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At least 19 recordsLinked to original sources
PubMed1995

The effects of maternal aerobic exercise on human placental development: placental volumetric composition and surface areas.

The histomorphometry of term placentae from women who exercised regularly throughout either the first half or all of pregnancy was compared to that of placentae from matched controls to determine if regular exercise during pregnancy produced histomorphometric evidence of altered development and transport capacity. Conventional stereological techniques were used to estimate placental volumetric composition, surface areas, and villous and vascular configurations in the three groups. Exercise confined to early pregnancy increased the parenchymal component of the placenta, total vascular volume and site-specific capillary volume and surface area. Exercise throughout pregnancy increased these and multiple other histomorphometric parameters associated with the rate of placental perfusion and transfer function. However, significant changes were confined to villi > 80 microns in diameter. The localization of both the timing of the stimulus and the anatomical sites affected indicates that regular, sustained exercise modifies placental development primarily in early and mid-pregnancy. We speculate that the lack of significant changes in the structure and configuration of the smaller villi indicates that other adaptive mechanisms, such as increased rates of placental blood flow, must be well developed by the latter portion of the mid-trimester and adequately maintain fetal oxygenation and substrate delivery throughout the third trimester.

Adult↗
PubMed1991

Transforming growth factor-beta 1 expression during placental development.

Placental growth has several malignant characteristics, including properties of invasiveness, rapid cell proliferation, and a lack of cell contact inhibition. These malignant characteristics of placental development are strictly regulated throughout normal gestation, because placental growth is limited in both extent and duration. Transforming growth factor-beta 1 inhibits growth of many normal and malignant cell lines. In this study, using Northern blot analysis, we found transforming growth factor-beta 1 expression to occur in human placenta throughout gestation. Peak expression was noted at midgestation (near 17 weeks) and again in late gestation (near 34 weeks). Immunohistochemical analysis localized transforming growth factor-beta 1 protein expression to the syncytiotrophoblastic layer. The process of trophoblastic invasion of the decidua and myometrium is usually complete by 18 weeks of gestation, and absolute growth of the placenta ceases in late gestation (near 35 weeks). The time frames of maximal transforming growth factor-beta 1 expression noted in our studies correlate with these events. We speculate that peak transforming growth factor-beta 1 expression at these stages of placental development is suggestive of its regulation of both trophoblastic invasion and proliferation.

Blotting, Northern↗
PubMed2000

Angiopoietin-1 and angiopoietin-2 activate trophoblast Tie-2 to promote growth and migration during placental development.

Human placental development involves coordinated angiogenesis and trophoblast outgrowth that are compromised in intrauterine growth restriction (IUGR). As Tie-2((-/-)) mice exhibit growth retardation and vascular network malformation, the expression of Tie-2 and its ligands, angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2), were investigated in human placenta from normal pregnancies and those complicated by severe IUGR. Ribonucleotide protection assays showed no significant change in the expression of Ang-2 mRNA between gestationally matched normal and IUGR placentas; however, immunoblots revealed that Ang-2 protein was significantly decreased in IUGR, suggesting that this may contribute to the abnormal development of the villous vasculature. In situ hybridization studies showed that Ang-1 and Tie-2 were detected in the cyto/syncytiotrophoblast bilayer in first-trimester placenta, whereas Ang-2 mRNA was restricted to the cytotrophoblast, suggesting their role in trophoblast function. At term, Ang-1 mRNA and immunoreactive protein were restricted to the paravascular tissues of the primary stem villi, supporting its role in vessel maturation. In contrast, Ang-2 was expressed throughout the term villous core, perhaps to permit the developing placental vascular network to remain in a state of fluidity. As these studies also revealed that trophoblast, in addition to endothelial cells, expressed Tie-2 receptors, we investigated the potential role of Ang-1/Ang-2 on trophoblast proliferation, migration, and the release of NO. Using spontaneously transformed first-trimester trophoblast cell lines that exhibit cytotrophoblast-like (ED(27)) and extravillous trophoblast-like (ED(77)) properties, we show that the addition of Ang-2 (250 ng/ml) stimulated DNA synthesis in ED(27) trophoblast cells and triggered the release of NO. Ang-1 stimulated trophoblast (ED(77)) migration in a dose-dependent manner that was inhibited by recombinant Tie-2-FC. These data thus imply, for the first time, a specific role for angiopoietins as regulators of trophoblast behavior in the development of the utero/fetoplacental circulation, an action independent of their well-established roles in vascular endothelium.

Angiopoietin-1↗
PubMed2006

Hepatocyte growth factor activator inhibitor-1 (HAI-1) is essential for the integrity of basement membranes in the developing placental labyrinth.

Hepatocyte growth factor activator inhibitor-1 (HAI-1) is a membrane-associated Kunitz-type serine protease inhibitor that regulates cell surface and extracellular serine proteases involved in tissue remodeling and tumorigenesis, such as HGFA, matriptase, prostasin and hepsin. We generated HAI-1 deficient mice, which died in utero due to placental defects. The HAI-1(-/-) placental labyrinth exhibited a complete failure of vascularization and a compact morphology of the trophoblast layer. Immunofluorescent staining of collagen IV and laminin and electron microscopy analysis revealed that this aberrant labyrinth architecture was associated with disrupted basement membranes located at the interface of chorionic trophoblasts and allantoic mesoderm. Unlike the placental labyrinth, basement membranes and vasculogenesis were normal in embryo and yolk sac. Therefore, basement membrane defects appear to be the underlying cause for the greatly impaired vascularization and trophoblast branching in HAI-1(-/-) placentas. In wild-type placentas, the expression of matriptase and prostasin co-localized with their physiological inhibitor HAI-1 to the labyrinthine trophoblast cells in proximity to basement membranes. In HAI-1(-/-) placentas, both the localization and expression of the two proteases remained unchanged, implying uncontrolled proteolytic activities of the two enzymes. Our study demonstrates the important role of HAI-1 in maintaining the integrity of basement membrane most likely by regulating extracellular proteolytic activities during placental development.

Animals↗
PubMed2005

Differential expression of the receptor tyrosine kinase EphB4 and its ligand Ephrin-B2 during human placental development.

Normal placentation involves the development of an utero-placental circulation following the migration of the extravillous cytotrophoblasts into the decidua and invasion of the spiral arteries, which are thereby transformed into large vessels of low resistance. Given the documented role of the receptor tyrosine kinase EphB4 and its ligand ephrin-B2 in the establishment of the embryonal vascular network, we hypothesized that these molecules are also instrumental in the development of the human placenta. Monitoring the expression during placental development revealed that in first trimester and term placentae both molecules are equally expressed at the RNA level. In contrast, the protein levels were significantly reduced during gestation. Immunohistochemistry revealed a distinct localization of the EphB4 and ephrin-B2 proteins. EphB4 was predominantly expressed in the villous syncytial trophoblast layer and in a subset of intravillous capillaries. Prominent expression was also observed in the extravillous cytotrophoblast giant cells. In contrast, ephrin-B2 expression was detected in the villous cytotrophoblast and syncytial trophoblast cell layers, as well as initially in all intravillous capillaries. Strong expression was also observed in extravillous anchoring cytotrophoblast cells. Hypoxia is a major inducer of placental development. In vitro studies employing trophoblast-derived cell lines revealed that predominantly ephrin-B2 expression is induced by hypoxia, however, in an Hif-1alpha independent manner. These experiments suggest that EphB4 and ephrin-B2 are instrumental in the establishment of a functional placental structure and of the utero-placental circulation.

Cell Line↗
PubMedDate not supplied

Temporal and spatial pattern of cellular myc oncogene expression during human placental development.

The human placental trophoblast component is of embryonic origin and is developmentally regulated; the tissue is highly proliferative and often described as pseudomalignant. Because cellular oncogenes have been implicated in normal cellular proliferation and differentiation processes, we have studied c-myc oncogene expression in relation to the progression of human placental development. The c-myc transcript shows a 20- to 30-fold variation over the course of placental development, with a peak at four to five weeks after conception. A clear decline in placental c-myc transcription is seen before the end of the first trimester of pregnancy. In situ hybridization to [125I]-labelled myc probes demonstrates an unequal distribution of myc transcripts in placenta, with particularly high expression in the cytotrophoblastic shell of the early placenta. The localization of myc transcripts to cytotrophoblast and the temporal pattern of myc expression support a strong correlation between myc transcript abundance and cytotrophoblastic proliferation. These findings are discussed in the light of a possible role for the c-myc gene in proliferation of normal cells.

Female↗
PubMed2003

Altered placental development in interleukin-10 null mutant mice.

Placental morphogenesis and nutrient transfer function are regulated by growth factors at the foeto-maternal interface. Interleukin (IL)-10, expressed in the decidua and placenta, is implicated in regulating extravillous cytotrophoblast invasion through inhibiting matrix metalloproteinase expression and influencing the quality of the maternal immune response. Our laboratory has previously found that IL-10 deficiency in both the mother and foetus increases foetal weight at day 18 without altering placental weight suggesting that the placenta has a greater functional capacity when IL-10 is absent. The present study has used IL-10 null mutant (IL-10-/-) mice to investigate the role of IL-10 in placental development. Placental structure was assessed in adult virgin IL-10-/- or wild-type (IL-10+/+) mice mated with males of the same genotype and sacrificed at day 18 of gestation. Mid-sagittal cross sections of placental tissue were stained with Masson's trichrome or immuno-labelled with MTS-12 and pan-cytokeratin reactive antibodies to identify foetal endothelial cells and trophoblasts, respectively, and examined with video image analysis. IL-10 deficiency increased the total cross sectional area of the placenta by 28 per cent (IL-10-/- n=22 placentae from 8 dams, IL-10+/+n =21 placentae from 9 dams, P=0.026), principally through increasing the cross sectional area of placental labyrinth by 37 per cent (P=0.025). The proportion of maternal blood space in the labyrinth was increased by 26 per cent (P=0.001) and that of trophoblast was decreased by 16 per cent (P=0.001) in IL-10-/- placentae. The surface area of trophoblast per gram of labyrinth was increased by 41 per cent (P=0.0005) in IL-10-/- placentae. In the absence of IL-10, structural correlates of placental function are enhanced consistent with concomitant increases in foetal growth. These data indicate that IL-10 is a regulator of placental morphogenesis, acting to retard expansion of the placental labyrinth and to modify the architecture of the maternal blood sinuses. Since previous studies have paradoxically shown that postnatal growth is impaired in IL-10 null mutants, these observations are consistent with a role for IL-10 in regulating placental development and foetal programming.

Animals↗
PubMed1998

Expression and function of the urokinase type plasminogen activator during mouse hemochorial placental development.

Mouse midlate placental development involves extensive tissue remodeling and cell invasion, processes which could be mediated by extracellular proteolytic enzymes. We have performed in situ expression analysis of urokinase type plasminogen activator (uPA), as well as functionally related molecules (uPA receptor, low density lipoprotein receptor-related protein, plasminogen activator inhibitor type-1) in day 10.5 to 18.5 post coitum (p.c.) murine placentas. In situ hybridization demonstrated the presence of uPA transcripts in the invasive trophoblast cells, in particular in glycogen-rich trophoblasts, a cell population that between embryonic days 12.5 and 15.5 infiltrates the maternal decidual tissue. In addition, we observed high uPA expression in the cells of uterine epithelium. Enzymatically active uPA was detected in both sites of uPA mRNA expression by in situ zymography. Expression and activity data suggest a role for this protease in the processes of cell invasion and uterine epithelial remodeling. Only low levels of uPA receptor (uPAR) transcripts were found in trophoblasts and decidual tissue at days 10.5 and 11.5 p.c. At the same stages, a prominent expression of plasminogen activator inhibitor type-1 (PAI-1) by spongiotrophoblasts and giant trophoblasts, as well as of LDL receptor-related protein (LRP) by spongiotrophoblasts and decidual cells could be detected, suggesting a role in regulating extracellular proteolysis in the area of fetomaternal interface. Analysis of uPA null placentas showed the presence of decidual extravascular fibrin deposits, which were not detected in wild type placentas. At the same time, the extent of infiltration of trophoblast cells in maternal decidual tissue, evaluated by anti-cytokeratin immunostaining, was similar in wild type and uPA null placentas. Our studies show that in murine hemochorial placentation, uPA has an essential role in the maintenance of the fibrinogenic/fibrinolytic balance in the decidua. The function of uPA in trophoblast invasion appears not to be indispensable, and its absence can be overcome by redundant or compensatory mechanisms.

Animals↗
PubMed2004

Connexin31-deficient trophoblast stem cells: a model to analyze the role of gap junction communication in mouse placental development.

The connexin (Cx) expression during placental development in rodents is subject to exacting spatiotemporal regulation. Following implantation, Cx31 characterizes the early trophoblast cell lineage and is expressed by the spongiotrophoblast during placental development until birth. Inactivation of the Cx31 gene results in a transient placental dysmorphogenesis with an imbalance in the trophoblast cell lineage differentiation in favor to giant cells [Dev. Biol. 231 (2001) 334]. In this study, we show that trophoblast stem (TS) cells exhibit the same connexin expression found in trophoblast cell lineage differentiation. Undifferentiated TS cells exclusively express Cx31 protein and Cx31.1 transcripts. Upon differentiation of TS cells, placental-specific Cx26 and Cx43 are induced. Cx31 knockout TS cells revealed an accelerated differentiation process to giant cells compared to controls, indicated by an overall shift in expression of connexins and marker genes such as Mash2, Pl-1, and Tpbpa. Moreover, proliferation was significantly reduced in Cx31 knockout TS cells upon differentiation. Both wild type and Cx31 knockout TS cells are able to invade and erode host vessels when injected into nude mice. We conclude that during trophoblast cell lineage differentiation, the Cx31 gap junction channel is involved in maintaining the proliferative diploid trophoblast cell population.

Animals↗
PubMed2003

3-dimensional colour power angiography for staging human placental development.

Maldevelopment of placental villous trees and their blood vessels results in impaired fetal growth, which can greatly compromise fetal, neonatal, childhood, and adulthood health. There are no means of directly assessing such maldevelopment. We have applied a new technique of imaging (colour power angiography [CPA]) with 3-dimensional reconstruction to assess directly villous development in human pregnancy in vivo in 20 uncomplicated pregnancies from 13 to 38 weeks' gestation. The chronology of villous trees was much the same in 3-dimensional CPA, scanning electron micrography, and classical histology from controls matched by age. This approach provides a unique opportunity to examine normal placental development directly, and should provide the bases for real-time investigation of placental pathology and a robust method for diagnosis and surveillance during pregnancy.

Angiography↗
PubMedDate not supplied

Gonadotropin-releasing hormone and chorionic gonadotropin gene expression in human placental development.

Control of human chorionic gonadotropin (hCG) synthesis during pregnancy is poorly understood, although in vitro data suggest a role for placental gonadotropin releasing hormone (GnRH) in its regulation. To study GnRH regulation during placental development, placental tissue of different gestational ages was analyzed for GnRH and beta hCG mRNA content. cRNA probes to exonic/intronic sequences of GnRH and beta hCG transcripts were constructed and used to perform solution hybridization/nuclease protection and in situ hybridization assays. The levels of GnRH mRNA were approximately 0.1-1% of that of beta hCG mRNA, in agreement with its suggested paracrine, rather than endocrine, role. While beta hCG mRNA content decreased significantly from first trimester to term (643 to 21.6 pg/microgram RNA), there was no significant change in GnRH mRNA (0.179 to 0.155 pg/microgram RNA). While beta hCG mRNA was localized almost exclusively in syncytiotrophoblasts, GnRH mRNA was present in all cell types of the placenta, including the stroma. In the course of performing sense-strand controls in the in situ hybridization, we noted that the placenta appeared to express more antisense GnRH than sense GnRH mRNA, again, in all cell types. Solution hybridization/nuclease protection analysis with exon 1 and exon 3 probes confirmed this observation, showing that there is two to three times more antisense GnRH RNA than sense GnRH mRNA. These studies suggest that GnRH gene expression and its role in regulating hCG production in human placenta is complex and does not fit a simple model for paracrine regulation of hCG.

Chorionic Gonadotropin↗
PubMed2002

Altered placental development and intrauterine growth restriction in IGF binding protein-1 transgenic mice.

IGF binding protein-1 (IGFBP-1) is a secretory product of decidualized endometrium and a major constituent of amniotic fluid. It is thought to modulate the actions of the IGFs on trophoblast cells and is therefore potentially important in regulating placental development and fetal growth. To investigate this hypothesis, we have studied the effects of decidual IGFBP-1 excess on fetoplacental growth in transgenic mice overexpressing human IGFBP-1. Endogenous fetal IGFBP-1 overexpression is associated with a transient impairment of fetal growth in midgestation. Maternal decidual IGFBP-1 excess is also associated with impaired fetal growth in midgestation independent of fetal genotype, indicating placental insufficiency. Our data also demonstrate that amniotic fluid IGFBP-1 is derived almost exclusively from maternal sources. Decidual IGFBP-1 overexpression has a marked effect on placental development. Placental morphology is abnormal in transgenic females due to altered trophoblast invasion and differentiation. These changes result in an increase in placental mass throughout pregnancy. This study provides the first compelling in vivo evidence that IGFBP-1 plays a role in placentation and suggests that IGFBP-1 has a pathological role in preeclampsia, a disorder characterized by shallow uterine invasion and altered placental development.

Amniotic Fluid↗
PubMed2001

X-linked inhibitor of apoptosis protein expression and the regulation of apoptosis during human placental development.

In this study, we have examined the expression and potential role of X-linked inhibitor of apoptosis protein (XIAP), Fas, and Fas ligand (FasL) in the regulation of apoptosis throughout placental development. Protein expression was determined by Western blot analysis and immunohistochemistry, whereas apoptotic cell death was assessed by DNA fragmentation analysis and TUNEL. The XIAP was present in trophoblast throughout placental development, but its content significantly decreased during late pregnancy, when apoptosis was maximal. The FasL content was low during early placental development but increased coincidentally to the decrease in XIAP during the third trimester. Our data also suggest that placental apoptosis is the culmination of the relative expression of these cell-death and -survival proteins, a phenomenon that is cell type-specific and dependent on cytodifferentiation and the stage of placental development. Moreover, the induction of syncytiotrophoblast apoptosis may involve the concomitant up-regulation of FasL for Fas activation and the removal of downstream inhibition of the apoptotic cascade by XIAP.

Apoptosis↗
PubMed1988

[Normal placental development and ovular anomalies during the 1st trimester of gestation].

Normal placental development and ovular anomalies during the first trimester of gestation. The normal sequences of placental development are first briefly summarized to allow a better understanding of ovular pathology. Fifteen percent of recognized pregnancies end with miscarriages, and probably one out of two conceptuses fail even before implantation. Most spontaneous abortions occur before 15 weeks of gestation, and are caused by zygotic defects: abnormal karyotypes represent more than 50% of the cases. Trisomies predominate (50 to 60%), followed by triploidy (20%), monosomy X (15%) and structural anomalies (4%). The phenotype of these lethal anomalies have been meticulously described so that the pathologist is allowed to diagnose aneuploidy on morphological features. It should be emphasized that similar abnormal phenotypes have been observed with normal karyotypes suggesting undetected genetic factors. Hydatidiform mole, twinning, whose incidence is much higher among aborted material than among live births, are other zygotic causes of abortion. Embryonic death or placental insufficiency leading to miscarriage can also result from abnormal implantation or be secondary to lesions of the membranes, as observed in amniotic band syndrome. Maternal causes of spontaneous abortions, local or general, are probably rare at this stage of gestation and difficult to diagnose by the pathologist. Retroplacental haematoma, infarcts or endometritis are often undistinguishable from leucocytic infiltrates or necrosis following the usual long period of retention.

Abortion, Spontaneous↗
PubMed2026

Autophagy in the Regulation of Placental Development: From Trophoblast Differentiation to Metabolic Stress Adaptation.

Successful pregnancy depends on precise placental development, where trophoblast differentiation, syncytialization, invasion, and adaptation to metabolic stress are critical. Autophagy, a lysosome-mediated degradation pathway, has emerged as an important regulator of cellular homeostasis, yet its integrated role in trophoblast fate and functions has not been comprehensively summarised. This review synthesises current evidence on autophagy's functions throughout placentation, from trophoblast differentiation to syncytialization and extravillous trophoblast invasion. We examine how autophagy enables cellular remodelling during differentiation, supports metabolic adaptation under hypoxia and nutrient stress, and maintains mitochondrial quality control through selective mitophagy. Autophagy is essential for syncytiotrophoblast formation via endoplasmic reticulum stress-coordinated activation and p53 downregulation. However, its effects on trophoblast invasion are context-dependent, influenced by oxygen tension, autophagic flux completeness, and differentiation state, which can potentially be shaped by parent-offspring genetic conflicts through genomic imprinting. Both excessive and insufficient autophagy contribute to pregnancy complications, including pre-eclampsia, foetal growth restriction, gestational diabetes mellitus, preterm birth, recurrent spontaneous abortion and obstetric antiphospholipid syndrome through distinct molecular mechanisms. Autophagy functions as a dynamically tuned homeostatic mechanism in placental development. Understanding condition-specific autophagy dysregulation is thereby crucial for improving pregnancy outcomes.

Autophagy↗
PubMed2000

The bovine placenta before and after birth: placental development and function in health and disease.

This paper reviews bovine placental development, anatomy (microscopic and gross), nomenclature and classification. The paper focuses on the biology of those specialized cells that arise from the outermost layer of very early embryos, the trophoblast cells, and on placental macrophages, cells that play a key role in fetal/placental defense. Data is presented from an immunohistochemical quantitative study that characterizes the ontogeny of placental macrophages using placental tissues from 21 cows (sampled from 4 months of pregnancy through the post partum period). Understanding of bovine placental development is essential for veterinarians, pathologists, diagnosticians and researchers. Lesions of diagnostic significance can be recognized for many economically important infectious abortifacient diseases, and there is growing evidence that pregnancy failure of cloned calves is due in part to unexplained placental failure. Placentology and placental pathology are becoming of increasing importance.

Animals↗
PubMed2001

Nodal regulates trophoblast differentiation and placental development.

Nodal has been thought to be an embryo-specific factor that regulates development, but nodal is also expressed in the mouse placenta beginning at midgestation, specifically in the spongiotrophoblasts. In an insertional null nodal mutant, not only is embryonic development disrupted, but mouse placental development is also grossly altered with the loss of the diploid spongiotrophoblasts and labyrinth and an expansion of the polyploid giant cell layer. A hypomorphic mutation in nodal results in an expansion of the giant cell and spongiotrophoblast layers, and a decrease in labyrinthine development. Expression of nodal in trophoblast cell cultures is sufficient to inhibit trophoblast giant cell differentiation, demonstrating that nodal can act directly on trophoblasts. The mechanism of nodal action includes the inhibition of junB gene transcription. These results suggest that nodal may be involved in redirecting trophoblast fate towards the midgestational expansion of the labyrinth region while maintaining the thin layer of trophoblast giant cells and the underlying layer of spongiotrophoblasts that form the boundary between the maternal and extraembryonic compartments.

Animals↗
PubMed2000

Cytokeratins 8 and 19 in the mouse placental development.

To investigate the expression and biological roles of cytokeratin 19 (K19) in development and in adult tissues, we inactivated the mouse K19 gene (Krt1-19) by inserting a bacterial beta-galactosidase gene (lacZ) by homologous recombination in embryonic stem cells, and established germ line mutant mice. Both heterozygous and homozygous mutant mice were viable, fertile, and appeared normal. By 7.5-8.0 days post coitum (dpc), heterozygous mutant embryos expressed lacZ in the notochordal plate and hindgut diverticulum, reflecting the fact that the notochord and the gut endoderm are derived from the axial mesoderm-originated cells. In the adult mutant, lacZ was expressed mainly in epithelial tissues. To investigate the possible functional cooperation and synergy between K19 and K8, we then constructed compound homozygous mutants, whose embryos died approximately 10 dpc. The lethality resulted from defects in the placenta where both K19 and K8 are normally expressed. As early as 9. 5 dpc, the compound mutant placenta had an excessive number of giant trophoblasts, but lacked proper labyrinthine trophoblast or spongiotrophoblast development, which apparently caused flooding of the maternal blood into the embryonic placenta. These results indicate that K19 and K8 cooperate in ensuring the normal development of placental tissues.

Animals↗