Regulator of G-Protein Signaling 2 Knockout in CD4+ T Cells Promotes Anti-Inflammatory T Cells, Enhancing Ovulation, and Oocyte Yield.

Objective: To determine the downstream effects on ovarian function and immune cell differentiation in the ovary and uterus using a model in which RGS2 was knocked out specifically in CD4+ T cells.

Design: Laboratory based experiments with female mice.

Animals: Female congenic (fully backcrossed) and non-congenic (mixed strain) mice with CD4 T cell-specific RGS2 knockout.

Generation of Human Regulatory Dendritic Cells from Cryopreserved Healthy Donor Cells and Hematopoietic Stem Cell Transplant Recipients.

Acute graft versus host disease (GVHD) remains a significant complication following hematopoietic stem cell transplant (HSCT), despite improved human leukocyte antigen (HLA) matching and advances in prophylactic treatment regimens. Previous studies have shown promising results for future regulatory dendritic cell (DCreg) therapies in the amelioration of GVHD. This study evaluates the effects of cryopreservation on the generation of DCreg, the generation of young and older DCreg in serum-free media, and the feasibility of generating DCreg from young and older HSCT patient monocytes.

Cellular Immunotherapy in Mice Prevents Maternal Hypertension and Restores Anti-Inflammatory Cytokine Balance in Maternal and Fetal Tissues.

Preeclampsia is the leading cause of maternal-fetal morbidity worldwide. The concept that persistent feto-placental intolerance is important in the pathogenesis of preeclampsia (PreE) has been demonstrated by our lab and others. Arginine vasopressin (AVP) infusion during pregnancy induces cardiovascular, renal, and T helper (T) cell alterations in mice consistent with human PreE.

Efferocytosis of viable versus heat-inactivated MSC induces human monocytes to distinct immunosuppressive phenotypes.

Background: Immunomodulation by mesenchymal stromal cells (MSCs) can occur through trophic factor mechanisms, however, intravenously infused MSCs are rapidly cleared from the body yet a potent immunotherapeutic response is still observed. Recent work suggests that monocytes contribute to the clearance of MSCs via efferocytosis, the body's natural mechanism for clearing dead and dying cells in a non-inflammatory manner. This begs the questions of how variations in MSC quality affect monocyte phenotype and if viable MSCs are even needed to elicit an immunosuppressive response.

Selective Serotonin Reuptake Inhibitor Use in Pregnancy and Protective Mechanisms in Preeclampsia.

Depression and preeclampsia share risk factors and are bi-directionally associated with increased risk for each other. Despite epidemiological evidence linking selective serotonin reuptake inhibitors (SSRIs) in pregnancy to preeclampsia, serotonin (5-HT) and vasopressin (AVP) secretion mechanisms suggest that SSRIs may attenuate preeclampsia risk. However, there is a need to clarify the relationship between SSRIs and preeclampsia in humans to determine therapeutic potential.

Association between plasma leptin and cesarean section after induction of labor: a case control study.

Background: Obesity in pregnancy is common, with more than 50% of pregnant women being overweight or obese. Obesity has been identified as an independent predictor of dysfunctional labor and is associated with increased risk of failed induction of labor resulting in cesarean section. Leptin, an adipokine, is secreted from adipose tissue under the control of the obesity gene.

Reduced Maternal Circulating Cell-Free Mitochondrial DNA Is Associated With the Development of Preeclampsia.

Background Circulating cell-free mitochondrial DNA (ccf-mtDNA) is a damage-associated molecular pattern that reflects cell stress responses and tissue damage, but little is known about ccf-mtDNA in preeclampsia. The main objectives of this study were to determine (1) absolute concentrations of ccf-mtDNA in plasma and mitochondrial DNA content in peripheral blood mononuclear cells and (2) forms of ccf-mtDNA transport in blood from women with preeclampsia and healthy controls. In addition, we sought to establish the association between aberrance in circulating DNA-related metrics, including ccf-mtDNA and DNA clearance mechanisms, and the clinical diagnosis of preeclampsia using bootstrapped penalized logistic regression.

Placenta-specific protein 1 (PLAC1) expression is significantly down-regulated in preeclampsia a hypoxia-mediated mechanism.

Objective: Examine a mechanism of PLAC1 regulation and its potential role in preeclampsia (PE).

Materials And Methods: Placental tissue samples and detailed clinical information were obtained through the University of Iowa Maternal Fetal Tissue Bank (IRB# 200910784) from gestational and maternal age-matched control ( = 17) and PE affected pregnancies ( = 12). PLAC1 and PLAC1 promoter-specific expression was measured using quantitative polymerase chain reaction (qPCR) and differences were assessed the standard ΔΔCt method.

Altered offspring neurodevelopment in an arginine vasopressin preeclampsia model.

Preeclampsia is a severe gestational hypertensive condition linked to child neuropsychiatric disorders, although underlying mechanisms are unclear. We used a recently developed, clinically relevant animal model of preeclampsia to assess offspring. C57BL/6J mouse dams were chronically infused with arginine vasopressin (AVP) or saline (24 ng/h) throughout pregnancy.

Beat-to-Beat Blood Pressure Variability in the First Trimester Is Associated With the Development of Preeclampsia in a Prospective Cohort: Relation With Aortic Stiffness.

Women with preeclampsia, a hypertensive disorder of pregnancy, exhibit greater beat-to-beat blood pressure variability (BPV) in the third trimester after clinical onset of the disorder. However, it remains unknown whether elevated BPV precedes the development of preeclampsia. A prospective study cohort of 139 women (age 30.

Correction: Chronic maternal interleukin-17 and autism-related cortical gene expression, neurobiology, and behavior.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Chronic maternal interleukin-17 and autism-related cortical gene expression, neurobiology, and behavior.

Chronic inflammation during pregnancy (e.g., preeclampsia, diabetes) is linked to increased risk for offspring neurodevelopmental disorders such as autism spectrum disorder (ASD).

Reduced mRNA Expression of RGS2 (Regulator of G Protein Signaling-2) in the Placenta Is Associated With Human Preeclampsia and Sufficient to Cause Features of the Disorder in Mice.

Cascade-specific termination of G protein signaling is catalyzed by the RGS (regulator of G protein signaling) family members, including . Angiotensin, vasopressin, and endothelin are implicated in preeclampsia, and is known to inhibit G protein cascades activated by these hormones. Mutations in are associated with human hypertension and increased risk of developing preeclampsia and its sequelae.

Arginine vasopressin infusion is sufficient to model clinical features of preeclampsia in mice.

Copeptin, a marker of arginine vasopressin (AVP) secretion, is elevated throughout human pregnancies complicated by preeclampsia (PE), and AVP infusion throughout gestation is sufficient to induce the major phenotypes of PE in mice. Thus, we hypothesized a role for AVP in the pathogenesis of PE. AVP infusion into pregnant C57BL/6J mice resulted in hypertension, renal glomerular endotheliosis, intrauterine growth restriction, decreased placental growth factor (PGF), altered placental morphology, placental oxidative stress, and placental gene expression consistent with human PE.

Elevated vasopressin in pregnant mice induces T-helper subset alterations consistent with human preeclampsia.

The pathogenesis of preeclampsia (PreE), a hypertensive disorder of pregnancy, involves imbalanced T helper (T) cell populations and resultant changes in pro- and anti-inflammatory cytokine release. Elevated copeptin (an inert biomarker of arginine vasopressin (AVP)), secretion precedes the development of symptoms in PreE in humans, and infusion of AVP proximal to and throughout gestation is sufficient to initiate cardiovascular and renal phenotypes of PreE in wild-type C57BL/6J mice. We hypothesize that AVP infusion in wild-type mice is sufficient to induce the immune changes observed in human PreE.

Vasopressin: the missing link for preeclampsia?

Preeclampsia is a devastating cardiovascular disorder of late pregnancy, affecting 5-7% of all pregnancies and claiming the lives of 76,000 mothers and 500,000 children each year. Various lines of evidence support a "tissue rejection" type reaction toward the placenta as the primary initiating event in the development of preeclampsia, followed by a complex interplay among immune, vascular, renal, and angiogenic mechanisms that have been implicated in the pathogenesis of preeclampsia beginning around the end of the first trimester. Critically, it remains unclear what mechanism links the initiating event and these pathogenic mechanisms.

Pregnant mice lacking indoleamine 2,3-dioxygenase exhibit preeclampsia phenotypes.

Preeclampsia is a cardiovascular disorder of late pregnancy that is, commonly characterized by hypertension, renal structural damage and dysfunction, and fetal growth restriction. Prevailing etiologic models of this disorder include T-cell dysfunction as an initiating cause of preeclampsia. Indoleamine 2,3-dioxygenase (IDO), an enzyme that mediates the conversion of tryptophan to kynurenine, has been linked to preeclampsia in humans, and is known to regulate T-cell activity and an endothelial-derived relaxing factor.

Vasopressin in preeclampsia: a novel very early human pregnancy biomarker and clinically relevant mouse model.

Preeclampsia, a cardiovascular disorder of late pregnancy, is characterized as a low-renin hypertensive state relative to normotensive pregnancy. Because other nonpregnant low-renin hypertensive disorders often exhibit and are occasionally dependent on elevated arginine vasopressin (AVP) secretion, we hypothesized a possible use for plasma AVP measurements in the prediction of preeclampsia. Copeptin is an inert prosegment of AVP that is secreted in a 1:1 molar ratio and exhibits a substantially longer biological half-life compared with AVP, rendering it a clinically useful biomarker of AVP secretion.

Characterization of regulatory dendritic cells that mitigate acute graft-versus-host disease in older mice following allogeneic bone marrow transplantation.

Despite improvements in human leukocyte antigen matching and pharmacologic prophylaxis, acute graft-versus-host disease (GVHD) is often a fatal complication following hematopoietic stem cell transplant (HSCT). Older HSCT recipients experience significantly increased morbidity and mortality compared to young recipients. Prophylaxis with syngeneic regulatory dendritic cells (DCreg) in young bone marrow transplanted (BMT) mice has been shown to decrease GVHD-associated mortality.