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Insulin-like growth factor-I messenger ribonucleic acid in the developing human placenta and in term placenta of diabetics.

Fetal growth and development are dependent upon the growth and development of the placenta. Control of placental growth and development is little understood. Immunoreactive insulin-like growth factor-I and -II (IGF-I and IGF-II) have been shown to be released by human placental tissue and human placental membranes have been observed to contain specific receptors for these growth factors. Furthermore, we have demonstrated the presence of IGF-II mRNA transcripts in the developing human placenta and at gestational term in placentae of diabetics. Thus, the IGFs may have a regulatory role in the growth and development of the placenta via autocrine and/or paracrine mechanism(s) of action. In this report we demonstrate the presence of four differing size species of placental poly(A)+ RNA which specifically hybridize to an IGF-I probe originally isolated from an adult human liver cDNA library and localize IGF-I and IGF-II mRNA to syncytiotrophoblasts and fibroblasts, respectively, of the placenta by in situ hybridization. The major transcript is 7500 bases in size and the remaining three transcripts are 5000, 1100, and 900 bases in length with no apparent changes from these sizes throughout gestation and at term in diabetics. Quantification by densitometry of placental IGF-I mRNA detected by dot blot hybridization indicated that first and second trimester placentae each express more IGF-I mRNA relative to that expressed in placenta at term. These results suggest that there are developmental changes in the relative amount of IGF-I mRNA expressed in the human placenta. IGF-I is, therefore, most likely important early in gestation as a placental growth factor. This time period is critical for fetal development and growth, when embryonic induction, organogenesis, and rapid cell proliferation occur.

Female

[The importance of regressive changes in the placenta during the so-called migration of the placenta (author's transl)].

Starting from the tenth to the sixteenth week of pregnancy ultrasonic placental localizations were performed in 22 pregnant women at four week intervals. In all cases the placenta was located in the anterior wall of the uterus and bordered or covered the internal os of the cervix. In 17 cases a cephalad migration of the placental localization was registered. In 5 cases the low implantation of the placenta did not change until delivery. In 14 of 19 cases marginal atrophic changes of the placenta were found. No morphologic abnormality was detected in five placentas from patients who showed migration of the placental localization. Since the placenta is tightly implanted in the endometrium a true migration of the placenta is unlikely. Our investigations show that areas of low implantation of the placenta are stretched with increasing growth of the uterus and then undergo regressive and pressure atrophy changes. It is likely that the cervical margin of the placenta cannot be detected by ultrasound in a large number of cases.

Atrophy

Levels of epidermal growth factor binding in third-trimester and term human placentas: elevated binding in term placentas of male fetuses.

Specific binding of iodine 125-labeled epidermal growth factor was measured in membrane homogenates of third-trimester and term human placentas of male and female fetuses. All placentas (n = 35) generated curvilinear Scatchard plots, and all placentas had similar equilibrium dissociation constants for both high-affinity (210 pmol/L) and low-affinity (830 pmol/L) binding sites. Mean maximum number of available binding sites of term placentas from male fetuses (330 +/- 110 fmol/mg protein; n = 11) was significantly higher (p less than 0.001) than that of female fetuses (170 +/- 80 fmol/mg protein, n = 13). Occupation of epidermal growth factor receptors by endogenous epidermal growth factor could not account for the difference in levels of epidermal growth factor binding. Kendall's rank order correlation test demonstrated a significant positive correlation of the gestational age in weeks with the maximum number of epidermal growth factor receptors in placentas from male fetuses (p less than 0.002; T = 0.527; n = 17) and female fetuses (p less than 0.01; T = 0.404; n = 18). These results indicate that there is a sexual dimorphism in the level of epidermal growth factor receptors in placentas of male and female fetuses during the third trimester and that the level of epidermal growth factor receptors increases during the third trimester for placentas of both male and female fetuses.

Epidermal Growth Factor

Placenta creta and placenta praevia creta.

The placental bed in placenta creta and placenta praevia creta was studied from pregnancy or immediate postpartum hysterectomy specimens. In all cases placental villi were seen in direct contact with myometrium, the sine qua non of placenta creta, but was focal in some cases. There was no apparent diminution of decidua parietalis or, in cases of focal accreta, of adjacent basalis. In all cases the extravillous trophoblast was mainly uninuclear or binuclear, in contrast to the placental bed syncytial giant cells seen in late normal placentation. There was an apparent proliferation of interstitial trophoblast at the junction of placenta with myometrium, but the density of interstitial trophoblast deeper in the myometrium was lower than it is in normal placentation. An unusual uteroplacental vasculature was seen in which physiological changes were present in large arteries of the radial/arcuate system deep in the myometrium, while there were also spiral arteries more superficially without physiological changes. These findings suggest that in placenta creta there is defective interaction between maternal tissues, particularly decidua, and migratory trophoblast in the early stages of placentation resulting in undue adherence of the placenta or penetration into the uterus coupled with the development of an abnormal uteroplacental circulation.

Arteries

[Continuous ultrasonic observation on the change of location of placenta in placenta previa].

Placenta previa was studied in 50 cases during 20-28 weeks of gestation by ultrasonic scanning. The change of location of placenta was monitored continuously for these cases. The rates of change of location to normal sites were 90% for low-lying placenta, 65% for marginal implantation, 13% for partial placenta previa and 11% for central placenta previa. It is suggested that partial or central placenta previa observed during mid-trimester should be categorized as a high risk state.

Female

[Quantitative investigations of the human placenta under normal conditions and in case of preeclampsia correlated to the human placenta-lactogen blood-level in the last third of pregnancy (author's transl)].

Thirty-two human placentas from normal and from pregnancies complicated by preeclampsia in last third of gestation were morphologically and morphometrically examined and correlated with human placenta-lactogen blood-level. HPL was determined by the radio-immunoassay (Carbon-Dextran-method). HPL-values, placenta villous surface, the weight of the newborn and placenta showed significant correlation. The placentas were classified according to the morphologic degree of severity (placenta-morphological-index) and compared to preeclamptic index (Goecke) and HPL-values. The results showed correlation between the studied datas according to the severity of preeclampsia. The significance of these results is discussed.

Birth Weight

Monoamine oxidase in rat placenta, human placenta, and cultured choriocarcinoma.

The activity of monoamine oxidase (MAO), an enzyme which metabolized catecholamines and indoleamines, was determined in rat placenta at various stages of gestation, in human term placenta, and in choriocarcinoma grown in culture. From Day 15 to Day 20 of gestation the specific activity (units/mg protein) of MAO in rat placenta increased at least 3-fold; from Day 20 to the time of parturition, it decreased about 50%. The specific activity of MAO in human placenta at term was about 50%. The specific activity of MAO in human placenta at term was about 8 times higher than that of rat placenta at term. No MAO activity was found in choriocarcinoma grown in culture.

Animals

Relationship of the sex of the foetus to the amount of human chorionic gonadotrophin in placentae; single and dizygotic twin placentae compared.

Human chorionic gonadotrophin (HCG) was assayed by biological and radioimmunological methods in placentae from 16 women with a normal twin pregnancy. When the concentration and total amount of HCG in placentae was related to the sex of the twin foetus, no significant difference between 'male' and 'female' placentae was found. This is contrary to findings that there is a significant (P less than 0-005) difference in the concentration of HCG per g and per placenta of singletons at term. A comparison between the grouped geometric mean data from bioassays shows that the amount of HCG per g and per placenta falls between the geometric mean values for 'male' and 'female' singleton placentae.

Adult

Placenta accreta: prospective sonographic diagnosis in patients with placenta previa and prior cesarean section.

A prospective evaluation for possible placenta accreta was performed in 34 patients with placenta previa and a history of one or more cesarean sections. Sonographic criteria used included (1) loss of the normal hypoechoic retroplacental myometrial zone, (2) thinning or disruption of the hyperechoic uterine serosa-bladder interface, and (3) presence of focal exophytic masses. Of 18 patients with positive sonographic results, 14 had proof of placenta accreta and 16 of the patients underwent hysterectomy. Of 16 patients with negative sonographic results, only one had placenta accreta, and two patients required hysterectomy. Presence of numerous intraplacental vascular lacunae appears to be an additional risk criterion for placenta accreta, separate from the other criteria listed above.

Cesarean Section

A normal 46,XX infant with a 46,XX/69,XXY placenta: a major contribution to the placenta is from a resorbed twin.

A predominantly triploid 69,XXY placenta was found associated with a normal 46,XX infant. Therefore, a triploid placenta is apparently capable of supporting normal fetal development. The chromosome and pathological results support the conclusion that the triploid placenta originates from a 'vanishing twin' pregnancy. This case is unusual in that persistence of the placenta from the vanished twin has virtually replaced most of the normal placenta.

Amniocentesis

Serum- and cell-mediated immune protection of mouse placenta and fetus against a Brucella abortus challenge: expression of barrier effect of placenta.

When mice are intravenously inoculated with a virulent Brucella abortus strain at day 12 to 14 of pregnancy and killed three to five days later, colonization of placentae, fetuses and spleens can be estimated by the frequency and level (bacterial count) of infection and by linkage between individual placental and paired fetal infections. This linkage indicates the placental barrier effect, defined as the number of non-infected fetuses linked to 100 colonized placentae. Immune mice serum raised against two Brucella fractions injected one day before challenge (1) restricted the placental colonization (the dose required to infect 50 per cent placentae was increased by 50 to 70 times compared to controls), (2) decreased the level of splenic and placental infection, and (3) increased the barrier effect so that most fetuses were protected even when linked to a heavily infected placenta. Immune (B + T) spleen cells from mice vaccinated with a Brucella cell-wall fraction transferred to recipients seven to eight days before mating, that is, 22 days before challenge (1) restricted the frequency of placental and fetal colonization, (2) decreased the level of splenic, placental and fetal infections, and (3) increased the barrier effect. However, separated B- and T-cells were less active, in particular on the level of fetal infection. In contrast with serum, the cells did not decrease infection of the fetuses linked to heavily infected placentae.

Animals

Can a low-lying placenta be the risk factor of cervical incompetence? A preliminary study on the relationship between placenta insertion and anatomical status of uterine cervix.

An attempt was made to verify the hypothesis that a low-lying placenta may be a factor leading to the dynamic form of cervical incompetence. A vaginal evaluation of the cervix was made in 143 pregnant women who by means of ultrasonographic method were found to have low-lying placentas. In as many as 68 out of the 143 studied cases (47.5%), the low-lying placenta coincided with a shortening of the cervix about half its normal length or in both shortening and patency of the uterocervical canal, measuring up to 2 cm in diameter (39 cases). The statistical calculations indicate that a low-lying placenta can influence cervical behaviour and that it appears to be a risk factor of cervical incompetence.

Cervix Uteri

Placenta membranacea with placenta increta: a case report and literature review.

The pregnancy of a patient with placenta membranacea associated with placenta increta and a live-born infant is described, and the literature covering placenta membranacea is reviewed. A total of 26 cases of placenta membranacea in the second and third trimesters have been reported. The condition appears to have an incidence of 1:20,000-40,000, and there have been 14 reported live births associated with this rare placental anomaly. Antepartum and postpartum hemorrhage were reported to complicate 83 and 50% of the cases, respectively. Approximately 30% of the cases involved some form of abnormal placental adherence.

Adult

Localization of human placenta lysyl oxidase on human placenta, skin and aorta by immunoelectronmicroscopy.

Polyclonal antibodies to human placenta lysyl oxidase (Kuivaniemi et al., 1984) were used to localize the enzyme at ultrastructural level in human placenta, skin and aorta, by using the indirect immunogold method. The antibodies were tested on thin sections of tissues fixed and embedded in various experimental conditions. With all methods employed, the immunoreaction was always positive on collagen fibers in all tissues examined, independently of the age of the subjects. In placenta, the reaction was also slightly positive on matrix microfilaments and cells. In dermis, fibroblasts and elastin were scarcely positive in a normal 5 day-old child, in a child with skin hyperelasticity, and in two babies with osteogenesis imperfecta type II; whereas they were negative in two 16 and 40 year-old normal subjects. In aorta, the immunoreaction was always positive on collagen, scarcely positive on cells and on elastin of a 24 week-old fetus, of a normal child, and of two babies who died of complications associated with O.I. type II; on the contrary, the reaction was negative on cells and elastin fibers of a 16 week-old fetus, and of a normal 19 year-old girl. When present on elastin, gold particles were localized mostly inside the fibers. Contrary to what was observed by Kagan and coworkers on bovine aorta by using antibodies against aortic lysyl oxidase (Kagan et al., 1986), no specific localization of gold particles could be observed on or adjacent to the elastin/associated microfibrils. The results indicate that antibodies raised against placenta lysyl oxidase recognize collagen-associated as well as elastin-associated epitopes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Isolation of plasminogen activator inhibitor-2 (PAI-2) from human placenta. Evidence for vitronectin/PAI-2 complexes in human placenta extract.

Plasminogen activator inhibitor-2 (PAI-2), found in human placenta and pregnancy plasma, was prepared in a highly purified and functionally active form from human placenta. The purification was achieved by a combination of Rivanol and ammonium sulfate precipitation, followed by chromatography on DEAE Affigel Blue, hydroxylapatite and phenylalanine-Sepharose. PAI-2, which is precipitated by low Rivanol concentrations, can be selectively redissolved from the pellet by increasing the Rivanol concentration in the presence of a reducing agent, i.e. dithiothreitol. The purified protein shows a molecular mass of 45 kDa in SDS PAGE, cross-reacts with monoclonal antibodies against PAI-2 (Mab'PAI-2), and inhibits the amidolytic activity of urokinase-type plasminogen activator (u-PA) towards the chromogenic substrate Glu-Gly-Arg-pNA (S-2444). The specific activity of the purified inhibitor was 52,300 units/mg, attaining 71,000 units/mg in peak fractions. In the immunopurification of placental extract on anti-PAI-2 Sepharose, the eluate showed the expected reaction with Mab' PAI-2, and it also cross-reacted with anti-vitronectin serum. In order to complement these results, anti-vitronectin Sepharose was used for immunopurification of placenta extract. In Western Blot experiments the eluates of anti PAI-2 Sepharose and anti-vitronectin Sepharose both showed a heterogeneous pattern of high molecular weight bands recognized by either polyclonal antiserum against vitronectin or Mab'PAI-2. In either case, reduction of the eluates releases mainly a 45-kDa band, which is recognized by Mab'PAI-2, or 80-kDa and 76-kDa bands recognized by anti-serum against vitronectin. These data suggest that the predominant form of PAI-2 in placenta extract is heterogeneous and of high molecular mass, containing complexes in which vitronectin is covalently bound to PAI-2 by disulfide bridges.

Blotting, Western

Development of trophoblast and placenta of the mouse. A reinvestigation with regard to the in vitro culture of mouse trophoblast and placenta.

At 5 days post conceptionem (p.c.) shortly after implantation, giant cell transformation starts at the abembryonic pole of the blastocyst, spreading over the mural trophoblast; 1 day later, the first ectoplacental giant cells appear at the base of the fast growing ectoplacental cone (derived from the polar trophoblast). Giant cell transformation expands over it periphery. Thus, by the 8th day p.c., the conceptus is separated from the maternal tissue by a continuous layer of giant cells, variable in thickness. Giant cells reach their greatest size by 10 days p.c. in the mural tophoblast and by 12 days p.c. in the chorioallantoic placenta. They are probably no longer formed after that stage. Around the 8th day p.c., the allantois reaches contact with the ectoplacental cone, which develops into the chorioallantoic (definitive) placenta. At 9 days p.c., its four zones can already be discriminated: chorionic plate, labyrinth, junctional zone (trophospongium), and zone of giant cells, respectively. Within the next day, the chorioallantoic placental circulation is established. The yolk sac placental circulation is established by the 9th day p.c. The villi of the proximal layer of the yolk sac increase in size and number, and their capillary network becomes more dense until the 12th to 14th day p.c. This provides evidence that the yolk sac placenta exerts its function--to a certain extent--beyond the establishment of the definitive placenta. Around the 14th day p.c., the placental labyrinth reaches its definitive features. Fetal capillaries in the labyrinth, branching from unbilical blood vessels within the septa of connective tissue are surrounded by trophoblast cells. They form a dense vascular network bathing in maternal blood. The structures of the placental zones remain almost the same during further development, the borders becoming sometimes little blurred. Adjacent to the chorionic plate, subchorionic clefts appear at the 14th day p.c. These clefts become confluent to form the intraplacental space, regularly communicating with the yolk sac cavity. At the end of gestation (19th day p.c.) there is a considerable amount of eosinophilic material ('fibrinoid') between the zone of giant cells and the decidua, probably produced by the giant cells.

Animals

[Pathology of the placenta. VI. Circulation disorders of the placenta. Maternal circulation (intervillous space)].

Disorders of intervillous circulation are covered in this sixth part of the account of Pathology of the Placenta. Proposed in this paper are a new setup and modified nomenclature in which the term of "infarction" is definitely abandoned, as there can be neither genuinely anaemic nor haemorrhagic infarction in the placenta. Alterations which we consider as a formally pathogenetic chain are discussed by the order of focus of villous collapse, reticular intervillous fibrin deposition, and chronic disorder of intervillous circulation. These should be distinguished from subchorionic fibrin deposition, a special case of chronic circulatory disorder. Reference is finally made to intervillous haemorrhage and retroplacental haemorrhage (premature detachment of the placenta). An attempt is made, in conclusion, to give an account of the causative genesis of impairment to intervillous circulation together with various pathologic-anatomic findings recordable from myometrial and decidual arteries.

Arteries