ABSTRACT
Persistent hypoxia caused by shallow trophoblast invasion and poor placental perfusion may underlie the pathophysiology of preeclampsia, a leading cause of maternal and neonatal morbidity and mortality. Previously, we found that estrogen-related receptor γ (ERRγ) serves a critical and O2-dependent role in differentiation of human trophoblasts in culture and expression of tissue kallikrein and voltage-gated K(+) channels. In this study, we surprisingly observed that ERRγ expression was significantly increased in placentas from preeclamptic women compared with that in gestation-matched normotensive women. To further investigate a functional role for ERRγ during pregnancy, we analyzed ERRγ-deficient mice. Maternal systolic blood pressure was significantly reduced in pregnant ERRγ(+/-) females bred to ERRγ(+/-) males compared with that in wild-type (WT) mice and was markedly up-regulated by treatment of WT pregnant mice with the ERRγ agonist DY131. Placentas of ERRγ(+/-) mice manifested increased vascular endothelial growth factor A expression compared with that in WT mice. Notably, circulating levels of the antiangiogenic factor, soluble fms-like tyrosine kinase-1, were significantly reduced in ERRγ(+/-) pregnant mice as was serum aldosterone. These effects were associated with a decrease in maternal adrenal Cyp11b1 (steroid 11ß-hydroxylase) and Cyp11b2 (aldosterone synthase) expression. In contrast, adrenal Cyp11b1 and Cyp11b2 mRNA were increased in pregnant WT mice treated with DY131. Moreover, chromatin immunoprecipitation and luciferase reporter assays identified Cyp11b2 as a transcriptional target of ERRγ. Collectively, these findings reveal a potential role of ERRγ in maternal blood pressure homeostasis during pregnancy and suggest that aberrant ERRγ expression may contribute to the pathogenesis of preeclampsia.
Subject(s)
Blood Pressure , Homeostasis , Receptors, Estrogen/metabolism , Animals , Cytochrome P-450 CYP11B2/genetics , Cytochrome P-450 CYP11B2/metabolism , Female , Gene Expression , Humans , Male , Mice, Inbred C57BL , Mice, Transgenic , Neovascularization, Physiologic , Placenta/blood supply , Placenta/metabolism , Pre-Eclampsia/metabolism , Pre-Eclampsia/physiopathology , Pregnancy , Promoter Regions, Genetic , Receptors, Estrogen/genetics , Steroid 11-beta-Hydroxylase/genetics , Steroid 11-beta-Hydroxylase/metabolism , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolismABSTRACT
Gaps exist in health professional education versus the demands of current practice. Leveraging front-line nurses to teach students exemplary practice in a Dedicated Education Unit (DEU) may narrow this gap. The DEU is an innovative model for experiential learning, capitalizing on the expertise of staff nurses as clinical teachers. This study evaluated the effectiveness of a new academic-practice DEU in facilitating quality and safety competency achievement among students. Six clinical teachers received education in clinical teaching and use of Quality and Safety Education for Nurses (QSEN) competencies to guide acquisition of essential knowledge, skills, and attitudes for continuous health care improvement. Twelve students assigned to the six teachers completed daily logs for the 10-week practicum. Findings suggest that DEU students achieved QSEN competencies through clinical teacher mentoring in interdisciplinary collaboration, using electronic information for best practice and patient teaching, patient/family decision making, quality improvement, and resolution of safety issues.
