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Cited by 131Pregnancy and preeclampsia studiesNeurological Complications and SyndromesReproductive System and Pregnancy

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Association between Placental Lesions, Cytokines and Angiogenic Factors in Pregnant Women with Preeclampsia

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Weel, Ingrid C., Baergen, Rebecca N., Romão-Veiga, Mariana, Borges, Vera T., Ribeiro, Vanessa R., Witkin, Steven S., Bannwart-Castro, Camila, Peraçoli, Jose C., De Oliveira, Leandro, Peraçoli, Maria T.·2016·PLoS ONE
DOI 10.1371/journal.pone.0157584PMC PMC4912084
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Abstract

Preeclampsia (PE) is considered the leading cause of maternal and perinatal morbidity and mortality. The placenta seems to play an essential role in this disease, probably due to factors involved in its formation and development. The present study aimed to investigate the association between placental lesions, cytokines and angiogenic factors in pregnant women with preeclampsia (PE). We evaluated 20 normotensive pregnant women, 40 with early-onset PE and 80 with late-onset PE. Placental samples were analyzed for histopathology, immunohistochemistry and determination of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-10 (IL-10), transforming growth factor-beta 1 (TGF-β1), tumor necrosis factor-alpha (TNF-α), placental growth factor (PlGF), vascular endothelial growth factor (VEGF), fms-like tyrosine-kinase-1 (Flt-1) and endoglin (Eng) levels. Higher percentages of increased syncytial knots and increased perivillous fibrin deposits, and greater levels of TNF-α, TGF-β1and Flt-1 were detected in placentas from early-onset PE. Levels of IL-10, VEGF and PlGF were decreased in PE versus normotensive placentas. Both the TNF-α/IL-10 and sFlt-1/PlGF ratios were higher in placental homogenate of early-onset PE than late-onset PE and control groups. The more severe lesions and the imbalance between TNF-α/IL-10 and PlGF/sFlt-1 in placentas from early-onset PE allows differentiation of early and late-onset PE and suggests higher placental impairment in early-onset PE.

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Crossref · 10.1371/journal.pone.0157584

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Figures

Fig 1 Representative photomicrography of placental histopathology of normotensive pregnant women and women with PE. A) Increase in syncytial knots (arrows) in placenta of a woman with early-onset PE. B) Few syncytial knots (arrow) in placenta of woman with late-onset PE. C) Placental infarction (arrows) of a woman with early-onset PE. D) Increase of fibrin deposits (arrow) in placenta of woman with early-onset PE. E) Accelerated villous maturation (arrows) in the placenta of woman with late-onset PE. F) Presence of syncytial knots (arrows) in the placenta of a normotensive pregnant woman at 38 weeks gestation.
Fig 1 Representative photomicrography of placental histopathology of normotensive pregnant women and women with PE. A) Increase in syncytial knots (arrows) in placenta of a woman with early-onset PE. B) Few syncytial knots (arrow) in placenta of woman with late-onset PE. C) Placental infarction (arrows) of a woman with early-onset PE. D) Increase of fibrin deposits (arrow) in placenta of woman with early-onset PE. E) Accelerated villous maturation (arrows) in the placenta of woman with late-onset PE. F) Presence of syncytial knots (arrows) in the placenta of a normotensive pregnant woman at 38 weeks gestation.CC BY · PubMed Central
Fig 2 Representative photomicrography showing positivity of cytokine and angiogenic factor in placental sections of pregnant women with PE. A) IL-10; B) PlGF; C) TNF-α; D) Flt-1. Red arrow shows positivity in the syncytiotrophoblast, green arrow shows positivity in cytoplasm of mesenchymal cells, black arrow shows positivity in the fetal capillary endothelium, and blue arrow shows positivity in the cytotrophoblast. Quantitative analysis of the cytokines TNF-α (E), IL-10 (F), GM-CSF (G), TGF-β1 (H), and angiogenic factors PlGF (I), VEGF (J), Flt-1 (K) and Eng (L) expression by placental tissues from normotensive (NT) pregnant women, women with early-onset preeclampsia (EOPE) or late-onset preeclampsia (LOPE). Results are represented in pixels/μm. * (p <0.05) vs normotensive group; # (p < 0.05) vs late-onset PE. Higher intensity of Flt-1 (arrows) expressed in syncytial knots in placenta of an early-onset preeclamptic women at 31 weeks of gestation (M).
Fig 2 Representative photomicrography showing positivity of cytokine and angiogenic factor in placental sections of pregnant women with PE. A) IL-10; B) PlGF; C) TNF-α; D) Flt-1. Red arrow shows positivity in the syncytiotrophoblast, green arrow shows positivity in cytoplasm of mesenchymal cells, black arrow shows positivity in the fetal capillary endothelium, and blue arrow shows positivity in the cytotrophoblast. Quantitative analysis of the cytokines TNF-α (E), IL-10 (F), GM-CSF (G), TGF-β1 (H), and angiogenic factors PlGF (I), VEGF (J), Flt-1 (K) and Eng (L) expression by placental tissues from normotensive (NT) pregnant women, women with early-onset preeclampsia (EOPE) or late-onset preeclampsia (LOPE). Results are represented in pixels/μm. * (p <0.05) vs normotensive group; # (p < 0.05) vs late-onset PE. Higher intensity of Flt-1 (arrows) expressed in syncytial knots in placenta of an early-onset preeclamptic women at 31 weeks of gestation (M).CC BY · PubMed Central
Fig 3 TNF-α/IL-10 ratio (A) and sFlt-1/PlGF ratio (B) determined in placental homogenates from normotensive (NT) pregnant women, women with early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE). * (p <0.05) vs normotensive group; # (p <0.05) vs late-onset PE group.
Fig 3 TNF-α/IL-10 ratio (A) and sFlt-1/PlGF ratio (B) determined in placental homogenates from normotensive (NT) pregnant women, women with early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE). * (p <0.05) vs normotensive group; # (p <0.05) vs late-onset PE group.CC BY · PubMed Central

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  1. DA Souza, 2011, Increase in perivillous fibrinoid material in placentas from pregnancies with preeclampsia, J Bras Patol Med Lab, 47, 71

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Metadata

Authors
Weel, I. C., Baergen, R. N., Romão-Veiga, M., Borges, V. T., Ribeiro, V. R., Witkin, S. S., Bannwart-Castro, C., Peraçoli, J. C., De Oliveira, L., & Peraçoli, M. T.
Affiliations
  • Universidade Estadual Paulista (Unesp) (BR)
  • NewYork–Presbyterian Hospital (US)
  • Weill Cornell Medicine (US)
Corresponding author
Peraçoli, Maria T.
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2016-06-17
Volume
11
Issue
6
Pages
e0157584
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0157584
PMC
PMC4912084
OpenAlex
W2430003272
Cited by
131
References
50
Citations by year
2026: 11 · 2025: 7 · 2024: 11 · 2023: 5 · 2022: 11 · 2021: 15 · 2020: 17 · 2019: 15 · 2018: 22 · 2017: 17
FWCI
23.25
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Americanae (AECID Library) (publishedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
Topics
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
  • Health Sciences › Medicine › Clinical Neurology › Neurological Complications and Syndromes
  • Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
Keywords
preeclampsia, placental lesions, cytokines, angiogenic factors, early-onset preeclampsia, late-onset preeclampsia, syncytiotrophoblastic knots, TNF-α, IL-10, TGF-β1, soluble fms-like tyrosine kinase-1, placental growth factor, vascular endothelial growth factor, CD105, TNF-α/IL-10 ratio, sFlt-1/PlGF ratio, placental pathology
MeSH terms
Placenta Growth Factor, Adult, Female, Humans, Placenta, Pre-Eclampsia, Pregnancy, Tumor Necrosis Factor-alpha, Granulocyte-Macrophage Colony-Stimulating Factor, Interleukin-10, Age of Onset, Vascular Endothelial Growth Factor Receptor-1, Vascular Endothelial Growth Factor A

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