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PubMed1994

Placental progestagens in the sheep and horse and the changes leading to parturition.

Placental progestagen production and metabolism during pregnancy, the changes which precede parturition and the extent of fetal involvement in the latter processes are compared in the sheep and the horse. Neither species requires the presence of a corpus luteum for maintenance of the latter part of pregnancy, but the mechanisms involved in placental progesterone/progestagen production are very different in the two species. In sheep the primary product is progesterone (P4), levels of which are high in the maternal but not the fetal circulations. By contrast, in the mare P4 is not detectable in maternal blood after 200 days gestation although it is present in the placenta and fetal circulation. A range of P4 metabolites (primarily 5 alpha-pregnanes) are produced by the equine placenta, while in the fetus pregnenolone and its metabolites are the predominant progestagens. In sheep the prepartum endocrine cascade in which the rise in fetal cortisol stimulates enzyme changes in the placenta so that P4 declines and estrogens and prostaglandins eventually rise, is fairly well established compared with the events preceding delivery in the mare. In the latter species there is a gradual rise in progestagens for 10-20 days before term, at a time when the fetal adrenal is relatively quiescent and unresponsive to ACTH i.e. fetal cortisol levels are low. In the last 24-48 h before delivery maternal progestagens fall, just after fetal plasma cortisol concentrations begin to escalate. The ways in which maternal and fetal prepartum endocrine changes may be interrelated and the possibility of a fetal trigger to parturition in the mare are discussed.

Animals↗

PubMed2001

Investigations on the activity of bovine placental oestrogen sulfotransferase and -sulfatase from midgestation to parturition.

To gain further information on the biological role of the high amounts of conjugated estrone (E1S) secreted by the bovine placenta, an in vitro assay system was developed to measure oestrogen sulfotransferase (OST) and oestrogen sulfatase (OS) activities in caruncular and cotyledonary homogenates and the respective subcellular fractions. Placental tissue was obtained from 150 (n = 3), 220 (n = 4), 240 (n = 3) and 270 days (n = 3) pregnant and parturient cows (n = 4). 3H-E1 and 3H-E1S served as substrates and 4-nitrophenyl sulfate potassium salt was used as a competitive inhibitor to block OS when testing for OST activity. OST-activity did not change during pregnancy and parturition and was higher (p < 0.001) in cotyledonary than in caruncular tissue with mean conversions (median) of 61.8% and 41.6% after 30 min of homogenate incubation. On a subcellular level OST-activity was clearly associated with the cytosol. OS-activity was higher (p < 0.001) in caruncular than in cotyledonary homogenates; it was constant during pregnancy (median of conversion: 88.0% and 66.4%, resp.), but was significantly decreased (p < 0.05) at parturition (median of conversion: 48.1% and 30.6%, resp.). On a subcellular level in both the cotyledon and the caruncle highest OS-activities were detected in the microsomal and the mitochondrial fractions. The decreased placentomal OS-activities in parturient cows are inconsistent with a substantial role of OS in the prepartal increase of free oestrogens. These results also suggest that bovine placental oestrogens may largely exert their action locally within the placentomes during most time of gestation as the enzymes catalyzing sulfoconjugation (i.e. inactivation of free oestrogens) and desulfation (i.e. activation of conjugated oestrogens) are expressed in close proximity to each other. In this respect the finding of oestrogen receptors in caruncular stromal cells is of particular interest.

Animals↗

PubMed2000

Evidence of in vivo differential bioavailability of the active forms of matrix metalloproteinases 9 and 2 in parturition, spontaneous rupture of membranes, and intra-amniotic infection.

OBJECTIVE: Matrix metalloproteinases (MMP-9 and MMP-2) have been implicated in the digestion of fetal membranes. The purpose of this study was to determine the amniotic fluid concentrations of active forms of MMP-2 and MMP-9 and to explore the participation of these enzymes in labor (term and preterm), rupture of membranes (term and preterm), and microbial invasion of the amniotic cavity. STUDY DESIGN: A cross-sectional study was conducted with 291 women in the following categories: (1) term not in labor, (2) term in labor, (3) preterm labor and intact membranes who delivered at term, (4) preterm labor who delivered preterm, (5) preterm labor with microbial invasion of the amniotic cavity, (6) preterm premature rupture of membranes without microbial invasion of the amniotic cavity, (7) preterm premature rupture of membranes with microbial invasion of the amniotic cavity, (8) term premature rupture of membranes not in labor, and (9) mid trimester. Active forms of MMP-2 and MMP-9 were measured by a novel assay that uses a substrate developed by protein engineering. RESULTS: (1) MMP-2 and MMP-9 were detected in 88% and 96% of amniotic fluid samples, respectively (255/291 and 279/291). (2) The concentrations of active forms of MMP-2 and MMP-9 changed with advancing gestational age. (3) Spontaneous term parturition was associated with a significant increase in the median concentration of the active forms of MMP-9 (P <.005) and a significant decrease in the median concentration of the active forms of MMP-2 (P <.003). (4) Preterm labor with intact membranes leading to preterm delivery in the absence of infection was associated with a significant increase in the median concentration of the active forms of MMP-9 (P <.005) but not of the active forms of MMP-2 (P =.2). (5) Rupture of membranes (either term or preterm) was associated with a significant increase in the concentration of the active forms of MMP-9 and with a significant decrease in the concentration of the active forms of MMP-2 (P <.005 for term and P <.03 and P <.003 for preterm, respectively). (6) Microbial invasion of the amniotic cavity in women with preterm premature rupture of membranes was also associated with a significant increase in the concentration of the active forms of MMP-9 (P <.03) and a decrease in the concentration of the active forms of MMP-2 (P <.05). (7) Microbial invasion of the amniotic cavity in patients with preterm labor was associated with a significant increase in the median concentration of the active forms of MMP-9 (P <.005) but not of the active forms of MMP-2 (P =.6). CONCLUSION: Spontaneous rupture of membranes (either term or preterm), parturition (either term or preterm), and microbial invasion of the amniotic cavity were associated with significant increases in the amniotic fluid concentration of the active forms of MMP-9. In contrast, the concentration of the active forms of MMP-2 either decreased or remained the same in these conditions. Our observations provide evidence for a novel regulation of gelatinolytic activity in vivo.

Amnion↗

PubMed2000

Lactoferrin in intrauterine infection, human parturition, and rupture of fetal membranes.

OBJECTIVE: Lactoferrin is an iron-binding protein with antimicrobial properties. This study was undertaken to determine whether amniotic fluid concentrations of this protein change with gestational age, infection, labor, and rupture of membranes. STUDY DESIGN: This cross-sectional study included women who underwent transabdominal amniocentesis (n = 268) in the following groups: (1) mid trimester of pregnancy; (2) preterm labor who delivered at term, preterm labor who delivered preterm with intra-amniotic infection, and preterm labor who delivered preterm without intra-amniotic infection; (3) preterm premature rupture of membranes in the presence or absence of intra-amniotic infection; (4) term with intact membranes not in labor, in labor, and in labor with intra-amniotic infection; and (5) premature rupture of membranes at term not in labor. In addition, lactoferrin concentrations were determined in maternal plasma and cord blood of patients at term not in labor. Lactoferrin concentration was measured with an immunoassay. RESULTS: (1) Lactoferrin was detectable in 85.4% (229/268) of amniotic fluid samples, not detectable in all fluid obtained in the mid trimester, and detectable in all maternal and cord plasma samples. (2) The concentration of lactoferrin increased with advancing gestational age (r = 0.68; P <.0001). (3) Intra-amniotic infection was associated with significant increases in amniotic fluid lactoferrin concentrations in patients with preterm labor (no intra-amniotic infection median, 1641.2 ng/mL; range, <1.24-35,090.0 ng/mL; vs intra-amniotic infection median, 3833.6 ng/mL; range, 746.0-47,020.0 ng/mL; P <.001), term labor (no intra-amniotic infection median, 2085.8 ng/mL; range, 425.0-23,230.0 ng/mL; vs intra-amniotic infection median, 5627.0 ng/mL; range, <1.24-19,220.0 ng/mL; P <. 001), and preterm premature rupture of membranes (no intra-amniotic infection median, 2190 ng/mL; range, <1.24-7456.1 ng/mL; vs intra-amniotic infection median, 3449.3 ng/mL; range, <1.24-83,600. 0; P <.01). (4) Spontaneous labor at term but not preterm was associated with a significant decrease in amniotic fluid lactoferrin concentration (P <.05). (5) Spontaneous term parturition was associated with a significant increase in umbilical cord plasma lactoferrin concentration (P <.005). CONCLUSION: (1) Intra-amniotic infection was consistently associated with dramatically increased concentrations of lactoferrin in amniotic fluid. (2) Term parturition was associated with a significant increase in lactoferrin concentration in the fetal compartment (umbilical cord blood) and a decrease in the amniotic compartment. We propose that lactoferrin is part of the repertoire of host defense mechanisms against intra-amniotic infection.

Cross-Sectional Studies↗

PubMed2001

The role of thrombin in preterm parturition.

OBJECTIVE: Previous reports from our laboratory have shown that thrombin is a potent uterotonic agonist; those studies have suggested a role for thrombin during parturition, especially with regard to intrauterine bleeding. Thrombin activation can be quantified in peripheral blood by measurement of thrombin-antithrombin III (TAT) complex levels. This study sought to determine whether thrombin activation, as measured by thrombin-antithrombin III levels, is associated with premature labor. STUDY DESIGN: Thrombin-antithrombin III levels were measured in patients and control subjects with preterm labor. Quantitative TAT levels were determined by use of an enzyme-linked immunoassay with a working range from 0 to 60 ng/mL. All patients were monitored for pregnancy outcome. Receiver operating curve analysis was performed to determine the optimal TAT cutoff values. Further statistical analyses with one-way ANOVA, the chi2 test, or the Fisher exact test were performed to determine statistical significance (P <.05). RESULTS: Patients admitted with preterm labor who were subsequently delivered within 3 weeks had significantly higher mean TAT levels (7.80 +/- 2.86 ng/mL; P <.05) than control subjects (5.77 +/- 1.43 mL) or patients with preterm labor who were not delivered within 3 weeks of presentation with preterm labor (5.57 +/- 1.69 ng/mL; P <.05). Given a diagnosis of preterm labor, a TAT level of 8.0 ng/mL had a positive predictive value of 80% for delivery within 3 weeks of enrollment. CONCLUSIONS: This study showed that TAT levels are elevated in patients with preterm labor who are destined to deliver before term. These results suggest that preterm labor resulting in premature delivery is associated with the activation of thrombin. Future studies will further elucidate the role of thrombin in preterm parturition and confirm whether tests for thrombin activation can accurately identify those patients destined for preterm delivery.

Adult↗

PubMed1997

Early onset of parturition induced by acute alcohol exposure in C57BL/6J mice: role of uterine PGE and PGF2alpha.

These studies were designed to determine the effect of acute alcohol treatment on gestational length and to probe for a mechanism underlying alcohol-induced early onset of parturition (EOP) in mice. Experiment 1: alcohol increases the incidence of EOP. Pregnant C57BL/6J mice were given alcohol (0, 4, 5 or 6 g kg(-1), i.g.) on Gestational Day (GD) 10, 15, 16, 17 or 18. Deliveries were monitored every 6 h from GD 18. Results indicated that 6 g kg(-1) alcohol treatment on GD 17 or 18 increased the incidence of EOP. Experiment 2: prostaglandins (PGs) play roles in parturition. The purpose of Experiment 2 was to determine whether PGs mediate alcohol-induced EOP in mice. The results indicated that pretreatment on GD 17 with aspirin, a prostaglandin synthesis inhibitor, prevented alcohol-induced EOP. These data suggest that alcohol-induced EOP in mice may be mediated by PGs. Experiment 3: PGs are influenced by alcohol and are triggers of labour. Experiment 3 measured uterine PGs associated with the onset of alcohol-induced EOP in mice. Alcohol increased uterine PGE and PGF2alpha, with PGE levels higher than control before labour, and elevated PGF2alpha levels correlating with labour. Changes in gestational length have important implications for pregnancy outcome, as well as for normal fetal growth and development.

Animals↗

PubMed2001

Fetal control of parturition in marsupials.

Among marsupials, the control of birth is best understood in the tammar wallaby. The young is tiny relative to the mother and is highly altricial. Adult female tammar wallabies weigh 5 kg, whereas the neonate weighs about 400 mg. However, despite this small size, there is clear evidence that the fetus provides the signal that sets the timing of birth through several mechanisms. A fetal signal activates a nitric oxide-guanylate cyclase system in the myometrium that may maintain myometrial inactivity, and this is down-regulated at term. There is also up-regulation of prostaglandin (PG) production in the gravid endometrium during the last two days of gestation that parallels increased placental PG synthesis, and a pregnancy-specific up-regulation of oxytocin receptors in the gravid myometrium that increases the responsiveness of the gravid uterus to mesotocin. These changes facilitate parturition, but an acute fetus-derived signal appears to trigger parturition. The fetal signal is probably related to glucocorticoid production. The fetal adrenal matures and is able to synthesize cortisol by Day 22 of the 26-day gestation. The fetal adrenals double in size between Day 24 and term, and their cortisol content increases over 10-fold. The pituitary of the neonate contains presumptive corticotrophs, and the adrenals increase cortisol production in response to adrenocorticotrophin. Prostaglandin E2, which is produced by the placenta, is also a potent stimulant of fetal adrenal cortisol synthesis. Treatment of tammars in late gestation with the cortisol agonist, dexamethasone, triggers birth around 23 h later. There is thus a strong case that fetal adrenal cortisol plays a key role in the preparation for birth and the timing of it. Further studies are in progress to more clearly define the mechanisms behind these actions of cortisol.

Adrenal Glands↗

PubMed1991

The placenta, prostaglandins and parturition: a review.

It is proposed that in sheep, during the last third of gestation, a progressive increase in the production of prostaglandin E2 (PGE2) by the fetal trophoblast activates the fetal hypothalamic-pituitary-adrenal axis leading to an increase in fetal cortisol concentrations. High cortisol levels increase placental 17 alpha-hydroxylase activity causing a decrease in maternal progesterone concentrations and an increase in oestrogen concentrations. The increase in the E/P ratio results in an increase in PGF2 alpha release from the maternal placenta, increased uterine activity and parturition. The increased production of PGE2 by the placenta has been linked to the rapid increase in the growth of the fetus from day 110 of gestation onwards. It is speculated that the growth pattern of the fetus represents a genetically programmed 'clock' which acts by stimulating placental PGE2 production leading to maturation of key organ systems in the fetus and finally parturition.

Animal Nutritional Physiological Phenomena↗

PubMed1991

Peripheral concentrations of immunoreactive inhibin during pregnancy and parturition in the ewe.

The aim of this study was to measure the peripheral concentrations of immunoreactive inhibin (ir-inhibin) and progesterone (P) during pregnancy and parturition in the ewe and to relate the concentrations of ir-inhibin to P and to the number and sex of the fetuses. P increased across pregnancy with higher levels in ewes with 2 fetuses (n = 5) than in those with 1 fetus (n = 6), and concentrations falling before birth. ir-Inhibin concentrations were relatively stable during the first 40 days of pregnancy for example (Day 20, 34.7 +/- 2.9 pmol L-1; mean +/- s.e.m., n = 11). After Day 40, inhibin fell in all ewes to reach less than or equal to 2.5 pmol L-1 after Day 80 (mean on Day 103, 6.3 +/- 1.2 pmol L-1), and remained low until 2 days before parturition when concentrations rose sharply, peaking at or around the day of birth in all ewes (21.5 +/- 2.1 pmol L-1). Thereafter, ir-inhibin fell and remained low or undetectable for up to 10 days in the six ewes still being sampled. ir-Inhibin concentrations in ewes carrying one (n = 6), two (n = 5) or three fetuses (n = 1) did not differ at any stage of pregnancy examined. The sex of the fetus did not appear to influence the peripheral concentrations of ir-inhibin in the ewe.

Analysis of Variance↗

PubMed1995

Chronic stress--the key to parturition?

It is clear that the timing of parturition is dependent on a cascade of endocrine signals from an intact fetal hypothalamo-pituitary-adrenal axis. What is not known, however is the nature or source of the central neural stimulation which results in the stimulation of adrenocorticotrophic hormone (ACTH) synthesis and secretion in late gestation. The changes which occur in the synthesis and posttranslational processing of the ACTH precursor, proopiomelanocortin (POMC), in the fetal anterior pituitary before birth and the consequence of these changes for expression of the corticosteroidogenic enzymes in the fetal adrenal are described in this review. Evidence for the functional heterogeneity of corticotrophic cell types in the fetal sheep pituitary and the proposal that there is a maturational change in the populations of corticotrophic cells in late gestation are discussed. Finally, the development of cortisol negative feedback in the late gestation fetal hypothalamo-pituitary axis and the relevance of chronic stress to the timing of parturition are also discussed.

Adrenocorticotropic Hormone↗

PubMed1982

The induction of parturition in sows using prostaglandin F2alpha.

Intramuscular injections (10 mg) of prostaglandin F2alpha were administered to 19 pregnant sows in one herd on either the 112th or 113th day of gestation and a similar number of untreated sows served as controls. Induced sows for up to 6h after injection generally showed more walking, drinking defaceating and postural changes. Over the last 20 h prepartum they spent more time lying and urinated more frequently. Mean interval from injection to onset of parturition in treated sows was 24.5 h and 16 of them commenced farrowing during the working day, compared with 6 in the control group. Induction of parturition did not influence litter size at birth, piglet body-weights at birth or 14 days of age, the incidence of the mastitis, metrititis agalactae syndrome, re-breeding interval of the sow or size of the subsequent litter at birth. Farrowing time was significantly longer (6.48 h v 4.08 h) for treated sows and litter pre-weaning mortality was higher but not significantly so. Most piglet deaths in each group resulted from overlaying or starvation but mortality from anaemia and septicaemia occurred only in the treated group. It is considered that the technique could have practical application on well-managed intensive pig units.

Journal Article↗

PubMed1995

Liver triacylglycerol concentrations around parturition in goats with either pre-partum restricted or free access to feed.

The hypothesis was tested that goats allowed ad libitum access to feed during the dry period develop higher post partum hepatic triacylglycerol concentrations than do goats given a restricted amount of feed during the dry period. Goats in their second or more pregnancies were either given a restricted amount of hay, maize silage and concentrate (n = 5) or had free access to this feed mixture while the composition was kept constant (n = 11). After parturition both groups were allowed ad libitum access to feed. Post partum liver triacylglycerol concentrations, as measured in liver biopsies, were significantly raised in goats allowed ad libitum access to feed during the dry period. The increase in liver triacylglycerols was associated with slightly higher plasma concentrations of non-esterified fatty acids but lower serum 3-hydroxybutyrate concentrations. The feeding regimen during the dry period did not significantly influence post partum liver glycogen concentrations and serum levels of glucose, cholesterol, and insulin. The increase in post partum liver triacylglycerol concentrations in the goats allowed ad libitum access to feed instead of a restricted ration during the dry period, was associated with a significant rise in serum alkaline phosphatase activities, whereas other liver function and cell damage indicators in serum, i.e. aspartate aminotransferase, lactate dehydrogenase, gamma glutamyl transpeptidase, and bilirubin, were unchanged. Feed intake after parturition tended to be higher in the goats allowed ad libitum access to feed during the dry period but milk production was significantly raised.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed2005

Increased bone turnover during the third trimester of pregnancy and decreased bone mineral density after parturition in adolescents as compared to age-matched control patients.

To evaluate the impact of pregnancy on bone, we studied bone turnover at the first (T1) and third (T3) trimester of gestation in 58 adolescents and 28 healthy adolescents who had never been pregnant. Total body (TB) and lumbar spine (LS) bone mineral density (BMD) and body composition were evaluated by dual-energy X-ray absorptiometry in all control patients (C) and after parturition in 28 pregnant patients (G). Paired and unpaired t tests, Mann-Whitney and Pearson correlation tests were used. Bone turnover markers were above the reference range for adult women in more than 80% of the adolescents, with no difference between C and G patients at T1. Increase in urinary N-telopeptide crosslinks of type I collagen and serum bone-specific alkaline phosphatase, markers of bone turnover, was seen during pregnancy ( p < 0.0001). Body composition did not differ between groups, but LS BMD, percentage of expected LS BMD, LS Z-score, percentage of expected TB BMD and TB Z-score were lower in G than C patients ( p < 0.05). TB BMD was positively correlated with LS BMD (r2 = 0.52). The inverse correlations between bone markers and LS BMD suggest that the increased bone turnover during pregnancy probably explains the low bone density after parturition. The impact on future peak bone mass must be studied.

Absorptiometry, Photon↗

PubMed2006

Fetal plasma cortisol and dehydroepiandrosterone sulfate concentrations in pregnancy and term parturition.

OBJECTIVE: To examine if changes in fetal plasma concentrations of cortisol or dehydroepiandrosterone sulfate (DHEAS) levels are associated with human term parturition. METHODS: Umbilical cord plasma cortisol and DHEAS concentrations were measured in 374 singleton pregnancies that delivered at term in the following six groups: group 1, cordocentesis for clinical indications before 36 weeks of gestation (n = 93); group 2, cordocentesis for clinical indications after 36 weeks of gestation (n = 9); group 3, cord blood sampling after elective cesarean section (CS) at term without labor (n = 140); group 4, cord blood sampling after CS at term with early labor (cervical dilatation < or =3 cm, n = 18); group 5, cord blood sampling after CS at term with active labor (cervical dilatation 4 cm or greater, n = 26); group 6, cord blood sampling after vaginal delivery at term (n = 88). Corticosteroids were not administered before blood collection. RESULTS: (1) Fetal plasma cortisol remained unchanged until 36 weeks of gestation and increased thereafter to term; (2) active labor was associated with a significant increase in fetal plasma cortisol; (3) fetal plasma DHEAS increased at term gestation (>36 weeks) but did not increase during active labor; (4) the cortisol/DHEAS ratio (stress index) increased with advancing gestation and with active labor at term. CONCLUSIONS. Human parturition at term is associated with an increase in fetal plasma cortisol and in the cortisol/DHEAS ratio, but not in DHEAS.

Adult↗

PubMed2003

Amniotic fluid levels of immunoreactive monocyte chemotactic protein-1 increase during term parturition.

OBJECTIVE: Parturition is characterized by an influx of inflammatory cells into gestational tissues, a phenomenon conducive to increased myometrial contractility, cervical ripening and decidual/membrane activation. Monocyte chemotactic protein-1 (MCP-1), a potent chemoattractant and activator of monocytes/macrophages, is expressed in gestational tissues and, thus, may participate in the final common pathway of labor. This study was undertaken to determine whether the amniotic fluid concentrations of immunoreactive MCP-1 are altered with gestational age or spontaneous labor at term with and without prelabor rupture of the gestational membranes. We also sought to identify intrapartum differences in the concentrations of immunoreactive MCP-1 between the upper and lower amniotic fluid compartments. METHODS: A cross-sectional study was conducted to assess the concentrations of immunoreactive MCP-1 in amniotic fluid. Amniotic fluid samples were obtained from 225 women as follows: (1) women undergoing mid-trimester (14-18 weeks of gestation) amniocentesis for genetic indications, whose pregnancy outcome was normal (n = 84); (2) women in labor (n = 52) and not in labor (n = 31) at term, with intact gestational membranes; (3) women with rupture of the gestational membranes in labor (n = 18) and not in labor (n = 26), at term; and (4) women in labor at term for whom paired amniotic fluid samples were obtained through transvaginal and transabdominal amniocenteses (n = 14). Immunoreactive MCP-1 was assessed with a specific and sensitive immunoassay that had been validated for amniotic fluid. Non-parametric statistics were used for analysis. RESULTS: Immunoreactive MCP-1 was detected in all amniotic fluid samples. Spontaneous human parturition was associated with a significant increase in the amniotic fluid concentrations of immunoreactive MCP-1 (not in labor: median 595 pg/ml, range 183-3579 pg/ml vs. in labor: median 862 pg/ml, range 183-9609 pg/ml; p = 0.01). The median amniotic fluid concentrations of immunoreactive MCP-1 were significantly higher in the lower amniotic fluid compartment than in the upper amniotic fluid compartment (lower compartment: median 2913 pg/ml, range 1360-17080 pg/ml vs. upper compartment: median 1603 pg/ml, range 1070-8062 pg/ml; p = 0.004.). Spontaneous rupture of the gestational membranes at term was not associated with a significant change in the amniotic fluid concentrations of immunoreactive MCP-1. CONCLUSIONS: Immunoreactive MCP-1 is a physiological constituent of the amniotic fluid. The amniotic fluid levels of immunoreactive MCP-1 increase during spontaneous labor at term. A topographic difference in the concentration of immunoreactive MCP-1 was observed in the amniotic cavity, with higher concentrations being noted in the lower amniotic fluid compartment, as compared with the upper amniotic fluid compartment. These findings support the hypothesis that MCP-1 may play a role in the final common pathway of spontaneous labor.

Adolescent↗

PubMed1999

A mechanistic-based approach for assessing chemical hazards to parturition.

Evaluations of environmental hazards to pregnancy often overlook the potential for chemicals to disrupt the final event, childbirth. There are relatively few epidemiologic studies on this topic and even fewer toxicologic investigations. Mechanistic-based approaches offset many of the difficulties that are anticipated with intact laboratory animals, such as interspecies variability in the initiating events, and may allow for rapid and relevant assessment of potential chemical hazards. In vitro systems based on knowledge of the cellular events that underlie parturition may, therefore, facilitate investigation of toxicologic aspects of parturition. Nonetheless, limitations of in vitro mechanistic-based approaches exist. Ultimately, the greatest understanding of risk to pregnancy from environmental chemicals is likely to result from the collaborative efforts of laboratory scientists and epidemiologists.

Animals↗

PubMed1997

Nitric oxide synthase activity and localization do not change in uterus and placenta during human parturition.

Animal studies have suggested that nitric oxide, a smooth muscle relaxant, is a fundamental mediator in the initiation of parturition. The purpose of this study was to test the hypothesis that the onset of human labour is associated with a reduction in the activity of the enzyme nitric oxide synthase (NOS), within the uterus. Samples of myometrium, placenta, decidua and fetal membranes were collected during Caesarean section from 11 women before and 11 women after the onset of labour at term. Immunocytochemistry was used to localize each of the three isoforms of NOS (endothelial NOS, brain NOS, and inducible NOS) in each of these tissues and the intensity of staining was qualitatively assessed. NOS enzyme activity was determined in homogenates of frozen myometrium, placenta and fetal membranes (with attached decidua), by measuring conversion of radio-labelled L-arginine to L-citrulline. Each of the three isoforms of NOS was localized in each of the tissues. We found no difference in either the expression or enzyme activity of NOS in myometrium, placenta or fetal membranes before and during labour at term. These results suggest that, in contrast to animal studies, a decrease in NOS enzyme activity may not be involved in the onset of parturition at term in the human.

Enzyme Activation↗

PubMed1999

Parturition at term: parallel increases in interleukin-8 and proteinase concentrations and neutrophil count in the lower uterine segment.

A relationship was sought between the tissue concentrations of interleukin (IL)-8, matrix metalloproteinase (MMP)-8 and MMP-9, and the numbers of the various leukocytes infiltrating the lower uterine segment stroma during parturition. Biopsy specimens of the lower uterine segment were obtained from 63 women undergoing Caesarean section at various stages of cervical dilatation at term. The concentrations of IL-8, MMP-8 and MMP-9 were determined with enzyme-linked immunosorbent assays, and the leukocytes were quantified immunohistochemically. The median IL-8 concentration (pg/mg total protein) rose significantly from 17.2 at < 2 cm dilatation, to 26.5 at 2 to < 4 cm dilatation, and 1954.0 at 4-6 cm dilatation, and remained at approximately this concentration at > 6 cm dilatation. The median MMP-8 concentration (ng/mg total protein) increased significantly from 32.2 at < 2 cm dilatation to 114.2 at > 6 cm dilatation. The median MMP-9 concentration (ng/mg total protein) rose significantly from 15.4 at < 2 cm dilatation to 102.1 at > 6 cm dilatation. The number of neutrophils was significantly higher at 4-6 cm and > 6 cm dilatation than at > 2 cm, reaching maximum values at > 6 cm dilatation. The findings in this study support the hypothesis that IL-8-induced infiltration of the cervical stroma by neutrophils and subsequent release of proteinases may play a key role in parturition.

Adult↗