210. Localisation of insulin-like growth factor-II (IGF-II) and its receptor in early murine pregnancy: a role in placentation and angiogenesis in the decidua?

2005 ◽  
Vol 17 (9) ◽  
pp. 80
Author(s):  
K. G. Pringle ◽  
C. T. Roberts
Keyword(s):  
Blood Vessels ◽  
Early Pregnancy ◽  
Close Contact ◽  
Protein S ◽  
Giant Cells ◽  
Maternal Blood ◽  
Extravillous Trophoblast ◽  
Placental Development ◽  
Direct Role ◽  
Intracellular Signalling Pathway

The highly invasive activity of the human placenta is tightly regulated by a variety of growth factors and other molecules. Contrary to the dominant view, recent data suggests that IGF-II, upon binding to the IGF2R, can stimulate an intracellular signalling pathway.1 Evidence in humans and mice suggests that IGF-II and the IGF2R are important regulators of placental growth; however, to date they have not yet been localised to early murine implantation sites. This study provides a photo micrographic account of early placental development and the decidual vasculature in the mouse, and localises IGF-II and the IGF2R from days 5.5 to 10.5 of pregnancy. During early pregnancy, the decidua displays a paucity of blood vessels, which appear to undergo angiogenesis, so that by day 10.5 the decidua has become a highly vascularized structure, with an extensive network of dilated vessels that presumably enable maximal blood supply to the placenta. Unlike humans, murine trophoblast cells do not invade the endometrium individually, but remain in close contact with the main giant cell layer. The trophoblast giant cells (TGCs) are the outermost cell type of the murine placenta and maternal blood spaces beneath this layer are not lined by endothelium. Due to their location, TGCs appear to play a direct role in displacing this endothelium and therefore may play a role in the transformation into trophoblast lined maternal blood spaces. IGF-II and its receptor were present throughout early pregnancy in the conceptus and maternal decidua supporting their role as regulators of fetal and placental development. Most interesting, however, was their association with the developing maternal blood vessels in the mesometrial decidua. It seems likely that in mice the maternal vessels are remodelled by a variety of locally derived molecules. By association, IGF-II and its receptor are likely candidates. (1)McKinnon T, et al. (2001). Stimulation of human extravillous trophoblast migration by IGF-II is mediated by IGF type 2 receptor involving inhibitory G protein(s) and phosphorylation of MAPK. J. Clin. Endocrinol. Metab. 86(8), 3665–3674.

scholarly journals Remodelling at the maternal–fetal interface: relevance to human pregnancy disorders

Reproduction ◽  
2010 ◽  
Vol 140 (6) ◽  
pp. 803-813 ◽  
Author(s):  
Judith E Cartwright ◽  
Rupsha Fraser ◽  
Karin Leslie ◽  
Alison E Wallace ◽  
Joanna L James
Keyword(s):  
Early Pregnancy ◽  
Immune Cells ◽  
Active Role ◽  
Maternal Blood ◽  
Placental Development ◽  
Successful Pregnancy ◽  
Human Pregnancy ◽  
Healthy Pregnancy ◽  
Maternal Fetal Interface ◽  
Pregnancy Disorders

In human pregnancy, successful placentation and remodelling of the uterine vasculature require the integration of a number of stages, which are crucial for a healthy pregnancy. As the demands of the developing fetus for nutrients and oxygen increase, the capacity of the maternal blood vessels to supply this must be altered radically, with deficiencies in this process implicated in a number of dangerous pregnancy complications. The complex signalling networks that regulate these tightly co-ordinated events are becoming clearer as more studies of early pregnancy are performed. It is the aim of this review to draw together our knowledge of events that occur to facilitate a successful pregnancy ranging from the preparation for implantation, through the invasion and differentiation of the trophoblast and the regulation of these processes by other cells within the decidual environment, to the active role that the trophoblast and maternal immune cells play in facilitating the remodelling of the uterine spiral arteries. The events involved in a healthy pregnancy will then be compared to aberrant placentation and remodelling, which are characteristics of many pregnancy disorders, and recent advances in detection of abnormal placental development will also be discussed.

scholarly journals CELLULAR MECHANISM UNDERLYING EMBRYO-MATERNAL RELATIONSHIP IN INTRASPECIFIC AND INTERSPECIFIC PREGNANCY

2012 ◽  
Vol 6 (2) ◽  
Author(s):  
Diah Tri Widayati ◽  
Katsuhiro Fukuta
Keyword(s):  
Blood Vessels ◽  
Inner Cell Mass ◽  
Close Contact ◽  
Cell Mass ◽  
Pregnant Mouse ◽  
Extravillous Trophoblast ◽  
Implantation Site ◽  
Electron Microscopic ◽  
Mouse Uterus ◽  
Interspecific Pregnancy

Mouse and vole embryos were transferred into pseudopregnant CD-1 and scid female mice. Cellular changes involved in the formation of decidua in the pregnant mouse uterus up to day 8 of pregnancy were examined by histological, electron microscopic, and histochemical techniques. On day 6 of pregnancy, the vole embryos were laid in interstitium of antimesometrial side of the uterus, as well as in intraspecific pregnancy. Compared with intraspesific pregnant mouse, blood vessels were numerous in the decidua around the vole embryos in interspecific pregnancy. Both distribution and dilation of the blood vessels were increased on day 8. A part of cells in the inner cell mass had not nuclei, suggesting damaged vole embryos on day 8. At the implantation site, the uterine decidua was invaded by extravillous trophoblast (EVT) cells whose function is to destroy the walls of the uterine spiral. Moreover, this decidua was infiltrated by a population of natural killer (NK) cells and macrophage. These cells were particularly numerous in the decidua basalis at the implantation site where they come into close contact with invading EVT cells. These results suggest that interaction between NK, macrophage, and EVT provides the controlling relationship of embryo-maternal in intraspecific and interspecific pregnancy.

scholarly journals Maternal Insulin-Like Growth Factors-I and -II Act via Different Pathways to Promote Fetal Growth

Endocrinology ◽  
2006 ◽  
Vol 147 (7) ◽  
pp. 3344-3355 ◽  
Author(s):  
Amanda N. Sferruzzi-Perri ◽  
Julie A. Owens ◽  
Kirsty G. Pringle ◽  
Jeffrey S. Robinson ◽  
Claire T. Roberts
Keyword(s):  
Fetal Growth ◽  
Early Pregnancy ◽  
Guinea Pigs ◽  
Mammalian Species ◽  
Total Surface Area ◽  
Maternal Blood ◽  
Placental Development ◽  
Growth And Survival ◽  
Igf I ◽  
Near Term

The placenta transports substrates and wastes between the maternal and fetal circulations. In mice, placental IGF-II is essential for normal placental development and function but, in other mammalian species, maternal circulating IGF-II is substantial and may contribute. Maternal circulating IGFs increase in early pregnancy, and early treatment of guinea pigs with either IGF-I or IGF-II increases placental and fetal weights by mid-gestation. We now show that these effects persist to enhance placental development and fetal growth and survival near term. Pregnant guinea pigs were infused with IGF-I, IGF-II (both 1 mg/kg·d), or vehicle sc from d 20–38 of pregnancy and killed on d 62 (term = 69 d). IGF-II, but not IGF-I, increased the mid-sagittal area and volume of placenta devoted to exchange by approximately 30%, the total volume of trophoblast and maternal blood spaces within the placental exchange region (+29% and +46%, respectively), and the total surface area of placenta for exchange by 39%. Both IGFs reduced resorptions, and IGF-II increased the number of viable fetuses by 26%. Both IGFs increased fetal weight by 11–17% and fetal circulating amino acid concentrations. IGF-I, but not IGF-II, reduced maternal adipose depot weights by approximately 30%. In conclusion, increased maternal IGF-II abundance in early pregnancy promotes fetal growth and viability near term by increasing placental structural and functional capacity, whereas IGF-I appears to divert nutrients from the mother to the conceptus. This suggests major and complementary roles in placental and fetal growth for increased circulating IGFs in early to mid-pregnancy.

scholarly journals 016.Role of cited genes in placental morphogenesis: studies in null mutant mice

2004 ◽  
Vol 16 (9) ◽  
pp. 16
Author(s):  
S. L. Dunwoodie ◽  
S. L. Withington ◽  
D. B. Sparrow ◽  
A. N. Scott ◽  
J. I. Preis ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Giant Cells ◽  
Maternal Blood ◽  
Postnatal Period ◽  
Null Mutant ◽  
Placental Development ◽  
Null Mutant Mice ◽  
And Function ◽  
Trophoblast Giant Cells ◽  
Null Mutants

Cited1 and Cited2 interact with CBP and p300. CBP/p300 bind numerous proteins and evidence exists, for Cited2 at least, that Cited binding prevents the binding of other proteins to CBP/p300. Since CBP/p300 interact with many proteins, can acetylate protein and DNA, and act as a ubiquitin ligase, it is likely that Cited1 and Cited2 function at a number of sites during development. We have generated mice that carry a null mutant allele for each of these genes. Analysis of null mutant embryos demonstrates that both Cited1 and Cited2 are required for normal embryonic development and survival. Although both Cited1 and Cited2 are expressed in the developing embryo and placenta, it appears that abnormal placental development and function is the cause of embryonic death. The defect that develops in the placentas of Cited1 null mutants is not apparent until late in gestation (16.5dpc). Cited1 null mutants are smaller than controls at birth and die during the early postnatal period. The placentas of these mutants are disorganised, with spongiotrophoblasts projecting in to the labyrinthine layer. In addition, resin casts of the maternal blood spaces within these placentas revealed extremely enlarged blood sinuses. We are searching for factors that could result in the increased size of the maternal blood sinuses. Cited2 null placentas and embryos are significantly smaller than controls; mutants die 3/4 the way through gestation (15.5dpc). The null mutant placentas have proportionally fewer spongiotrophoblasts, trophoblast giant cells and invasive trophoblasts. In addition, resin casts of fetal vasculature of the placenta reveal that the capillary network is underdeveloped. Through the isolation of trophoblast stem (TS) cells we are exploring the possibility that TS cell proliferation and/or differentiation is impaired due to a lack of Cited2. We suspect that the development of the phenotype may relate to the Hypoxia Inducible Factor-1a (HIF1a) transcription factor as Cited2 expression is induced by HIF1 and it acts to negatively regulate its activity.

scholarly journals Placental development during early pregnancy in sheep: Effects of embryo origin on fetal and placental growth and global methylation

2013 ◽  
Vol 79 (1) ◽  
pp. 94-102 ◽  
Author(s):  
Anna T. Grazul-Bilska ◽  
Mary Lynn Johnson ◽  
Pawel P. Borowicz ◽  
Loren Baranko ◽  
Dale A. Redmer ◽  
...  
Keyword(s):  
Early Pregnancy ◽  
Placental Development ◽  
Global Methylation ◽  
Embryo Origin

scholarly journals Oxygen regulation of macrophage migration inhibitory factor in human placenta

2007 ◽  
Vol 292 (1) ◽  
pp. E272-E280 ◽  
Author(s):  
Francesca Ietta ◽  
Yuanhong Wu ◽  
Roberta Romagnoli ◽  
Nima Soleymanlou ◽  
Barbara Orsini ◽  
...  
Keyword(s):  
High Altitude ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Inhibitory Factor ◽  
Extravillous Trophoblast ◽  
Macrophage Migration ◽  
Low Oxygen ◽  
Placental Development

Macrophage migration inhibitory factor (MIF) is an important proinflammatory cytokine involved in regulation of macrophage function. In addition, MIF may also play a role in murine and human reproduction. Although both first trimester trophoblast and decidua express MIF, the regulation and functional significance of this cytokine during human placental development remains unclear. We assessed MIF expression throughout normal human placental development, as well as in in vitro (chorionic villous explants) and in vivo (high altitude placentae) models of human placental hypoxia. Dimethyloxalylglycine (DMOG), which stabilizes hypoxia inducible factor-1 under normoxic conditions, was also used to mimic the effects of hypoxia on MIF expression. Quantitative real-time PCR and Western blot analysis showed high MIF protein and mRNA expression at 7–10 wk and lower levels at 11–12 wk until term. Exposure of villous explants to 3% O2 resulted in increased MIF expression and secretion relative to standard conditions (20% O2). DMOG treatment under 20% O2 increased MIF expression. In situ hybridization and immunohistochemistry showed elevated MIF expression in low oxygen-induced extravillous trophoblast cells. Finally, a significant increase in MIF transcript was observed in placental tissues from high-altitude pregnancies. Hence, three experimental models of placental hypoxia (early gestation, DMOG treatment, and high altitude) converge in stimulating increased MIF, supporting the conclusion that placental-derived MIF is an oxygen-responsive cytokine highly expressed in physiological in vivo and in in vitro low oxygen conditions.

scholarly journals Objective assessment of alcohol consumption in early pregnancy using phosphatidylethanol: a cross‐sectional study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Leonieke J. Breunis ◽  
Sophie Wassenaar ◽  
Barbara J. Sibbles ◽  
Ab A. Aaldriks ◽  
Hilmar H. Bijma ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Early Pregnancy ◽  
Gestational Age ◽  
Care Provider ◽  
Objective Assessment ◽  
Obstetric Care ◽  
Tertiary Hospital ◽  
Maternal Blood ◽  
Added Value ◽  
Cross Sectional

Abstract Background Alcohol consumption during pregnancy is associated with major birth defects and developmental disabilities. Questionnaires concerning alcohol consumption during pregnancy underestimate alcohol use while the use of a reliable and objective biomarker for alcohol consumption enables more accurate screening. Phosphatidylethanol can detect low levels of alcohol consumption in the previous two weeks. In this study we aimed to biochemically assess the prevalence of alcohol consumption during early pregnancy using phosphatidylethanol in blood and compare this with self-reported alcohol consumption. Methods To evaluate biochemically assessed prevalence of alcohol consumption during early pregnancy using phosphatidylethanol levels, we conducted a prospective, cross-sectional, single center study in the largest tertiary hospital of the Netherlands. All adult pregnant women who were under the care of the obstetric department of the Erasmus MC and who underwent routine blood testing at a gestational age of less than 15 weeks were eligible. No specified informed consent was needed. Results The study was conducted between September 2016 and October 2017. In total, we received 1,002 residual samples of 992 women. After applying in- and exclusion criteria we analyzed 684 samples. Mean gestational age of all included women was 10.3 weeks (SD 1.9). Of these women, 36 (5.3 %) tested positive for phosphatidylethanol, indicating alcohol consumption in the previous two weeks. Of women with a positive phosphatidylethanol test, 89 % (n = 32) did not express alcohol consumption to their obstetric care provider. Conclusions One in nineteen women consumed alcohol during early pregnancy with a high percentage not reporting this use to their obstetric care provider. Questioning alcohol consumption by an obstetric care provider did not successfully identify (hazardous) alcohol consumption. Routine screening with phosphatidylethanol in maternal blood can be of added value to identify women who consume alcohol during pregnancy.

Memoirs: Notes on the Structure and the Development of the Elephant's Placenta

1905 ◽  
Vol s2-49 (193) ◽  
pp. 1-38
Author(s):  
RICHARD ASSHETON ◽  
THOMAS G. STEVENS
Keyword(s):  
Blood Vessels ◽  
Vascular System ◽  
Single Layer ◽  
Blood Stream ◽  
Maternal Blood ◽  
Full Term ◽  
Maternal Tissue ◽  
Term Placenta ◽  
Uterine Mucosa ◽  
Foetal Blood

1. The full-term after-birth of the elephant consists of a chorion from which spring many much-branched villi, which spread out in all directions into plate-like branches. These end in (a) proximal foliaceous terminations, in which the fœtal blood vessels ramify, which interlace with a complicated system of much larger blood channels filled with maternal blood, having well-defined but non-nucleated walls; (b) more distal lobate terminations, which are covered by a wellmarked columnar or cubical epithelium -- presumably the trophoblast -- which are partly embedded in a kind of coagulum or detritus, and partly appear to hang loosely in irregular blood spaces without walls ; (c) the stems of still more prolonged villi, which have been torn off and probably left embedded in the walls of the uterus; (d) a few torn ends of blood-vessels. 2. The main trunks of the villi and their foliaceous terminations are everywhere separated from the maternal bloodchannels by a syncytial layer, which is continuous with the epithelium covering the lobate terminations, and is presumably trophoblastic. 3. The half-term placenta originally examined by Owen in 1850 shows, in its more central region, characters which are essentially similar to those of the full-term specimen, and goes far to prove the existence of longer villi which penetrate deeply into the uterine mucosa. The lateral areas of the zonary belt exhibit many most interesting previous conditions. We are able to see in these the simple terminations of the foetal villi covered with a single layer of trophoblast separated from the uterine tissues by a layer of matei'ial partly maternal and partly of foetal origin. There is no process of growth round existing maternal capillaries to form an angio-plasmode, nor apparently any phagocytic action on the part of the trophoblast. The vascularisation of the after-birth is effected by the invasion of the trophoblast by extravasated maternal blood, which flows at first in intercellular and intervillous passages which form the larger channels of the after-birth maternal vascular system, and then makes its way along intra-cellular or intrasyncytial canals through a plasmodium produced by the breaking down of the trophoblast of two adjoining villi. We think the evidence is in favour of considering the corpuscles floating in this invading stream, which contains no red non-nucleated corpuscles in its more advanced portions, to be of maternal rather than trophoblastic origin. 4. The tissues of the full-term placenta contain pigment granules, which are deposited chiefly in the syncytial layer. This we regard as an excretory product; it is almost quite absent from the tissues of the half-term specimen. Leucocytes, either of maternal or foetal origin, seem to be concerned in the transference of this pigment into the maternal blood stream. 5. The subcircular bodies of Owen we find as described by him and Turner, though we note the presence of minute villi on their outer surface. 6. We confirm the opinion of previous writers that the zonary band in part is a "deciduous" form of placenta, although there is not much maternal tissue except the blood. It is not correct to speak of the after-birth being composed of a "much hypertrophied mncosa layer of the uterus." 7. The placenta of the elephant shows by its long villi, which tend to remain embedded in the uterus wall, a resemblance to the condition found in the Sirenia; by the villous patches at the poles and other villi which come out from the uterus, either with or without their trophoblastic covering, but with no maternal cells attached, a resemblance to the ungulata vera of the Perissodactyl type ; by the invasion of the trophoblast--if such it is--by the maternal blood stream, a resemblance to the Discoplacental type, although the actual manner by which this invasion occnrs would seem to be--so far as our very limited material affords us opportunity of observation--unlike anything hitherto described.1 8. The resemblance, at first sight obvious enough to the zonary placenta of the carnivora, is superficial. The elephant's placenta differs from that of the carnivora in (a) consisting of three areas of attachment instead of one, two of which, are wholly in the non-deciduous type, the other partly deciduous, partly non-deciduous. (b) There is nothing formed comparable to an angio-plasmode. (c) The maternal capillaries do not directly become the maternal vessels of the after-birth.

scholarly journals Maternal Nutrition in Early Pregnancy Effects Placental Development

2011 ◽  
Vol 1 (2) ◽  
pp. 22-29
Author(s):  
JJ Babu Geddam ◽  
Radhakrishna KV ◽  
Ramalaxmi BA ◽  
Balakrishna N ◽  
Qadri SSYH ◽  
...  
Keyword(s):  
Early Pregnancy ◽  
Maternal Nutrition ◽  
Placental Development
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