High levels of collagenase are present in cervical extracts and in the circulation in women at parturition. This study examines the content of collagenase in human placentas at term, the possible contribution to circulating enzyme, and the changes that occur at parturition. Active and latent forms of collagenase are detectable in placentas with apparent relative molecular mass of 60,000 and 65,000 d, respectively. Gel-filtration chromatography was used to identify the presence of excess tissue inhibitor of metalloproteinase as the major collagenase inhibitor in the extracellular matrix of human placentas. After the onset of labor, there was a significant increase in total collagenase activity. Inactivation of the tissue inhibitor of metalloproteinase by reduction of placental extracts with dithiothreitol and alkylation with iodoacetamide resulted in a twelvefold to seventeenfold increase in collagenase activity. Umbilical cord collagenase levels were significantly lower than those in maternal circulation. The possibility of circulating collagenase originating from placenta in labor is discussed.

Chromatography, Gel↗

Systemic administration of interleukin-1 induces preterm parturition in mice.

Interleukin-1 has been postulated as a signal for the initiation of preterm labor and delivery. Interleukin-1 is produced by human decidua, stimulates prostaglandin production by intrauterine tissues, and is present in the amniotic fluid of women with preterm labor and intraamniotic infection. The purpose of these studies was to determine whether interleukin-1 could induce parturition in an animal species. Timed-pregnant C3H/HeJ inbred mice (n = 24) (genetically endotoxin resistant) were randomized to receive either recombinant human interleukin-1 or sterile phosphate-buffered saline solution between days 15 and 17 of gestation (normal length of pregnancy, 20 to 21 days). Three consecutive subcutaneous injections of interleukin-1 or phosphate-buffered saline solution were administered within 6 hours. Examinations of the animals were performed by blinded observers. Parturition occurred within 24 hours in all of the interleukin-1-treated mice and in none of the control group. Vaginal bleeding was first noted 4 hours after the first interleukin-1 injection, and delivery began within 12 hours after the last interleukin-1 injection. Premature delivery occurred in all interleukin-1-injected mice. Laparotomy revealed that there were no remaining fetuses in utero. All mice in the control group delivered spontaneously between days 20 and 22. We conclude that systemic administration of interleukin-1 induces preterm labor and delivery in mice.

Animals↗

Parturitional factors associated with membrane stripping.

OBJECTIVE: Our purpose was to determine what factors occurring after digital separation of the chorionic membranes from the lower uterine segment (membrane stripping) are involved in observed clinical changes compared with patients not so treated. STUDY DESIGN: Thirty patients were randomly divided among a study population and two control groups to assess uterine contractions and microbiologic, histologic, and biochemical markers associated with parturitional events over a 7-hour time frame. RESULTS: Clinically, an increased frequency of uterine contractile activity was observed among patients in the membrane-stripped group (p < 0.03). There was a significant increase in plasma 13,14-dihydro-15-keto-prostaglandin F2 alpha (p < 0.001) and endocervical phospholipase A2 activity (p < 0.04) among those who underwent membrane stripping. Blood leukocyte counts, sedimentation rates, prostaglandin E2 metabolite concentrations, and fibronectin levels revealed no significant change during the 7-hour study session. CONCLUSION: Membrane stripping was associated with increases in phospholipase A2 activity and prostaglandin F2 alpha concentrations, indicating a possible correlation with initiation of the cascade of parturitional events.

Amnion↗

Analgesia is produced by uterocervical mechanostimulation in rats: roles of afferent nerves and implications for analgesia of pregnancy and parturition.

Afferent activity from the reproductive tract activates intrinsic pain attenuating processes. For example, analgesia results from vaginocervical mechano-stimulation in nonpregnant rats and occurs during pregnancy and parturition. In the present study, the effect of uterocervical mechanostimulation on pain thresholds was investigated in order to determine whether direct stimulation of the uterine cervix could play a role in the analgesia of pregnancy. Uterocervical mechanostimulation was applied to nonpregnant rats via a silastic disc implanted in the uterus. The disc abutted against the cervix and was attached to a thread externalized through the vaginal orifice. Application of a force of 150 g, but not 100 g, produced a significant increase in tail flick latency (110.4 +/- 40.6%, P less than 0.03). This effect was abolished by pelvic neurectomy, but was not altered by hypogastric neurectomy. Stimulation of the uterine cervix in combined pelvic and hypogastric neurectomy rats produced a decrease in tail flick latency. These results indicate that the analgesia that occurs during pregnancy and/or parturition may result, at least in part, from the uterocervical mechanostimulation that occurs during this condition.

Afferent Pathways↗

Steroid hormone profile during gestation and parturition of the guppy (Poecilia reticulata).

The guppy is an ovoviviparous teleost with fertilization and gestation occurring intrafollicularly, and ovulation and hatching at around parturition. The levels of estradiol-17 beta (E), testosterone (T), cortisol (F), 17 alpha-hydroxyprogesterone (17-OHP), 17 alpha-20 beta-dihydroxy-4-pregnen-3-one (17,20 beta-P), and progesterone (P) in the guppy at different stages of gestation were measured in 60 microliters of serum with a highly specific, sensitive, precise, and accurate procedure involving high-performance liquid chromatography and radioimmunoassay. Levels of E and T increased during vitellogenic growth of oocytes and declined sharply after fertilization, increasing again gradually during late gestation to reach prefertilization levels at periparturition. F levels decreased significantly during fertilization followed by an increase during gestation and a sharp decline again at periparturition. The level of 17-OHP was significantly lower at periparturition than at other stages, while that of 17,20 beta-P was significantly higher in periparturition than in late gestation. There was no significant change in the levels of P at all stages of gestation, suggesting that, unlike mammals, P may not be involved in maintaining gestation in this fish. Changes in the levels of E and T seem to be related to oocyte growth rather than gestation. The role of F in gestation is uncertain since the effect of stress could not be discounted or defined in this study. Thus, on the present results, the role of any particular steroid in maintaining gestation of the guppy is not obvious. The elevated levels of E at term may facilitate parturition in addition to its role in vitellogenesis during oocyte growth.

Animals↗

Exogenous progesterone or indomethacin delays parturition in the viviparous lizard Sceloporus jarrovi.

Female Sceloporous jarrovi in late pregnancy given an ip injection of progesterone (50 ng/g body wt) or indomethacin (4 micrograms/g body wt) exhibited no change in the length of pregnancy when compared to saline-treated controls. In contrast, pregnant females given subcutaneous implants (constant release pellets) containing progesterone or indomethacin exhibited significantly delayed parturition when compared with females given control implants. Indomethacin treatment also disrupted the normal birth process when it occurred, as all females receiving this compound exhibited parturition of only a portion (24-32%) of the total clutch. A similar phenomenon occurred in one experiment following implantation of progesterone pellets. Histological examination of the corpora lutea and oviduct indicated no obvious difference in structure among any of the treatment groups.

Animals↗

Primate parturition and the role of the maternal circadian system.

Several 24-h rhythms have been observed in the mother and in the fetus during primate gestation. In the mother, 24-h rhythms occur in biophysical variables, pregnancy-associated plasma hormones and preparturient myometrial activity. In addition, both pregnant non-human primates and pregnant women deliver preferentially during the night and early morning hours. A crucial question pertaining circadian rhythms is whether 24-h rhythms that may be observed during pregnancy are endogenous in nature and entrained by the light-dark cycle or whether the daily photoperiod is a causal stimulus. Our work has addressed the role of the maternal and fetal circadian system for 24-h rhythms in pregnancy-associated maternal plasma hormones, preparturient myometrial activity and parturition in human and non-human primate pregnancy. In the present review, the results of some of our studies are being discussed in combination with data available from the literature. It is apparent that 24-h rhythms that may be observed during primate pregnancy are determined by the maternal circadian system, suggesting that the developing fetus receives information about the ambient time of the day via the mother. Fetal entrainment by the mother may ensure fetal cooperation so that parturition occurs at the most favorable time of the day. We conclude that the functioning of the maternal circadian system is integral to the pregnant state. Thus, proper care and management of pregnant women and the ultimate outcome of obstetrics may benefit from more timely methodologies. A chronopharmacological attitude towards the prevention of premature labor and the induction and augmentation of labor at term may yield new therapeutic strategies. Such an approach will enable delivery to take place under optimal conditions for mother and child.

Animals↗

Serum collagenase levels during pregnancy and parturition.

Recent studies have described the origin of the collagenase responsible for the degradation and loss of collagen during cervical ripening and dilatation to be polymorphonuclear leukocytes. In the present study the clinical feature of cervical dilatation was correlated to the serum levels of human granulocyte collagenase. The serum collagenase level was measured in 19 premenopausal women and in 181 pregnant women. In 15 of these pregnant women serum samples were obtained from the onset of labour to the active phase of labour at four different times. The collagenase concentrations remained low up to the 35th week of gestation (19.4 ng/ml) in comparison with the beginning of pregnancy. From the 35th week of gestation on we found a slight increase in collagenase in maternal serum. The maximum peak was reached during parturition at a cervical dilatation of 6-8 cm (71.2 ng/ml). The serum levels returned to non-pregnant values the first day following delivery. The results show that collagenases are critically involved in parturition.

Collagenases↗

Timing of parturition and postpartum mating in Norway rats: interaction of an interval timer and a circadian gate.

Two temporal variables have been implicated in the timing of postpartum heat in Norway rats: time of day and time since parturition. The nature of the interaction between these variables is not clearly understood. We extend previous observations on this problem to freely behaving animals continuously videotaped during parturition and postpartum mating in a seminatural habitat. The timing of postpartum mating is best described by a model in which an interval timer is coupled to a circadian gating mechanism. Interactions between circadian and interval timing mechanisms may be widespread in the neuroendocrine control of behavior.

Animals↗

Trigeminal lesions and maternal behavior in Norway rats: II. Disruption of parturition.

Profound deficits in maternal behavior occur following postpartum bilateral infraorbital denervation (IO-X), with substantial recovery 12-24 h later. In the present experiment, primiparous rats were subjected to IO-X or sham surgery on gestation day 22. Whereas parturition behavior was normal in controls, it was severely disrupted in all IO-X dams. Impairments included absent, abbreviated, or delayed perioral behaviors-nest building, participation in delivery, placentophagia, licking and retrieval of pups-accompanied by increased general activity and delayed onset of nursing. There was increased mortality in the litters of IO-X dams at birth and by postpartum day (PD) 3, and impaired retrieval by IO-X dams on PD1-3. A surgery-birth interval of < 7 h vs. > or = 22 h was associated only with poor litter growth. Thus, prepartum IO-X disrupts onset of maternal behavior during parturition, with long-term consequences for offspring well-being.

Animals↗

Effects of reducing dietary ([Na+ + K+]-[Cl- + SO4 =]) on bone in 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 bone morphology at parturition were studied. Nine monozygotic twin pairs of pregnant cows (five pairs of parity 1 or 2 and four 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. Bone biopsies were taken from the tuber coxae between three and eight hours after parturition. The plasma concentrations of calcium and inorganic phosphorus, the total plasma alkaline phosphatase activity and the urinary hydroxyproline:creatinine ratio were not significantly affected by diet during the experimental period. In low parity (2 or less) cows the percentage trabecular bone volume, the percentage osteoclast surface and the mean number of osteoclasts per microscopic field (identified by Goldner staining) were lower on the anion diet than on the cation diet (P < 0.02). In the high parity cows, the percentage osteoid volume (P < 0.05) and the ratio of percentage osteoid volume to percentage osteoid surface (P < 0.001) were greater in the cows fed the anion diet than in the cows fed the cation diet. The results show that reducing the mEq of dietary ([Na+ + K+]-[Cl- + SO4 =]) to -4 mEq kg-1 dietary dry matter affected some of the parameters of bone formation but did not enhance bone resorption.

Alkaline Phosphatase↗

Human plasma prekallikrein and high molecular weight kininogen decrease during parturition.

Prekallikrein and high molecular weight kininogen were measured in plasma taken from nine women during parturition. Prekallikrein decreased significantly (p less than 0.01) from 1.49 +/- 0.15 S-2302 U/ml (mean +/- SEM) in early labor to 1.26 +/- 0.13 S-2302 U/ml in the immediate postpartum period. Immunoreactive high molecular weight kininogen also significantly decreased from 76 +/- 5 micrograms/ml to 68 +/- 5 micrograms/ml one day postpartum (p less than 0.01). Both proteins rose to normal levels within two days. The data suggest that the kallikrein-kinin system is utilized during parturition.

Adult↗

The control of myometrial functions during parturition with Abeta(2) - mimeticcompound, Planipart(R).

A betamimetic and tocolytic compound (Planipart(R) = 4-amino-alpha-[(tert.-butyl-amino)-methyl] 3-5-dichlor-benzylalcohol-hydrochloride; Boehringer Ingelheim, Vetmedica GmbH) was used to effectively interrupt or postpone parturition in 39 cows and heifers, 13 pigs and three sheep. Its fast action, long duration, and freedom of clinical side effects were confirmed in clinical and tocographical in-vivo studies. Parturition was interrupted during stage I and early stage II of labor. With declining effects of Planipart(R), oxytocin can initiate renewed labor. Oxytocin is ineffective if the myometrium is under full control of Planipart, while Planipart(R) is ineffective when oxytocin (endogenous or exogenous) exerts its control on the myometrium. Deliveries after postponement or interruption seem subjectively to proceed faster and easier. No deleterious effects on mother or offsprings were observed in the postpartum phase or during lactation. Planipart may be used effectively in obstetrics and for biotechnical purposes.

Journal Article↗

Synchronization of parturition in beef cattle using delay as well as induction.

Two methods for synchronization of parturition in beef cattle were examined. In the first experiment, four groups of cows and heifers were used: untreated (C, n=9), 10 mg flumethasone on day 281 of gestation (F, n=9), 100 mg progesterone daily from days 276 through 283 and 50 mg progesterone on day 284 (P, n=6), and (P+F on day 284, n=7). Variances in gestation lengths (C, 26.01; F, 0.77; P, 11.97; P+F, 1.93) and proportions of cows and heifers with retained placentas (C, 0/9; F, 4/9; P, 1/6; P+E, 0/7) differed significantly among groups. Differences among groups in calving difficulty scores and proportions of dead calves were not significant. Four of the thirteen cows and heifers treated with progesterone required assistance in calving and all four delivered dead calves. Pulling of these calves was not accompanied by uterine contractions. Conversely, the difficult calvings in the control- and flumethasone-treated cows and heifers were accompanied by uterine contractions. In the second experiment, two groups of cows were used: 1) a single injection of 20 mg dexamethasone on either day 276, 277 or 278 followed by injections of saline every 12 h for 2.5 additional days (n=6), and 2) repeated injections of 20 mg dexamethasone every 12 h for 3 days beginning on day 276, 277 or 278 (n=8). The interval from time of first treatment to calving was not different between groups (43.6 and 43.0 h, respectively). Differences between calving difficulty scores, proportions of dead calves and incidence of retained placentas were not significant. Induction very close to the expected calving date could reduce the problems of retained placenta; however, methods must be identified to safely delay parturition.

Journal Article↗

The effect of experimentally induced hypocalcaemia on uterine activity at parturition in the ewe.

The effect of hypocalcaemia experimentally induced by the intravenous infusion of ethylene-diamine tetraacetic acid, disodium salt (Na(2)EDTA) upon myometrial activity at parturition was studied in eleven ewes. Infusions of Na(2)EDTA were performed during first stage of labour (three animals), second stage (four animals), third stage (three animals) and postpartum (two animals); one in the latter group had been previously treated during second and third stages. Uterine activity was recorded using balloon-tipped catheters surgically implanted into the uterus and was expressed in Montevideo Units (M.U.). Plasma calcium (nonchelated) concentrations were monitored throughout the infusion. Induced hypocalcaemia resulted in a reduction of the activity of the uterus when Na(2)EDTA was administered during the first stage of labour. In the ewes infused during the second stage of labour, there was difficulty in reducing the activity of the uterus and, consequently, in delaying parturition. Reduction in uterine activity was easier in the ewes infused during the third stage of labour and during postpartum. Uterine activity started decreasing when plasma calcium concentrations were 6.6 and 7.1 mg/100 ml in the ewes infused during third stage of labour and postpartum, respectively, compared with 4.9 mg/100 ml in those infused during first stage of labour; the difference between this last group and the first two was significant (p < 0.05). After the end of the infusion, the plasma calcium started rising and normal uterine activity quickly resumed.

Journal Article↗

Hourly distribution of time of parturition in the domestic goat.

Data on 2589 records collected during 12 years in one breed of dairy goats that were maintained in stables were analysed to examine the influence of various factors on the time of parturition. Parturitions were observed from mid-January to the end of April. Hourly frequencies of birth showed an unimodal distribution with maximum births at midday and minimum births around midnight with 90.6% of deliveries occurring between 0600 and 2000 h. The distribution showed a noticeable homogeneity when the following parameters were taken into account: litter-size, litters with live or stillborn kids, time of the year and length of gestation. In two other herds, 117 and 166 records obtained after 4 and 3 years of observation were studied. As in the first herd, births were more frequent between 0700 to 1900 h (day; 72.3 and 70.2 %, respectively) than between 1900 and 0700 h (night; P<0.001). These observations on the time of birth of the domestic goat suggest a regulation of the birth process by circadian events which themselves remain unknown.

Journal Article↗