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Effects of spinal blockade with bupivacaine on parturition in rats.

On the day of expected delivery, primigravid rats received 0.5% bupivacaine continuously through a chronically implanted intrathecal cannula to produce intense sensory and motor blockade below the T10 level. The mean duration of delivery was prolonged to 3.1 h compared with 1.4 h in a control group without intrathecal blockade and a group which received an intrathecal infusion of Hartmann's solution. The mean percentages of live births per litter surviving the first 6 h was 94% in the control groups and 42% in those receiving bupivacaine by intrathecal infusion. No increased perinatal mortality was observed in another control group receiving an i.p. infusion of 0.5% bupivacaine in the same dose as that given intrathecally. Two mother rats died during delivery under spinal blockade because of prolonged labour. It is concluded that, without obstetric intervention, intense sensory and motor blockade delayed parturition and increased fetal mortality in the pregnant rats.

Anesthesia, Spinal↗

The effects on offspring of premature parturition.

The time of parturition defines the length of the intrauterine period of fetal life, a requisite to achieve adequate adaptation to the external environment. Immaturity, a condition whose severity is inversely related to the length of pregnancy, is the main determinant of the increased morbidity and mortality associated with preterm birth. Despite great advances in medical technology and expertise, mainly after the introduction of the neonatal intensive care units, only one- to two-thirds of infants from the subsets with lower birthweight/gestational age reach survival at discharge. Distinct major neurological and sensorial sequelae, including cerebral palsy, retinopathy of prematurity, and hearing loss, as well as reduced neuropsychological abilities, leading to deficient academic achievement and deterioration of several aspects of health status, are still highly prevalent among the most immature children. Interestingly, decreasing mortality rates, which are not followed by detectable increases of disability, are being observed in recent years. Future advances may be expected from clinical and basic research on uterine contractility and cervical softening. Also, changes in reproductive technology procedures, a main factor in the incidence of multiple pregnancies, and a more refined approach to obstetric care, compose some of the clinical interventions which may reduce the problem.

Developed Countries↗

Changes in the expression of nitric oxide synthase in the human uterine cervix during pregnancy and parturition.

Nitric oxide (NO) has been proposed as a mediator of cervical ripening. We investigated the expression, using Western blotting, and localization, using immunohistochemistry, of the nitric oxide synthase (NOS) enzymes, inducible NOS (iNOS), endothelial NOS (eNOS) and neuronal NOS (bNOS) in the human cervix during pregnancy and parturition. Cervical biopsies were obtained from non-pregnant women, women in the first trimester of pregnancy, and pregnant women at term before and after the onset of labour. Each of the NOS isoforms was localized in the cervices of both non-pregnant and pregnant subjects using immunohistochemistry. iNOS expression was significantly greater in early pregnancy compared with the non-pregnant state (P: < 0.005). iNOS expression was up-regulated further in samples obtained in the third trimester compared with the first trimester. bNOS expression was greater in samples from the first trimester of pregnancy than in non-pregnant samples (P: < 0. 005), but showed no additional increase in late pregnancy or with the onset of labour. eNOS expression was increased in samples obtained in the third trimester both before (P: = 0.002) and after the onset of labour (P: < 0.002) when compared with non-pregnant samples. The increased expression of NOS isoforms in late pregnancy supports the hypothesis that NO is involved in the process of cervical ripening.

Blotting, Western↗

Lipoxygenase gene expression in baboon intrauterine tissues in late pregnancy and parturition.

Myometrium (upper and lower segment), cervix, chorion and decidua were obtained at the time of Caesarean hysterectomy in 15 baboons, 10 at varying gestational ages prior to the onset of labour in the last trimester of pregnancy, and five in spontaneous labour at term. Expression of currently recognized human lipoxygenase (LOX) genes was determined using Northern blot analysis relative to each of three housekeeping genes. Signals of similar size to human 5-LOX and human platelet 12-LOX genes were detected in all tissues. Expression of 5-LOX mRNA in the cervix decreased with advancing gestational age. In decidua, expression of 5-LOX mRNA was higher in tissues from animals in labour (compared to those not in labour), whereas in chorion, its expression was lower in tissues from animals in labour. Expression of the platelet 12-LOX gene decreased in chorion with advancing gestational age, and in cervix was lower in tissues from animals in labour. We postulate that the variation in expression of LOX genes may play a role in the onset or promotion of parturition in the baboon.

Animals↗

Studies on the endocrinology of parturition: relative steroidogenesis in coexisting genetically dissimilar ovine fetuses, concomitant with the temporal patterns of maternal C18 and C19 steroids and prostaglandin F2 alpha release.

Ovine embryos collected from two breeds of ewes possessing different gestational periods [Finnish Landrace (Finn), 145.5 +/- 1.4 days; Rambouillet (Ra), 150.7 +/- 1.3 days] were transferred to common, randomly selected recipients. Fetal plasma samples were collected from mixed-breed (MB, one Finn and one Ra; n = 6) and single-breed (SB, single Finn, n = 3; single Ra, n = 3) chronic fetal preparations during the last trimester. In the MB pregnancy, the Ra sibling had temporal patterns of androstenedione similar to those observed in the Finn co-twin; however, these particular changes were greatly accelerated in comparison to the same day of gestation in SB Ra fetuses. Similarly, temporal patterns of change in unconjugated estrone, estrone sulfate, and 17 beta-estradiol were accelerated by as much as 4.6 to 5 days in Ra fetuses of MB pregnancies when compared to Ra fetuses in the SB pregnancies (P less than 0.001), with no difference noted between Ra and Finn co-twins. Maternal progesterone concentrations changed from 8 to 2 ng/ml, androstenedione from 200 to 400 pg/ml, estrone from 65 to 250 pg/ml, and 15-keto-13,14-dihydroprostaglandin F2 alpha from 200 pg/ml to 6000 pg/ml over the last 4 or 5 days of gestation. Chronic fetal manipulation accelerated parturition, with mean gestational lengths in MB, SB Finn, and SB Ra pregnancies being 141.5 +/- 0.7, 141.7 +/- 0.7, and 149.3 +/- 0.9 days, respectively. In this study fetal endocrine changes were largely controlled in the MB pregnancy by the fetal co-twin exhibiting a shorter gestational period.

Androstenedione↗

Oxytocin and bovine parturition: a steep rise in endometrial oxytocin receptors precedes onset of labor.

Oxytocin receptors were measured in myometrium and intercaruncular endometrium of cows during pregnancy and parturition. Concentrations of estradiol-17 beta, estrone, and progesterone in peripheral blood were also measured. Receptor concentrations in the endometrium rose almost 200-fold from Day 20 to term (p < 0.0001, ANOVA), from 40 +/- 11 to 7300 +/- 1430 fmol/mg protein. Myometrial receptor concentrations increased 10-fold from 180 +/- 36 fmol/mg on Day 20 to 1850 +/- 360 fmol/mg protein at term (p < 0.0001, ANOVA). During labor, endometrial receptors (6600 +/- 1300 fmol/mg) remained at prelabor values, whereas myometrial receptor concentrations had decreased to 1190 +/- 316 fmol/mg (not significant) and declined further postpartum. Plasma concentrations of progesterone declined from 4-5 ng/ml to about 2 ng/ml between Days 250 and 282 and dropped to < 0.2 ng/ml shortly before delivery. Plasma concentrations of estrone and estradiol-17 beta were below 10-20 pg/ml until Day 230. Estrone concentrations were significantly (p < 0.05) increased by Day 250 and estradiol-17 beta by Day 270, and then both rose rapidly. During labor, plasma estrone was 1135 +/- 245 pg/ml and plasma estradiol-17 beta was 226 +/- 131 pg/ml. The molar ratio of estrone and estradiol-17 beta to progesterone rose from less than 0.01 to 4.4 during labor, and was correlated with oxytocin receptor concentrations in endometrium (r = 0.5160, p < 0.001), but not those in myometrium (r = 0.0122). The regulation of oxytocin receptors by ovarian hormones in the two tissues may therefore differ.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Striking changes in the structure and organization of rat fetal membranes precede parturition.

Premature rupture of fetal membranes can harm infant and mother. It is unclear whether structural changes predispose these membranes to breaking. We thus assessed rat visceral yolk sac placenta (VYSP) and amnion by light and by transmission electron microscopy on Days 18-21 of gestation. Light microscope sections were stained for connective tissue (extracellular matrix) components: collagen, glycoprotein, and glycosaminoglycans/proteoglycans. Some tissue was incubated with chondroitinase ABC. We observed that fetal membranes became increasingly fragile, rupturing readily on Day 21. On Days 18-20, the two epithelial layers of the capsular VYSP were separated by a well-developed, well-vascularized connective tissue layer that stained intensely for all matrix components studied; on Day 21, the connective tissue layer was thinner, moderately stained, and less vascularized. On Days 18-20, the two cellular layers of the amnion were separated by a narrow, compact connective tissue layer that stained modestly for all matrix components; on Day 21, this area was widened and stained faintly. Transmission electron microscopy showed that collagen fibrils of the amnion were abundant, closely packed, and well organized on Days 18-20, whereas on Day 21 they were few in number, widely spaced, and disorganized. Similar changes were present after incubation with chondroitinase ABC. In addition, amniotic epithelial cells were moribund and delaminating, basal laminae were deteriorating or absent, and few cells were at the outer surface of the amnion. All changes preceded parturition. We conclude that the structural integrity of rat fetal membranes is impaired before birth through the loss of connective tissue components and cells, changes that presumably underlie membrane rupture. Lastly, the similarity of structural changes in rat and human fetal membranes point to the potential usefulness of the rat model.

Amnion↗

92-kDa gelatinase (matrix metalloproteinase-9) is induced in rat amnion immediately prior to parturition.

The fetal membranes undergo striking changes in structure before delivery that involve catabolism of the extracellular matrix. To investigate the role of specific enzymes in this process, we examined gelatinase activities in rat amnion, visceral yolk sac placenta, and placenta and amniotic fluid between Days 18-21 of pregnancy. Matrix metalloproteinase (MMP)-2 was present in amnion on all days, and its activity increased slightly on Day 21. The 92-kDa gelatinase, MMP-9, was not detected on Days 18-20 but appeared by the morning of Day 21. There was a marked increase in MMP-9 mRNA in the amnion on Day 20, preceding the appearance of MMP-9 activity. Western blotting confirmed an increase in MMP-9 protein in amnion on Day 21. MMP-2 and MMP-9 activities were detected in extracts of whole yolk sac placenta, placenta, and amniotic fluid, but there were no striking changes in these gelatinases between Days 18 and 21. However, the capsular regions of the visceral yolk sac placentae, which thin and rupture during labor, did show higher MMP-9 activity on Day 21 than on Days 18 and 20. We suggest that the striking increase in MMP-9 expression in amnion and possibly the capsular region of the visceral yolk sac placenta approximately 12 h prior to delivery is responsible, in part, for the alterations in the structure of these fetal membranes before parturition.

Amnion↗

Fetal and maternal endocrine changes approaching parturition in the goat: lack of evidence for prostaglandins E2 and F2alpha as signals for luteolysis.

We investigated the temporal relationship of fetal cortisol secretion to circulating concentrations of fetal ACTH1-39 and its high-molecular weight precursors in goats. We also measured the concentrations of progesterone, estradiol-17beta estrone sulfate, prostaglandin (PG) E, PGF2alpha, and PGF2alpha metabolite (PGFM) in maternal arterial plasma over the last month of gestation. Prostaglandin concentrations were also measured in utero-ovarian venous plasma. There was a positive association between ACTH1-39 in fetal plasma and the prepartum surge in fetal cortisol that commenced 8 days before labor. The fetal cortisol surge was followed by a simultaneous decrease in maternal progesterone and an increase in plasma estrogens commencing 3-4 days before labor. No change in basal prostaglandin concentration occurred before this time. There was a positive veno-arterial difference of PGE and PGF2alpha across the uterine vascular bed, confirming the uteroplacental unit as a major source of these eicosanoids in the plasma of the pregnant doe. We conclude that the fetal signal for parturition precedes luteolysis by some 5 days and find no evidence of changes in the basal concentrations of PGE and PGF2alpha in maternal plasma at the time of luteolysis.

Adrenocorticotropic Hormone↗

Immunolocalization of progesterone receptors in bovine placentomes throughout mid and late gestation and at parturition.

The corpus luteum is the main source of progesterone (P(4)) responsible for maintenance of gestation in cattle. So far it has not been possible to assign any biological role to placental P(4), which contributes only marginally and temporarily to peripheral maternal blood levels. In order to identify possible P(4) target cells within the placenta, placentomes from 150-, 220-, 240-, and 270-day-pregnant cows and from parturient cows (3 animals per group) were screened immunohistochemically for expression of the progesterone receptor (PR). During gestation, PR-positive staining was found exclusively in the nuclei of caruncular stromal cells (CSC; maternal part of the placentome) and of caruncular vascular pericytes. In placentomes from parturient cows, occasional positive nuclear staining was also observed in the walls of small caruncular arteries. The percentage of PR-positive CSC increased slightly from 51.8 +/- 2.6% on Day 150 to 56.2 +/- 5.6% at Day 270 (p < 0.05) and was 58.9 +/- 1.8% at parturition. These results suggest that in pregnant cattle, CSC are under the control of P(4) of placental rather than luteal origin. Thus, whereas luteal P(4) may regulate "coarse" systemic progestational functions in the maternal compartment in the classical hormonal manner, placental P(4) may act as a paracrine factor involved in the local regulation of caruncular growth, differentiation, and functions.

Animals↗

Parturition-induced pelvic dislocation: a report of four cases.

OBJECTIVE: To describe our experience with four cases of severe pelvic dislocation associated with difficult parturition. DESIGN: Retrospective case series. PATIENTS: Four patients, each with rupture of the symphysis pubis and sacroiliac joints during labor. All injuries were associated with significant initial pain and disability. All developed persistent symptoms related to the sacroiliac disruption. INTERVENTIONS: The three patients who had presented acutely were freated with closed reduction and application of a pelvic binder. Two underwent closed reduction of their pelvic dislocation while anesthetized with a general anesthetic. One patient (N.A.), who presented late, had not been treated with a binder. RESULTS: All four patients had persistent posterior pelvic (sacroiliac) pain. In two patients a postpartum neuropathy persisted. CONCLUSIONS: Severe pelvic dislocations are rare during labor, with conservative treatment reported to be successful in most cases. The persistence of symptoms in our patients emphasizes the need for careful examination and follow-up of these rare injuries. Because the outcome in our patients was poor and results in the literature are equivocal, we suggest the consideration of an operative approach to treatment in patients with symphyseal diastasis of > 4.0 cm.

Adult↗

Prostaglandin fever in rats throughout the estrous cycle late pregnancy and post parturition.

We have examined the influence of natural variations in endocrine status on the ability to generate a prostaglandin-induced fever in virgin female, pregnant and lactating rats and compared responses to those in male rats. Endocrine status of virgin female rats was assessed from examination of vaginal smears and time of parturition noted to enable accurate dating of pre- and postparturient fevers. Unanesthetized rats, previously prepared with intraventricular guide cannulas and intraperitoneal telemetry thermistors, were given intraventricular injections of prostaglandin E1 (2-100 ng/5 microliters) and temperatures monitored for 3 h after injection. Virgin females developed significantly larger fevers than did males at higher doses. There were no significant alterations in either fever height or duration as a function of the phase of the reproductive cycle in the females. Both pregnant and postparturient rats within the several days around birth displayed significantly lower fevers than did virgin females, but there was no further reduction in the immediate periparturient period. These data indicate that there are sex-, and possibly hormone-dependent differences in the central mechanisms involved in fever generation and antipyresis.

Alprostadil↗

Adrenergic and cholinergic nerve supply in the porcine myometrium and cervix. A histochemical investigation during pregnancy and parturition.

The distribution of adrenergic and acetylcholinesterase-containing (cholinergic) nerves in the porcine myometrium and cervix was investigated neurohistochemically. In early and mid-pregnancy the number of adrenergic nerves increased from the adtubal part of the horns to corpus uteri, being more abundant in non-placental than in placental regions. No obvious difference in the distribution of cholinergic nerves was observed among the regions examined. The cervix was richest innervated by both types of nerves throughout gestation. The diameter of the adrenergic nerves decreased during pregnancy, while cholinergic nerves showed no such a decrease. In late pregnancy and at parturition the adrenergic innervation was richest at the adtubal part of the horns and in the cervix and scanty in the rest of the uterus. Adrenergic nerves were seen both in vascular and in non-vascular smooth muscle, while cholinergic nerves were mostly associated to blood vessels.

Adrenergic Fibers↗

Alterations in neutrophil phagocytosis and lymphocyte blastogenesis in dairy cows around parturition.

The bovine blood neutrophil phagocytosis and the blood and milk lymphocyte proliferative response upon stimulation with Phytohaemagglutinin, Concanavalin A and Pokeweed mitogens was studied from 3 weeks prior to calving until 3 weeks after calving. Neutrophil phagocytosis and the total and differential blood leukocyte counts were performed by flow cytometry. A gradual increase in the percentage of phagocytized bacteria and the average number of bacteria per phagocyte was observed before calving followed by a sharp fall on the first postpartum. This was followed by a steady increase in the above parameters reaching the highest levels at two weeks postpartum. There was a gradual increase in the number of neutrophils in blood as calving approached followed by a sharp decrease after calving. The number of lymphocytes in blood dropped before calving, being at the lowest level on the day before calving. The proliferative response of blood and milk lymphocytes upon stimulation with the three mitogens was low during the week preceding parturition with the lowest value on the day before calving. The response of blood lymphocytes returned to a higher level the second week after calving while that of milk lymphocytes remained at a low level during the first and the second postpartum weeks.

Animals↗

Biochemical events in cervical ripening dilatation during pregnancy and parturition.

In specimens taken from the posterior lip of the cervix uteri we determined the collagenase activity and the glycosaminoglycan concentration. In biopsies obtained from the lower uterine segment during cesarian section we measured cytokines (IL-8, IL-2, TNF alpha) and matrix metalloproteinases (MMP-8, MMP-9). We found that the release of collagenases is critically involved in the process of cervical dilatation. The glycosaminoglycan concentration increases during pregnancy and shows remarkable changes of the distribution patterns of the different glycosaminoglycans. The parturition is characterized by a dramatic loss of most of the glycosaminoglycans. Furthermore, the IL-8 shows a close correlation to the clinical feature of cervical ripening and is closely associated with the release of MMP-8 and MMP-9. Summarizing the process of cervical maturation and dilatation is a complex enzymatic controlled process with substantial remodelling of the cervical extracellular matrix. The cytokines IL-8 seems to play an essential role in triggering the process of cervical dilatation.

Biopsy↗

Melatonin in amniotic fluid during human parturition.

Concentrations of melatonin have been measured in amniotic fluid obtained during late pregnancy and labour. Samples obtained by amniotomy during labour contained higher concentrations of melatonin than samples taken at amniotomy for the induction of labour. Amniotic fluid obtained by amniocentesis in late pregnancy contained lower concentrations of melatonin than amniotic fluid obtained by amniotomy. The implications of these findings are discussed in relation to pineal influences on parturition.

Amniotic Fluid↗

Prostacyclin production increases during human parturition.

The role of prostacyclin (PGI2) in human parturition was studied by measuring the concentrations of its main metabolite, 6-keto-prostaglandin F1 alpha, before, during and after term labour in the plasma of 9 women and after delivery in umbilical artery and vein plasma. The mean level of 6-keto-PGF1 alpha rose significantly over the course of labour. The mean level was 266 pg/ml before labour, 341 pg/ml in the presence of regular contraction, 387 pg/ml at a cervical dilatation of 5 cm, 386 pg/ml at delivery, and 397 pg/ml at the expulsion of the placenta. The 6-keto-PGF1 alpha concentration dropped to below pre-labour levels of 233 pg/ml within 2 hours of delivery, and this level was maintained for the first four postpartum days. The mean levels of 6-keto-PGF1 alpha in the umbilical artery and vein plasma, 1667 and 1193 pg/ml respectively, were significantly higher than the maternal plasma levels. PGI2 is characterized by its antiaggregatory and vasodilating abilities, so that the rise in PGI2 during labour may play a role in the prevention of intrapartum thromboembolic complications in the maternal and the uteroplacental circulation.

6-Ketoprostaglandin F1 alpha↗