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Identification of expressed sequence tags preferentially expressed in human placentas by in silico subtraction.

OBJECTIVES: To identify expressed sequence tag (EST) clusters preferentially expressed in placentas. METHODS: The National Center for Biotechnology's online UniGene database contains 14 placenta libraries. In silico (computer-based) subtraction compared placenta libraries against the remaining libraries to identify transcripts preferentially expressed in placentas. For known genes, placental expression or their use in prenatal diagnosis was then explored online using LocusLink and PubMed. RESULTS: Placentas preferentially expressed 475 EST clusters. Of these, 18 EST clusters with no known function were expressed exclusively in placentas. Of the remaining 457 EST clusters, 90 showed preferential placental expression by >/=25 times. Of these 90, literature searches on the 45 EST clusters with known functions showed 44 linked to placental physiology or proposed as markers for prenatal diagnosis [i.e. beta-hCG, pregnancy-specific glycoproteins, human placental lactogens, pregnancy-associated plasma protein A (PAPP-A)]. Selected genes with known function in pregnancy but whose preferential placental expression fell below the factor of 25 threshold were also identified. CONCLUSION: In silico subtraction identified 44 previously studied genes involved in placental physiology as well as 63 EST clusters preferentially expressed in placental tissue, which may serve as targets for future studies seeking novel markers for prenatal diagnosis or to better understand placental genetics.

Adult↗

The thick heterogeneous (jellylike) placenta: a strong predictor of adverse pregnancy outcome.

OBJECTIVE: To present a series of cases with a sonographic thick and heterogeneous placenta, and to review the literature. METHODS: A series of 16 cases were analyzed. A heterogeneous placenta was defined as a thick placenta with a patchy decrease of echogenicity, which quivered like jelly to sharp abdominal pressure. A comprehensive morphologic and Doppler evaluation of the fetus and the uteroplacental circulation was performed. The pregnancy course and the neonatal outcome of the present series and of those reported in the literature were reviewed. RESULTS: Placental thickness was greater than the 95th centile in all cases. The placenta was located laterally in 13 (81.3%) cases. Twelve women delivered earlier than 34 weeks either spontaneously or because of deteriorating maternal and/or fetal conditions (n = 10). Perinatal death occurred in eight cases. The uterine artery Doppler and the umbilical artery were abnormal in eight and eight cases respectively. A discordancy between the umbilical artery size was present in six cases. Abruptio placentae occurred in three cases. A strong association between hypertensive disorders and fetal growth restriction was found in our series and in literature. CONCLUSIONS: The sonographic presence of thick heterogeneous placenta is strongly associated with an adverse pregnancy outcome and often with perinatal death.

Adult↗

Protein profiles of bovine placenta derived from somatic cell nuclear transfer.

Practical application of animal cloning by somatic cell nuclear transfer (SCNT) has been hampered by an extremely low success rate. To address whether placental dysfunction in SCNT causes fetal loss during pregnancy, we have used a global proteomics approach using 2-DE and MS to analyze the differential protein patterns of three placentae from the afterbirth of cases of postnatal death, derived from SCNT of Korean Native cattle, and three normal placentae obtained from the afterbirth of fetuses derived from artificial insemination. Proteins within a pI range of 4.0-7.0 and 6.0-9.0 were analyzed separately by 2-DE in triplicate. A total of approximately 2000 spots were detected in placental 2-DE gels stained with CBB. In the comparison of normal and SCNT samples, 60 spots were identified as differentially expressed proteins, of which 33 spots were up-regulated proteins in SCNT placentae, while 27 spots were down-regulated proteins. Most of the proteins identified in this analysis appeared to be related with protein repair or protection, cytoskeleton, signal transduction, immune system, metabolism, extracellular matrix and remodeling, transcription regulation, cell structure or differentiation and ion transport. One of up-regulated proteins in SCNT was TIMP-2 protein known to be related to extracellular matrix and remodeling during pregnancy. Western blot analysis showed an increased level of TIMP-2 in SCNT placenta compared to normal. Our results revealed composite profiles of key proteins involved in abnormal placenta derived from SCNT, and suggested expression abnormality of these genes in SCNT placenta, resulting in fetal losses following SCNT.

Animals↗

Correlation of increased levels of class I MHC H-2Kk in the placenta of murine trisomy 16 conceptuses with structural abnormalities revealed by magnetic resonance microscopy.

Murine trisomy 16 (mts16) placentas and fetuses, 17-day gestation age, were examined histologically and by magnetic resonance imaging at 9.4 T and compared with control littermate tissues. Placentas were studied by immunohistochemical methods, at 15-days gestational age, for expression of the major histocompatibility complex (MHC) class I H-2Kk cell surface marker. Immunohistochemical studies revealed a markedly increased expression of the MHC marker H-2Kk on cells in the labyrinth of the placenta of mts16. There were differences between the magnetic resonance (MR) images of the trisomic and normal placentas, which may be correlated with the increased expression of H-2Kk in the mts16 placental labyrinth. The decidual and labyrinthine components of the normal placentas showed similar high signal intensities (SI) while in trisomic placentas a marked high SI was characteristic only of the decidual region on proton spin density images. The MRI also revealed a smaller cerebellum in the ts16 fetuses. The potential effects of the compromised structure of the placental labyrinth and the overexpression of the H-2Kk marker on the mts16 neural and placental dysgenesis are discussed.

Animals↗

PDGFB regulates the development of the labyrinthine layer of the mouse fetal placenta.

PDGFB is a growth factor which is vital for the completion of normal prenatal development. In this study, we report the phenotypic analysis of placentas from mouse conceptuses that lack a functional PDGFB or PDGFRbeta gene. Placentas of both types of mutant exhibit changes in the labyrinthine layer, including dilated embryonic blood vessels and reduced numbers of both pericytes and trophoblasts. These changes are seen from embryonic day (E) 13.5, which coincides with the upregulation of PDGFB mRNA levels in normal placentas. By E17, modifications in shape, size, and number of the fetal blood vessels in the mutant placentas cause an abnormal ratio of the surface areas between the fetal and the maternal blood vessels in the labyrinthine layer. Our data suggest that PDGFB acts locally to contribute to the development of the labyrinthine layer of the fetal placenta and the formation of a proper nutrient-waste exchange system during fetal development. We point out that the roles of PDGFB/Rbeta signaling in the placenta may be analogous to those in the developing kidney, by controlling pericytes in the labyrinthine layer and mesangial cells in the kidney.

Animals↗

Endocrine activity of the corpus luteum and placenta during pregnancy in Chalcides chalcides (Reptilia, Squamata).

The structure of the corpus luteum and the steroidogenic activity of the corpus luteum and placenta in the viviparous reptile Chalcides chalcides have been investigated. The corpus luteum has a compact structure, almost without internal vascularized connective septa. It begins to degenerate after the middle of pregnancy, when plasma progesterone (P) remains high. The sections of the corpora lutea taken during early pregnancy showed an intense 3beta-HSDH reaction, whereas the sections taken in late pregnancy gave weak reactions localized exclusively in the peripheral luteal cells. In contrast, sections of placentae taken at the beginning and in the middle of pregnancy always gave negative 3beta-HSDH reactions, whereas those of late pregnancy were always strongly positive, localized in the maternal component of the placenta. In vitro, the corpora lutea from early pregnancy secreted significant amounts of P, whereas appreciable amounts of P were not detected in incubates of early pregnancy placentae. Near the time of delivery, P levels decreased in the culture medium of the corpora lutea, but increased in that of the placentae. The addition of pregnenolone (a precursor of P biosynthesis) to the culture medium caused an increase in the luteal and placental P levels, whereas the addition of trilostane (an inhibitor of 3beta-HSDH) reduced them. The placenta of C. chalcides is suggested to have an endocrine function and to replace the corpus luteum in the production of P when the gland degenerates in late pregnancy.

Animals↗

Altered protein profile and possible hypoxia in the placenta of 2,3,7,8-tetrachlorodibenzo-p-dioxin-exposed rats.

Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during pregnancy causes fetal death in many animal species. In an earlier study we observed alteration of placental glucose kinetics at the same TCDD exposure level that resulted in fetal death (Ishimura et al., Toxicol. Appl. Pharmacol. 178, 161-171, 2002). In the present study, in order to identify the molecules that might explain the alterations of placental function and the mechanism of fetal death, we used two-dimensional gel electrophoresis (2D/E) to detect and identify placental proteins whose amounts changed after exposure to TCDD and we examined the expression properties of these proteins in the placenta during hypoxia by using the uterine artery ligation model. Pregnant Holtzman rats were given a single oral dose of 1600 ng TCDD/kg body wt or an equivalent volume of vehicle (control) on gestational day (GD) 15 and placental tissue was collected on GD16 and GD20. The 15,000 g supernatant fractions of placental homogenates from the control group and TCDD-exposed group were subjected to the 2D/E analysis, and the protein spots whose amounts had changed after exposure to TCDD were characterized by amino acid sequence analysis. The amounts of heat shock protein 27 (Hsp27) and beta-tropomyosin (beta-TM) in TCDD-exposed placentas tended to have increased on GD16 and had increased significantly on GD20, and these changes were followed by an approximately twofold increase in glyceraldehyde 3-phosphate dehydrogenase (GAPDH) on GD20. Next, the uterine-artery ligation model was prepared on GD15, and the hypoxic placentas were collected on GD20. Two-D/E analysis of the 15,000 g supernatant proteins of the placentas revealed an increased level of GAPDH but not of other proteins, including Hsp27 and beta-TM. The results of this study showed that the increase in GAPDH level during hypoxia previously observed in endothelial cells occurs in the placenta and indicated that the TCDD-exposed placentas were in a hypoxic state at the end of pregnancy. Finally, the results of this study suggested the possibility that the increased incidence of fetal death after exposure to TCDD was due to the placental hypoxia.

Amino Acid Sequence↗

Evaluation of the placenta: suggestions for a greater role in developmental toxicology.

Both in human and in rat, two types of placenta are present: the yolk sac (YS) and the chorioallantoic placenta. Histiotrophy, alpha-fetoprotein synthesis and blood cell formation occur in YS of both species. Besides, the midgut, primordial germ cells and possibly immunological structures originate from the YS tissue. The specialised cells of the chorioallantoic placenta attach the embryo to the uterus and form the vascular connections necessary for the nutrient transport. The placenta redirects maternal endocrine, immune and metabolic functions to conceptus advantage. These complex activities are sensitive to direct toxicity. Indirect effects on the placental functions might be elicited by immunomodulators and endocrine disrupters. Some experimental models could be utilised to identify possible toxic effects on placenta. Among the in vitro models the rodent giant yolk sac culture may be used to study the transport of materials, morphological and/or biochemical alterations and biotransformation activity of the visceral YS epithelium. Other in vitro approaches utilise human derived trophoblastic cells and tissues to investigate implantation and perimplantation toxicology. Besides specific studies, in vivo reproductive toxicity tests could pay more attention to the evaluation of placental tissues. Nowadays, some physiologically based pharmacokinetic models for developmental toxicity are also available to describe the disposition of toxic substances and their metabolites during pregnancy in rodents. Thus, more detailed studies on the embryo-foetal placenta may provide an important tool to understand developmental toxicity mechanisms, with particular regard to embryolethality and delayed development.

Allantois↗

Human placenta and the hypothalamic-pituitary-adrenal axis.

Maternal plasma bound and free cortisol rises during pregnancy, while maternal plasma IR-ACTH is initially low but soon rises inspite of the further increase of plasma free cortisol. This rise of plasma ACTH during pregnancy, can not be attributed to changes of plasma levels of estrogens or progesterone. It is possible that the human placenta is responsible for the rise in maternal plasma ACTH during pregnancy. There are two possible mechanisms by which this effect could occur: 1) by the placental secretion of CRH into the maternal circulation, which stimulates the maternal pituitary to secrete ACTH, and 2) the secretion of placental POMC-derived peptides. Recent data indicate that the human placenta is capable of both of these actions: A) The POMC and CRH genes are expressed in human placenta; B) the human term placenta is able to secrete both CRH and POMC-derived peptides in vitro; C) the CRH present in the plasma of pregnant women is bioactive and in sufficient levels to be effective on maternal pituitary; D) synthetic hCRH can stimulate the release of placental POMC peptides in vitro. We conclude that the human placenta may be a modulator of the HPA axis during pregnancy in a number of possible ways. Additional experimental work should clarify the intriguing interaction between the HPA axis and the human placenta during pregnancy, labor and delivery.

Adrenocorticotropic Hormone↗

The shadow of life: psychosocial explanations for placenta rituals.

Culturally determined patterns of behavior associated with placenta disposal are characteristic of many modern and ancient societies. This paper defines this type of placenta disposal as a ritual event that delimits a "portion of reality"; explanations are provided leading to the conclusion that placenta rituals operate as anxiety releasing mechanisms that provide a means of control over the future health and welfare of mother, child, and community. The question of why the placenta figures so prominently in folk beliefs and practices has previously been attributed to its morphological and physiological properties; this paper argues that attributes associated with it from a psychosocial model are equally important. The data for this study were drawn from a compilation of ethnographic reports of post-partum practices in African, Asian, European, and Latin American societies. Additional information on placenta disposal was derived from interviews with 1,859 Peruvian informants. Analysis of the data obtained from the Peruvian studies show a significant difference between rural and semi-urban patterns of placenta disposal.

Ceremonial Behavior↗

Synthesis of somatomedin C/insulin-like growth factor I by human placenta.

We have reported the presence of insulin-related poly A+ RNA sequences in human placenta by RNA to DNA hybridization. In this study we have used a monoclonal antibody to somatomedin C/insulin-like growth factor I (Sm-C/IGF-I) to identify somatomedin-like proteins whose synthesis is directed by placental mRNA. Poly A+ RNA from first trimester and term placenta was translated in a cell-free system using micrococcal nuclease-treated reticulocyte-lysate and [35S]methionine as a label. From 2.0 X 10(6) cpm of specifically incorporated [35S]methionine labeled protein, an immunoprecipitate with an apparent molecular weight of 14,000 represented about 0.1% of total radioactivity in the translational products of poly A+ RNA of first trimester placenta. A less prominent band (0.006%) of the same apparent molecular weight was also evident from translational products of term placental mRNAs. This protein could be competed with either acromegalic serum or synthetic Sm-C/IGF-I when added prior to immunoprecipitation. Translational products synthesized from mRNA of term placenta showed a second labeled band of 24,000 daltons. This band was less effectively competed by acromegalic serum and not competed with either Sm-C/IGF-I or IGF-II and therefore its identity is uncertain. A protein similar to Sm-C/IGF-I is, therefore synthesized in first trimester placenta and to a lesser extent at term, suggesting developmental changes in Sm-C/IGF-I synthesis. Because Sm-C/IGF-I may act in a paracrine fashion, our findings suggest a role for Sm-C/IGF-I in growth of the placenta during early gestation.

Female↗

Oxygen diffusive conductance in placentae from control and diabetic women.

Random tissue sections of placentae from control and diabetic deliveries were analysed stereologically. The aim was to test whether or not adaptations in oxygen diffusive conductances occur to help compensate for fetal hypoxic stress in utero. Organs were from 34 control and 55 diabetic deliveries (39 from White's classes A, B, C and 16 from classes D, F/R) arranged in two major groups (ABC and DFR). Tissue samples were fixed in formalin and processed for wax histology. Stereological and physicochemical quantities were used to calculate the partial conductances of six tissue layers, viz. maternal erythrocytes and plasma, villous trophoblast, villous stroma, fetal plasma and fetal erythrocytes. From partial conductances and birthweights, total and specific conductances for each placenta were determined. No differences were detected between diabetic placentae in different classes (A, B, C, D, F/R). However, both the ABC and DFR groups of diabetic placentae had higher total diffusive conductances than control organs. The increase was in the order of 7-25% and persisted even when adjustments were made for apparent differences in birthweights. The principal contributors to these changes were the post-trophoblastic (fetally located) tissue layers. These findings suggest that the diabetic placenta adapts to facilitate the diffusion of oxygen across the placenta and, thereby, to assist the hypoxic fetus.

Adult↗

A review of the evolution of viviparity in lizards: structure, function and physiology of the placenta.

The aim of this review is to collate data relevant to understanding the evolution of viviparity in general, and complex placentae in particular. The wide range of reproductive modes exhibited by lizards provides a solid model system for investigating the evolution of viviparity. Within the lizards are oviparous species, viviparous species that have a very simple placenta and little nutrient uptake from the mother during pregnancy (lecithotrophic viviparity), through a range of species that have intermediate placental complexities and placental nutrient provision, to species that lay microlecithal eggs and most nutrients are provided across the placenta during development (obligate placentotrophy). In its commonest form, lecithotrophic viviparity, some uptake of water, inorganic ions and oxygen occurs from the mother to the embryo during pregnancy. In contrast, the evolution of complex placentae is rare, but has evolved at least five times. Where there is still predominantly a reliance on egg yolk, the omphaloplacenta seems to be paramount in the provision of nutrition to the embryo via histotrophy, whereas the chorioallantoic placenta is more likely involved in gas exchange. Reliance on provision of substantial organic nutrient is correlated with the regional specialisation of the chorioallantoic placenta to form a placentome for nutrient uptake, particularly lipids, and the further development of the gas exchange capabilities of the other parts of the chorioallantois.

Animals↗

Detection of HCMV DNA in placenta, amniotic fluid and fetuses of seropositive women by nested PCR.

Human cytomegalovirus (HCMV) is the most common viral cause of intrauterine infection throughout the world. Its distribution patterns in different clinical samples are poorly understood. This study was performed to determine the frequency of CMV DNA positivity in maternal/fetus sera, placentas and amniotic fluid, together with maternal/fetus serology. Clinical specimens were obtained from 92 pregnant women who delivered by cesarean section. 98% of women and their neonates were HCMV IgG positive and 5.4% of these mothers were IgM positive, while no IgM was detected in neonates of IgM positive mothers. Among the IgG positive mothers, IgM was detected in 3.3% of their fetuses. 5.4% and 3.3% of maternal and fetal sera were HCMV DNA positive, respectively. The three neonates who were positive for HCMV DNA in sera were also positive for HCMV IgM and the PCR of their amnions was positive (p < 0.0001). 9.8% of placenta samples and 4.3% of amniotic fluid specimens were positive for HCMV DNA while among these placenta samples, two amnions were PCR positive (p = 0.046). Our results showed that there is not always a correlation between placenta and amnion infections. This may be due to reactivation of HCMV leading to placenta infection, as all affected placentas do not pass infection to fetuses and amniotic fluids. Detection of HCMV DNA in amnion and fetus plasma and the existence of fetus IgM against HCMV can also occur without clinical symptoms.

Amniotic Fluid↗

Blunt abdominal trauma: are there any predictive factors for abruptio placentae or maternal-fetal distress?

OBJECTIVES: Our objectives were to determine the incidence of abruptio placentae and fetal distress in pregnant women with noncatastrophic blunt abdominal trauma and to determine the utility of historical factors, clinical presentation, coagulation profile, and fetal monitoring in predicting fetal and maternal morbidity. STUDY DESIGN: We reviewed 233 consecutive hospitalizations for noncatastrophic blunt abdominal trauma. Outcome variables included abruptio placentae, fetal distress, preterm birth, and abnormal laboratory values. RESULTS: Preterm delivery (< 34 weeks) occurred within 1 week of trauma in only two patients (< 1%). Fetal distress was diagnosed between 4 and 48 hours after observation in four women (1.7%). These four patients had frequent contractions, but none had abruptio placentae at delivery. Six patients (2.6%) had abruptio placentae. None of these had fetal distress. All had a good neonatal outcome. Coagulation studies and Kleihauer-Betke tests were not predictive of fetal or maternal morbidity. CONCLUSION: Noncatastrophic blunt abdominal trauma is associated with a low frequency of abruptio placentae, fetal distress, maternal coagulopathy, and poor neonatal outcome. Prolonged monitoring is indicated only when there is evidence of impending abruptio placentae. Kleihauer-Betke testing is necessary only for patients who are Rh negative. Coagulation profiles are not clinically helpful. Routine hospitalization beyond 4 hours is not warranted.

Abdominal Injuries↗

The fatty acid composition of placenta in intrauterine growth retardation.

To examine the impact of intrauterine growth retardation (IUGR) on essential fatty acids in human placenta, fatty acid composition in total acylglycerol and in the major phosphoglycerides phosphatidylcholine (PC) and phosphatidylethanolamine (PE), of 15 placentas from small for gestational age (SGA) births was compared with that of 7 control placentas. The acylglycerol fatty acid content was similar between the two groups, but the proportion of fatty acids of the linoleic acid series, including arachidonic acid, was significantly lower in SGA placentas. When the fatty acid composition in PC was studied, the reduction in fatty acids of the linoleic acid series was even more striking, and fatty acids of the linolenic acid series was also significantly less in the SGA group. These fatty acid changes in placenta membrane phospholipids can affect the transport of important nutrients to the fetal compartment. The decreased level of arachidonic acid and docosahexanoic acid might also lead to a disturbed formation of fetal thromboxane and prostacyclin. However, cord plasma PC fatty acid patterns were nearly identical in the two groups suggesting that in IUGR, the essential fatty acids will be transported to the fetus at the expense of the placenta.

Adult↗

Biotransformation of benzo[a]pyrene and 7-ethoxyresorufin and heme-staining proteins in microsomes from human fetal liver and placenta.

Microsomal proteins from human fetal livers and mid-gestational and term placentas were stained for heme in an attempt to detect multiple forms of cytochrome P-450. In fetal liver microsomes five protein bands staining for heme in the mol. wt region 46,000-60,000 were found. In the placentas two bands were seen in the region 46,000-52,000. Fetal liver and placental microsomes were assayed for metabolism of benzo[a]pyrene (B[a]P and 7-ethoxyresorufin (7-EOR). The B[a]P metabolites were separated using high performance liquid chromatography. Following incubations with fetal liver microsomes, in general only phenols were detectable, while after incubations with mid-gestational as well as term placentas from smoking women, the 9,10-, 4,5- and 7,8-dihydrodiols were also formed. No quinones were detected. Placental microsomes from non-smoking women did not catalyse the formation of B[a]P metabolites. The 7-EOR O-de-ethylase activity was in the same range (2-5 pmol/min x mg microsomal protein) in the fetal livers as in the mid-gestational placentas. The activities were somewhat higher in the placentas originating from smokers. No correlation between enzymatic activities in vitro and intensity of any specific protein band was observed for the fetal livers of placentas studied.

Benzo(a)pyrene↗

Preparation and characterization of monoclonal antibodies specific to placenta ferritin.

Ferritins are a group of isomeric proteins which function as the major iron-storage protein of mammalian tissues. Some of the isoferritins have low isoelectric points, and are found in placenta and in malignant tissues and have therefore been termed carcinofetal ferritins. With the use of hybridoma technology, monoclonal antibodies (McAbs) specific to human placenta ferritin(s) were produced in order to characterize the heterogeneity of the molecule and to answer the question whether a specific antigenic determinant is associated with placenta and/or carcinofetal ferritin(s). Two McAbs designated H-9 and G-8 were developed. McAb H-9 bound specifically and exclusively to the ferritin isolated from human placenta, whereas G-8 McAb bound to placenta ferritin and cross-reacted with ferritins isolated from human spleen and liver. No cross-reaction was observed between H-9 and G-8 reactive determinants. It was found further that the two antigenic determinants - the one recognized by G-8 and that recognized by H-9 McAbs - are molecularly associated on placenta ferritin. The results of this study led us to term the G-8 a 'common' ferritin antigenic determinant and H-9 a 'private' embryonic ferritin determinant.

Animals↗