Correlation between placental bed biopsy findings, vascular cell adhesion molecule and fibronectin levels in pre-eclampsia

Objective To determine the correlation between placental bed biopsy findings, and blood levels of the vascular cell adhesion molecule (VCAM-1) and fibronectin in pre-eclampsia/eclampsia, and to evaluate the relationship between these variables and severity of the disease.
Design A prospective case-control study.
Setting Department of Obstetrics and Gynaecology, Cerrahpasa Medical Faculty, Istanbul.
Sample Thirty-five women with pre-eclampsia/eclampsia were compared with 25 healthy women with uncomplicated pregnancies. Twenty-one placental bed biopsies from pre-eclamptic pregnancies were compared with 17 from normal pregnancies.
Main outcome measures Peripheral venous blood levels of VCAM-1 and fibronectin, measured by enzyme-linked immunoassay and radial immune diffusion technique.
Results In pre-eclampsia/eclampsia, blood VCAM-1 and fibronectin levels were higher than in normal pregnancy. Levels of both fibronectin and VCAM-1 correlated significantly with the diastolic blood pressure ( r = 0.49 and r = 0.65,   P < 0.001  ). There was also a significant direct linear correlation between plasma fibronectin and VCAM-1 levels ( r = 0.57,   P < 0.001  ). Normotensive women all had normal placental bed biopsy findings and the incidence of pathological placental bed biopsy findings increased with the severity of the pre-eclampsia.
Conclusion Inadequate trophoblastic invasion of spiral arteries, and elevated levels VCAM-1 and fibronectin were found in women with pre-eclampsia. The magnitude of defective trophoblastic invasion, and blood levels of VCAM-1 and fibronectin correlate with the clinical severity of pre-eclampsia.     

Prostacyclin does not influence placental blood pool in vivo

In 20 healthy pregnant women placental blood pool was estimated by means of placental scintigrams before, during and after infusion of either prostacyclin (PGI2) or placebo for 10 min to study the effect of PGI2 on the local regulation of uterine blood flow. There was no difference in the mean number of counts between the PGI2- and the placebo-treated group. Therefore no effect of PGI2 on uteroplacental blood pool could be detected in healthy gravidae.     

Labetalol does not decrease placental perfusion in the hypertensive term-pregnant rat

The acute effect of labetalol hydrochloride, a combined nonspecific beta-adrenergic and postsynaptic alpha 1-adrenergic blocker, on maternal hemodynamics and organ perfusion was investigated in 10 hypertensive, term-pregnant, spontaneously hypertensive rats with the use of the radioactive-labeled microsphere technique. The normal fall in blood pressure during pregnancy was prevented by the reduction of litter size to two conceptuses on day 7 of gestation. Labetalol (1 to 6 mg/kg) effectively lowered mean arterial pressure 22% by decreasing cardiac output 16%; total peripheral resistance was not significantly decreased. Thus, the blood pressure lowering effect of labetalol was due primarily to its beta-adrenergic blocking effect. Regional flows to the carcass and splanchnic circulation were decreased 19% and 15%, respectively, after labetalol administration. Uterine wall and ovarian perfusion were significantly reduced, but placental perfusion was not significantly altered. Because labetalol lowers blood pressure without reducing placental perfusion, it may be a useful alternative to hydralazine for the treatment of hypertensive emergencies in pregnancy.     

Expression of TGF beta in the placental bed is not altered in sporadic miscarriage

Extravillous trophoblast invasion of uterine stroma and spiral arteries (SA) is essential for normal pregnancy and is reduced in preeclampsia and late miscarriage. The control mechanisms are not understood, but transforming growth factor-beta (TGF-beta) may be a candidate. Placental and placental bed biopsies were obtained from early (8(+0)-12(+6) weeks) euploid miscarriages (n = 10), early aneuploid miscarriages (n = 10), late (13(+0)-19(+6) weeks) euploid miscarriages (n = 10) and controls of the same gestation (n = 20). Frozen sections were immunostained for TGF-beta1, 2 and 3. Immunoreactivity of trophoblast and uterine cell populations was assessed semi-quantitatively. TGF-beta1 immunolocalization was limited to extracellular matrix in cytotrophoblast islands and cytotrophoblast shell, perivascular fibrinoid and interstitial trophoblast and did not differ in miscarriage compared with controls. TGF-beta2 was expressed additionally in endovascular trophoblast and multinucleate trophoblast giant cells. There was no aberrant TGF-beta2 immunolocalization in late miscarriage, but TGF-beta2 immunoreactivity was increased in extracellular matrix in cytotrophoblast islands in early miscarriage. TGF-beta3 was absent from all cell populations. Stromal and extravillous trophoblast TGF-beta2 immunolocalization suggests a more important role in trophoblast invasion than TGF-beta1, but neither isoform was altered in miscarriage. Altered TGF-beta localization is therefore unlikely to play a role in abnormal trophoblast invasion and SA transformation in miscarriage.     

Labetalol does not alter the placental and fetal blood flow or maternal prostanoids in pre-eclampsia

Summary. The effect of intravenously administered labetalol (1 mg/kg) on placental and fetal blood flow was studied in 13 pre-eclamptic women. Although the maternal blood pressure decreased, no changes occurred in the blood flows in the intervillous space, the umbilical vein or the fetal descending aorta, nor did the indices of peripheral vascular resistance in the fetal aorta change, but the placental vascular resistance did decrease. Labetalol had no effect on prostacyclin or thromboxane A₂ as measured by urinary 6-keto-prostaglandin F_1α and serum thromboxane B₂ respectively. These findings are clinically relevant since they suggest that labetalol reduces maternal blood pressure without interfering with the placental or fetal blood flow.     

Labetalol does not alter the placental and fetal blood flow or maternal prostanoids in pre-eclampsia

The effect of intravenously administered labetalol (1 mg/kg) on placental and fetal blood flow was studied in 13 pre-eclamptic women. Although the maternal blood pressure decreased, no changes occurred in the blood flows in the intervillous space, the umbilical vein or the fetal descending aorta, nor did the indices of peripheral vascular resistance in the fetal aorta change, but the placental vascular resistance did decrease. Labetalol had no effect on prostacyclin or thromboxane A2 as measured by urinary 6-keto-prostaglandin F1 alpha and serum thromboxane B2 respectively. These findings are clinically relevant since they suggest that labetalol reduces maternal blood pressure without interfering with the placental or fetal blood flow.     

Punch biopsy of the human placental bed

OBJECTIVE: The purpose of this study was to report our experience with placental bed biopsy with the use of forceps. STUDY DESIGN: Placental bed biopsies were undertaken transcervically under ultrasound guidance in 313 women who underwent termination of pregnancy between 7 and 20 weeks of gestation, in 104 women with a missed abortion who underwent evacuation of retained products of conception between 7 and 21 weeks of gestation, and in 13 women after vaginal delivery. Placental bed biopsies were also undertaken in 139 women who underwent caesarean delivery. Frozen sections were immunostained with monoclonal antibodies to cytokeratin, factor VIII-related antigen, and desmin. RESULTS: Of the 417 cases attempted at <22 weeks, the placental bed was successfully sampled 281 women (67%); in 229 women (55%), at least one of the biopsy specimens contained a uterine spiral artery. Success was correlated with gestational age. Figures for the late cases that were sampled during caesarean delivery were 108 of 139 cases (78%) and 66 of 139 cases (47%) and after vaginal delivery were 11 of 13 cases (84%) and 6 of 13 cases (46%), respectively. The sampling procedure did not result in any significant morbidity. CONCLUSION: With the use of forceps, uterine spiral arteries can be sampled successfully throughout pregnancy in approximately 50 % of cases.     

Chronic nitric oxide synthase inhibition in pregnant rats does not result in placental oxidative stress.

OBJECTIVE: This investigation examined the physiological and biochemical changes in pregnant rats following treatment with the nitric oxide synthase inhibitor, L nitroarginine methyl ester (L-NAME). METHODS: Pregnant and non-pregnant animals were administered L-NAME, and blood pressure and proteinuria were monitored. On day 21 of pregnancy, the animals were euthanized, and fetal and placental weight and number were recorded. Placental tissues were homogenized and assayed for lipid peroxides, protein carbonyls, superoxide dismutase, glutathione peroxidase, and thioredoxin reductase. RESULTS: Significant increases in blood pressure, urinary protein concentrations, and reduced pup weights were observed in pregnant rats treated with L-NAME. There was no significant increase in lipid or protein oxidation after treatment with L-NAME, and no difference was found in the activities of superoxide dismutase, glutathione peroxidase, and thioredoxin reductase. DISCUSSION: The L-nitroarginine methyl ester model of experimental preeclampsia induces a number of the physiological characteristics typical of the human disease however fails to initiate biochemical changes in the placenta that occur during human preeclampsia.     

Placental site does not change background uterine electromyographic activity in the middle trimester of pregnancy

OBJECTIVE: This study was performed in order to assess the potential influence of placental implantation site on transabdominal electromyographic (EMG) assessment of the uterine electrical activity in the middle trimester of pregnancy. STUDY DESIGN: In this prospective study 251 unselected, nulliparous asymptomatic women with a singleton pregnancy underwent transabdominal uterine EMG. Uterine electrical activity was recorded using bipolar electrodes placed on the abdominal surface for 20min. Regarding the placental implantation site and presence of action potentials (AP) pregnant women were divided into two groups: the anterior placenta group (APG) and the posterior placenta group (PPG). Outcome measures were differences in the median frequency (MF) and median amplitude (MA) of AP between the two groups. RESULTS: Action potentials were detected in 56 women: 33/56 in the APG versus 23/56 in the PPG. The parameters analyzed (MF, p=0.527, Fisher's exact test, and MA, p=0.255, Fisher's exact test) did not produce any statistical significant differences between the two groups. CONCLUSION: Background uterine EMG activity measured from the abdominal surface in the middle trimester of pregnancy does not depend on the placental implantation site.     

Pre-eclampsia is associated with elevated CXCL12 levels in placental syncytiotrophoblasts and maternal blood

Objectives

Placental derived vasculogenic/angiogenic substances in maternal blood are dysregulated in pre-eclampsia. We hypothesized that CXCL12, a chemokine with vasculogenic actions, is amongst such molecules.

Study design

CXCL12, CXCL16, CXCR4, and CXCR6 immunolocalization in placental tissue was analyzed in pre-eclampsia (n = 8) in comparison to controls (n = 8). CXCL12, measured by ELISA in blood, in women diagnosed with pre-eclampsia (n = 14) and prior to the development of pre-eclampsia (at 20 weeks’ gestation, n = 20) was compared with CXCL12 concentrations in gestation-matched, healthy control subjects (n = 34).

Results

In placental tissue, syncytiotrophoblast staining for CXCL12 was increased in pre-eclampsia. Maternal serum CXCL12 was increased in pre-eclampsia [2000 (SD 402) vs 1484 (SD 261) pg/ml, P = 0.01] but not in plasma obtained at 20 weeks of gestation prior to the onset of pre-eclampsia [1183 (SD 336) vs 1036 (SD 144) pg/ml, P = 0.09].

Conclusion

Our data suggest that the syncytiotrophoblast contributes to a pre-eclampsia-associated increase in CXCL12 levels in maternal blood. These findings support the hypothesis that an imbalance of angiogenic factors contributes to the pathogenesis of pre-eclampsia.     

Bone-marrow origin of endometrial granulocytes in the early human placental bed

A large number of cells in the first trimester human placenta have been shown to express leucocyte-common antigen by the use of a monoclonal antibody in an immunoperoxidase technique. The distribution of endometrial granulocytes in the decidua of early pregnancy indicates that a large proportion of these cells bear the leucocyte-common antigen and are thus bone-marrow derived.     

Adhesion molecules expression in the placental bed of pregnancies with pre-eclampsia

Objective To compare the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), platelet endothelial cell adhesion molecule-1 (PECAM-1) and E-selectin in placental bed biopsies (endothelium of spiral arteries as well as trophoblastic cells) from normal and pre-eclamptic pregnancies
Design A prospective study.
Setting 1. First Department of Obstetrics and Gynaecology, Alexandra Hospital, University of Athens, Greece. 2. Laboratory of Pathophysiology, Laikon Hospital, University of Athens
Population Sixteen placental bed biopsies from women with pre-eclampsia were compared with 20 placental bed biopsies from uncomplicated normotensive women
Main outcome measures Immunocytochemical staining of the placental bed biopsies for ICAM-1, VCAM-1, PECAM-1 and E-selectin
Results No statistically significant differences were found in the expression of the adhesion molecules ICAM-1, VCAM-1, PECAM-1 and E-selectin in the endothelium of the spiral arteries and the trophoblastic cells of the placental bed of the two studied groups
Conclusions Adhesion molecules ICAM-1, VCAM-1, PECAM-1, but not E-selectin, are expressed in the placental bed of normal and pre-eclamptic pregnancies, but there are no differences between the two groups of women. It seems that the above molecules are not likely to be implicated in the aetiology of pre-eclampsia     

Histopathological study of placental bed biopsy in placenta previa

BACKGROUND: To study placental bed biopsy changes in placenta previa and normally implanted placenta. SUBJECT AND METHOD: Fifty placental bed biopsies from 50 patients with placenta previa and 50 placental bed biopsies from normally implanted placenta were taken at cesarean section. Placental bed biopsy was stained with hematoxyline and eosin for histological examination. Both the groups were compared for trophoblastic invasion and vascular changes of placental bed spiral arteries. Statistical analysis was done by Chi-square test. RESULTS: Placenta bed biopsy was representative in 42/50 (84%) biopsy samples of the study group (placenta previa) and 35/50 (70%) of the control group (normally located placenta). Trophoblastic giant cell migration into decidua was present in 100% of representative samples of both the groups while migration into myometrium was seen in 66.67% and 51.14% of samples of study and control group. Average number of trophoblastic giant cells per sample was significantly higher in placenta previa (decidua 41.3%, myometrium 52%) than the control group (decidua 17.4%; myometrium 14.5%). Trophoblastic giant cell infiltration into myometrial spiral arterioles was higher in placenta previa (81.83 cells per vessel). Percentage of myometrial spiral arterioles showing physiological changes was significantly higher in the study group (50.39%) compared to the control group (21.14%). Incidence of inflammatory cell infiltration was higher in the study group (42.86%). Hemorrhage into decidua and myometrium were seen in biopsy samples of the placenta previa. CONCLUSION: Placenta previa is associated with significantly higher trophoblastic giant cell infiltration and physiological changes of the myometrial spiral arterioles.     

William B. Robertson - the pioneer of the placental bed

A fortuitous collaboration between British and Belgian researchers more than 50 years ago led to discovery that major obstetrical disorders, such as preeclampsia and fetal growth restriction, originate from vascular lesions in placental bed, i.e. the myometrial portion of the uterine spiral arteries. William B Robertson, a gregarious pioneering vascular pathologist, played a key role in this seminal discovery that continues to shape obstetrical research to date.