• Login
    View Item 
    •   UMB Digital Archive
    • UMB Open Access Articles
    • UMB Open Access Articles 2017
    • View Item
    •   UMB Digital Archive
    • UMB Open Access Articles
    • UMB Open Access Articles 2017
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UMB Digital ArchiveCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    Display statistics

    IInactivation of maternal Hif-1α at mid-pregnancy causes placental defects and deficits in oxygen delivery to the fetal organs under hypoxic stress

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Publisher version
    View Source
    Access full-text PDFOpen Access
    View Source
    Check access options
    Check access options
    Author
    Kenchegowda, D.
    Natale, B.
    Lemus, M.A.
    Date
    2017
    Journal
    Developmental Biology
    Publisher
    Academic Press Inc.
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1016/j.ydbio.2016.12.013
    Abstract
    A critical transition occurs near mid-gestation of mammalian pregnancy. Prior to this transition, low concentrations of oxygen (hypoxia) signaling through Hypoxia Inducible Factor (HIF) functions as a morphogen for the placenta and fetal organs. Subsequently, functional coupling of the placenta and fetal cardiovascular system for oxygen (O2) transport is required to support the continued growth and development of the fetus. Here we tested the hypothesis that Hif-1α is required in maternal cells for placental morphogenesis and function. We used Tamoxifen-inducible Cre-Lox to inactivate Hif-1α in maternal tissues at E8.5 (MATcKO), and used ODD-Luciferase as a reporter of hypoxia in placenta and fetal tissues. MATcKO of Hif-1α reduced the number of uterine natural killer (uNK) cells and Tpbpa-positve trophoblast cells in the maternal decidua at E13.5 -15.5. There were dynamic changes in all three layers of E13.5-15.5 MATcKO placenta. Of note was the under-development of the labyrinth at E15.5 associated with reduced Ki67 and increased TUNEL staining consistent with reduced cell proliferation and increased apoptosis. Labyrinth defects were particularly evident in placentas connected to effectively HIF-1α heterozygous null embryos. MATcKO had no effect on basal ODD-Luciferase activity in fetal organs (heart, liver, brain) at any stage, but at E13.5-15.5 resulted in enhanced induction of the ODD-Luciferase hypoxia reporter when the dam’s inspired O2 was reduced to 8% for 4 hours. MATcKO also slowed the growth after E13.5 of fetuses that were effectively heterozygous for Hif-1α, with most being non-viable at E15.5. The hearts of these E15.5 fetuses were abnormal with reduction in size, thickened epicardium and mesenchymal septum. We conclude that maternal HIF-1α is required for placentation including recruitment of uNK and trophoblast cells into the maternal decidua and other trophoblast cell behaviors. The placental defects render the fetus vulnerable to O2 deprivation after mid-gestation.
    Sponsors
    This work was supported by the Department of Defense (PR140388) and National Institute of Health (R01 HL65314) to S.A.F.
    Keyword
    Feto-placental unit
    Trophoblast
    Uterine natural killer cells
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85008487828&doi=10.1016%2fj.ydbio.2016.12.013&partnerID=40&md5=8c469f24863227f8aa1fd270d263c8c8; http://hdl.handle.net/10713/11291
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.ydbio.2016.12.013
    Scopus Count
    Collections
    UMB Open Access Articles 2017

    entitlement

    Related articles

    • Hypoxia induced HIF-1/HIF-2 activity alters trophoblast transcriptional regulation and promotes invasion.
    • Authors: Highet AR, Khoda SM, Buckberry S, Leemaqz S, Bianco-Miotto T, Harrington E, Ricciardelli C, Roberts CT
    • Issue date: 2015 Dec
    • Oxygen and lack of oxygen in fetal and placental development, feto-placental coupling, and congenital heart defects.
    • Authors: Llurba Olive E, Xiao E, Natale DR, Fisher SA
    • Issue date: 2018 Dec 1
    • Trophoblast-Specific Expression of Hif-1α Results in Preeclampsia-Like Symptoms and Fetal Growth Restriction.
    • Authors: Albers RE, Kaufman MR, Natale BV, Keoni C, Kulkarni-Datar K, Min S, Williams CR, Natale DRC, Brown TL
    • Issue date: 2019 Feb 26
    • Placental cell fates are regulated in vivo by HIF-mediated hypoxia responses.
    • Authors: Adelman DM, Gertsenstein M, Nagy A, Simon MC, Maltepe E
    • Issue date: 2000 Dec 15
    • Oxygen and placental development during the first trimester: implications for the pathophysiology of pre-eclampsia.
    • Authors: Caniggia I, Winter J, Lye SJ, Post M
    • Issue date: 2000 Mar-Apr
    DSpace software (copyright © 2002 - 2021)  DuraSpace
    Quick Guide | Policies | Contact Us | UMB Health Sciences & Human Services Library
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.