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PubMed1991

Developmental expression of cathepsin L and c-rasHa in the mouse placenta.

An investigation is described of the expression of the cysteine proteinase cathepsin L during placental development. In addition, whether cathepsin L expression is linked to c-rasHa expression in development, as it is in metastatic cells, is examined. Large amounts of cathepsin L and its transcript are present in the mouse placenta, more than six times more than in adult kidney and liver. Throughout gestation, cathepsin L and its transcript are located in the giant cells and spongiotrophoblasts of the placenta. Several forms of different mobility on denaturing gels are found in the placenta. Their apparent molecular weights, as determined from the gels, are 43,000, 39,000, 29,000, and 20,000. The 39-kDa form is procathepsin L. The 29-kDa and 20-kDa forms are lysosomal cathepsin Ls. The 39-kDa procathepsin L and the 20-kDa mature cathepsin L are the most abundant species in the placenta and are present in about equal amounts throughout gestation. At any time during gestation, placental minces synthesize and secrete only procathepsin L. The amniotic fluid of the fetus contains the 43-kDa form of cathepsin L and procathepsin L, but no detectable amounts of mature cathepsin L. By contrast, serum from nonpregnant or pregnant mice contains three forms of cathepsin L (i.e., the 43-kDa form, procathepsin L, and mature cathepsin L). Cathepsin L and the rasHa oncogene are expressed in two coincident waves corresponding to periods during which the placenta is invasive and just before parturition. The presence of large amounts of cathepsin L in the placenta suggests that the proteinase has a significant function there. Expression of cathepsin L in the placenta is potentially under the control of the ras gene product p21; both are under developmental control.

Animals↗

PubMed1999

Tissue distribution of placenta-type 6-phosphofructo- 2-kinase/fructose-2,6-bisphosphatase.

Several isozymes of 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase have been characterized from mammalian tissues and, based on tissue origin, they are classified as liver, skeletal muscle, heart, testis, and placenta isozymes. In this paper, we examined the tissue distribution of placenta-type isozyme in rat tissues at the levels of transcription and translation. Analysis by Northern blotting showed that placenta, brain, testis, liver, kidney, and skeletal muscle expressed mRNA of placenta-type isozyme. Western blot analysis of fractions from POROS-HQ column chromatography of extracts from various rat tissues showed that proteins of placenta-type isozyme are expressed in placenta, brain, testis, liver, spleen, heart and lung, but not in kidney and skeletal muscle. An immunohistochemical study showed that, in liver, placenta-type isozyme is localized in Kupffer cells. These results indicate that isozymes of this particular enzyme may occur in particular cell types within each tissue.

Animals↗

PubMed2002

GTP-binding proteins G(salpha), G(ialpha), and Ran identified in mitochondria of human placenta.

GTP-binding proteins (GTPases) have been detected in the mitochondria of human placenta. It has been proposed that porin interacts with GTPases in the mitochondrion to modulate contact site function, however, their identity and location is not known. In this study, we investigated the location of GTPases in mitochondria from term placentae as well as the expression of mitochondrial GTPases in mid-term placentae. Mitochondria obtained from human term and mid-term placentae were purified by sedimentation. Sub-mitochondrial vesicles prepared from ruptured and sonicated mitochondria were separated by ultracentrifugation in sucrose density gradients. The location of membrane vesicles was determined using marker enzymes. Mitochondrial proteins were separated by SDS-PAGE. Western blots were incubated in [alpha-(32)P]-GTP and detected using autoradiography or antibodies against known GTPases and porin followed by enhanced chemiluminescence. [alpha-(32)P]-GTP bound 24 and 28 kDa proteins located in the outer membrane. The G(salpha)antibody detected 42.5, 53 and 67 kDa proteins. The G(ialpha)antibody identified a 40.5 kDa band in contact sites and the outer membrane, as well as 55 and 105 kDa proteins in contact site vesicles. The Ran antibody detected a 28 kDa protein, mainly in the outer membrane. Porin migrated at 30 kDa. G(ialpha)and Ran were detected in mitochondria from both term and mid-term placentae. The location of porin and GTPases leave open the possibility that these proteins interact in contact sites and may also be responding to extra-mitochondrial signals. Ran and G(ialpha)are expressed by mid-term in human placentae and may be necessary for placental functions at this stage of development. It will be important in future experiments to characterise the physiological functions of these GTP-binding proteins in the mitochondria of human placenta.

Binding Sites↗

PubMed1994

Insulin receptors in syncytiotrophoblast and fetal endothelium of human placenta. Immunohistochemical evidence for developmental changes in distribution pattern.

The localisation of insulin receptors (IR) was investigated on cryosections of human non-pathologic first trimester and full term placentae by indirect immunohistochemistry with three different monoclonal antibodies (MABS). In placentae from 6 to 10 weeks postmenstruation (p-m.), only syncytiotrophoblast was stained, predominantly that of mesenchymal villi and syncytial sprouts, which are areas of high proliferative activity. In placentae from 11 to 14 weeks p-m., endothelial cells commenced to react with the IR MABS and the syncytiotrophoblast was less intensely labelled than at weeks 6 to 10 p-m. In term placentae, the microvillous membrane of the syncytiotrophoblast showed only patches of weak immunoreactivity. In contrast, the endothelial cells in the placenta but not in the umbilical cord were strongly stained. The amniotic epithelium in the chorionic plate and fibroblasts in the stroma were conspicuously labelled. The data indicate: (1) the receptor density on villous syncytiotrophoblast decreases and that of fetal endothelium increases' throughout gestation; (2) syncytiotrophoblast of human term placentae expresses a low level per unit area of surface IR; and (3) the majority of IR in human term placentae is located in fetal endothelium. Apart from yet unknown functional effects of maternal and fetal insulin at the placental barrier, the results suggest a growth promoting effect on the trophoblast of maternal insulin in first trimester as well as developmental effects of fetal insulin on the feto-placental vessels at term.

Antibodies, Monoclonal↗

PubMed2002

Human chorionic gonadotropin in human placentas from normal and preeclamptic pregnancies.

OBJECTIVE: The aim of this study was to examine the distribution of human chorionic gonadotropin (hCG) in the human placenta of normotensive and preeclamptic pregnancies and to determine by computer image analysis, whether differences in hCG immunoreactivity occurred in preeclamptic as apposed to normotensive pregnancies. We discuss how far elevated maternal serum levels of hCG normally observed in preeclamptic patients reflect an increased secretory activity of the syncytiotrophoblast. METHODS: We used the immunoperoxidase technique to locate hCG. Quantification of immunostaining intensity was done by computer image analysis. RESULTS: In normotensive placentas from all the gestational ages human chorionic gonadotrophin immunoreactivity was specifically detected in the syncytiotrophoblast. There is an apparent decrease in the intensity of the hCG immunostaining in the syncytiotrophoblast from the 29th to 36th week of gestation in normotensive placentas. No hCG immunostaining was observed in the villous or extravillous cytotrophoblast of all placentas. In preeclamptic placentas the expression of hCG was homogeneous with a moderate to intense immunoreactivity in the syncytiotrophoblast. Microdensitometric analysis of the section from normotensive and preeclamptic placentas indicated that there is a statistically significant preeclampsia-induced increase in immunohistochemical reaction intensity for hCG (p < 0.05). CONCLUSION: This study seems to demonstrate that increased production of hCG by preeclamptic placentas is associated with strong hCG immunostaining of the syncytiotrophoblast.

Chorionic Gonadotropin↗

PubMed1979

Natural history of placenta previa ascertained by diagnostic ultrasound.

Placental localization by diagnostic ultrasound was performed at 16 to 18 weeks' gestation in 1,098 patients prior to amniocentesis for genetic indications. Placenta previa was diagnosed in 58 patients, 47 of whom went on to delivery uncomplicated by placenta previa. There were five patients with placenta previa at delivery, four of whom had third-trimester bleeding. One patient was diagnosed as having a normal placental implantation at midtrimester but placenta previa was demonstrated at delivery. The incidence of placenta previa at 16 to 18 weeks' was 5.3% and fell to 0.58% at delivery, indicating a 90% conversion rate. Thus the vast majority of cases of asymptomatic placenta previa remain so and convert before delivery. These patients should be observed with serial ultrasound at 6 to 8 week intervals until delivery or unequivocal conversion. No restriction in activity seems indicated unless the placenta previa persists beyond 30 weeks or becomes clinically manifest.

Adult↗

PubMed1981

Induced abortion: a risk factor for placenta previa.

A threefold increase in the incidence of placenta previa, from one in 318 deliveries (0.3%) in 1972-1974 to one in 109 deliveries (0.9%) in the twelve-month period ending June 30, 1980, was noted at Vanderbilt University Hospital. Two large groups of patients not present in 1972-1974 were found to be responsible for this increased incidence of placenta previa: one-way maternal transports and women who had had induced first trimester abortions. The frequency of maternal transports having placenta previa was 3.3% (p less than 0.0001), and the frequency of placenta previa in women after an induced first trimester abortion was 3.8% (p less than 0.0001). When correction for maternal transports was made, the endogenous induced first trimester abortion population had a frequency of placenta previa of 2.1% (p less than 0.004), whereas the remainder of the endogenous population had an incidence of placenta previa similar to that found in the years 1972-1974. Induced first trimester abortion is seen as a significant factor predisposing to placenta previa.

Abortion, Induced↗

PubMed1991

Cigarette smoking during pregnancy in relation to placenta previa.

To evaluate the relationship between cigarette smoking and the occurrence of placenta previa, we used interview and medical record data to conduct a case-control analysis of 69 placenta previa cases and 12,351 controls. The unadjusted relative risk estimate of placenta previa for women reported to have "ever smoked" during pregnancy relative to nonsmoking mothers was 1.9 (95% confidence interval, 1.2 to 3.0). The risk rose after adjusting for potential confounders (odds ratio, 2.6; 95% confidence interval, 1.3 to 5.5). In contrast to a previous report, the duration of smoking was not an independent risk factor for placenta previa. These results suggest that cigarette smoking during pregnancy is a determinant of placenta previa. Carbon monoxide hypoxemia, which is one possible mechanism for this association, may result in compensatory placental hypertrophy. Placentas with increased surface areas are more likely to cover the cervical os, causing placenta previa.

Adult↗

PubMed1992

Transforming growth factor-alpha and epidermal growth factor messenger ribonucleic acid and protein levels in human placentas from early, mid, and late gestation.

OBJECTIVE: Human placenta expresses receptors for transforming growth factor-alpha and epidermal growth factor throughout pregnancy. Experiments were performed to determine whether epidermal growth factor or transforming growth factor-alpha might be synthesized by placental cells and act through an autocrine mechanism to influence functioning of placental cells in vivo. STUDY DESIGN: Human placentas from early, mid, and late gestations were analyzed for transforming growth factor-alpha and epidermal growth factor messenger ribonucleic acid and proteins. Polyadenylic acid-positive ribonucleic acid was isolated from placentas from 10, 11, 13, 21, 32, 38, 39, and 40 weeks of gestation and analyzed by Northern analysis for hybridization with complementary deoxyribonucleic acid probes specific for epidermal growth factor or transforming growth factor-alpha. Levels of immunoreactive epidermal growth factor and transforming growth factor-alpha were measured by specific radioimmunoassays in pools of placentas from early, mid, and late gestations, and levels of epidermal growth factor and transforming growth factor-alpha receptor-active protein were measured by radioreceptor assay. RESULTS: All placentas had a strong transforming growth factor-alpha hybridization band at 4.5 kb and a weak epidermal growth factor hybridization band at 5.2 kb. High levels of transforming growth factor-alpha immunoreactive protein (90 to 180 ng/mg protein) and low levels of immunoreactive epidermal growth factor (3 to 9 pg/mg protein) were detected in pools of placentas from early, mid, and late gestations. High levels of epidermal growth factor and transforming growth factor-alpha receptor-active protein (250 ng/mg protein) were also detected. CONCLUSION: Human placentas contain relatively high levels of immunoreactive and receptor-active transforming growth factor-alpha, as well as transforming growth factor-alpha messenger ribonucleic acid, throughout gestation. This finding suggests that transforming growth factor-alpha may act by an autocrine system to influence human placental cell function in vivo.

Blotting, Northern↗

PubMed1995

A stereologic study of postmature placentas fixed by dual perfusion.

OBJECTIVE: Placental insufficiency has been considered the cause of increased morbidity in infants delivered postmaturely. Former quantitative studies have indicated a decrease in some placental structures just before term. In this study we describe a method of dual perfusion fixation to provide tissue for stereologic examination. Postmature placentas were examined with this method. STUDY DESIGN: Eleven postmature placentas and 14 placentas delivered at term were fixed by dual perfusion. The volume and the surface area of villi, the trophoblast volume, and the volume, surface area, and length of villous capillaries were estimated by stereologic examination. The Mann-Whitney test (p < or = 0.05) was used for statistical analysis. RESULTS: Morphologic features were normal in all placentas. No significant differences were disclosed in the stereologic estimates of placentas delivered at term and postmature placentas. CONCLUSION: No morphologic or significant quantitative changes were found in postmature placentas.

Female↗

PubMed1987

Ontogeny of insulin receptors in the rat hemochorial placenta.

Binding of 125I-insulin to rat placental membranes was time and protein concentration dependent, reversible, and specific. Unlabeled porcine insulin competed for 125I-insulin binding with an IC50 of 65 nM, while IGF-I was much less potent with an IC50 of 2.12 mM. Specific binding of 125I-insulin decreased during the second half of gestation from Days 11 to 19. Scatchard analysis of the binding data for membranes prepared from Gestation Days 11 and 19 yielded typical curvilinear plots which showed a marked decrease in the number of binding sites in late gestation placenta. Beginning on Day 14, insulin binding was characterized with isolated labyrinth and basal zone portions of the hemochorial placenta. There was no evidence for differences in Kd values or the number of binding sites in these two functionally distinct portions of the rat placenta. Crosslinking of 125I-insulin followed by SDS-PAGE showed a single protein with a molecular weight of 130,000 from placental tissues on Gestation Days 11 and 19 and confirmed a gestational decrease in the number of insulin receptors. In solubilized, lectin-purified preparations from placenta and liver membranes, insulin stimulated the phosphorylation of a Mr 95,000 protein. 32P-incorporation into this 95,000 protein was stimulated fivefold by insulin in Day 11 placenta receptor, whereas no detectable 32P-incorporation was found in Day 19 placenta. Thus, while the alpha- and beta-subunits of insulin receptors in mid and late gestation placenta have molecular weights which are similar to receptors in maternal liver, data indicate the presence of a functional difference in insulin-stimulated kinase activities.

Animals↗

PubMed1995

The outcome of placenta accreta in Kuwait (1981-1993).

OBJECTIVES: To study the demographic characteristics of patients with placenta accreta and to identify the clinical features, maternal and neonatal complications of this condition. METHODS: Sixteen cases of placenta accreta were identified in the Maternity Hospital of Kuwait during the period January 1981 to July 1993. Medical records were reviewed regarding past obstetric history, type of placenta, clinical presentation, maternal and fetal outcome. RESULTS: The rate of placenta accreta was found to be 98 per 1,000,000 deliveries. Emergency hysterectomy was needed in 87.5% of cases. There was one maternal death (6.25%) and three perinatal deaths (18.75%). Hemorrhage was the major presenting symptom either externally and antenatally in previa accreta or postpartum in accreta of the upper segment or internally in the same cases. The major postoperative complications were coagulopathy, urinary injury, pelvic hematoma and abscess, in addition to cardiac arrest. These complications, when considered separately, were not affected by a previous history of uterine scarring. CONCLUSIONS: Placenta accreta is a major cause of obstetric hemorrhage and has an adverse effect on maternal and neonatal outcome. It ought to be considered a possibility in patients with previous uterine scarring, placenta previa or retained placenta. It will remain a growing problem in the developing countries due to the rising incidence of previous multiple cesarean sections. Unfortunately the latter do not deter women in this part of the world from insisting upon having big families and refusing tubal ligation.

Adult↗

PubMed1988

Origin of deoxycorticosterone and deoxycorticosterone sulfate in human pregnancy: absence of steroid 21-sulfatase activity in sulfatase-deficient placenta.

The activity of steroid 21-sulfatase, the enzyme that catalyzes the hydrolysis of deoxycorticosterone sulfate (DOC-SO4) is demonstrable in human placenta. Thus, it is possible that this placental enzyme, by way of the hydrolysis of either DOC-SO4 or 21-hydroxypregnenolone mono- or di-sulfate of fetal origin, may be important in the biosynthesis of DOC, which is present in the plasma of pregnant women in high concentration. To investigate this issue further, we evaluated steroid 21-sulfatase activity in microsomal preparations of a sulfatase-deficient placenta. Immediately after delivery, at term, of a living male fetus with sulfatase deficiency, a microsome-enriched fraction of placental tissue was prepared; sulfatase activity was evaluated by use of three substrates, viz. dehydroisoandrosterone sulfate (DS), estrone sulfate (E1-SO4), and DOC-SO4, in various concentrations. Similar incubations were conducted with aliquots of a microsome-enriched fraction prepared from placental tissue of a normal fetus that was delivered, at term, within minutes of the time of delivery of the infant with sulfatase deficiency. In microsomal fractions from the normal placenta, each of the steroid sulfates was hydrolyzed. In the absence of microsomes, and in the presence of microsomal fractions from the sulfatase-deficient placenta, the hydrolysis of DOC-SO4 and DS was not detected. Moreover, in microsomes prepared from the sulfatase-deficient placenta, E1-SO4 was hydrolyzed at a rate that was only 10% of that in incubations with microsomal preparations of the normal placenta. We conclude that with sulfatase deficiency, the placenta is deficient not only in sulfatase activity for steroid-3-sulfates but for steroid 21-sulfates, e.g. DOC-SO4, as well.

17-alpha-Hydroxypregnenolone↗

PubMed1987

Abruptio placentae--risk factors and outcome of the newborn.

A total of 180 (0.21%) out of 85.177 deliveries were complicated by abruptio placentae (AP) during the period 1962-1981. Of these the obstetric records of 130 deliveries were retrospectively studied in order to elucidate risk factors for the occurrence of abruptio placentae as well as to find out factors influencing the outcome of the newborn. The control group consisted of 120 randomly chosen contemporary parturients. Preterm contractions during pregnancy seemed to be most significantly associated with the occurrence of abruptio placentae. Also mothers with gestational hypertension or pre-eclampsia, smokers and unmarried mothers seemed to run a more than two-fold risk of premature separation of the placenta, while twin pregnancy and high parity seemed to increase the risk only slightly. However, a history of abruptio placentae revealed an 11-fold risk of premature separation of placentae in subsequent pregnancy. The factors most significantly associated with favourable prognosis of the newborn were: duration of gestation, birth weight and the degree of separation of the placenta. However, degree of cervical dilatation, presentation, mode of delivery or the time interval between diagnosis of AP and delivery seemed to have only weak discriminative power between newborns who survived and those who were lost.

Abruptio Placentae↗

PubMed1995

One or multiple previous cesarean sections are associated with similar increased frequency of placenta previa.

OBJECTIVE: The purpose of this study was to determine whether multiple previous cesarean sections would be associated with a higher frequency of placenta previa in subsequent deliveries than in women with only one previous cesarean section. STUDY DESIGN: Data of all pregnant women and deliveries were obtained from the computerized records of our department for the period 1985-1992. The study group included symptomatic placenta previa diagnosed by real time ultrasound or during labor. The data included maternal age, gravidity, parity and previous cesarean sections. Nulliparous women were excluded from the study. RESULTS: There were 58,633 deliveries during the study period, including 284 patients with placenta previa (0.48%). Increasing maternal age was associated with a higher frequency of placenta previa. Similar results were found with increasing parity. A more significant trend was found with increasing number of previous abortions. Among placenta previa deliveries 21.1% of patients had previous cesarean section, and among normal deliveries only 10.9% had previous cesarean section (P < 0.0001). The frequency of placenta previa in women with previous normal deliveries was 0.79/1000; in women with one previous cesarean section 15.39/1000; with two previous cesarean section 13.91/1000; with three previous cesarean sections 10.37/1000. While the difference between none and one previous cesarean sections was highly significant (P < 0.0001), the difference between one and more cesarean sections was not significant. CONCLUSION: Although the rate of placenta previa was significantly lower among deliveries without previous cesarean section in comparison with deliveries with one previous cesarean section, this difference was not enhanced with the increasing number of previous cesarean sections.

Adult↗

PubMed1985

Histological and histochemical changes of the placenta in fetal alcohol syndrome due to maternal administration of acute doses of ethanol in the mouse.

In both clinical and experimental research on the fetal alcohol syndrome (FAS) the possible involvement of the placenta has not been considered. In an attempt to investigate the effects of alcohol on the placenta, single doses of 0.02 ml and 0.03 ml/g body weight of freshly prepared solutions (25%, v/v) of absolute alcohol in saline were administered to MF1 mice on day 8 of gestation. Controls were saline treated or/and pair fed and pair watered. Fetuses and placentas were collected on day 18, weighed individually, observed for malformations and fixed. Paraffin sections of placentas of control and of fetuses with FAS were stained with hematoxylin and eosin, Best's carmine and PAS with and without diastase (saliva). The experimental fetuses and placentas were lighter in weight than the controls. The decidua basalis of placentas of FAS cases were occasionally vacuolated and infiltrated by lymphocytes. The glycogen and mucopolysaccharide content in the basal zone was reduced. In most situations the glycogen cells had degenerated and were replaced by an acidophilic mass. The cytoarchitecture of the labyrinthine zone had been altered. Large cysts filled most parts of the placenta; besides fibrinoid accumulation, extensive vacuolisation was also clearly visible. The overall width of this zone and arborisation of fetal vasculature were also reduced. The consistent association of these placental abnormalities with FAS in this mouse model is suggestive of placental mechanisms in FAS.

Animals↗

PubMedDate not supplied

Localization of fibrillin-1 in the human term placenta.

OBJECTIVE: We determined the level of message for fibrillin-1, a single-stranded glycoprotein found in the elastic microfibrils of the extracellular matrix, in human placenta compared with other adult human tissues and localized the protein in the term human placenta. METHODS: Northern blot analysis using a cDNA specific for fibrillin-1 was used to compare message levels in several adult human tissues and placenta. Immunohistochemical staining, using a monoclonal antibody to human fibrillin-1, was used to visualize the site of fibrillin-1 in term human placenta. RESULTS: Larger amounts of message for fibrillin-1 were present in placenta than in any of the other tissues tested. Staining for fibrillin-1 was present in the villous stroma but not in the basement membranes, trophoblast cells, or in blood vessels of stem, mature intermediate, or terminal villi. CONCLUSIONS: Fibrillin-1 is distributed extensively in the villous stroma of the term human placenta and may contribute elastic properties to the placenta and basal plate required for an active uterus.

Adult↗

PubMed2004

Elevation of granulocyte-macrophage colony-stimulating factor in the placenta and blood in preeclampsia.

OBJECTIVE: This study investigated whether granulocyte-macrophage colony-stimulating factor (GM-CSF) levels in the placenta and blood in preeclampsia differed from those in normal pregnancies. Macrophage colony-stimulating factor (M-CSF) levels in the placenta were also measured. STUDY DESIGN: The subjects were 44 pregnant women carrying single fetuses, of whom 22 were women with normal pregnancies and 22 were women with preeclampsia. Their average gestational age at entry was 37 to 38 weeks of gestation. Peripheral blood was collected before the onset of labor. Separated serum was obtained after centrifugation and stored at -20 degrees C. A tissue segment of the placenta was cut immediately after delivery. The frozen placental tissue was placed into a plastic tube containing phosphate-buffered saline solution. The tissue was fully homogenized and then centrifuged. Separated supernatant was frozen at -80 degrees C for subsequent determination. GM-CSF levels in separated serum were measured, and GM-CSF, M-CSF, and total protein (TP) levels in separated supernatant were also measured. RESULTS: Not only GM-CSF levels in blood but also GM-CSF/TP levels in the placenta were significantly higher (P<.05) in preeclampsia than in normal pregnancies. Similar results were obtained for M-CSF/TP levels in the placenta. CONCLUSIONS: We demonstrated a significant increase in placenta levels of GM-CSF/TP in preeclampsia. Elevated GM-CSF in the placenta may be related to immunologic abnormalities contributing to the etiology of preeclampsia.

Adolescent↗