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

Ingrid C Weel, Rebecca N Baergen, Mariana Romão-Veiga, Vera T Borges, Vanessa R Ribeiro, Steven S Witkin, Camila Bannwart-Castro, Jose C Peraçoli, Leandro De Oliveira, Maria T Peraçoli, Ingrid C Weel, Rebecca N Baergen, Mariana Romão-Veiga, Vera T Borges, Vanessa R Ribeiro, Steven S Witkin, Camila Bannwart-Castro, Jose C Peraçoli, Leandro De Oliveira, Maria T Peraçoli

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.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Representative photomicrography of placental histopathology…
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 2. Representative photomicrography showing positivity of…
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 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 3. TNF-α/IL-10 ratio (A) and sFlt-1/PlGF…
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 vs normotensive group; # (p <0.05) vs late-onset PE group.

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