The Angiopoietin-Tie2 axis contributes to placental vascular disruption and adverse birth outcomes in malaria in pregnancy

Tran, Vanessa; Weckman, Andrea M.; Crowley, Valerie M.; Cahill, Lindsay S.; Zhong, Kathleen; Cabrera, Ana; Elphinstone, Robyn E.; Pearce, Victoria; Madanitsa, Mwayiwawo; Kalilani-Phiri, Linda; Mwapasa, Victor; Khairallah, Carole; Conroy, Andrea L.; Kuile, Feiko O. Ter; Sled, John G.; Kain, Kevin C.

doi:10.1016/j.ebiom.2021.103683

Cited by 16 publications

(14 citation statements)

References 55 publications

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“…Detection of vascular development regulators, such as VEGF and ANG2, in maternal placenta and serum has been used in obstetric diagnosis and research . Abnormal pregnancy status can induce up-regulation of VEGF, VEGFR2, and ANG2, ,− consistent with our findings of the up-regulation of placental vascular biomarkers following prenatal PFAS exposure. Although mediation analysis has been applied to explore causality in studies on environmental health and obstetrics, , whether the placental vascular effects of PFASs mediate the relationship between adverse birth outcomes and prenatal PFAS exposure has not been deciphered.…”

Section: Discussionsupporting

confidence: 87%

Unveiling Distribution of Per- and Polyfluoroalkyl Substances in Matched Placenta-Serum Tetrads: Novel Implications for Birth Outcome Mediated by Placental Vascular Disruption

Pan

Qiu

et al. 2023

Environ. Sci. Technol.

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The placenta is pivotal for fetal development and maternal–fetal transfer of many substances, including per- and polyfluoroalkyl substances (PFASs). However, the intraplacental distribution of PFASs and their effects on placental vascular function remain unclear. In this study, 302 tetrads of matched subchorionic placenta (fetal-side), parabasal placenta (maternal-side), cord serum, and maternal serum samples were collected from Guangzhou, China. Eighteen emerging and legacy PFASs and five placental vascular biomarkers were measured. Results showed that higher levels of perfluorooctanoic (PFOA), perfluorooctane sulfonic acid (PFOS), and chlorinated polyfluorinated ether sulfonic acids (Cl-PFESAs) were detected in subchorionic placenta compared to parabasal placenta. There were significant associations of PFASs in the subchorionic placenta, but not in the serum, with placental vascular biomarkers (up to 32.5%) and lower birth size. Birth weight was negatively associated with PFOA (β: −103.8, 95% CI: −186.3 and −21.32) and 6:2 Cl-PFESA (β: −80.04, 95% CI: −139.5 and −20.61), primarily in subchorionic placenta. Mediation effects of altered placental angiopoietin-2 and vascular endothelial growth factor receptor-2 were evidenced on associations of adverse birth outcomes with intraplacental PFOS and 8:2 Cl-PFESA, explaining 9.5%–32.5% of the total effect. To the best of our knowledge, this study is the first to report on differential intraplacental distribution of PFASs and placental vascular effects mediating adverse birth outcomes and provides novel insights into the placental plate-specific measurement in PFAS-associated health risk assessment.

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Section: Discussionsupporting

confidence: 87%

Unveiling Distribution of Per- and Polyfluoroalkyl Substances in Matched Placenta-Serum Tetrads: Novel Implications for Birth Outcome Mediated by Placental Vascular Disruption

Pan

Qiu

et al. 2023

Environ. Sci. Technol.

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“…In a secondary analysis of trial data, primigravid women with asymptomatic infections in early pregnancy had an increased risk of placental malaria (adjusted odds ratio [aOR] 12.19, 95% CI 5.23, 28.43), whereas for multigravid women infection later in pregnancy was associated with placental malaria [17]. Placental malaria infection and associated inflammatory responses can affect placental angiogenesis by disrupting the angiopoietin-Tie2 axis and interfering with fetal growth and contributing to LBW and stillbirths [18,19].…”

Section: Placental Malariamentioning

confidence: 99%

Pregnancy and malaria: the perfect storm

Rogerson

Unger

2022

Current Opinion in Infectious Diseases

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Purpose of reviewMalaria in pregnancy continues to exert a toll on pregnant women and their offspring.Recent findingsThe burden of Plasmodium falciparum infection is especially large in Africa, and new data show lasting effects of maternal infection on the infant's neurocognitive development. Elsewhere, P. vivax infection causes relapsing infections that are challenging to prevent. Infection in first trimester of pregnancy is an area of increasing focus, and its adverse effects on pregnancy outcome are increasingly recognised. First-trimester infection is common and frequently acquired prior to conception. Although newer rapid diagnostic tests still have limited sensitivity, they may be useful in detection of early pregnancy malaria for treatment. Artemisinin-based combination therapies are efficacious in later pregnancy but have yet to be recommended in first trimester because of limited safety data. In Africa, intermittent preventive treatment in pregnancy (IPTp) with monthly sulfadoxine-pyrimethamine improves pregnancy outcomes, but sulfadoxine-pyrimethamine resistance is worsening. The alternative, IPTp with dihydroartemisinin-piperaquine, has greater antimalarial efficacy, but does not appear to improve pregnancy outcomes, because sulfadoxine-pyrimethamine has poorly understood nonmalarial benefits on birthweight.SummaryNovel IPTp regimens must be combined with interventions to strengthen protection from malaria infection acquired before and in early pregnancy.

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“… 10 , 20 , 46 Dysregulated angiogenesis has been linked to compromised placental function and inadequate placental vascular development required to support the rapidly growing fetus and leading to adverse birth outcomes. 19 , 48 , 49 Therefore, downstream disruption of angiogenesis is a biologically plausible mechanism by which early inflammation could contribute to placental insufficiency and PTB.…”

Section: Discussionmentioning

confidence: 99%

Sequential disruptions to inflammatory and angiogenic pathways and risk of spontaneous preterm birth in Malawian women

et al. 2023

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The Angiopoietin-Tie2 axis contributes to placental vascular disruption and adverse birth outcomes in malaria in pregnancy

Cited by 16 publications

References 55 publications

Unveiling Distribution of Per- and Polyfluoroalkyl Substances in Matched Placenta-Serum Tetrads: Novel Implications for Birth Outcome Mediated by Placental Vascular Disruption

Unveiling Distribution of Per- and Polyfluoroalkyl Substances in Matched Placenta-Serum Tetrads: Novel Implications for Birth Outcome Mediated by Placental Vascular Disruption

Pregnancy and malaria: the perfect storm

Sequential disruptions to inflammatory and angiogenic pathways and risk of spontaneous preterm birth in Malawian women

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