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C J Lockwood

Publications and source records attributed to C J Lockwood.

At least 37 records · Page 2Linked to original sources
PubMed2000

Expression of angiopoietin-2 by human endometrial endothelial cells: regulation by hypoxia and inflammation.

The functional endometrial layer receives the implanting blastocyst, but is sloughed off during menstruation. Angiogenesis regulates growth and repair of cycling human endometrium. While vascular endothelial growth factor initiates angiogenesis, the angiopoietins (Angs) acting via the Tie2 receptor, are key regulators of subsequent angiogenic steps. This study is the first to localize Ang-2 and Tie2 in human endometrium and to study Ang-2 regulation in cultured human endometrial endothelial cells (HEECs). Immunohistochemistry revealed that expression of Ang-2 and Tie2 was absent from the glands, low in stromal cells, and intense in the endothelial cells. In contrast, only weak expression of Ang-1 was detected. The phase of the menstrual cycle did not appear to affect the expression of Ang-2 or Tie2. In vitro studies were carried out utilizing isolated HEECs, the most relevant model for endometrial microvascular biology studies. Both hypoxia and phorbol-myristate-acetate enhanced Ang-2 mRNA levels in HEECs. These results suggest that Ang-2 plays a role in endometrial pathologies complicated by impaired blood flow and inflammation.

Angiopoietin-1↗
PubMed2000

The role of tissue factor in regulating endometrial haemostasis: implications for progestin-only contraception.

Abnormal uterine bleeding accounts for the unacceptably high discontinuation rate of progestin-only contraceptives. Previously, we found that in-vivo and in-vitro decidualization of human endometrial stromal cells was associated with elevated concentrations of tissue factor (TF), the primary initiator of haemostasis. Moreover, enhanced TF expression required progesterone receptor (PR) and epidermal growth factor receptor (EGFR) mediation. In the current study, endometrial biopsies were sampled from bleeding (BL) and non-bleeding (NBL) sites under camera-directed hysteroscopic guidance after Depo-provera injections. When compared with control biopsies, immunohistochemical examination revealed that 3 months of Depo-provera contraception reduced TF concentrations at the BL sites. However, there were ample EGFR and PR concentrations at BL and NBL sites. Moreover, there was a trend towards the appearance of pathologically enlarged blood vessels at the BL sites. The use of Western blotting revealed that after 3 months of Depo-provera, concentrations of both PRB and PRA isoforms were lower at BL versus NBL sites with decreased PRA concentrations attaining statistical significance. Separate sampling of endometrial BL and NBL sites as shown here for Depo-provera contraception could prove particularly useful in identifying local factors that determine the onset of bleeding during the more protracted time-course of Norplant contraception.

Biopsy↗
PubMed2000

Human endometrial endothelial cells: isolation, characterization, and inflammatory-mediated expression of tissue factor and type 1 plasminogen activator inhibitor.

Binding of Ulex europaeus lectin to microvessels was used to isolate endothelial cells from cycling human endometrium. Cultured human endometrial endothelial cells (HEECs) exhibited endothelial cell-specific characteristics such as tube formation on a basement membrane matrix and sequestration of acetylated low-density lipoprotein. Markers for potentially contaminating epithelial, stromal, smooth muscle, and bone marrow-derived cells were not detected in the HEEC cultures. Basal and proinflammatory-stimulated immunostaining profiles for endothelial cell-specific adhesion markers, as exemplified by Von Willebrand's factor and E-selectin, were similar for cultured HEECs and human umbilical venous cord endothelial cells (HUVECs). However, HUVECs expressed several extracellular matrix proteins that were absent from cultured HEECs. In the latter, the protein kinase C agonist phorbol myristate acetate transiently enhanced tissue factor (TF) mRNA levels and elicited a more prolonged elevation in TF protein levels, but did not affect plasminogen activator inhibitor-1 (PAI-1) mRNA and protein levels. Inappropriate expression of TF, which initiates hemostasis by generating thrombin, and of PAI-1, which regulates hemostasis by acting as the primary inhibitor of fibrinolysis, can each lead to thrombosis. The differential regulation of TF and PAI-1 expression revealed in the current study emphasizes the importance of using HEECs to evaluate mechanisms regulating the hemostatic/thrombotic balance in human endometrium.

Biomarkers↗
PubMed2000

Cell type-specific regulation of fetal fibronectin expression in amnion: conservation of glucocorticoid responsiveness in human and nonhuman primates.

The appearance of oncofetal fibronectin (FFN) in cervical and vaginal secretions is predictive of human labor. Levels of FFN in amnion increase with the onset of labor in rhesus monkeys. Since glucocorticoid (GC) levels in serum and amniotic fluid increase in association with parturition, we compared GC-mediated regulation of FFN expression in cultures of amnion epithelial cells and fibroblasts isolated from human and baboon amnions. Cells were maintained with and without dexamethasone (DEX), and levels of FFN in the conditioned media were determined by ELISA. We observed that DEX treatment suppressed FFN levels in both human and baboon amnion epithelial cells, whereas it increased FFN levels in amnion fibroblasts. DEX treatment reduced FFN levels in cytotrophoblasts from human placenta and increased FFN levels in placental fibroblasts. Northern blots revealed that DEX reduced levels of fibronectin (FN) mRNA in amnion epithelial cells and cytotrophoblasts, whereas it increased FN mRNA in amnion and placental fibroblasts. We conclude that GC differentially regulates FFN expression in epithelial and mesenchymal cells from amnion and placenta. In addition, this pattern of cell type-specific FFN regulation by GC is conserved in human and nonhuman primates and may be responsible for parturition-dependent changes in FFN expression in gestational tissues.

Amnion↗
PubMed2000

Plasma apolipoprotein A-I and B concentrations in growth-retarded fetuses: a link between low birth weight and adult atherosclerosis.

Apolipoprotein B is elevated in growth-retarded compared with normally grown fetuses, demonstrating a link between low birth weight and risk of subsequent atherosclerosis. Increased apolipoprotein B levels and an elevated apolipoprotein B to A-I ratio are predictors of atherogenesis. Elevated apolipoprotein B levels in young adults have been linked to atherosclerosis in later life, whereas impaired fetal growth has been linked to higher than normal apolipoprotein B levels in adulthood. We conducted this research to test the hypothesis that circulating apolipoprotein A-I and B concentrations differ in growth-retarded compared with normal fetuses. Fetal umbilical plasma samples were obtained at diagnostic cordocenteses in 18 growth-retarded and 23 normally grown fetuses. Levels of apolipoprotein A-I and B were measured by turbidimetric assay. There were no differences in median (range) plasma apolipoprotein A-I concentrations between growth-retarded and normal fetuses [0.61 (0.30-1.42) vs. 0.60 (0.30-1.63) g/L, respectively; P = 0.94]. In contrast, we found significantly higher plasma apolipoprotein B levels in growth-retarded vs. normal fetuses [0.62 (0.37-1.84) vs. 0.40 (0.16-1.47) g/L, respectively; P<0.001]. Moreover, the ratio of apolipoprotein B to A-I was significantly higher in growth-retarded than in normal fetuses [1.00 (0.38-2.42) vs. 0.53 (0.31-1.80); P = 0.005]. Levels of apolipoprotein B are elevated in growth-retarded fetuses, suggesting a linkage between low birth weight and adult-onset atherosclerosis.

Adult↗
PubMed2000

Progestin-epidermal growth factor regulation of tissue factor expression during decidualization of human endometrial stromal cells.

Perivascular decidualized human endometrial stromal cells (HESCs) are ideally positioned to prevent peri-implantational hemorrhage during endovascular trophoblast invasion by expressing tissue factor (TF), the primary cellular mediator of hemostasis. Earlier in vivo and in vitro studies have demonstrated enhanced TF expression in estradiol (E2)-primed HESCs during progestin-induced decidualization. However, the absence of estrogen or progesterone response elements from the TF gene promoter suggests that paracrine factor(s) may mediate these effects. We now demonstrate that significant elevation of TF messenger RNA and protein levels in the cultured HESCs require incubation with both epidermal growth factor (EGF) and the progestin medroxyprogesterone acetate (MPA) added, with or without E2. By contrast, no effects were elicited by adding EGF with E2, or by the separate additions of EGF, MPA, or E2 plus MPA. Our finding, that transforming growth factor-alpha, but not transforming growth factor-beta or interleukin 1-beta mimics these EGF effects, indicates that progestin-enhanced TF expression in cultured HESCs requires activation of the EGF receptor (EGFR). Western blot analysis indicated that MPA increased EGFR levels 2-to 3-fold in cultured HESCs. The current results suggest that the progestin up-regulation of TF levels in decidualized HESCs is mediated by enhanced EGFR expression.

Adult↗
PubMed2000

Effects of norplant on endometrial tissue factor expression and blood vessel structure.

Abnormal uterine bleeding after Norplant administration is primarily responsible for the high discontinuation rate of this safe and effective long-acting implantable progestin-only contraceptive agent. Although tissue factor (TF) is the primary initiator of hemostasis, previous studies indicated that Norplant-associated bleeding persists despite relatively high TF levels in the stromal compartment. Recently, we determined that progestin-enhanced TF expression during decidualization of human endometrial stromal cells involves both the epidermal growth factor receptor and progesterone receptor (PR]. The current study evaluated TF levels in endometrial bleeding (BL) and nonbleeding (NBL) sites obtained by camera-guided hysteroscopy during Norplant contraception. After 1 yr of therapy, immunohistochemical TF levels were unexpectedly higher at BL than at NBL sites. Use of immunohistochemistry and Western blotting indicated that both sites displayed elevated epidermal growth factor receptor levels and that the BL sites exhibited high levels of the PR, as well as the PR(A) and the PR(B) isoforms. Microscopic examination of 1-yr biopsies revealed that significantly larger numbers of enlarged, distended vessels were present in BL, compared with NBL sites. Elevated TF levels and abnormally enlarged blood vessels in the BL sites are consistent with the recently discovered angiogenic role of TF. By promoting aberrant angiogenesis, chronic endometrial overexpression of TF could produce fragile vessels, which are at increased risk to bleed. Analysis of endometrial BL and NBL sites, during Norplant contraception, offers the potential of elucidating local mechanisms that control enhanced TF expression, leading to abnormal angiogenesis at specific endometrial sites.

Adult↗
PubMed2000

Regulation of tissue factor gene expression in human endometrium by transcription factors Sp1 and Sp3.

Prior studies indicate that tissue factor (TF), the primary cellular initiator of hemostasis, is persistently up-regulated in human endometrial stromal cells (HESCs) undergoing progestin-induced decidualization in vivo and in vitro. The mechanism underlying progestin enhancement of TF mRNA and protein levels in these cells involves transcriptional activation of the TF gene. Transient transfections of HESCs with the truncated TF promoters driving the luciferase reporter gene have demonstrated that the region spanning -111 to +14 bp retained differential progestin-enhancing effects. We now demonstrate that RU486 displays inhibitory effects on the progestin-induced TF promoter activity, confirming the involvement of the progesterone receptor. Since the TF minimal promoter (pTF 111 spanning -111 to +14 bp) contains three overlapping Sp1 and three Egr-1 sites, the present study determined whether Sp1 and/or Egr-1 were required for progestin-regulated TF expression. The results indicate that the three Sp1 sites are primarily responsible for both the constitutive and progestational activity of the pTF 111 promoter, whereas the Egr-1 sites have only a minor involvement in both activities. Overexpression of the Sp1 protein resulted in greater than a 6-fold induction in TF promoter activity. In contrast, no enhancement was observed when the Sp3 protein was overexpressed. The concomitant overexpression of Sp1 and Sp3 demonstrated that Sp3 completely blocked the induction of TF promoter activity by Sp1. Moreover, the addition of 10 nM mithramycin, a concentration that inhibits Sp1 binding to target DNA, blocked the progestational induction of TF mRNA expression. Immunohistochemical studies demonstrated increased Sp1 levels in perivascular stromal cells in secretory phase compared with proliferative phase endometria. In contrast, Sp3 expression was greatly decreased in stromal cells of secretory, compared with proliferative phase tissues. The levels of Egr-1 were low in both proliferative and secretory endometria. Immunocytochemistry of E2 vs. E2 + medroxyprogesterone acetate-treated HESCs demonstrated a dramatic reduction in Sp3 expression after progestin treatment, and Northern blots demonstrated progestational increases in Sp1 and reduction in Sp3 mRNA expression compared with controls. Taken together, our results demonstrate that progestin enhancement of TF gene expression in HESCs is mediated principally by Sp1. We propose that progestins regulate HESC TF gene expression in vivo by altering the ratio of Sp1 to Sp3 nuclear factors.

Base Sequence↗
PubMed2000

Minimally invasive endoscopy in the treatment of preterm premature rupture of membranes by application of fibrin sealant.

We report only the 3rd case of closure of amniorrhexis following genetic amniocentesis. Our technique is the first to use endoscopic visualization of the rupture site and apply maternal platelets and fibrinogen/thrombin (Hemaseel Haemacure Corp Sarasota F1). The patient underwent repair at 20.6 weeks, 26 days after spontaneous rupture of membranes post-amniocentesis. At the time of the procedure the amniotic fluid index was 1 cm. Patient was delivered at 32.3 weeks secondary to complications of diabetes and severe preeclampsia. The neonate had APGARS of 7 at 1 min and 8 at 5 min and was discharged home on Day 21 of life.

Adult↗
PubMed2000

Biological mechanisms underlying the clinical effects of mifepristone (RU 486) on the endometrium.

The abortifacient and menstrual effects of the potent antiprogestin, RU 486 (mifepriston) are associated with both endometrial hemorrhage and extracellular matrix (ECM) degradation. Such processes reflect reduced perivascular decidual cell hemostatic and increased ECM-degrading protease activity. In this review, we summarize the effects of RU 486 on different proteases involved in these processes and expressed by in vitro decidualized endometrium stromal cells. The expression of tissue factor (TF), the primary initiator of hemostasis; urokinase-type plasminogen activator (uPA); tissue-type plasminogen activator (tPA); plasminogen activator inhibitor-1 (PAI-1) as well as the potent matrix metalloprotease, MMP-3 was assessed. These endpoints of decidualization are regulated by progesterone. It was observed, that RU 486 blocks and reverses progestin-enhanced stromal cell TF protein and mRNA expression and PAI-1 protein and mRNA expression, whereas blocks and reverses progestin-inhibited stromal cell uPA, tPA and MMP-3 protein and mRNA expression. These coordinate enhancement of plasminogen activator and MMP-3 expression promotes proteolysis of the decidual ECM, which leads to endometrial sloughing during menstruation. Moreover, destabilization of endometrial microvessels resulting from degradation of their surrounding ECM is consistent with the heavy bleeding after RU 486 administration. On the other hand, with blocking the expression of TF and PAI-1, RU 486 creates a haemorrhagic and fibrinolytic milieu around the endometrial vessels, suggesting a mechanism for RU 486-induced endometrial hemorrhage. The steroid antagonist RU 486 (mifepristone) causes menstrual bleeding when given during the luteal phase of the menstrual cycle (1) and induces abortion in 64-85% of pregnant patients when administered before the 50. postmenstrual days (2, 3). These clinical actions are thought to reflect the antiprogestational effects of RU 486. Pathologic studies showed, that the effects of RU 486 on primate and human luteal phase endometrium include reduced stromal edema, increased venular diameter. Erythrocyte and leukocyte diapedesis, focal hemorrhage, degeneration of the stromal extracellular matrix, and eventual disruption of the superficial layer of the endometrium (4, 5). This antihormone acts at the receptor level and possibly also at the postreceptor level(s) (6). The most important mechanism of action is to compete with progesterone at the level of their respective binding site in the ligand binding domain of the progesterone receptors. The binding of RU 486 to the receptor leads to conformational changes in the DNA-binding site of the progesterone-receptor (7). As a consequnce of these changes, the interaction between the receptor and the progesterone-response elements in the promoter region of progesterone-responsive genes is altered (7). The menorrhagic and abortifacient properties of RU 486 are associated with the induction of endometrial hemorrhage. The physiological mechanisms by which human endometrium permits menstrual hemorrhage in the absence of pregnancy yet maintains hemostasis during endovascular trophoblast invasion (avoiding early abortion) has been investigated in our laboratory by evaluating endometrial expression of different proteins that play role in the process of hemostasis. Besides the endometrial haemostasis, we also examined the proteolytic processes leading extracellular matrix (ECM) degradation, which is also an integral part of menstruation. In this review we sought to summarize the biological mechanisms underlying the clinical effects of RU 486 on endometrial haemorrhage/haemostasis and on ECM degradation.

Abortifacient Agents, Steroidal↗
PubMed1999

Cervical length in uncomplicated pregnancy: A study of sociodemographic predictors of cervical changes across gestation.

OBJECTIVE: We conducted this study to evaluate sociodemographic factors associated with changes in the length of the cervix across gestation in pregnancies that resulted in term deliveries. STUDY DESIGN: This study is an observational cohort design of sonographically determined cervical length measured at 3- to 4-week intervals in 125 women with a singleton pregnancy between 20 and 32 weeks gestation. We developed a structured questionnaire to collect psychosocial and sociodemographic characteristics. We used bivariate analysis, analysis of variance, and regression analysis to study variation in cervical length. RESULTS: Overall, cervical length decreased minimally as gestational age progressed. However, among black women cervical length decreased significantly with increasing gestational age (P =.006). In addition, high psychosocial stress was associated with significantly shorter cervices later in gestation, independent of race (P =.003). Finally, women whose occupations involved skilled manual labor had shorter cervices (P =.02). CONCLUSIONS: Women who are black, under stress, or working as skilled manual laborers demonstrate significant shortening of the cervix during gestation. Given that a shorter cervix predisposes to preterm delivery, our findings provide new insights into the well-described association of these psychosocial and sociodemographic factors with an increased risk of preterm delivery.

Adolescent↗
PubMed1999

Neopterin concentrations in fetal and maternal blood: a marker of cell-mediated immune activation.

OBJECTIVE: Neopterin is generated by macrophages and monocytes in response to cytokine and endotoxin stimulation and is a sensitive marker of the severity of infectious-, autoimmune-, and alloimmune-mediated inflammatory disorders. This study was designed to evaluate fetal and maternal neopterin concentrations during the second half of pregnancy. STUDY DESIGN: We conducted a cross-sectional analysis of serum neopterin values with a sensitive radioimmunoassay in 35 paired fetal and maternal and 8 neonatal samples. The fetal and maternal samples were obtained between 20 and 38 weeks' gestation at the time of diagnostic cordocentesis. All maternal, fetal, and neonatal samples were derived from uncomplicated pregnancies resulting in term delivery of appropriately grown fetuses. RESULTS: Fetal neopterin concentrations increased across gestation (r = 0.64, P <.001), and mean values were significantly higher than paired maternal values (6.28 [+/-2.44] ng/mL vs 2.05 [+/-0.87] ng/mL, P <.001]. In contrast, maternal neopterin concentrations did not correlate with gestational age (r = 0.22, P =.24). No significant correlation was found between fetal and maternal values (r = 0.34, P =.07). CONCLUSION: Fetal neopterin values rise significantly across gestation. They are substantially greater than maternal levels and are not correlated significantly with paired maternal levels. These findings are the first report of a physiologically normal range for fetal neopterin concentrations in a sample of uncomplicated pregnancies. The values suggest progressive increases in fetal cell-mediated immunity and macrophage-monocyte activation as gestation progresses.

Biomarkers↗
PubMed1999

A central theory of preterm and term labor: putative role for corticotropin-releasing hormone.

Near the end of human pregnancy the concentration of placental corticotropin-releasing hormone in maternal blood rises exponentially. The rate of elevation of corticotropin-releasing hormone and its duration through time have been linked to the time of onset of labor. Paradoxically, although glucocorticoids are known to inhibit corticotropin-releasing hormone production within the hypothalamic-pituitary-adrenal axis, cortisol actually increases corticotropin-releasing hormone levels in several areas outside the hypothalamus, including the placenta. Placental corticotropin-releasing hormone may be an important component of a system that controls the normal maturation of the fetus and signals the initiation of labor. Abnormal elevations in corticotropin-releasing hormone, which may be a hormonal response to stressors arising in either the mother, placenta, or fetus, may prove to participate in the premature onset of parturition.

Corticotropin-Releasing Hormone↗
PubMed1999

Stress-associated preterm delivery: the role of corticotropin-releasing hormone.

OBJECTIVE: The study's objective was to provide an introduction to the role of corticotropin-releasing hormone in preterm delivery associated with stress. STUDY DESIGN: A selective review of the current literature relevant to the objective was undertaken. Published data were analyzed for relevance to the biochemical model presented. RESULTS: Preterm delivery is a leading cause of neonatal morbidity and mortality. Efforts to prevent preterm delivery have been greatly hampered by a poor understanding of the underlying pathophysiology. There is increasing clinical and laboratory evidence that many preterm deliveries result from maternal and fetal stress, which activates cells in the placenta, decidua, and fetal membranes to produce corticotropin-releasing hormone. Corticotropin-releasing hormone in turn enhances prostaglandin production in these tissues to promote parturition. CONCLUSION: Corticotropin-releasing hormone plays an important role in the etiology of preterm delivery associated with maternal or fetal stress.

Corticotropin-Releasing Hormone↗
PubMed1999

Implications of decidualization-associated protease expression in implantation and menstruation.

During progesterone-induced decidualization of estradiol (E2)-primed human endometrial stromal cells (HESCs), the interstitial-type extracellular matrix (ECM) of the follicular phase endometrium is transformed in the luteal phase to a mixture of residual interstitial- and new basal laminar-type components. This transformation is accelerated by reduced proteolytic activity of HESCs undergoing decidualization (DZ). In cultured HESCs, progestins, but not E2, induce the expression of several DZ markers, and E2 enhances these effects despite the lack of response to E2 alone. Using this well-characterized in vitro DZ model we evaluated the expression of plasminogen activators (PAs), which degrade ECM components that undergo rapid turnover, and matrix metalloproteinases (MMPs), which degrade the bulk of ECM components. Medroxyprogesterone acetate (MPA) inhibited the catalytic activity of urokinase-type PA (uPA) and tissue-type PA (tPA) as well as the expression of such MMPs as interstitial collagenase (MMP-1) and stromelysin-1 (MMP-3). Moreover, E2 + MPA elicited greater inhibitory effects on the expression of all of these proteases. Progestin inhibition of PA activities reflected reciprocal upregulation in the output of the PA inhibitor PAI-1, which produced large molar excesses of PAI-1 compared with the PAs in HESC-conditioned medium. By contrast, the tissue inhibitor of the MMPs, TIMP1, as well as gelatinase A (MMP-2), was constitutively expressed by the HESCs. In the absence of implantation, menstruation-associated degradation of the functional endometrial ECM is triggered by withdrawal of circulating ovarian steroids. This process was evaluated in cultured HESCs that were first decidualized during 10 days of exposure to E2 + MPA, and then withdrawn to steroid-free medium with and without the antiprogestin RU 486. As expected, steroid withdrawal reversed progestin-inhibited PA activity as well as the expression of MMP-1 and MMP-3 and progestin-enhanced PAI-1; much greater reversal was observed in medium supplemented with RU 486. Unlike the changes in PAI-1, neither TIMP1, nor MMP-2 expression was affected by withdrawal to steroid-free or to RU 486-medium. By altering the composition of the ECM of the luteal phase endometrium, progestin-elicited inhibition of the PAs, uPA and tPA, as well as that of the MMPs, MMP-1 and MMP-3, modulates trophoblast adhesion, migration and differentiation. Conversely, steroid withdrawal elicited increases in uPA, MMP-1 and MMP-3 activities would promote endometrial sloughing by degrading the mixture of decidual cell-derived basement membrane-like proteins and interstitial components that comprise the stromal ECM of the perimenstrual endometrium.

Decidua↗
PubMed1999

The decidua regulates hemostasis in human endometrium.

Survival of the implanting human blastocyst requires that trophoblasts gain access to the maternal circulation. This is initially achieved when syncytiotrophoblasts breach endometrial capillarlies and venules. Subsequently, extravillous cytotrophoblasts penetrate the spiral arteries to induce their morphological transformation into high-flow, low-resistance vessels. This process provides the embryo with a requisite source of oxygen and nutrients, but risks decidual hemorrhage leading to abortion and abruption. Endovascular trophoblast invasion occurs within a matrix of decidualizing endometrial stromal cells. These decidual cells are temporally and spatially positioned to create a local hemostatic milieu which can counteract the threat of hemorrhage. Prior studies from our laboratory have established that decidual cells of luteal phase and pregnant endometrium express two crucial modulators of hemostasis: 1) tissue factor (TF), the primary initiator of hemostasis via factor Xa activation; and 2) plasminogen activator inhibitor type 1 (PAI-1), the fast inhibitor of the primary fibrinolytic agent, tissue type plasminogen activator. This coordinate increase in TF and PAI-1 expression provides a mechanism by which decidual cells control local hemostasis during endovascular trophoblast invasion. Cultures of human endometrial stromal cells and decidual cells isolated from first trimester endometrium demonstrate that progestins enhance TF and PAI-1 protein and mRNA expression via the induction of crucial intermediate transcription factors. Integration of these in vivo observations and in vitro studies suggest a model by which decidua acts to maintain hemostasis during implantation and placentation.

Cells, Cultured↗
PubMed1999

Heritable coagulopathies in pregnancy.

UNLABELLED: Heritable coagulopathies are leading causes of maternal thromboembolism and are associated with an increased risk of maternal and perinatal morbidity and mortality. The most common of these disorders are antithrombin III deficiency, protein C deficiency, protein S deficiency, activated protein C resistance resulting from the factor V Leiden mutation, elevated prothrombin activity associated with a mutation in the prothrombin gene, and hyperhomocystinemia. The maternal risk of a thromboembolic episode is increased by a factor of eight in the presence of any of these heritable states. In addition, the relative risk for a stillbirth in the presence of one of these disorders is 3.6. These conditions are also associated with intrauterine growth retardation and preeclampsia. Proper management of heritable coagulopathies during pregnancy is essential to reduce the risk of these serious sequelae. Patients with newly diagnosed deep-vein thromboses or pulmonary emboli should be treated with therapeutic levels of unfractionated or low molecular weight heparin, followed by subsequent prophylactic heparin therapy. All patients with a history of thromboembolism before pregnancy or evidence of any of these coagulopathies may be offered prophylactic therapy with low molecular weight heparin. Patients with antithrombin III deficiency should receive full therapeutic heparin therapy for the entire pregnancy, irrespective of their thromboembolic history. Postpartum therapy with either heparin or warfarin is required in all cases. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES: After completion of this article, the reader will be able to describe the various heritable coagulopathies that can complicate pregnancy, to state the potential adverse effects of heritable coagulopathies in pregnancy, and to explain the management of heritable coagulopathies during pregnancy.

Activated Protein C Resistance↗