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Delayed ovulation and parturition in a viviparous alpine lizard (Niveoscincus microlepidotus): morphological data and plasma steroid concentrations.

The southern snow skink, Niveoscincus microlepidotus, exhibits an unusual biennial reproductive cycle with an extended gestation period of approximately 1 year. Morphological data were gathered on a monthly basis, providing a detailed picture of the reproductive cycle. Vitellogenesis begins in spring, immediately after parturition. Maximum follicular diameter is reached before the winter hibernation period and ovulation occurs the following spring. Embryos are fully developed and reach maximum size by early autumn. Yolk reserves are depleted before winter. Birth of between one and four young occurs the following spring. Plasma progesterone concentrations are low (2.7 +/- 0.9 ng mL(-1)) in post-partum females, begin to rise in autumn in vitellogenic females and peak (38.5 +/- 7.9 ng mL(-1)) in pre-ovulatory females after hibernation. Concentrations are high (15.4 +/- 5.9 ng mL(-1)) in early pregnancy and decline to basal levels before winter and well before birth in spring. Plasma oestradiol concentrations peak during vitellogenesis (1.0 +/- 0.3 ng mL(-1)) and decline to basal levels during pregnancy (0.2 +/- 0.03 ng mL(-1)). A second oestradiol peak occurs before parturition (0.7 +/- 0.2 ng mL(-1)). Thus, functional completion of vitellogenesis and gestation is achieved by autumn in successive years. The mechanisms that defer ovulation and parturition by a further six months are unknown.

Animals↗

Neutrophil elastase and secretory leukocyte protease inhibitor in prelabor rupture of membranes, parturition and intra-amniotic infection.

OBJECTIVE: Neutrophil elastase (NE), a multifunctional serine protease stored in azurophilic granules of mature neutrophils, is capable of intracellular degradation of proteins during phagocytosis and extracellular degradation of connective tissue during an inflammatory process. Secretory leukocyte protease inhibitor (SLPI) is a natural NE inhibitor present in amniotic fluid, fetal membranes and cervical mucus. An imbalance between NE and SLPI has been implicated as a mechanism of abnormal tissue destruction in chronic inflammatory diseases. The purpose of this study was to determine if parturition, premature rupture of the membranes (PROM) and microbial invasion of the amniotic cavity are associated with changes in amniotic fluid concentrations of NE and SLPI. STUDY DESIGN: Amniotic fluid was retrieved by amniocentesis from 380 patients in the following groups: (1) preterm labor and intact membranes without microbial invasion of the amniotic cavity who delivered at term (n = 13) or prematurely (n = 26), and preterm labor with microbial invasion of the amniotic cavity (n = 9); (2) preterm PROM with (n = 34) and without (n = 51) microbial invasion of the amniotic cavity; and (3) term gestation without microbial invasion of the amniotic cavity with intact membranes not in labor (n = 63), in labor (n = 158), and with rupture of membranes not in labor (n = 26). Microbial invasion of the amniotic cavity was determined by a positive amniotic fluid culture for micro-organisms including aerobic, anaerobic and Mycoplasma species. NE and SLPI amniotic fluid levels were determined by highly specific and sensitive immunoassays. RESULTS: Preterm PROM was associated with a significant increase in the amniotic fluid concentration of NE. Microbial invasion of the amniotic cavity was associated with a significant increase in the amniotic fluid concentration of NE in women with preterm labor and intact membranes, as well as in women with preterm PROM. Term and preterm parturition was associated with a significant increase in the amniotic fluid concentration of NE. In the absence of microbial invasion of the amniotic cavity, preterm and term PROM were associated with a significant reduction in the amniotic fluid concentration of SLPI. CONCLUSION: Preterm PROM, microbial invasion of the amniotic cavity, and parturition at term and preterm are associated with a significant increase in the amniotic fluid concentration of NE. PROM is associated with a reduced amniotic fluid concentration of SLPI.

Adult↗

Lipopolysaccharide-binding protein in microbial invasion of the amniotic cavity and human parturition.

OBJECTIVE: Lipopolysaccharide-binding protein (LBP) is an acute-phase protein of predominantly hepatic origin, capable of binding the lipid A fraction of bacterial lipopolysaccharide (LPS). The complex LBP-LPS binds to CD14, and has been implicated in the host response to gram-negative infection. The purpose of this study was to determine whether microbial invasion of the amniotic cavity (MIAC) and parturition (term and preterm) are associated with changes in the amniotic fluid concentration of LBP. STUDY DESIGN: Amniotic fluid was retrieved by amniocentesis from 343 patients in the following groups: (1) those in mid-trimester with a subsequent normal pregnancy outcome (n = 84); (2) those in mid-trimester with a fetal loss after the procedure (n = 10); (3) those with preterm labor and intact membranes without MIAC who delivered at term (n = 36) or prematurely (n = 52), and those with preterm labor with MIAC (n = 26); (4) those with preterm premature rupture of membranes (PROM) with (n = 26) and without (n = 26) MIAC; and (5) those delivering at term with intact membranes in the absence of MIAC, in labor (n = 52) and not in labor (n = 31). The concentration of LBP in amniotic fluid was determined with a specific and sensitive immunoassay. Non-parametric statistics were used. A p value of < 0.05 was considered significant. RESULTS: LBP was detected in 98% (335/343) of the amniotic fluid samples. MIAC was associated with a significant increase in amniotic fluid concentration of LBP in women with preterm labor and intact membranes, but not in preterm PROM. Spontaneous preterm parturition was associated with a significant increase in amniotic fluid concentration of LBP. Patients who had a spontaneous fetal loss after a mid-trimester amniocentesis had a significantly higher median amniotic fluid LBP concentration than those who had a mid-trimester amniocentesis and a normal perinatal outcome. CONCLUSION: Preterm labor with MIAC and preterm parturition are associated with higher amniotic fluid concentrations of LBP than those with sterile amniotic fluid.

Acute-Phase Proteins↗

Parturition in the rat: a physiological pain model.

BACKGROUND: Pain during labor is a common and severe phenomenon, but its clinical management remains haphazard because its neurophysiology is poorly understood. In the current study, the authors evaluate the parturient rat as a relevant model to study the pharmacology of labor pain. METHODS: Control of birth timing in term pregnant rats was achieved by gavage with RU 486 (5 mg/kg) the day before the expected day of parturition. The behavioral events preceding the expulsion of the first pup were analyzed, and immunodetection of the c-Fos protein was used to evaluate the spinal neuronal activity at the lumbosacral level where genital and perineal inputs terminate. RESULTS: Hind limb and abdominal stretches occurred during labor (mean number, 57 +/- 10), arbitrarily defined as the time elapsed between the first stretch and the expulsion of the first pup (mean duration, 62 +/- 5 min). Subcutaneous oxytocin increased the frequency of stretches, accounting for the fact that these manifestations are linked to uterine contractions. Finally, epidural morphine (30 microg/10 microl) in oxytocin-treated rats, although resulting in no change of labor duration, significantly decreased the number of stretches (8 +/- 2 vs. 57 +/- 12 for epidural saline) and the number of c-Fos-positive neurons in the lumbosacral spinal segments (80 +/- 25 vs. 165 +/- 17 for epidural saline). CONCLUSIONS: These results indicate that stretches during labor in the rat correspond to a behavioral response to nociception associated with uterine contractions and suggest that parturition in the rat could be a relevant model to investigate nociceptive mechanisms associated with parturition in women.

Animals↗

The prediction of parturition date in canine pregnancy.

In bitches, the length of gestation is highly variable when measured from the day of mating, thus prediction of parturition may be greatly inaccurate when determined from this point. The ability to precisely predict the duration of pregnancy is of practical importance for managing parturition or planning caesarean section and this review analyses the methods that can be used to accurately forecast the day of parturition. At the time of breeding, determination of the luteinizing hormone surge and the initial rise in progesterone provide reliable information on gestational length of the bitch, but when pregnancy is ascertained, ultrasonography is the most useful tool to predict the delivery day. In fact, by ultrasonographic measurements of the extra-foetal and foetal structures an accurate prediction can be made both in early and late pregnancy.

Animals↗

The preterm parturition syndrome.

The implicit paradigm that has governed the study and clinical management of preterm labour is that term and preterm parturition are the same processes, except for the gestational age at which they occur. Indeed, both share a common pathway composed of uterine contractility, cervical dilatation and activation of the membranes/decidua. This review explores the concept that while term labour results from physiological activation of the components of the common pathway, preterm labour arises from pathological signalling and activation of one or more components of the common pathway of parturition. The term "great obstetrical syndromes" has been coined to reframe the concept of obstetrical disease. Such syndromes are characterised by: (1) multiple aetiology; (2) long preclinical stage; (3) frequent fetal involvement; (4) clinical manifestations that are often adaptive in nature; and (5) gene-environment interactions that may predispose to the syndromes. This article reviews the evidence indicating that the pathological processes implicated in the preterm parturition syndrome include: (1) intrauterine infection/inflammation; (2) uterine ischaemia; (3) uterine overdistension; (4) abnormal allograft reaction; (5) allergy; (6) cervical insufficiency; and (7) hormonal disorders (progesterone related and corticotrophin-releasing factor related). The implications of this conceptual framework for the prevention, diagnosis, and treatment of preterm labour are discussed.

Cytokines↗

Differential impact of prostaglandin H synthase 1 knockdown on platelets and parturition.

Platelet activation is a hallmark of severe preeclampsia, and platelet PGH synthase 1-derived (PGHS1-derived) thromboxane A(2) (TxA(2)) has been implicated in its pathogenesis. However, genetic disruption of PGHS1 delays parturition. We created hypomorphic PGHS1 (PGHS1(Neo/Neo)) mice, in which the substantial but tissue-dependent variability in the inhibition of PGHS1-derived eicosanoids achieved by low-dose aspirin treatment is mimicked, to assess the relative impact of this strategy on hemostatic and reproductive function. Depression of platelet TxA(2) by 98% in PGHS1(Neo/Neo) mice decreased platelet aggregation and prevented thrombosis. Similarly, depression of macrophage PGE(2) by 75% was associated with selectively impaired inflammatory responses. PGF(2alpha) at 8% WT levels was sufficient to induce coordinated temporal oxytocin receptor (OTR) expression in uterus and normal ovarian luteolysis in PGHS1(Neo/Neo) mice at late gestation, while absence of PGHS1 expression in null mice delayed OTR induction and the programmed decrease of serum progesterone during parturition. Thus, extensive but tissue-dependent variability in PG suppression, as occurs with low-dose aspirin treatment, prevents thrombosis and impairs the inflammatory response but sustains parturition. PGHS1(Neo/Neo) mice provide a model of low-dose aspirin therapy that elucidates how prevention or delay of preeclampsia might be achieved without compromising reproductive function.

Animals↗

Utilization of different aquaporin water channels in the mouse cervix during pregnancy and parturition and in models of preterm and delayed cervical ripening.

Biochemical changes of cervical connective tissue, including progressive disorganization of the collagen network and increased water content, occur during gestation to allow for cervical dilatation during labor, but the mechanisms that regulate cervical fluid balance are not fully understood. We examined whether aquaporins (AQPs), a family of membrane channel proteins that facilitate water transport, help mediate fluid balance in the mouse cervix during parturition. Of the 13 known murine AQPs, AQP0-2, 6, 7, 9, 11, and 12 were absent or at the limits of detection. By Northern blot and real-time PCR, AQP3 expression was low in nongravid and mid-pregnancy cervices with peak expression on d 19 and postpartum d 1 (PP1). AQP4 expression was generally low throughout pregnancy but showed a small upward trend at the time of parturition. AQP5 and AQP8 expression were significantly increased on d 12-15 but fell to nongravid/baseline by d 19 and PP1. By in situ hybridization and immunohistochemistry, AQP3 was preferentially expressed in basal cell layers of the cervical epithelium, whereas AQP4, 5, and 8 were primarily expressed in apical cell layers. Females with LPS-induced preterm labor had similar trends in AQP4, 5, and 8 expression to mice with natural labor at term gestation. Mice with delayed cervical remodeling due to deletion of the steroid 5alpha-reductase type 1 gene showed significant reduction in the levels of AQP3, 4, and 8 on d 19 or PP1. Together, these studies suggest that AQPs 3, 4, 5, and 8 regulate distinct aspects of cervical water balance during pregnancy and parturition.

Animals↗

Dynamic changes in the cervical epithelial tight junction complex and differentiation occur during cervical ripening and parturition.

Cervical epithelia have numerous functions that include proliferation, differentiation, maintenance of fluid balance, protection from environmental hazards, and paracellular transport of solutes via tight junctions (TJs). Epithelial functions must be tightly regulated during pregnancy and parturition as the cervix undergoes extensive growth and remodeling. This study evaluated TJ proteins, as well as markers of epithelial cell differentiation in normal and cervical ripening defective mice to gain insights into how the permeability barrier is regulated during pregnancy and parturition. Although numerous TJ proteins are expressed in the nonpregnant cervix, claudins 1 and 2 are temporally regulated in pregnancy. Claudin 1 mRNA expression is increased, whereas claudin 2 expression declines. The cellular localization of claudin 1 shifts at the end of pregnancy (gestation d 18.75) to the plasma membrane in a lattice pattern, consistent with TJs in the apical cells. The timing of claudin 1-enriched TJs coincides with initiation of terminal differentiation of cervical squamous epithelia as evidenced by the increased expression of genes by differentiated epithelia late on gestation d 18. The cervical ripening defective steroid 5alpha-reductase type 1 deficient mouse, which has an elevated local progesterone concentration, also has aberrant claudin 1 and 2 expressions, fails to form claudin 1-enriched TJs, and lacks normal expression of genes involved in epithelial terminal differentiation. These data suggest that changes in permeability barrier properties during cervical ripening are, in part, negatively regulated by progesterone, and that dynamic changes in barrier properties of the cervix occur during pregnancy and parturition.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Ablation of connexin43 in uterine smooth muscle cells of the mouse causes delayed parturition.

Gap junctions are characteristically increased in the myometrium during term and preterm delivery and are thought to be essential for the development of uterine contractions during labour. Expression of connexin43 (Cx43), the major myometrial gap junction protein, is increased during delivery. We have generated a mouse mutant (Cx43fl/fl:SM-CreERT2), in which the coding region of Cx43 can be specifically deleted in smooth muscle cells at any given time point by application of tamoxifen. By this approach, we were able to study long-term effects on myometrial functions that are necessary for parturition as well as gap junction intercellular communication in primary myometrial cell cultures. We found a prolongation of the pregnancy in 82% of tamoxifen-treated Cx43fl/fl:SM-CreERT2 mice as well as decreased dye coupling in cultured primary myocytes of these animals. Other parturition-specific parameters such as the regulation of oxytocin receptor, prostaglandin F receptor or progesterone remained unchanged. Our results indicate the important function of Cx43 during parturition in the living animal and suggest further strategies to investigate the role of connexins in uterine contractility in transgenic mice.

Animals↗

Differentiation and elimination of uterine natural killer cells in delayed implantation and parturition mice.

To clarify the roles of uterine natural killer (uNK) cells in implantation and parturition, differentiation and elimination of uNK cells in the pregnant uterus was examined using artificial delayed implantation (DI) and delayed parturition (DP) mice. To prepare DI mice, pregnant mice were ovariectomized on the third day of pregnancy (D3) and treated with 2 mg progesterone daily. The same amount of progesterone was administered on D15 or D17 of normal pregnant mice at 24 h intervals until sampling to prepare DP mice. The uNK cells contained PAS-positive granules on D8 in DI mice. The uNK cells in DI mice were smaller in size, and differentiation of these cells was delayed compared to those of the control mice. From D19 to D21 in DP mice, the metrial gland was well developed and uNK cells were present. The number of uNK cell granules decreased on D21, and there were no uNK cells in the normal pregnant mice. This result suggests that differentiation of uNK cells is not directly related to implantation, but elimination of these cells is closely involved in parturition.

Animals↗

Excretion patterns of fecal progestagens, androgen and estrogens during pregnancy, parturition and postpartum in okapi (Okapia johnstoni).

The aim of the present study was to establish a simple method to monitor ovarian activity and non-invasively diagnose pregnancy in okapi (Okapia johnstoni). The feces of a female okapi were collected daily or every 3 days for 28 months. Steroids in lyophilized feces were extracted with 80% methanol, and the fecal levels of immunoreactive progestagens (progesterone and pregnanediol-glucuronide), androgen (testosterone), and estrogens (estradiol-17beta and estrone) were determined by enzyme immunoassays with commercially available antisera. Using the progesterone profiles, the durations of the luteal phase, follicular phase, and estrous cycle were determined to be 11.1 +/- 0.4, 5.3 +/- 0.6, and 16.5 +/- 0.7 days (n=22), respectively. Fecal levels of immunoreactive progesterone, pregnanediol glucuronide, and testosterone gradually increased from early pregnancy and peaked several months before parturition. More pregnanediol glucuronide was excreted in feces than progesterone during late pregnancy, but not during the estrous cycle. Although the fecal concentrations of immunoreactive estradiol-17beta and estrone change a little throughout pregnancy and non-pregnancy, they rose sharply and temporarily on the day following parturition. The present study indicates that fecal assays with commercial antisera for progesterone and pregnanediol glucuronide are useful for evaluating luteal activity and diagnosing pregnancy and indicates that estrogens might have some role as a trigger of parturition.

Androgens↗

Matrix metalloproteinase 3 in parturition, premature rupture of the membranes, and microbial invasion of the amniotic cavity.

OBJECTIVE: Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that are expressed in many inflammatory conditions and contribute to connective tissue breakdown. Stromelysin 1 [matrix metalloproteinase 3 (MMP-3)], a novel member of this family, is produced in the context of infection and is able to activate the latent forms of other MMPs. The purpose of this study was to determine if parturition (either term or preterm), premature rupture of the membranes (PROM), and microbial invasion of the amniotic cavity are associated with changes in amniotic fluid concentrations of MMP-3. STUDY DESIGN: A cross-sectional study was conducted, which included women who underwent transabdominal amniocentesis (n = 365) in the following categories: (1) mid-trimester with a subsequent normal pregnancy outcome (n = 84) and a subsequent fetal loss (n = 10); (2) preterm labor with intact membranes without microbial invasion of the amniotic cavity who delivered at term (n = 36), or prematurely (n = 50), and preterm labor with microbial invasion of the amniotic cavity (n = 25); (3) preterm PROM with (n = 25) and without (n = 26) microbial invasion of the amniotic cavity; (4) term with intact membranes in the absence of microbial invasion of the amniotic cavity, in labor (n = 52) and not in labor (n = 31); and (5) term with PROM in the absence of microbial invasion of the amniotic cavity and not in labor (n = 26). MMP-3 concentrations in amniotic fluid were measured by a sensitive and specific immunoassay that was validated for amniotic fluid. MMP-3 concentrations were normalized using logarithmic transformation for statistical analysis. Parametric statistics were used and a p value < 0.05 was considered statistically significant. RESULTS: (1) MMP-3 was detected in 99.5% (363/365) of amniotic fluid samples, and its concentration did not change with advancing gestational age. (2) Spontaneous parturition at term and preterm was associated with a significant increase in amniotic fluid MMP-3 concentrations (p = 0.04 and p = 0.002, respectively). (3) Spontaneous rupture of membranes in term and preterm gestations was not associated with significant changes in amniotic fluid MMP-3 concentrations. (4) Intra-amniotic infection was associated with a significant increase in amniotic fluid MMP-3 concentrations in both women with preterm labor and intact membranes (p = 0.03), and women with preterm PROM (p = 0.02). (5) Subsequent fetal loss after genetic amniocentesis was not associated with significant changes in mid-trimester concentrations of amniotic fluid MMP-3. CONCLUSIONS: (1) MMP-3 is a physiologic constituent of amniotic fluid. (2) MMP-3 may play a role in the mechanisms of human parturition and in the regulation of the host response to intrauterine infection.

Amnion↗

Parturition body size and body protein loss during lactation influence performance during lactation and ovarian function at weaning in first-parity sows.

We investigated the effect of body protein mass at parturition and different degrees of body protein loss in lactation on sow performance. In a 2 x 2 factorial arrangement, 77 Genex gilts were fed to achieve either a standard or high body mass at parturition and to lose either a moderate (MPL) or high (HPL) amount of protein in lactation. Pregnant gilts were fed either 24.4 MJ of ME, 266 g of CP, and 11 g of lysine/d or 34.0 MJ of ME, 436 g of CP, and 20 g of lysine/d resulting in divergent (P < 0.01) live weights (165 vs. 193 kg) and calculated protein masses (24.3 vs. 30.0 kg) and slightly different backfat depths (20.0 vs. 22.8 mm; P < 0.05) at parturition. Diets fed during lactation were formulated to deliver 731 g of CP and 37 g of lysine/d or 416 g of CP and 22 g of lysine/d to induce differential body protein mobilization. Sows were slaughtered at weaning (d 26), and the weight of the organs and the lean, fat, and bone in five primal cuts was measured. The external diameter of the eight largest follicles on each ovary was recorded, and the follicular fluid from these follicles was collected, weighed, and analyzed for estradiol. Losses in lactational live weight (26 vs. 20 kg; P < 0.01) and calculated protein mass (17.8 vs. 10.7%; P < 0.001) were greater, and the carcass lean mass at weaning was 10% lighter (P < 0.05) in HPL sows. Backfat (5.1 +/- 0.8 mm; P = 0.29) and calculated fat mass (25.8 +/- 1.5%; P = 0.84) losses did not differ between treatments. Both sow body mass (P < 0.05) and lactation protein loss (P < 0.01) affected litter growth rate. Litter growth rate decreased (P < 0.05) at the end of lactation in HPL sows once these sows had lost 10 to 12% of their calculated protein mass. Ovarian follicular development was most advanced in high body mass sows that lost the least protein; these sows had the heaviest (P < 0.05) uterine weight and highest (P < 0.05) follicular fluid estradiol concentration. Follicular development was least advanced in standard body mass sows that lost the most protein. These sows had the lowest (P < 0.05) muscle:bone ratio at weaning and likely lost the largest proportion of their muscle mass compared with the other treatments. In conclusion, ovarian function at weaning and litter performance was higher in high body mass sows and in sows that lost the least protein in lactation, suggesting that a larger lean mass may delay the onset of a decrease in performance in sows that lose protein in lactation.

Adipose Tissue↗

Effect of mastectomy on milk fever, energy, and vitamins A, E, and beta-carotene status at parturition.

The objective of this study was to compare blood profiles of intact and mastectomized periparturient cows to discriminate those metabolic changes associated with the act of parturition from the metabolic changes caused by lactation. Mastectomized and intact cows had similar increases in plasma estrogens and cortisol concentrations around the time of calving. Mastectomy eliminated hypocalcemia and the rise in 9,13-di-cis retinoic acid observed in intact cows. Mastectomy reduced but did not eliminate decreases in plasma phosphorus, alpha-tocopherol, and beta-carotene associated with parturition in intact cows, suggesting the mammary gland is not the sole factor affecting plasma concentrations of these compounds. Dry matter intake was similar in both groups before calving. The day of calving, dry matter intake was lower in intact cows than in mastectomized cows, but after calving the mastectomized cows exhibited a pronounced decline in feed intake. Plasma nonesterified fatty acid (NEFA) concentrations rose rapidly in intact cows at calving and did not return to baseline level for > 10 d. In contrast, NEFA concentrations in mastectomized cow plasma rose moderately at calving and returned to baseline level 1 to 2 d after calving. This study provides evidence that hypocalcemia in the cow is solely a result of the calcium drain of lactation. The act of parturition affects blood phosphorus, dry matter intake, and NEFA concentration independent of the effect of lactation.

Animals↗

Calcium metabolism in cows receiving an intramuscular injection of 1,25-dihydroxyvitamin D3 combined with prostaglandin F(2alpha) closely before parturition.

To determine the effect of exogenous 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] combined with induced parturition on calcium (Ca) metabolism, cows received a single intramuscular injection of 1,25(OH)2D3 and prostaglandin F(2alpha) (PGF(2alpha)) closely before calving. Ten late-pregnant, multiparous Holstein cows were assigned to 1,25(OH)2D3 group (five treated with both 1,25(OH)2D3 and PGF(2alpha)) and control group (five treated with PGF(2alpha)). 1,25(OH)2D3 group showed an increase in plasma Ca concentration around parturition, whereas control group revealed a decrease in plasma Ca level. Plasma Ca concentration in 1,25(OH)2D3 group were significantly higher than that in control group during -0.5 to 3 days after parturition.

Animals↗

Matrix metalloproteinases-9 in preterm and term human parturition.

OBJECTIVE: Spontaneous rupture of the fetal membranes occurs after the commencement of labor in 90% of cases. Recent evidence indicates that the process of parturition requires not only an increase in myometrial contractility and cervical ripening, but also degradation of extracellular matrix in fetal membranes (i.e., leakage of fibronectin into cervico-vaginal secretions). This study was undertaken to determine if parturition is associated with in vivo evidence of increased bioavailability of matrix metalloproteinases-9 (MMP-9) and its inhibitor, tissue inhibitor of metalloproteinases-1(TIMP-1). METHODS: A cross-sectional study was conducted with women in the following categories: 1) midtrimester (n = 25); 2) preterm labor and intact membranes in the absence of intraamniotic infection (n = 78); 3) term not in labor (n = 25); and 4) term with intact membranes in labor (n = 25). MMP-9, and TIMP-1 were measured using sensitive and specific immunoassays. RESULTS: 1) Spontaneous labor at term was associated with a significant increase in MMP-9 but not in TIMP-1.2) Women with preterm labor who delivered prematurely had significantly higher concentrations of MMP-9 but not TIMP-1 in amniotic fluid than those with preterm labor who delivered at term. 3) The concentrations of TIMP-1 decreased with advancing gestational age. In contrast, MMP-9 concentrations did not change with advancing gestational age. CONCLUSIONS: Spontaneous human parturition is associated with specific changes in the enzymatic machinery responsible for extracellular matrix degradation.

Amniotic Fluid↗

The role of prostaglandins in parturition, with special reference to the rat.

The evidence which suggests a role for prostaglandins in parturition is reviewed, with special reference to experimental observations on the rat. The pregnant uterus can both synthesize and metabolize prostaglandins. The biosynthetic capacity of the rat uterus increases as pregnancy proceeds. This increase, which is especially marked during the last few days of pregnancy, may be oestrogen-controlled. During pregnancy the tissue levels of the major prostaglandin-metabolizing enzyme, 15-hydroxyprostaglandin dehydrogenase (EC 1.1.1.141) is greatly increased. This may prevent aberrant production of prostaglandins from terminating the pregnancy prematurely. The capacity for prostaglandin metabolism begins to fall (perhaps under hormonal control) as the expected day of delivery approaches; this, coupled with an augmented biosynthesis, produces a net increase in uterine prostaglandins which contribute to the process of parturition by causing a decrease in progesterone concentration, increasing the muscular tone of the uterus, and altering uterine haemodynamics. Agents which block either prostaglandin synthesis or metabolism delay or accelerate the parturition process in the rat.

Animals↗