Impact of reduced uterine perfusion pressure model of preeclampsia on metabolism of placenta, maternal and fetal hearts

Abstract

Preeclampsia is a cardiovascular pregnancy complication characterised by new onset hypertension and organ damage or intrauterine growth restriction. It is one of the leading causes of maternal and fetal mortality in pregnancy globally. Short of pre-term delivery of the fetus and placenta, treatment options are limited. Consequently, preeclampsia leads to increased cardiovascular disease risk in both mothers and offspring later in life. Here we aim to examine the impact of the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia on the maternal cardiovascular system, placental and fetal heart metabolism. The surgical RUPP model was induced in pregnant rats by applying silver clips around the aorta and uterine arteries on gestational day 14, resulting in ~ 40% uterine blood flow reduction. The experiment was terminated on gestational day 19 and metabolomic profile of placentae, maternal and fetal hearts analysed using high-resolution 1H NMR spectroscopy. Impairment of uterine perfusion in RUPP rats caused placental and cardiac hypoxia and a series of metabolic adaptations: altered energetics, carbohydrate, lipid and amino acid metabolism of placentae and maternal hearts. Comparatively, the fetal metabolic phenotype was mildly affected. Nevertheless, long-term effects of these changes in both mothers and the offspring should be investigated further in the future.

Lipid metabolism drives allele-specific early-stage hypertrophic cardiomyopathy

“…We combined RNA-sequencing and metabolomics with computational modeling using CardioNet 41,42,[46][47][48] to identify flux distributions that could explain the observed metabolic patterns. CardioNet predicts an increased contribution of glycolysis and pentose phosphate pathway towards ATP provision and reductive metabolism, along with reduction in oxidative phosphorylation in R92W-TnT hearts (Figure 6D).…”

Preeclampsia Correlates with an Increase in Cannabinoid Receptor 1 Levels Leading to Macromolecular Alterations in Chorionic Villi of Term Placenta

“…Along with the increase in collagen deposition and lipid peroxidation, the FTIRI analyses showed much higher levels of phosphorylated compounds, containing a phosphoester bond, in the preeclamptic CV than in the control ones. Among these phosphorylated compounds, phosphocholine levels have been reported to change in a rat model of preeclampsia [ 49 ] and in human preeclamptic placenta [ 50 ]. The binding of phosphocholine to C-reactive protein localized the SCTB villi cells has been reported to induce arterial hypertension and placental damage [ 51 , 52 ].…”

Nobiletin Inhibits Hypoxia-Induced Placental Damage via Modulating P53 Signaling Pathway

“…In this model, the perfusion to the utero-placental circulation of pregnant rats is partially blocked, thereby simulating the decrease in perfusion due to impaired spiral artery remodeling [ 23 ]. RUPP procedure impairs placental blood flow, triggering enhanced HIF1α expression and placental hypoxia [ 24 ]. RUPP can also damage the structure of the placental junction and labyrinth areas, causing placental insufficiency [ 25 ].…”