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C J Lockwood

Publications and source records attributed to C J Lockwood.

At least 73 records · Page 4Linked to original sources
PubMed1997

Biological mechanisms underlying the clinical effects of RU 486: modulation of cultured endometrial stromal cell stromelysin-1 and prolactin expression.

During in vitro decidualization of human endometrial stromal cells (HESCs), medroxyprogesterone acetate (MPA) inhibits expression of the potent extracellular matrix (ECM)-degrading protease stromelysin-1 (MMP-3), but enhances PRL expression. Consistent with its priming role in vivo, estradiol (E2) augments these effects. In the current study, immunoblot analysis revealed that coincubation with 10(-6) M RU 486 blocked the inhibition in HESC-secreted MMP-3 levels (50,000 mol wt) evoked by 10(-8) M E2 + 10(-7) M MPA. Although MPA can act as a glucocorticoid, the HESCs were refractory to 10(-7) M dexamethasone added alone or with E2. Because E2 elevates progesterone but not glucocorticoid receptor levels, MPA and RU 486 control MMP-3 expression as a progestin and antiprogestin, respectively. To study RU 486 involvement in steroid withdrawal leading to menstruation, HESCs were decidualized during 10 days incubation with E2 + MPA, and parallel cultures were kept in E2 + MPA or withdrawn to either control or RU 486-containing medium. Compared with E2 + MPA-suppressed HESCs, increases in levels of secreted MMP-3 (2.0-fold), and its 2.1-kilobase messenger RNA (10-fold) were observed in HESCs after 4 days of withdrawal to control medium, with much greater increases seen in RU 486-containing medium (10-fold protein, 100-fold messenger RNA). Previously, we showed that RU 486 up-regulated E2 + MPA-inhibited plasminogen activator expression in the cultured HESCs. Extrapolation of these in vitro observations to endometrial events following RU 486 administration suggests that coordinate enhancement of MMP-3 and plasminogen activator expression promotes proteolysis of the stromal/decidual ECM, which leads to endometrial sloughing. Moreover, destabilization of endometrial microvessels resulting from degradation of their surrounding ECM is consistent with the heavy menstrual bleeding stemming from RU 486 administration. However, in contrast to the marked RU 486-initiated reversal of MMP-3 expression, RU 486 did not significantly reverse E2 + MPA-enhanced PRL secretion by the cultured HESCs. Interestingly, decidual PRL, unlike decidual MMP-3, does not appear to play a role in menstruation. Interleukin-1 beta counteracted E2 + MPA-mediated inhibition of secreted MMP-3 levels, implying that leukocyte/trophoblast-derived cytokines can modulate steroid-regulated MMP-3 expression by stromal/decidual cells during menstruation and pregnancy.

Cells, Cultured↗
PubMed1997

Alterations in endometrial stromal cell tissue factor protein and messenger ribonucleic acid expression in patients experiencing abnormal uterine bleeding while using Norplant-2 contraception.

A high incidence of irregular uterine bleeding is the primary patient complaint limiting the utility of long term, progestin-only contraceptive agents such as Norplant. The onset of hemorrhage requires both inadequate hemostasis and impaired vascular integrity. Thus, we first tested whether Norplant-associated endometrial bleeding was accompanied by altered expression of perivascular stromal cell tissue factor (TF), the primary initiator of hemostasis. Norplant effects on TF messenger ribonucleic acid (mRNA) and protein expression by endometrial stromal cells were assessed by in situ hybridization and immunohistochemical examination of endometrial biopsies obtained from normally cycling control women (n = 14) and from patients experiencing Norplant-induced abnormal uterine bleeding (n = 24). TF mRNA and protein expression was increased 150% in secretory vs. proliferative phase endometrial specimens. By contrast, endometrial TF mRNA and protein levels were reduced during 1-6 months of Norplant treatment by about 2-fold (P < 0.05 for protein) compared to the values for control secretory phase specimens. These changes were consistent with observations that patients on Norplant begin to bleed during this interval. Further reductions of TF mRNA and protein levels to 2- and 3-fold of those in secretory phase control specimens were observed in endometria obtained after 6-12 months of Norplant therapy (P < 0.05 and P < 0.01, respectively). A modest rebound in TF mRNA and protein expression was observed after 12 months of Norplant therapy, which occurred commensurate with reduced patient complaints of abnormal uterine bleeding. Pathologically enlarged venous sinusoids were ubiquitous in endometrial specimens obtained after Norplant therapy. The combination of fragile blood vessels and reduced TF expression may account for bleeding in patients receiving Norplant therapy.

Contraceptive Agents, Female↗
PubMed1997

Human endometrial decidual cell-associated 11 beta-hydroxysteroid dehydrogenase expression: its potential role in implantation.

During pregnancy excess corticosteroid exposure can disturb the normal pattern of growth and differentiation of the primate fetus. This is normally prevented by the action of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), which converts cortisol to its biologically inactive 11-oxo form, thereby ensuring that little or no cortisol is transferred to the fetus. During implantation, extravillous trophoblasts breech uterine vessels that are embedded in a decidual cell matrix. Through this invasive process the embryo gains requisite access to the maternal blood supply, while risking exposure to high circulating glucocorticoid levels. Thus, the expression of 11 beta-HSD by the decidual cell layer may be essential in regulating cortisol exposure of the developing embryo prior to placentation. In order to investigate the potential contribution of decidual cells to glucocorticoid metabolism, we evaluated the expression of both known 11 beta-HSD isoforms, 11 beta-HSD1, whose catalytic activity is NADP(+)-dependent, and NAD(+)-dependent 11 beta-HSD2, during decidualization of monolayers of human endometrial stromal cells. The differential actions of ovarian steroids on human endometrium are simulated in this in vitro model. Thus, progestins induce the expression of several decidualization markers in the cultured stromal cells, and consistent with its priming action in vivo, estradiol augments this expression. The results of our studies established a link between in vitro decidualization and enhanced glucocorticoid metabolizing capacity. Accordingly, the catalytic activities of both 11 beta-HSD isoforms were enhanced by incubation of the precursor stromal cells with medroxyprogesterone acetate, and further enhanced by estradiol, despite a lack of response to estradiol alone. This differential response to estradiol and progestin was reflected in parallel changes in steady state levels of 11 beta-HSD1 messenger RNA. The role of glucocorticoid metabolizing activity of the decidual cell is discussed in terms of its implications in determining the exposure of the implanting embryo to biologically active glucocorticoids.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1997

[Average length of spontaneous labor in Chinese primigravidas].

OBJECTIVE: To determine if labor duration is affected by ethnicity, we measured the average length of normal spontaneous labor in recently immigrated Chinese primigravidas and compared our findings to reference primigravida populations of differing ethnicity. MATERIALS AND METHODS: In this descriptive, retrospective study of 1,006 recently immigrated low-risk Chinese primigravidas delivering singleton, vertex, term infants (37-42 weeks gestation, inclusively) without conduction anesthesia or oxytocin, the length of first-, second-, and third-stage labor, maternal age, gestational age, and infant weight was measured and compared to labor lengths previously reported for women of differing ethnicity. RESULTS: Mean first stage labor duration was 326 minutes (SD +/- 185 min, range 25-1640 min), mean second stage labor duration was 52 minutes (SD +/- 42 min, range 2-450 min), and a mean third stage labor duration was 4.6 min (SD +/- 4.5 min, range 1-62 min). Interquartile range (IQR)/median for first-, second-, and third-stage labor was 225 min/300 min, 50 min/40 min, and 3 min/3 min respectively. Weak correlations were observed between first- and second-stage labor lengths, and second- and third-stage labor lengths. Average birth weight was 3250 g (SD +/- 376 g, range 2280-4660 g). Chinese parturients showed a significantly shorter duration of first-stage (P < 0.0001) when compared to parity-matched patients of differing ethnicity. Second-stage labor in Chinese parturients was also shorter, but did not differ significantly (P = 0.185) from previously reported non-Asian controls. CONCLUSION: When compared to previously collected data from non-Chinese women, clinically significant differences in first-stage labor lengths were measured in our study population. While second-stage labor durations were also shorter, the difference was not significant. Labor management should be individualized to account for these differences, and previous reports attempting to show equivalency of labor progress regardless of ethnicity warrant reinterpretation given these findings.

Asian People↗
PubMed1996

Corticotropin-releasing factor and its binding protein: maternal serum levels in term and preterm deliveries.

OBJECTIVE: The primary objective of this investigation was to evaluate whether maternal serum corticotropin-releasing factor levels during pregnancy were predictive of spontaneous preterm delivery. STUDY DESIGN: Maternal serum levels of corticotropin-releasing factor and its binding protein were measured from 20 weeks of gestation in a cross-sectional study of 396 asymptomatic women at high risk for preterm delivery. RESULTS: Gestational age-specific corticotropin-releasing factor levels were not consistently or substantially increased for preterm compared with term deliveries, whether preterm delivery was due to preterm labor or preterm premature rupture of membranes. The binding protein for corticotropin-releasing factor did not vary according to gestational age until term, when it dropped substantially. CONCLUSION: Serum corticotropin-releasing factor levels do not appear to be an important predictor of preterm birth in asymptomatic patients who subsequently have either preterm labor or preterm premature rupture of membranes. Nevertheless, the drop in the corticotropin-releasing factor binding protein level at term suggests that the bioavailability of corticotropin-releasing factor increases as parturition approaches.

Adult↗
PubMed1996

Production of premature delivery in pregnant rhesus monkeys by androstenedione infusion.

The endocrine mechanism involved in term and preterm delivery in primates, including pregnant women, are poorly understood. In the term monkey, fetal plasma androgen concentration rises to two hundred times the maternal concentration which remains unchanged. Placental conversion of androgen to estrogen results in increased maternal plasma estrogen concentration at term in both pregnant nonhuman primates and women. In the present study, continuous infusion of androstenedione to 0.8 gestation monkeys resulted in the premature occurrence of labor-type myometrial activity and increases in maternal plasma estrogen, oxytocin and amnion fibronectin concentrations similar to those measured at normal-term labor. Androstenedione induction of these normal-term biochemical and endocrine changes accompanied by fetal membrane rupture, cervical dilatation and live delivery provides a rich opportunity to study the molecular and physiological mechanisms of both term and preterm labor in primates.

Androstenedione↗
PubMed1996

Expression of 11 beta-hydroxysteroid dehydrogenase during decidualization of human endometrial stromal cells.

This study evaluated the expression of the corticosteroid-metabolizing enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) during in vitro decidualization of human endometrial stromal cells. The cultured stromal cells displayed both NADP(+)-dependent (type 1) and NAD(+)-dependent (type 2) 11 beta HSD activities under basal conditions. Although the cells did not respond to estradiol (E2) added alone, catalytic levels of both isoforms were enhanced by medroxyprogesterone acetate (MPA) and further enhanced by E2 plus MPA. Type I messenger RNA (mRNA) was undetected by Northern analysis of total RNA, but was evident as a 1.5-kilobase band in polyadenylated selected RNA from E2- plus MPA-treated cultures. Use of RT-PCR to augment the sensitivity of mRNA detection revealed the presence of type I mRNA as a faint band in the MPA-treated cultures and as an intense band in the E2- plus MPA-treated cultures. Thus, type I mRNA is present as a low abundance message in the cultured stromal cells whose steady state levels parallel progestin-enhanced enzyme activity. As the expression of several progestin-regulated decidualization markers is also augmented by E2, the results of the present study reveal a correlation between enhanced 11 beta HSD expression and the decidualization reaction. Time-course measurements indicated that elevated 11 beta HSD expression is an early event in the decidualization response, which precedes E2- plus MPA-enhanced PRL production by several days. Clear dose-response effects on both type 1 and type 2 11 beta HSD activities were obtained in cells incubated with 10(-8) mol/liter E2 added together with MPA at concentrations that approximated circulating progesterone levels from the luteal phase (10(-9) mol/liter) through pregnancy (10(-7) mol/liter). Corticosteroids are thought to exert toxic and teratogenic effects on the implanting embryo and could influence trophoblast invasion by regulating extracellular matrix turnover. Therefore, the novel finding that decidualization involves marked enhancement of the corticosteroid-metabolizing capacity of stromal cells suggests a mechanism by which decidual cells could affect the health and invasiveness of implanting trophoblastic cells.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1996

Effects of thrombin on steroid-modulated cultured endometrial stromal cell fibrinolytic potential.

By virtue of their unique chronic expression of tissue factor, the primary initiator of hemostasis, decidualized endometrial stromal cells are capable of significant thrombin generation after vascular disruption. In addition to its potent procoagulant effects, thrombin modifies endothelial and glomerular cell fibrinolytic activity. Therefore, we evaluated whether thrombin affected the expression of endometrial stromal cell urokinase-type (uPA) and tissue-type (tPA) plasminogen activators and their primary inhibitor, type 1 plasminogen activator inhibitor (PAI-1), and whether ovarian steroids modulated putative thrombin effects. Confluent stromal cell cultures were incubated in a defined medium containing vehicle control, 10(-8) mol/L estradiol (E2), 10(-7) mol/L medroxyprogesterone acetate (MPA), or E2 plus MPA for 4 days. The medium was then collected and exchanged for medium containing the corresponding steroids with or without thrombin and the specific thrombin inhibitor, D-phenyl-alanyl-propyl-arginine-chloromethyl ketone, for an additional 24 h. The conditioned medium was then collected and analyzed for immunoreactive (ir) uPA, tPA, and PAI-1 by enzyme-linked immunosorbent assay and for PA activity by chromogenic assay, whereas Northern analysis of the cells was employed to evaluate the expression of thrombin receptor, uPA, tPA, and PAI-1 messenger ribonucleic acid (mRNA) species. The latter studies revealed that confluent cultures incubated in defined medium expressed the 3.45-kilobase thrombin receptor message. Steady state levels of thrombin receptor mRNA were unaffected by exogenous steroids. Thrombin added in the absence of exogenous steroids elevated concentrations of ir tPA, uPA, and PAI-1 compared with control cultures. Conversely, in the absence of added thrombin, MPA added alone or together with E2 inhibited levels of ir tPA and uPA while stimulating PAI-1 levels despite the lack of a response to E2 alone. Interestingly, thrombin counteracted this progestin inhibition of tPA and uPA expression and augmented the progestin-enhanced expression of PAI-1. Northern analysis revealed that steady state levels of tPA and uPA mRNA were also enhanced by thrombin in both control and steroid-containing cultures. Net PA activity reflects the balance between PA and PAI-1. In the absence of thrombin, there is virtually no detectable tPA activity and minimal uPA activity in progestin-exposed cultures. However, thrombin elicited significant increases in tPA and uPA activity in control and E2-treated cultures. Despite the molar excess of PAI-1 in MPA-treated and E2- plus MPA-treated cultures, thrombin reversed progestin inhibition of PA activity. Predictably, the addition of D-phenyl-alanyl-propyl-arginine-chloromethyl ketone, blocked the effects of thrombin on PAI-1, tPA, and uPA protein and mRNA expression and PA activity. In summary, thrombin enhances endometrial stromal cell fibrinolytic and extracellular matrix-degrading protease activity in vitro. Such processes occurring in vivo would probably play a role in menstruation and abnormal uterine bleeding.

Cells, Cultured↗
PubMed1996

Expression of Fas ligand by human cytotrophoblasts: implications in placentation and fetal survival.

Recent data indicated that local production of Fas ligand (FasL) by cells of the eye and testis may confer immune tolerance at these sites. In the present study, we examined the in vivo and in vitro patterns of expression of FasL in the human placenta to provide a potential mechanism through which the fetus is afforded protection against the cytolytic actions of lymphocytes present within maternal decidua across gestation. Immunohistochemical staining of first trimester human placental tissue sections revealed the presence of FasL in cytotrophoblasts in free floating villi, anchoring villi, and cytotrophoblastic islands. FasL staining was also pronounced in syncytiotrophoblasts of term placenta indicating that FasL expression is maintained across gestation. Multiple molecular forms of FasL, suggestive of altered patterns of glycosylation, were detected in extracts of term placenta, amnion and chorion by Western blotting. In addition, in vitro expression of FasL was demonstrated to increase 2 to 3-fold during differentiation of primary cultures of cytotrophoblasts isolated from human term placentas. Local production of FasL by human cytotrophoblasts provides a mechanism through which cytotrophoblasts may induce immune tolerance and self-regulate survival during invasion and subsequent placentation.

Antigens, Surface↗
PubMed1996

Corticotropin-releasing hormone and related pituitary-adrenal axis hormones in fetal and maternal blood during the second half of pregnancy.

There is little information available concerning the ontologic development of the human hypothalamic-pituitary-adrenal (HPA) axis nor of the potential interactions among fetal, maternal and placental-derived HPA axis hormones. This study evaluated levels of these hormones in matched maternal and fetal pairs during the second half of uncomplicated pregnancies. Immunoassays were used to measure serum concentrations of corticotropin-releasing hormone (CRH), adrenocorticotropin (ACTH) and cortisol in 104 matched fetal and maternal blood samples. Fetal specimens were obtained by percutaneous umbilical blood sampling (PUBS) between 18 and 40 weeks in patients whose pregnancies resulted in healthy, term infants. Correlations among these hormones, and the effect of gestational age were assessed. Maternal CRH concentrations [median (range)] [1.10 ng/ml (0.15 to 23.69)] were significantly greater than fetal values [0.35 ng/ml (0.07 to 1.0)]. Levels of maternal CRH (r = 0.73; p < 0.001) but not fetal CRH (r = 0.01; p = 0.98) correlated with gestational age. Maternal ACTH decreased (r = -0.21; p = 0.04) while fetal ACTH increased (r = 0.35; p < 0.003) with gestational age. Both maternal (r = 0.45; p < 0.001) and fetal (r = 0.57; p < 0.001) cortisol levels increased with gestational age. Maternal serum CRH values correlated best with fetal cortisol (r = 0.40; p = 0.0002) and correlated modestly with maternal cortisol (r = 0.28; p = 0.01), fetal ACTH (r = 0.24; p = 0.03) and fetal CRH (r = 0.23; p = 0.04); but not with maternal ACTH (r = -0.12; p = 0.3). Maternal CRH concentrations increase in the third trimester and correlate with rising fetal cortisol levels.

Adrenocorticotropic Hormone↗
PubMed1995

Fetal and maternal plasma endothelin levels during the second half of pregnancy.

OBJECTIVE: Our objective was to evaluate maternal and fetal endothelin concentrations in uncomplicated pregnancies across the second half of pregnancy. STUDY DESIGN: Paired (n = 64) maternal venous and fetal umbilical venous or arterial samples were obtained during cordocentesis. In addition, eight neonatal umbilical vein samples were obtained immediately after delivery. Samples were assessed for hematocrit and pH, and concentrations of endothelin were measured by sensitive enzyme immunoassay. RESULTS: No significant correlation was found between either fetal or maternal endothelin levels and gestational age (r = 0.01, p = 0.91 and r = 0.07, p = 0.5, respectively). Fetal plasma endothelin concentrations were significantly lower than neonatal umbilical vein endothelin levels [median 2.5 pg/ml (range 0.9 to 5.73) vs 15.77 pg/ml (8.12 to 19.58), respectively; p < 0.0001] but significantly higher than maternal levels [1.3 pg/ml (0.8 to 3.25); p < 0.0001]. In addition, endothelin values were higher in the umbilical artery than in the umbilical vein, but this difference failed to achieve statistical significance [2.89 pg/ml (1.61 to 5.73) vs 2.29 pg/ml (0.9 to 5.70), respectively; p = 0.06]. No correlation was noted between fetal and maternal endothelin levels (r = 0.12, p = 0.36). CONCLUSION: Fetal endothelin levels were significantly higher than maternal levels, but neither correlated with gestational age across the second half of pregnancy.

Endothelins↗
PubMed1995

Alloimmune thrombocytopenia: fetal and neonatal losses related to cordocentesis.

OBJECTIVE: This report describes the increased risks of cordocentesis in fetuses affected with alloimmune thrombocytopenia. STUDY DESIGN: As part of a multicenter treatment study clinical and laboratory data from five pregnancies with alloimmune thrombocytopenia in which there was a fetal or neonatal loss associated with cordocentesis were reviewed. The fetal or neonatal deaths were all thought to be a result of exsanguination. These fetuses were compared with a group of 44 affected fetuses who underwent the same procedure but who survived. The data were analyzed by the Wilcoxon rank-sum test and the two-tailed Fisher's exact test. A p value < 0.05 was considered significant. RESULTS: The mean platelet count at cordocentesis was significantly lower in the cases than in the controls (5.8 vs 32.8 x 10(9)/L, p = 0.005). The incidence of antenatal intracranial hemorrhage in the untreated sibling of the prior affected pregnancy was significantly greater in the cases than in the controls (two of five vs one of 42, p = 0.02). CONCLUSION: Fetuses affected with alloimmune thrombocytopenia are at increased risk for fatal exsanguination associated with cordocentesis.

Antigens, Human Platelet↗
PubMed1995

Accuracy of ultrasound estimation of fetal weight in multiple pregnancies.

Our objective was to assess the accuracy of ultrasonographic estimation of fetal weight in twins and triplets as compared to singleton pregnancies. Retrospective analysis was undertaken of ultrasound data of all fetuses who underwent an examination within 1 week of delivery (singletons 1832, twins 518, triplets 51). At birth weights below 2500 g, there was a significant overestimation of fetal weight in twins as compared to singletons, but the accuracy of the estimate was the same, except in twins between 1500 and 2499 g, when the weight was based on abdominal circumference and femur length alone. At birth weights of more than 2500 g, no difference was detected between twins and singletons. At all birth weights below 2500 g, the accuracy of weight estimation in triplets was equal to that in singletons and there were no triplets above this weight. We conclude that ultrasonographic estimation of fetal weight is as accurate in twins and triplets as it is in singletons.

Body Weight↗
PubMed1995

Maternal serum levels of alpha-fetoprotein and fetal fibronectin as markers of labor in the third trimester.

Unexplained elevations of maternal serum alpha-fetoprotein (MSAFP) in the second trimester have been found to be associated with a two- to fourfold increase in the rate of preterm delivery, but the sensitivity is low. Therefore, we reasoned that MSAFP levels in the third trimester could prove to be a more useful biochemical marker to predict labor. The presence of placental and membrane-derived fetal fibronectin (FFN) in cervicovaginal secretions has recently been shown to predict preterm delivery with a sensitivity of 81.7% and specificity of 82.5%. We postulated that damage to membranes and microscopic breakdown of fetomaternal blood barrier during labor might result in release of AFP or FFN into maternal serum. Maternal serum alpha fetoprotein and fetal fibronectin levels were measured prospectively in 29 patients in active labor at term and in 25 controls undergoing elective cesarean section. Neither MSAFP nor serum FFN levels were associated with labor at term. We did, however, note significantly higher MSAFP levels in mothers bearing male fetuses versus female fetuses (p < 0.01). Since the current literature supports a sex difference in the MSAFP levels in the second trimester, this does not appear to change as gestation advances. Further studies are needed to determine if, in addition to maternal weight and race, MSAFP levels should be also adjusted for fetal sex diagnosed on sonography.

Adult↗
PubMed1995

Incidence of pregnancy-induced hypertension among gestational diabetics.

Although hypertensive disorders of pregnancy are more likely to occur in pregestational diabetics, the question of whether they occur more frequently in gestational diabetics or certain subsets of gestational diabetics remains unclear. This study compared 197 gestational diabetics with 197 control patients matched on the basis of age, race, parity, and prepregnancy weight. No significant difference was found between the two groups in the incidence of either pregnancy-induced hypertension or preeclampsia. There was, however, a small but significant elevation in mean arterial blood pressure in the third trimester in gestational diabetics compared with control patients (90.1 versus 87.5 mm Hg; p = 0.006). Mean arterial pressures were also higher in diabetic patients on insulin compared with those on diet, and higher in diabetic patients diagnosed early (less than 24 weeks) compared with those diagnosed late (more than 24 weeks) in pregnancy; however, there were larger numbers of chronic hypertensives in these two groups. We conclude that gestational diabetics do not develop pregnancy-induced hypertension more frequently. Small increases in blood pressure late in pregnancy in these patients achieve statistical significance, but their clinical relevance is unclear.

Adult↗
PubMed1995

The diagnosis of preterm labor and the prediction of preterm delivery.

Clinical approaches to the diagnosis of PTL and the prediction of PTD are complicated by the absence of a gold standard for the pathogenic process leading to PTD. There is also substantial overlap between the signs and symptoms of PTL and impending PTD, and the normal processes of pregnancies destined to remain uncomplicated (e.g., our inability to convincingly differentiate PTL from Braxton-Hicks contractions). Our emphasis on the diagnosis of PTL rather than the pathogenic process preceding PTD also results in failure to detect the 50% of spontaneous PTDs in which uterine contractions follow PPROM. Thus, clinical predictors of incipient PTD including cervical change, uterine contractions, vaginal bleeding, risk scoring schemes, and fetal breathing activity, either have poor sensitivity or specificity, or are accurate only at late stages in the pathogenic process. The most promising approaches to the detection of impending PTD are laboratory indices of the putative pathogenic processes including: maternal serum or plasma CRH, salivary E3, serum collagenase and cervicovaginal cytokines, granulocyte elastase, and FFN levels. However, even if these indices prove sensitive, specific, and early predictors of PTD, they will be useful only if more appropriate therapies are found to treat patients. The latter will depend on addressing the primary causes of chorionic-decidual cell activation (e.g., infection, stress, utero-placental ischemia, hemorrhage, endocrinopathies).

Cervix Uteri↗
PubMed1995

Opposing actions of transforming growth factor-beta and glucocorticoids in the regulation of fibronectin expression in the human placenta.

Alterations in the expression of extracellular matrix (ECM) proteins in the placenta and fetal membranes have been linked to parturition whether occurring before or at term. In the present study, we examined the individual and combined effects of transforming growth factor (TGF)-beta and dexamethasone (DEX) on the expression of oncofetal fibronectin (onfFN), i.e. a major ECM protein synthesized by placenta, in cytotrophoblasts isolated from human term placentas to establish a model system from which to evaluate the actions of positive and negative regulators of ECM protein expression in the human placenta. Cytotrophoblasts were maintained for 21=62 h in medium supplemented with 4% charcoal-stripped calf serum in the presence or absence of TGF-beta (2 ng/mL) and DEX (10(-7) mol/L). Levels of onfFN in culture media were determined by immunoassay. TGF-beta treatment alone induced approximately a 150% increase in media levels of onfFN after 21 and 45 h of culture when compared with control, whereas DEX treatment alone reduced levels of onfFN to 15% of control levels. Media levels of onfFN in cells treated with both TGF-beta and DEX were 40-90% of control levels. Similarly, treatment of cells with TGF-beta alone promoted a 100-250% increase in rates of FN synthesis and levels of FN messenger ribonucleic acid, whereas DEX treatment alone reduced these indices of FN expression to approximately 10% of control levels. In cells treated with TGF-beta and DEX, levels of ECM protein synthesis and FN messenger ribonucleic acid were between 30 and 100% of control values. Similar patterns of regulation of FN expression by TGF-beta and DEX were observed when experiments were carried out in serum-free medium. Our results suggest that during pregnancy, TGF-beta and glucocorticoids may be important opposing physiological regulators of placental ECM protein expression.

Adult↗