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L Vercruysse

Publications and source records attributed to L Vercruysse.

At least 19 recordsLinked to original sources
PubMed2006

The uterine spiral arteries in human pregnancy: facts and controversies.

Uterine spiral arteries play a vital role in supplying nutrients to the placenta and fetus, and for this purpose they are remodelled into highly dilated vessels by the action of invading trophoblast (physiological change). Knowledge of the mechanisms of these changes is relevant for a better understanding of pre-eclampsia and other pregnancy complications which show incomplete spiral artery remodelling. Controversies still abound concerning different steps in these physiological changes, and several of these disagreements are highlighted in this review, thereby suggesting directions for further research. First, a better definition of the degree of decidua- versus trophoblast-associated remodelling may help to devise a more adequate terminology. Other contestable issues are the vascular plugging and its relation with oxygen, trophoblast invasion from the outside or the inside of the vessels (intravasation versus extravasation), the impact of haemodynamics on endovascular migration, the replacement of arterial components by trophoblast, maternal tissue repair mechanisms and the role of uterine natural killer (NK) cells. Several of these features may be disturbed in complicated pregnancies, including the early decidua-associated vascular remodelling, vascular plugging and haemodynamics. The hyperinflammatory condition of pre-eclampsia may be responsible for vasculopathies such as acute atherosis, although the overall impact of such lesions on placental function is far from clear. Several features of the human placental bed are mirrored by processes in other species with haemochorial placentation, and studying such models may help to illuminate poorly understood aspects of human placentation.

Arteries↗
PubMed2005

The placental bed in pregnancies complicated by primary antiphospholipid syndrome.

UNLABELLED: Pregnancy in women with primary antiphospholipid syndrome (APS) is frequently associated with placental insufficiency leading to intrauterine growth restriction (IUGR)+/-fetal death, pre-eclampsia, placental abruption, premature delivery or thrombosis. The aim of this study was to investigate the placental bed in APS pregnancies for evidence of impaired trophoblast invasion, endothelial cell activation (ECA) and macrophage infiltration. METHODS: Biopsies from the presumed site of the placental bed were obtained from 12 women with treated primary APS and 16 controls. Immunohistochemical methods were employed to investigate expression of cytokeratin (trophoblasts), alpha-actin (smooth muscle), CD68 (macrophages) and VCAM-1 (as marker of ECA). Fibrinoid and elastin distribution and expression were determined by periodic acid/Schiff and orcein stain, respectively. RESULTS: Three APS pregnancies developed IUGR, one with concurrent pre-eclampsia. Eight of 12 APS biopsies were confirmed to be from the placental bed; one patient failed to meet APS criteria and was excluded from analysis; six included spiral arteries in the biopsy; 11 of 16 controls' biopsies were from the placental bed. APS biopsies had a higher concentration of inflammatory cells (p=0.0001), particularly macrophages (p=0.014). Three APS biopsies showed necrosis with hyperplastic vessels; one demonstrated arterial thromboses, but none had profound vasculopathy/atherosis or ECA. CONCLUSION: Inflammatory mechanisms in the placental bed may contribute to APS pregnancy complications.

Antiphospholipid Syndrome↗
PubMed2005

Interstitial trophoblast invasion in the decidua and mesometrial triangle during the last third of pregnancy in the rat.

Like other species with haemochorial placentation, pregnant rats show marked invasion of the uterine wall by trophoblast. While an endovascular pathway of invasion has been recognized for a long time, only recently, by application of cytokeratin immunostaining, the existence of an interstitial pathway of invasion has been established. Interstitial invasion is mainly effected by glycogen cell-like trophoblast arising from glycogen cell islands of the trophospongium opening up into the decidua, and from glycogen cell sheaths surrounding the intraplacental maternal arterial channels which are connected with the spiral arteries in decidua and mesometrial triangle. Quantitative evaluation of interstitial invasion in both maternal compartments was carried out on days 15-21, using PAS staining and cytokeratin and alpha-actin immunostaining for detecting trophoblast and defining maternal tissue compartments. Measurements of compartment size, cytokeratin-positive areas and invasion extent were performed using the KS400 image analysis system. A distinct pattern of interstitial trophoblast invasion emerged, starting from central decidual areas around the maternal arterial channels, and mushrooming into the mesometrial triangle reaching a peak at day 18, followed by gradual regression of the invaded areas. These measurements may serve as a basis for further experiments to evaluate factors which may influence the depth of trophoblast invasion.

Animals↗
PubMed2005

Endovascular trophoblast invasion and associated structural changes in uterine spiral arteries of the pregnant rat.

The involvement of endovascular trophoblast in fibrinoid deposition, replacement of the endothelium and vascular smooth muscle breakdown is studied in spiral arteries of the mesometrial triangle from day 15 to day 21 of rat pregnancy, by examining arterial cross sections after staining for cytokeratin, PAS, CD31 and alpha-actin. From day 15 to day 18 of pregnancy, fibrinoid deposition underneath the endovascular trophoblast increases gradually, whereas the amount of endovascular trophoblast in invaded arteries remains constant. CD31 staining is significantly reduced in sub-ET (= underlying the endovascular trophoblast) as compared to extra-ET (= outside the endovascular trophoblast) and no-ET (= non-invaded arterial sections) at each time-point of pregnancy examined (P < 0.005 and P < 0.0005 at each day of pregnancy), whereas alpha-actin staining is reduced both in sub-ET and in extra-ET as compared to no-ET. During pregnancy, CD31 staining in sub-ET initially declines, but increases significantly on day 21 (P < 0.001 versus d20) suggesting re-endothelialization of the vascular wall. In conclusion, changes in spiral arteries of pregnant rats reveal striking similarities with physiological changes seen in human pregnancy, thus emphasizing the usefulness of this species as an experimental model for studying normal and complicated pregnancies in humans.

Actins↗
PubMed2005

ACE inhibitor captopril reduces ecdysteroids and oviposition in moths.

By using the selective ACE inhibitor captopril, we studied the effect of the angiotensin converting enzyme (ACE) on larval growth, metamorphosis, and reproduction in a lepidopteran species, the cotton leafworm, Spodoptera littoralis. Captopril was detrimental to adult formation and oviposition, and in female moths it elicited decreasing ecdysteroid levels, but increasing trypsin activities. Our results suggest that captopril downregulates oviposition by two independent pathways. Apparently, oviposition is influenced by a complex interaction of ACE, trypsin activity, and ecdysteroid levels.

Age Factors↗
PubMed2004

The angiotensin converting enzyme inhibitor captopril reduces oviposition and ecdysteroid levels in Lepidoptera.

The role of angiotensin converting enzyme (ACE, peptidyl dipeptidase A) in metamorphic- and reproductive-related events in the Egyptian cotton leafworm, Spodoptera littoralis (Lepidoptera, Noctuidae) was studied by using the selective ACE inhibitor captopril. Although oral administration of captopril had no effect on larval growth, topical administration to new pupae resulted in a large decrease of successful adult formation. Oviposition and overall appearance of adults emerging from treated larvae did not differ significantly from those emerging from non-treated larvae. In contrast, topical or oral administration of captopril to newly emerged adults caused a reduction in oviposition. By evaluating the effect of captopril on ecdysteroid titers and trypsin activity, we revealed an additional physiological role for ACE. Captopril exerted an inhibitory effect on ecdysteroid levels in female but not in male adults. Larvae fed a diet containing captopril exhibited increased trypsin activity. A similar captopril-induced increase in trypsin activity was observed in female adults. In male adults, however, captopril elicited reduced levels of trypsin activity. Our results suggest that captopril downregulates oviposition by two independent pathways, one through ecdysteroid biosynthesis regulation, and the other through regulation of trypsin activity. Apparently, fecundity is influenced by a complex interaction of ACE, trypsin activity, and ecdysteroid levels.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Cytotoxic effects of tumour necrosis factor (TNF)-alpha and interferon-gamma on cultured human trophoblast are modulated by fibronectin.

Tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma, produced by maternal inflammatory cells, may compromise trophoblast survival at the trophoblast-maternal interface and notably in the placental bed which is invaded by trophoblast. Extracellular matrix components, e.g. fibronectin, may enhance trophoblast survival. A possible protective effect of fibronectin against toxic effects of TNF-alpha and IFN-gamma was investigated in cultured trophoblasts isolated from six human term placentas, grown on uncoated and fibronectin-coated plastics. IFN-gamma and increasing doses of TNF-alpha resulted in decreasing viability of trophoblast on uncoated as well as fibronectin-coated dishes, as shown by 3-[4, 5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assays, but for each TNF/IFN treatment condition viability on fibronectin was higher (P < 0.001). Epidermal growth factor (EGF), a growth factor reported to protect against TNF-alpha/IFN-gamma induced toxicity, resulted in further increased viability, but not if IFN-gamma was included in the treatment. EGF caused increased fibronectin secretion into the medium (P < 0.001), and double cytokeratin/fibronectin immunostaining confirmed the trophoblastic nature of fibronectin secreting cells. We conclude that fibronectin increases viability, but does not completely abolish the cytotoxic action of TNF-alpha and IFN-gamma on trophoblast. The protective effect of EGF may be related to stimulation of fibronectin secretion by trophoblast.

Cell Survival↗
PubMed1999

Pathogenesis of fetal hypomineralization in diabetic rats: evidence for delayed bone maturation.

There is some evidence that fetuses of diabetic rats (FDR) are hypomineralized. To explore the pathogenic role of decreased maternal duodenal Ca absorption, fetal hypotrophy, and decreased placental calbindin-D9K, respectively, spontaneously diabetic rats fed a 1.0% Ca diet were compared with diabetic rats treated with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] (15 ng/ 100 g) during week 3 of pregnancy, which restored duodenal calbindin-D9K concentrations to normal; with nondiabetic rats semistarved during week 3, which resulted in similar fetal hypotrophy; and with nondiabetic rats fed high cation diets (1.5% Ca-1.5% Sr and 1.5% Ca-3.5% Sr) during week 3, the latter of which repressed duodenal and placental calbindin-D9K toward concentrations measured in diabetic rats. In addition, fetal tibiae were studied histologically. Ca content was lower in 21.5-d-old FDR than in control fetuses. FDR had lower plasma osteocalcin (OC) levels and, on histomorphometry, increased hypertrophic cartilage width, indicating retarded bone maturation. Maternal 1,25(OH)2D3 treatment did not change Ca content and hypertrophic cartilage width in FDR. Fetuses of semistarved rats had plasma OC levels and hypertrophic cartilage width comparable to those of control fetuses. Fetuses of rats fed the 1.5% Ca-3.5% Sr diet were more severely hypomineralized than FDR but had higher plasma OC than both FDR and control fetuses, compatible with fetal Ca deficiency. Whereas diabetic placentas showed weak but homogeneous staining of calbindin-D9K in the labyrinth on immunohistology, degenerative zones were present in placentas of rats fed the 1.5% Ca-3.5% Sr diet. Thus, there is no mineralization defect in FDR caused by disturbed maternal duodenal Ca absorption or transplacental Ca transport, but a delay in bone maturation that is unexplained by their lower body weight.

Animals↗
PubMed1998

Interaction of interstitial trophoblast with placental bed capillaries and venules of normotensive and pre-eclamptic pregnancies.

While endovascular trophoblast invasion of the human placental bed spiral arteries has been studied extensively, no information is available on the interaction between interstitially invading trophoblast and uterine capillaries and venules. Placental bed biopsies of eight normotensive and 15 pre-eclamptic patients were double-immunostained for cytokeratin and the endothelial marker CD31, providing satisfactory staining results in six and 10 biopsies, respectively. Interstitial trophoblast tissue density did not differ between the two series of biopsies, implying that this pathway of invasion is not impaired in pre-eclampsia. Both groups showed a similar incidence of approach of non-arterial vascular structures by perivascular trophoblast. Differences in CD31 staining intensity were noticed in different vascular cross-sections. Lower staining intensity was related to the presence of perivascular trophoblast. Because of the identity of CD31 with the platelet-endothelial cell adhesion molecule (PECAM)-1, the trophoblast-dependent downregulation of CD31 may play a role in the control of leukocytic traffic within the placental bed. The phenomena described in this paper did not show any difference between the normotensive and pre-eclamptic patients, implying that interaction of interstitial trophoblast with venous and capillary structures is not related to the pathogenesis of pre-eclampsia.

Adult↗
PubMed1998

Immunolocalization of tumour necrosis factor-alpha (TNF-alpha) in the placental bed of normotensive and hypertensive human pregnancies.

To identify tumour necrosis factor (TNF)-alpha immunopositive cells, third trimester human placental bed biopsies were selected from nine normotensive control women, 16 severely pre-eclamptic patients and seven patients with pre-existing hypertension with superimposed pre-eclampsia. In addition, five first and early second trimester specimens were included in the study. Immunostaining was performed with a mouse IgG1 monoclonal antibody (J1D9) reactive specifically with human TNF-alpha (1:300 ascitic fluid), using a biotin-streptavidin-peroxidase technique. Variable staining of stromal cells was noted in all biopsies. Specimens of early pregnancy showed marked immunostaining for TNF-alpha on proliferating tips of anchoring villi, invasive interstitial cytotrophoblast (but not the multinuclear giant cells), and endovascular trophoblast invading the spiral arteries. At term, weak staining was found in trophoblast incorporated within spiral artery walls. In biopsies from pre-eclamptic patients, spiral arteries without physiological change showed very little staining except in atherotic vessels where the infiltrated lipophages often showed intense immunolabelling. The marked presence of TNF-alpha in extravillous cytotrophoblast of young specimens is suggestive of a role in early invasion. Immunostaining of foam cells in non-invaded spiral arteries in pre-eclampsia at or near-term indicates a potential role of this cytokine in the development of atherotic lesions.

Animals↗
PubMed1998

Renin-like immunoreactivity in uterus and placenta from normotensive and hypertensive pregnancies.

OBJECTIVES: (1) To identify the distribution of renin-like immunoreactivity in placental bed, placenta-free uterine wall, placenta, fetal membranes, and intertwin membranes obtained from normal pregnancies and (2) to compare the findings in normal pregnancies with those in pregnancies complicated by various hypertensive disorders. STUDY DESIGN: Biopsies were taken from 31 normotensive pregnant women, eight of whom had twin pregnancies, and from 28 women with various hypertensive disorders of pregnancy. The anti-human renal renin monoclonal antibody, F37.1A1, was used for immunostaining. Histological structures were identified with standard H&E and PAS techniques, supplemented with immunostaining using the specific cell markers CD68 and cytokeratin. RESULTS: Renin-like immunoreactivity was found in cytokeratin immunolabelled placental syncytiotrophoblast, amnionic and glandular epithelium, but most consistently in CD68 immunolabelled maternal and fetal macrophages. The distribution of renin-like immunoreactivity throughout the pregnant uterus roughly parallelled reported renin concentrations in the various tissues, while its localization conforms also with that of cathepsin D. There were no obvious differences in renin-like immunolabelling between normotensive or hypertensive women. Renin-like immunoreactivity was particularly common in the atherotic lesions that are observed more often in pregnancies complicated with hypertensive disorders of pregnancy and/or intra-uterine growth restriction. CONCLUSIONS: The data complement earlier findings showing that only two of four anti-renal renin monoclonal antibodies, both of which cross-react with cathepsin D, give a positive immunostaining in placental tissue. They question whether classical concepts on renin localisation in uteroplacental tissues all relate to one and the same enzyme. The demonstration of renin-like enzymes in different cell types, including macrophages, may explain the diversity of functions that has been attributed to uterine renin. There were no differences between tissues obtained from normotensive and hypertensive pregnancies, except for the consistent presence of renin-like immunoreactivity in atherotic lesions.

Antigens, CD↗
PubMed1997

Quantitative differences in arterial morphometry define the placental bed in preeclampsia.

The purpose of this study was to quantitatively analyze normal and preeclamptic uteroplacental vasculature. Myometrial arteries from eight placental bed biopsies from uncomplicated term deliveries and 12 from proteinuric preeclampsia were characterized as uteroplacental, spiral, or basal arteries. Basal lumens within 0.2 mm radius and spiral/uteroplacental lumens within 0.4 mm radius were considered as the same artery. The biopsy area, lumen density, and arterial density (after correction for multiple lumens), lumen area, lumen perimeter, mean wall thickness, inflated diameter, and a slant factor, measuring the obliqueness of arterial transection, and ratios of lumen characteristics to mean wall thickness were analyzed. In preeclamptic cases, there were more basal lumens/mm2 and basal arteries/mm2 (P=.003, P=.03), and more spiral lumens/mm2 and spiral arteries/mm2 (P = .01, P = .03). Basal lumen area (P = .0003) and wall thickness (P = .007), and basal and spiral artery lumen perimeters and inflated diameters (for each, P = .0001, P = .048, respectively) and inflated diameter/wall ratios (P = .04, P = .05) were reduced compared with normal cases. Preeclamptic spiral and basal arteries are more tortuous or densely distributed than normal placental bed arteries, with smaller-caliber lumens and thicker walls. Failure of proper placentation may result in abnormal spatial anatomy in the placental bed. Alternatively, an anatomic variant of spiral and basal arteries may be more susceptible to hemodynamic stresses and endothelial damage and may predispose to preeclampsia.

Arteries↗
PubMed1997

The endocrine pancreas in virgin and pregnant offspring of diabetic pregnant rats.

Diabetes of the mother during pregnancy induces structural and functional adaptations in the fetal endocrine pancreas. We have previously shown in our experimental rat model, that the impact of this abnormal intra-uterine milieu leads, in the adult offspring, to a disturbance of the glucose homeostasis and to the development of gestational diabetes. The aim of the present work is to investigate wether these functional differences can be explained by structural differences at the level of the endocrine pancreas. Therefore the size and the structure of the endocrine pancreas, as well as the contribution of the insulin-, glucagon-, somatostatin- and PP-cells, were investigated morphometrically in the adult youngsters of mildly and of severely diabetic mothers, since both display a disturbed glucose tolerance but with divergent characteristics. Also the adaptation of their endocrine pancreas to pregnancy was measured and compared to that of a control pregnancy. In the offspring of mildly diabetic mothers, the size of the endocrine pancreas and the distribution of the islets of Langerhans are normal. Also the doubling of the endocrine mass during pregnancy is similar to controls. The high proportion of A-cells, especially in relation to a normal B-cell mass and the low amount of PP-cells, might play a role in the impairment of the insulin response in these animals and in the development of gestational diabetes. In the offspring of severely diabetic mothers a clear hypertrophy of the endocrine pancreas is noted, which is mainly due to the presence of numerous small islets and which does not increase further during pregnancy. In these animals, the size of the endocrine pancreas and of the B-cell mass have reached 'pregnant' values without pregnancy, which coincides with an exaggerated insulin output and peripheral insulin resistance, as during normal pregnancy. No further increase in islet mass is seen during pregnancy, which is associated with gestational diabetes.

Animals↗
PubMed1996

Attachment and differentiation in vitro of trophoblast from normal and preeclamptic human placentas.

OBJECTIVE: Trophoblast from preeclamptic patients shows impairment of various functions, including restricted invasive behavior of extravillous trophoblast. In this light the effect of different matrix components on attachment and differentiation of primary trophoblast cultures derived from normal and preeclamptic pregnancies was investigated. STUDY DESIGN: Trophoblast was isolated from placentas of normotensive (n = 5) and preeclamptic patients (n = 5) and cultured up to 7 days on LabTek slides precoated with fibronectin, laminin, or vitronectin. Attachment was evaluated 24 hours after plating, the degree of syncytialization was evaluated, and slides were immunocytochemically stained for cytokeratin, vimentin, human chorionic gonadotropin, and human placental lactogen. RESULTS: Trophoblast from placentas of preeclamptic patients showed a significantly lower attachment on fibronectin and vitronectin compared with controls. Diminished multinuclear cell formation was found on uncoated and laminin-coated slides in preeclamptic cases. No difference was found in the percentage of human chorionic gonadotropin- and human placental lactogen-positive cells between groups. CONCLUSIONS: Lower trophoblast attachment on fibronectin and vitronectin was observed in preeclamptic pregnancies, which may reflect differences in expression of matrix receptors. Lower syncytialization of trophoblast in this group indicates an intrinsic defect in differentiation, but otherwise no differences were found in differentiation between normotensive and preeclamptic patients.

Adult↗
PubMed1996

Evaluation of trophoblast invasion in placental bed biopsies of the baboon, with immunohistochemical localisation of cytokeratin, fibronectin, and laminin.

Biopsies of placentas (n = 21), placental bed (n = 17) and decidua (n = 26) of various gestation periods (30 to 140 days) were used to study trophoblast invasion in the baboon. Application of immunohistochemical staining for cytokeratin allowed proper identification of trophoblast. Earlier reports showing restricted trophoblast invasion in this species were confirmed by the finding that endovascular trophoblast was present in only one third of biopsies containing spiral arteries. Moreover, immunostaining for cytokeratin revealed that in several arteries only a few isolated trophoblastic cells were present, while the vessel had not undergone the normal physiological change. Trophoblast invasion could only be detected within decidual, but not in myometrial, segments of spiral arteries. Interstitial trophoblast invasion was very limited and multinuclear giant cells were absent. Immunohistochemical staining suggested a contribution of laminin to the fibrinoid deposition within the physiologically changed spiral arteries, while fibronectin was present intracellularly in the invaded trophoblast. Because of differences in the trophoblast invasion pattern, the baboon cannot be regarded as a satisfactory experimental model to explore results of inadequate endovascular trophoblast invasion which, in the human, leads to pregnancy complications such a preeclampsia.

Animals↗
PubMed1995

Renin-like immunoreactivity in human placenta and fetal membranes.

Five antibodies that stained renin in the kidney were used to investigate the presence of renin in human placenta and fetal membranes. Despite a large number of experimental approaches to enhance penetration of the immunoglobulins, only two of them showed immunostaining in placenta and fetal membranes. Staining was found in placental syncytiotrophoblast, the amnionic epithelium overlying the placenta, and in glandular epithelial cells present in the decidua adhering to the fetal membranes. It was most consistent, however, in a small infiltrating cell type dispersed through the fetoplacental layers. The two antibodies that revealed immunostaining in all preparations showed high affinity cross-reactivity with cathepsin D. Among other, less plausible, explanations, this raises the possibility that the bulk of 'renin' found in placenta and fetal membranes is not identical to renal renin, but may be cathepsin D or a substance related to both cathepsin D and renin.

Animals↗