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  • Does Malaria Affect Placental Development? Evidence from In Vitro Models

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    Author(s)
    Umbers, AJ
    Stanisic, DI
    Ome, M
    Wangnapi, R
    Hanieh, S
    Unger, HW
    Robinson, LJ
    Lufele, E
    Baiwog, F
    Siba, PM
    King, CL
    Beeson, JG
    Mueller, I
    Aplin, JD
    Glazier, JD
    Rogerson, SJ
    Griffith University Author(s)
    Stanisic, Danielle
    Year published
    2013
    Metadata
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    Abstract
    Background Malaria in early pregnancy is difficult to study but has recently been associated with fetal growth restriction (FGR). The pathogenic mechanisms underlying malarial FGR are poorly characterized, but may include impaired placental development. We used in vitro methods that model migration and invasion of placental trophoblast into the uterine wall to investigate whether soluble factors released into maternal blood in malaria infection might impair placental development. Because trophoblast invasion is enhanced by a number of hormones and chemokines, and is inhibited by pro-inflammatory cytokines, many of which are ...
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    Background Malaria in early pregnancy is difficult to study but has recently been associated with fetal growth restriction (FGR). The pathogenic mechanisms underlying malarial FGR are poorly characterized, but may include impaired placental development. We used in vitro methods that model migration and invasion of placental trophoblast into the uterine wall to investigate whether soluble factors released into maternal blood in malaria infection might impair placental development. Because trophoblast invasion is enhanced by a number of hormones and chemokines, and is inhibited by pro-inflammatory cytokines, many of which are dysregulated in malaria in pregnancy, we further compared concentrations of these factors in blood between malaria-infected and uninfected pregnancies. Methodology/Principal Findings We measured trophoblast invasion, migration and viability in response to treatment with serum or plasma from two independent cohorts of Papua New Guinean women infected with Plasmodium falciparum or Plasmodium vivax in early pregnancy. Compared to uninfected women, serum and plasma from women with P. falciparum reduced trophoblast invasion (P = .06) and migration (P = .004). P. vivax infection did not alter trophoblast migration (P = .64). The P. falciparum-specific negative effect on placental development was independent of trophoblast viability, but associated with high-density infections. Serum from P. falciparum infected women tended to have lower levels of trophoblast invasion promoting hormones and factors and higher levels of invasion-inhibitory inflammatory factors. Conclusion/Significance We demonstrate that in vitro models of placental development can be adapted to indirectly study the impact of malaria in early pregnancy. These infections could result in impaired trophoblast invasion with reduced transformation of maternal spiral arteries due to maternal hormonal and inflammatory disturbances, which may contribute to FGR by limiting the delivery of maternal blood to the placenta. Future prevention strategies for malaria in pregnancy should include protection in the first half of pregnancy.
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    Journal Title
    PL o S One
    Volume
    8
    Issue
    1
    DOI
    https://doi.org/10.1371/journal.pone.0055269
    Copyright Statement
    © 2013 Umbers et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License CCAL. (http://www.plos.org/journals/license.html)
    Subject
    Infectious agents
    Publication URI
    http://hdl.handle.net/10072/58530
    Collection
    • Journal articles

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