Effect of Post Covid-19 Hypoxia on Placenta of Normal Pregnant Women: A Possible Role of Hypoxia Inducible Factor-1α.
NCT ID: NCT05158868
Last Updated: 2021-12-15
Study Results
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Basic Information
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UNKNOWN
50 participants
OBSERVATIONAL
2022-01-01
2023-06-30
Brief Summary
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Detailed Description
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The hypoxia-inducible factors (HIF) are considered master regulators of oxygen homeostasis and are oxygen level sensitive. HIF1a is a heterodimeric transcription factor that bind to hypoxia response elements, which participates through the regulation of the expression of several genes in numerous cellular events such as O2 sensing, glucose metabolism, lipid metabolism, angiogenesis and other aspects of endothelial biology.
PIGF is a proangiogenic protein and member of the vascular endothelial growth factor (VEGF) family. It is one of the key molecules in angiogenesis and vasculogenesis especially during embryogenesis and placental trophoblast is the main source of PIGF throughout the gestational period of pregnancy. It shares structural as well as amino acid sequence similarity with VEGF, but PIGF has binding affinity only for VEGF receptor1(VEGFR-1). The inter-and intramolecular cross-talk between the VEGFR-1 and VEGFR-2 is regulated by PIGF. It binds toVEGFR-1 and displaces VEGF from this receptor, which results in activation and intermolecular trans phosphorylation of VEGFR-2 thereby amplify the VEGF-induced angiogenesis.
Hypoxic environment is essential for the proliferation and differentiation of cytotrophoblast for maintenance of materno-fetal circulation at early periods of pregnancy. But its prevalence in later stages of pregnancy causes several complications that may lead to maternal and fetal morbidity and mortality.
Several researchers have proved that the overexpression of HIF-1α is associated with the increased maternal serum concentration of soluble Fms-like tyrosine kinase 1 (sFlt1) during hypoxic conditions. High circulating levels of sFlt1 exerts an antiangiogenic state that is associated with low levels of proangiogenic factors, such as PIGF, and inhibition of PIGF with its receptor VEGFR-1.
Currently, there is no information regarding the expression of HIF-1a in normal pregnant women with COVID-19 infection and its potential involvement in the placentation of this condition. Therefore, in the present work we will detect the expression of hypoxia induced factor 1a (HIF1a) and possible molecular link between the expression of HIF-1α and PIGF based on previous studies which show significant negative association between HIF-1α and PIGF expression in patients suffering from preeclampsia.
Conditions
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Keywords
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Study Design
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CASE_CONTROL
RETROSPECTIVE
Study Groups
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Post covid infected group
normal pregnant women infected by covid during 3rd trimester
HiF-1 alpha measurement
HIF1- α is a heterodimeric transcription factor that bind to hypoxia response elements, which participates through the regulation of the expression of several genes in numerous cellular events such as O2 sensing, glucose metabolism, lipid metabolism, angiogenesis and other aspects of endothelial biology
Control group
normal pregnant women
HiF-1 alpha measurement
HIF1- α is a heterodimeric transcription factor that bind to hypoxia response elements, which participates through the regulation of the expression of several genes in numerous cellular events such as O2 sensing, glucose metabolism, lipid metabolism, angiogenesis and other aspects of endothelial biology
Interventions
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HiF-1 alpha measurement
HIF1- α is a heterodimeric transcription factor that bind to hypoxia response elements, which participates through the regulation of the expression of several genes in numerous cellular events such as O2 sensing, glucose metabolism, lipid metabolism, angiogenesis and other aspects of endothelial biology
Eligibility Criteria
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Inclusion Criteria
* Gestational age is between 28-40 weeks.
The women will be divided into two groups:
* Covid-19 infection during 3rd trimester group (n = 25)
* Control normal pregnancy group (n = 25).
Exclusion Criteria
18 Years
40 Years
FEMALE
No
Sponsors
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Assiut University
OTHER
Responsible Party
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FYAli
Principal investigator
Central Contacts
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References
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Young BE, Ong SWX, Kalimuddin S, Low JG, Tan SY, Loh J, Ng OT, Marimuthu K, Ang LW, Mak TM, Lau SK, Anderson DE, Chan KS, Tan TY, Ng TY, Cui L, Said Z, Kurupatham L, Chen MI, Chan M, Vasoo S, Wang LF, Tan BH, Lin RTP, Lee VJM, Leo YS, Lye DC; Singapore 2019 Novel Coronavirus Outbreak Research Team. Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore. JAMA. 2020 Apr 21;323(15):1488-1494. doi: 10.1001/jama.2020.3204.
Kashani KB. Hypoxia in COVID-19: Sign of Severity or Cause for Poor Outcomes. Mayo Clin Proc. 2020 Jun;95(6):1094-1096. doi: 10.1016/j.mayocp.2020.04.021. Epub 2020 Apr 23. No abstract available.
Majmundar AJ, Wong WJ, Simon MC. Hypoxia-inducible factors and the response to hypoxic stress. Mol Cell. 2010 Oct 22;40(2):294-309. doi: 10.1016/j.molcel.2010.09.022.
Iyer S, Leonidas DD, Swaminathan GJ, Maglione D, Battisti M, Tucci M, Persico MG, Acharya KR. The crystal structure of human placenta growth factor-1 (PlGF-1), an angiogenic protein, at 2.0 A resolution. J Biol Chem. 2001 Apr 13;276(15):12153-61. doi: 10.1074/jbc.M008055200. Epub 2000 Nov 7.
Autiero M, Waltenberger J, Communi D, Kranz A, Moons L, Lambrechts D, Kroll J, Plaisance S, De Mol M, Bono F, Kliche S, Fellbrich G, Ballmer-Hofer K, Maglione D, Mayr-Beyrle U, Dewerchin M, Dombrowski S, Stanimirovic D, Van Hummelen P, Dehio C, Hicklin DJ, Persico G, Herbert JM, Communi D, Shibuya M, Collen D, Conway EM, Carmeliet P. Role of PlGF in the intra- and intermolecular cross talk between the VEGF receptors Flt1 and Flk1. Nat Med. 2003 Jul;9(7):936-43. doi: 10.1038/nm884.
FOX H. THE VILLOUS CYTOTROPHOBLAST AS AN INDEX OF PLACENTAL ISCHAEMIA. J Obstet Gynaecol Br Commonw. 1964 Dec;71:885-93. doi: 10.1111/j.1471-0528.1964.tb04375.x. No abstract available.
Kingdom JC, Kaufmann P. Oxygen and placental villous development: origins of fetal hypoxia. Placenta. 1997 Nov;18(8):613-21; discussion 623-6. doi: 10.1016/s0143-4004(97)90000-x.
Nevo O, Soleymanlou N, Wu Y, Xu J, Kingdom J, Many A, Zamudio S, Caniggia I. Increased expression of sFlt-1 in in vivo and in vitro models of human placental hypoxia is mediated by HIF-1. Am J Physiol Regul Integr Comp Physiol. 2006 Oct;291(4):R1085-93. doi: 10.1152/ajpregu.00794.2005. Epub 2006 Apr 20.
Li H, Gu B, Zhang Y, Lewis DF, Wang Y. Hypoxia-induced increase in soluble Flt-1 production correlates with enhanced oxidative stress in trophoblast cells from the human placenta. Placenta. 2005 Feb-Mar;26(2-3):210-7. doi: 10.1016/j.placenta.2004.05.004.
Other Identifiers
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Hif-1cov
Identifier Type: -
Identifier Source: org_study_id