Fetal Perinatal Morbidity Research Articles

A novel regulatory mechanism network mediated by lncRNA TUG1 that induces the impairment of spiral artery remodeling in preeclampsia

Preeclampsia (PE) is associated with maternal and fetal perinatal morbidity and mortality, which brings tremendous suffering and imposes an economic burden worldwide. The failure of uterine spiral artery remodeling may be related to the abnormal function of trophoblasts and lead to the occurrence and progression of PE. Aberrant expression of long non-coding RNAs (lncRNAs) is involved in the failure of uterine spiral artery remodeling. However, the regulation of lncRNA expression in PE is poorly characterized. Here, we reported that hypoxia-induced microRNA (miR)-218 inhibited the expression of lncRNA TUG1 by targeting FOXP1. Further RNA sequencing and mechanism analysis revealed that silencing of TUG1 increased the expression of DNA demethylase TET3 and proliferation-related DUSP family, including DUSP2, DUSP4, and DUSP5, via binding to SUV39H1 in the nucleus. Moreover, TUG1 modulated the DUSP family invitro through a TET3-mediated epigenetic mechanism. Taken together, our results unmask a new regulatory network mediated by TUG1 as an essential determinant of the pathogenesis of PE, which regulates cell growth and possibly the occurrence and development of other diseases.

A Case Report of Influence of Free Tyrosine Kinase/Placental Growth Factor (SFLT-1/PLGF) Ratio Test for Preeclampsia on Clinical Decision Making in Screening Positive Women

Summary Preeclampsia (PE) is characterized by hypertension and proteinuria after the 20th gestational week (GW). It is a significant cause of maternal and fetal perinatal morbidity and mortality during pregnancy. There is increasing evidence suggesting that PE is due to an impaired balance between maternal placental angiogenic and antiangiogenic factors that harm maternal vascular endothelium. The study aimed to assess the clinical and financial aspects of introducing into practice the soluble fms-like tyrosine kinase (sFlt-1) to placental growth factor (PlGF) ratio test to improve the management of preeclampsia and adverse pregnancy outcome, intrauterine growth retardation, iatrogenic prematurity, and placental abruption. We report a case study in which we used the sFlt-1/PlGF ratio in the management of a high-risk pregnancy. Unnecessary hospitalization was avoided, and the patient was managed appropriately.

Abstract 581: Protective Effects Of Bilirubin Administration On Placental Ischemia-induced Hypertension

Preeclampsia is one of the most common complications of pregnancy in humans, and is a leading cause of premature birth and fetal perinatal morbidity and mortality. The hallmark of the disorder is the manifestation of new-onset hypertension-typically after the 20th week of gestation. While the underlying cause of the disorder remains obscure, it is widely held that failure of the maternal vasculature to adequately remodel and supply the developing placenta with adequate blood flow leads to placental insufficiency and resulting ischemia. In response placental derived factors, namely the anti-angiogenic protein sFlt-1 and reactive oxygen species- are released into the maternal circulation resulting in the symptomatic phase of the. We have recently demonstrated that induction of heme oxygenase in a rodent model of placental ischemia attenuates the associated hypertension by blocking both of these pathways, presumably through byproducts carbon monoxide and bilirubin. Here, we have investigated the in vivo effects of exogenous bilirubin administration on a rodent model of placental ischemia-induced hypertension, the reduced uterine perfusion pressure (RUPP) model. RUPP animals exhibited significant increases in MAP when compared to sham animals (109 ± 3 vs 120 ± 4 mmHg, p<0.05). Exogenous administration of bilirubin (30mg/kg/q 48h, i.p.) had no significant effect on MAP in sham animals (101 ± 2 mmHg), but significantly decreased MAP in RUPP animals (107 ± 2 mmHg, p<0.05), returning pressure to sham control levels. Promisingly, bilirubin administration had no detrimental effect on fetal weight (2.5 ± 0.14 vs 2.2 ± .28 g) or incidence of fetal loss (6 ±2% shams vs 3 ± 2% treated). In RUPP animals, which have significantly increased incidence of fetal loss compared to controls (69 ± 6%, p<0.005), bilirubin tended to decrease fetal loss (43 ± 13%), however, this did not meet statistical significance. In summary, bilirubin administration attenuated the hypertension associated with placental ischemia, and moderately increased bilirubin is a potential mechanism to explain the therapeutic effects of heme oxygenase induction in this clinically relevant model for the study of preeclampsia.