Preeclampsia As Modulator of Offspring Health1

Stojanovska, Violeta; Scherjon, Sicco A.; Plösch, Torsten

doi:10.1095/biolreprod.115.135780

Cited by 64 publications

(51 citation statements)

References 127 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Several previous studies have shown that low birth weight increases the risk of cardiovascular and metabolic diseases, for example, stroke, diabetes, obesity, etc. [23][24][25][26][27] Potential factors include malnutrition and toxins present during pregnancy. Our data demonstrate that fetal exposure to sFlt-1 is associated with asymmetrical growth restriction, however to what extent this contributes to developmental programming of the fetus still remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

In utero sFlt-1 exposure differentially affects gene expression patterns in fetal liver

Stojanovska

Holwerda

Graaf

et al. 2019

J Dev Orig Health Dis

View full text Add to dashboard Cite

The soluble fms-like tyrosine kinase factor 1 (sFlt-1) is a major contributor to antiangiogenesis during preeclampsia. However, little is known about the effects of sFlt-1 on fetal health. In this study we aim to evaluate the effects of the sFlt-1 concentration during pregnancy on fetal liver physiology. We used adenoviral gene delivery in Sprague-Dawley dams (seven females, 10 weeks old) during mid-gestation (gestational day 8) with adenovirus overexpressing sFlt-1, and age-matched controls (six females, 10 weeks old) with empty adenoviral virus in order to quantify the sFlt-1 concentrations in pregnant dams. Dams exposed to adenoviral sFlt-1 delivery were subdivided into a low (n=4) and high sFlt-1 (n=3) group based on host response to the virus. One-way analysis of variance showed that fetuses (five per dam) exposed to high sFlt-1 concentrations in utero show fetal growth restriction (1.84±0.043 g high sFlt-1 v. 2.32±0.036 g control; mean (M)±s.e.m.; P<0.001), without hypertension or proteinuria in the dams. In continuation, the microarray analysis of the fetal liver of the high sFlt-1 group showed significant enrichment of key genes for fatty acid metabolism and Ppara targets. In addition, using pyrosequencing, we found that the Ppara enrichment in the high sFlt-1 group is accompanied by decreased methylation of its promoter (1.89±0.097 mean % methylation in high sFlt-1 v. 2.26±0.095 mean % methylation in control, M±s.e.m., P<0.02). Our data show that high sFlt-1 concentrations during pregnancy have detrimental effects on the fatty acid metabolism genes and the Ppara targets in the fetal liver.

show abstract

Section: Discussionmentioning

confidence: 99%

In utero sFlt-1 exposure differentially affects gene expression patterns in fetal liver

Stojanovska

Holwerda

Graaf

et al. 2019

J Dev Orig Health Dis

View full text Add to dashboard Cite

show abstract

“…In the long-term, stroke risk at Age 65 appears elevated, though coronary artery disease was not increased [98]. Metabolic consequences such as obesity, insulin resistance and increased vascular inflammatory markers have also been noted at younger ages and animal studies suggest possible causal links [99].…”

Section: Preeclampsia and Later Infant Healthmentioning

confidence: 99%

The first-trimester of pregnancy – A window of opportunity for prediction and prevention of pregnancy complications and future life

Poon

McIntyre

Hyett

et al. 2018

Diabetes Research and Clinical Practice

View full text Add to dashboard Cite

The International Federation of Gynecology and Obstetrics (FIGO) has identified non communicable maternal diseases (NCDs) as a new focus area. NCDs and exposures as related to pregnancy complications and later impairment of maternal and offspring health will form the basis for action in the forthcoming years. This paper summarizes recent advances, centered on the use of first-trimester testing, as a window of opportunity to predict and prevent many pregnancy complications; and for potential future prevention of NCDs in mother and offspring. Recent results from a large-scale randomized control trial have provided definitive proof that effective screening for preterm preeclampsia (preterm-PE), requiring delivery before 37 weeks' gestation, can be achieved with a combined test of maternal factors and biomarkers at 11-13 weeks and that aspirin, given to high-risk women, is effective in reducing the risk of preterm-PE and the length of stay in neonatal intensive care unit. This is the first successful example to illustrate that pregnancy complications is predictable and preventable in early pregnancy. Similar prediction and prevention strategies are being developed for hyperglycemia in pregnancy and preterm birth, with the intention for longer lasting interventions leading to significant downstream impact in improving long-term health in both mothers and babies.

show abstract

“…Although PE is a multifactorial disorder, several pathophysiological mechanisms including angiogenic imbalance, excessive inflammation, ischaemia/perfusion and imbalances in the renin angiotensin system are all implicated in its pathogenesis. 22,23 During a pregnancy complicated by PE, the placenta releases circulating factors, including sFlt and sEng, 24,25 into the maternal circulation as a result of syncytiotrophoblast stress due to a variety of insults including placental ischemia/hypoxia, contributing to excessive inflammation and generation of reactive oxygen species. [26][27][28][29] Consistent with a causal role for these placental factors in programming of progeny CVD, overexpression of sFlt in a mouse model of PE mimicking the placenta of a pregnancy affected by PE results in elevated systolic and diastolic blood pressure in male offspring.…”

Section: Developmental Programming Of Cvd Risk By In Utero Exposure Tmentioning

confidence: 99%

Mechanisms linking exposure to preeclampsia in utero and the risk for cardiovascular disease

Gatford

Care

Bianco‐Miotto

et al. 2020

J Dev Orig Health Dis

View full text Add to dashboard Cite

Preeclampsia (PE) is now recognised as a cardiovascular risk factor for women. Emerging evidence suggests that children exposed to PE in utero may also be at increased risk of cardiovascular disease (CVD) in later life. Individuals exposed to PE in utero have higher systolic and diastolic blood pressure and higher body mass index (BMI) compared to those not exposed to PE in utero. The aim of this review is to discuss the potential mechanisms driving the relationship between PE and offspring CVD. Exposure to an adverse intrauterine environment as a consequence of the pathophysiological changes that occur during a pregnancy complicated by PE is proposed as one mechanism that programs the fetus for future CVD risk. Consistent with this hypothesis, animal models of PE where progeny have been studied demonstrate causality for programming of offspring cardiovascular health by the preeclamptic environment. Shared alleles between mother and offspring, and shared lifestyle factors between mother and offspring provide alternate pathways explaining associations between PE and offspring CVD risk. In addition, adverse lifestyle habits can also act as second hits for those programmed for increased CVD risk. PE and CVD are both multifactorial diseases and, hence, identifying the relative contribution of PE to offspring risk for CVD is a very complex task. However, considering the emerging strong association between PE and CVD, those exposed to PE in utero may benefit from targeted primary CVD preventive strategies.

show abstract

Preeclampsia As Modulator of Offspring Health1

Cited by 64 publications

References 127 publications

In utero sFlt-1 exposure differentially affects gene expression patterns in fetal liver

In utero sFlt-1 exposure differentially affects gene expression patterns in fetal liver

The first-trimester of pregnancy – A window of opportunity for prediction and prevention of pregnancy complications and future life

Mechanisms linking exposure to preeclampsia in utero and the risk for cardiovascular disease

Contact Info

Product

Resources

About