Prenatal intake of omega‐3 promotes Wnt/β‐catenin signaling pathway, and preserves integrity of the blood–brain barrier in preeclamptic rats

ShamsEldeen, Asmaa Mohammed; Mehesen, Marwa Nagi; Aboulhoda, Basma Emad; Rashed, Laila Ahmed; Elsebaie, Mohamed Mahmoud; Mohamed, Enas Ahmed; Gamal, Maha

doi:10.14814/phy2.14925

Cited by 9 publications

(5 citation statements)

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“…Also, Zhang et al revealed disturbed integrity of the BBB due to loss of tight junction proteins in neonatal and adult mouse models of cerebral ischemia [ 66 ]. In a PE rat model, it is shown that PE induced a cascade of neuroinflammation and oxidative injury to the BBB [ 67 ], which is in accordance with the findings in this study. As shown in Lara et al's study, cognitive alterations present in children born from preeclamptic pregnancies are strongly associated with impaired cerebral Vegf levels and changed angiogenesis phenotype, a finding which is also seen in this study with lower levels of Vegfd upon hsFLT1 overexpression [ 25 ].…”

Section: Discussionsupporting

confidence: 91%

Systemic Maternal Human sFLT1 Overexpression Leads to an Impaired Foetal Brain Development of Growth-Restricted Foetuses upon Experimental Preeclampsia

Vogtmann

Burk

Serdar

et al. 2022

Oxidative Medicine and Cellular Longevity

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The pregnancy disorder preeclampsia (PE) is characterized by maternal hypertension, increased level of circulating antiangiogenic soluble fms-like tyrosine kinase-1 (sFLT1), and reduced placental perfusion, leading to foetal growth restriction (FGR) and preterm birth. All these adverse effects are associated with neurocognitive disorders in the offspring. However, the direct interplay between increased antiangiogenesis during PE and disturbed foetal brain development independent of prematurity has not been investigated yet. To examine foetal brain development in sFLT1-related PE, hsFLT1/rtTA-transgenic mice with systemic (maternal or maternal/fetoplacental) human sFLT1 (hsFLT1) overexpression since 10.5 days postconception (dpc) were used, and histological and molecular analyses of foetal brains were performed at 18.5 dpc. Consequences of elevated hsFLT1 on placental/foetal vascularization and hypoxia of placentas and foetal brains were analysed using the hypoxia markers pimonidazole and hemeoxygenase-1 (HO-1). Immunohistochemical analysis revealed increased hypoxia in placentas of PE-affected pregnancies. Moreover, an increase in HO-1 expression was observed upon elevated hsFLT1 in placentas and foetal brains. PE foetuses revealed asymmetrical FGR by increased brain/liver weight ratio. The brain volume was reduced combined with a reduction in the cortical/hippocampal area and an increase of the caudate putamen and its neuroepithelium, which was associated with a reduced cell density in the cortex and increased cell density in the caudate putamen upon hsFLT1 overexpression. Mild influences were observed on brain vasculature shown by free iron deposits and mRNA changes in Vegf signalling. Of note, both types of systemic hsFLT1 overexpression (indirect: maternal or direct: maternal/fetoplacental) revealed similar changes with increasing severity of impaired foetal brain development. Overall, circulating hsFLT1 in PE pregnancies impaired uteroplacental perfusion leading to disturbed foetal oxygenation and brain injury. This might be associated with a disturbed cell migration from the caudate putamen neuroepithelium to the cortex which could be due to disturbed cerebrovascular adaption.

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Section: Discussionsupporting

confidence: 91%

Systemic Maternal Human sFLT1 Overexpression Leads to an Impaired Foetal Brain Development of Growth-Restricted Foetuses upon Experimental Preeclampsia

Vogtmann

Burk

Serdar

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…And the study population with a relatively small sample size needs to be considered during drawing a conclusion on the status of serum sVEGFR-1 in patients with several types of clinical presentation of PE. Recently, various pharmacological agents that can prevent the effects of sVEGFR-1 for treating PE have been investigated ( 27 , 28 , 29 ) . These agents may have a significant effect on reducing neonatal morbidity and mortality, given that they are considered safe enough to delay delivery for several weeks and alleviate end-organ findings.…”

Section: Discussionmentioning

confidence: 99%

Predictive and diagnostic value of serum sVEGFR-1 level in women with preeclampsia: A prospective controlled study

Şalk¹,

Yurtçu²,

Çetin³

2022

tjod

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Objective: Pre-eclampsia (PE), a pregnancy-specific syndrome consisting of hypertension and proteinuria occurring de novo after the 20th week of gestation, remains the leading cause of maternal and fetal morbidity and mortality worldwide. Endothelial dysfunction is proposed to be a central feature of the pathophysiology of preeclampsia. However, the mechanism by which this endothelial dysfunction occurs remains uncertain. We investigated the predictive and diagnostic value of serum soluble vascular endothelial growth factor receptor-1 (VEGFR-1) with by comparison of its prepartum and postpartum serum levels in the management of women with PE. Materials and Methods: This prospective case-controlled study was composed of pre-eclamptic (n=44) and normal, healthy pregnant (n=44) women. Blood samples were collected before any intervention at the first antenatal examination of the women in the control group and at the admission of the women to the hospital in the PE group, additionally, from all women in the study groups within six hours of the postpartum period, and used for the serum VEGFR-1 analyses. Results: Within both groups, prepartum serum levels of sVEGFR-1 were higher than postpartum levels (p<0.05). In PE, pre-partum and postpartum serum levels of sVEGFR-1 were higher than levels in the control group (p<0.05). Serum sVEGFR-1 levels of preeclamptic women were positively correlated with the degree of proteinuria (p<0.05, r=0.25), systolic (p<0.05, r=0.25), and diastolic blood pressure (p<0.05, r=0.31). Conclusion: These findings seem to point to an involvement of sVEGFR-1 in the pathophysiology of PE. Serum sVEGFR-1 has the potential to be used as a valuable biomarker in the prediction, diagnosis, and risk management of women with subtypes of PE including mild and severe PE, HELLP syndrome, and eclampsia. There is a need to study serum sVEGFR-1 as a biomarker in pregnant women with different subtypes of PE.

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“…L-NAME (50 mg/kg/day; Sigma-Aldrich ( 30 , 101 )) or phosphate buffered saline (PBS; 137 mM NaCl, 10 mM Na 2 HPO 4 , 1.8 mM KH 2 PO 4 , and 2.7 mM KCl, pH 7.4) as control was administered daily from embryonic day (E)7.5 to E17.5 of pregnancy (approximately early second trimester to term in human equivalent to model early onset disease) via 100 μl subcutaneous injection. On E14.5 and E17.5 of pregnancy, urine was collected (spot collection on/upon handling), and blood pressure measured.…”

Section: Methodsmentioning

confidence: 99%

The L-NAME mouse model of preeclampsia and impact to long-term maternal cardiovascular health

et al. 2022

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Preeclampsia affects ∼2–8% of pregnancies worldwide. It is associated with increased long-term maternal cardiovascular disease risk. This study assesses the effect of the vasoconstrictor N(ω)-nitro-L-arginine methyl ester (L-NAME) in modelling preeclampsia in mice, and its long-term effects on maternal cardiovascular health. In this study, we found that L-NAME administration mimicked key characteristics of preeclampsia, including elevated blood pressure, impaired fetal and placental growth, and increased circulating endothelin-1 (vasoconstrictor), soluble fms-like tyrosine kinase-1 (anti-angiogenic factor), and C-reactive protein (inflammatory marker). Post-delivery, mice that received L-NAME in pregnancy recovered, with no discernible changes in measured cardiovascular indices at 1-, 2-, and 4-wk post-delivery, compared with matched controls. At 10-wk post-delivery, arteries collected from the L-NAME mice constricted significantly more to phenylephrine than controls. In addition, these mice had increased kidney Mmp9:Timp1 and heart Tnf mRNA expression, indicating increased inflammation. These findings suggest that though administration of L-NAME in mice certainly models key characteristics of preeclampsia during pregnancy, it does not appear to model the adverse increase in cardiovascular disease risk seen in individuals after preeclampsia.

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Prenatal intake of omega‐3 promotes Wnt/β‐catenin signaling pathway, and preserves integrity of the blood–brain barrier in preeclamptic rats

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 9 publications

References 61 publications

Systemic Maternal Human sFLT1 Overexpression Leads to an Impaired Foetal Brain Development of Growth-Restricted Foetuses upon Experimental Preeclampsia

Systemic Maternal Human sFLT1 Overexpression Leads to an Impaired Foetal Brain Development of Growth-Restricted Foetuses upon Experimental Preeclampsia

Predictive and diagnostic value of serum sVEGFR-1 level in women with preeclampsia: A prospective controlled study

The L-NAME mouse model of preeclampsia and impact to long-term maternal cardiovascular health

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