scholarly journals Combinations of Maternal KIR and Fetal HLA-C Genes Influence the Risk of Preeclampsia and Reproductive Success

2004 ◽  
Vol 200 (8) ◽  
pp. 957-965 ◽  
Author(s):  
Susan E. Hiby ◽  
James J. Walker ◽  
Kevin M. O'Shaughnessy ◽  
Christopher W.G. Redman ◽  
Mary Carrington ◽  
...  
Keyword(s):  
Reproductive Success ◽  
Physiological Role ◽  
Reciprocal Relationship ◽  
Trophoblast Invasion ◽  
Human Populations ◽  
Placental Development ◽  
Increased Risk ◽  
Key Factor ◽  
Missing Self ◽  
Risk Of Preeclampsia

Preeclampsia is a serious complication of pregnancy in which the fetus receives an inadequate supply of blood due to failure of trophoblast invasion. There is evidence that the condition has an immunological basis. The only known polymorphic histocompatibility antigens on the fetal trophoblast are HLA-C molecules. We tested the idea that recognition of these molecules by killer immunoglobulin receptors (KIRs) on maternal decidual NK cells is a key factor in the development of preeclampsia. Striking differences were observed when these polymorphic ligand: receptor pairs were considered in combination. Mothers lacking most or all activating KIR (AA genotype) when the fetus possessed HLA-C belonging to the HLA-C2 group were at a greatly increased risk of preeclampsia. This was true even if the mother herself also had HLA-C2, indicating that neither nonself nor missing-self discrimination was operative. Thus, this interaction between maternal KIR and trophoblast appears not to have an immune function, but instead plays a physiological role related to placental development. Different human populations have a reciprocal relationship between AA frequency and HLA-C2 frequency, suggesting selection against this combination. In light of our findings, reproductive success may have been a factor in the evolution and maintenance of human HLA-C and KIR polymorphisms.

Epigenetic processes during preeclampsia and effects on fetal development and chronic health

2021 ◽  
Vol 135 (19) ◽  
pp. 2307-2327
Author(s):  
Usman M. Ashraf ◽  
Dalton L. Hall ◽  
Adam Z. Rawls ◽  
Barbara T. Alexander
Keyword(s):  
Fetal Growth ◽  
Trophoblast Invasion ◽  
Placental Development ◽  
Regulatory Processes ◽  
Effective Interventions ◽  
Downstream Effects ◽  
Increased Risk ◽  
Exact Etiology ◽  
Cv Disease ◽  
Epigenetic Processes

Abstract Preeclampsia (PE), the leading cause of maternal and fetal morbidity and mortality, is associated with poor fetal growth, intrauterine growth restriction (IUGR) and low birth weight (LBW). Offspring of women who had PE are at increased risk for cardiovascular (CV) disease later in life. However, the exact etiology of PE is unknown. Moreover, there are no effective interventions to treat PE or alleviate IUGR and the developmental origins of chronic disease in the offspring. The placenta is critical to fetal growth and development. Epigenetic regulatory processes such as histone modifications, microRNAs and DNA methylation play an important role in placental development including contributions to the regulation of trophoblast invasion and remodeling of the spiral arteries. Epigenetic processes that lead to changes in placental gene expression in PE mediate downstream effects that contribute to the development of placenta dysfunction, a critical mediator in the onset of PE, impaired fetal growth and IUGR. Therefore, this review will focus on epigenetic processes that contribute to the pathogenesis of PE and IUGR. Understanding the epigenetic mechanisms that contribute to normal placental development and the initiating events in PE may lead to novel therapeutic targets in PE that improve fetal growth and mitigate increased CV risk in the offspring.

scholarly journals Effects of extracellular vesicles on placentation and pregnancy disorders

Reproduction ◽  
2019 ◽  
Vol 158 (5) ◽  
pp. R189-R196 ◽  
Author(s):  
Changwon Yang ◽  
Gwonhwa Song ◽  
Whasun Lim
Keyword(s):  
Extracellular Vesicles ◽  
Vascular Remodeling ◽  
Inflammatory Responses ◽  
Physiological Role ◽  
Trophoblast Invasion ◽  
Adaptation To Hypoxia ◽  
Cell Of Origin ◽  
Placental Development ◽  
Pregnancy Disorders

In humans, pregnancy maintenance depends on normal placental formation following trophoblast invasion into the endometrium and vascular remodeling. In the early stages of pregnancy, immune tolerance, inflammatory response and adaptation to hypoxia need to be precisely regulated in the placental microenvironment. Various types of cells, such as trophoblasts, endothelial cells, immune cells, mesenchymal stem cells (MSCs) and adipocytes, induce normal placental development via intercellular interactions through soluble factors. Extracellular vesicles (EVs) are used to diagnose various diseases because their constituents vary depending on the type of cell of origin and pathological characteristics. EV-derived microRNAs (miRNAs) and proteins in the placenta regulate inflammatory responses and the invasion of trophoblasts through intercellular delivery in the placental microenvironment. If the placenta does not adapt to the changed environment during early pregnancy, pregnancy disorders such as pre-eclampsia, preterm birth and gestational diabetes mellitus can occur. Thus, the important roles of EVs during pregnancy and development is fast emerging. This review describes the physiological role of EVs during placentation and their composition in the human placenta. It also suggests the possibility of finding EV markers that can diagnose pregnancy disorders. Furthermore, it describes the properties of EVs that affect pregnancy in livestock.

scholarly journals Characterization of the adverse effects of nicotine on placental development: in vivo and in vitro studies

2014 ◽  
Vol 306 (4) ◽  
pp. E443-E456 ◽  
Author(s):  
A. C. Holloway ◽  
A. Salomon ◽  
M. J. Soares ◽  
V. Garnier ◽  
S. Raha ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Cell Line ◽  
Angiogenic Factor ◽  
Trophoblast Invasion ◽  
Placental Development ◽  
Nicotine Receptors ◽  
Increased Risk ◽  
The Impact

In utero exposure to nicotine is associated with increased risk of numerous adverse fetal and neonatal outcomes, which suggests that it acts directly to affect placental development and the establishment of the fetomaternal circulation (FC). This study used both in vivo [Wistar rats treated with 1 mg/kg nicotine from 2 wk prior to mating until gestational day (GD) 15] and in vitro (RCHO-1 cell line; treated with 10−9 to 10−3M nicotine) models to examine the effects of nicotine on these pathways. At GD 15, control and treated placentas were examined for the impact of nicotine on 1) trophoblast invasion, proliferation, and degree of hypoxia, 2) labyrinth vascularization, 3) expression of key genes of placental development, and 4) expression of placental angiogenic factors. The RCHO-1 cell line was used to determine the direct effects of nicotine on trophoblast differentiation. Our in vivo experiments show that nicotine inhibits trophoblast interstitial invasion, increases placental hypoxia, downregulates labyrinth vascularization as well as key transcription factors Hand1 and GCM1, and decreases local and circulating EG-VEGF, a key placental angiogenic factor. The in vitro experiments confirmed the inhibitory effects of nicotine on the trophoblast migration, invasion, and differentiation processes and demonstrated that those effects are most likely due to a dysregulation in the expression of nicotine receptors and a decrease in MMP9 activity. Taken together, these data suggest that adverse effects of maternal smoking on pregnancy outcome are due in part to direct and endocrine effects of nicotine on the main processes of placental development and establishment of FC.

scholarly journals Increased risk of preeclampsia after use of paracetamol during pregnancy – causal or coincidence?

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hetti von Hellens ◽  
Leea Keski-Nisula ◽  
Heidi Sahlman
Keyword(s):  
Third Trimester ◽  
Retrospective Case ◽  
Reverse Causation ◽  
Gestational Period ◽  
The Third ◽  
Precise Data ◽  
Increased Risk ◽  
Study Population ◽  
The Difference ◽  
Risk Of Preeclampsia

Abstract Background The maternal use of paracetamol during pregnancy has been associated with the development of preeclampsia. This study aims to clarify whether the connection is causal or whether it is due to reverse causation. Methods This study is a continuation of the retrospective case cohort study examining 2,508 pregnant women using a variety of drugs and the development of preeclampsia (1,252 women with preeclampsia and 1,256 controls). For the purposes of this study, more precise data was collected from several hospital databases of the women among this cohort who had reported taking paracetamol during pregnancy (indications, gestational period etc.); this was evaluated in association with the development of preeclampsia. Results 5.5% (100 cases and 37 controls) of all the study population (2,508) had clearly reported paracetamol use. Women with preeclampsia had used significantly more often paracetamol during pregnancy compared to controls (cases 8.0%, controls 2.9%, p < 0.001). The difference was most evident in the third trimester (after the 29th GW) and the use of paracetamol was associated with both mild and severe preeclampsia. Headache and “general pain” were the most common indications for medication among all paracetamol users. Conclusions The use of paracetamol in the third trimester of pregnancy was associated with preeclampsia. This observation indicates that association between paracetamol use and preeclampsia is probably due to reverse causation, i.e. women with preeclampsia experience more headaches due to preeclampsia symptoms since this association was not detected with the use of paracetamol in earlier stages of pregnancy.

Antiplatelet drugs in patients with enhanced platelet turnover: biomarkers versus platelet function testing

2015 ◽  
Vol 114 (09) ◽  
pp. 459-468 ◽  
Author(s):  
Susanne Gruber ◽  
Erik Grove ◽  
Thomas Weiss ◽  
Johann Wojta ◽  
Kurt Huber ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Platelet Reactivity ◽  
Platelet Inhibition ◽  
Antiplatelet Drugs ◽  
P2y12 Inhibitors ◽  
Reticulated Platelets ◽  
Increased Risk ◽  
Key Factor ◽  
Coronary Syndromes ◽  
Function Testing

SummaryPlatelets are key players in atherothrombosis. Antiplatelet therapy comprising aspirin alone or with P2Y12-inhibitors are effective for prevention of atherothrombotic complications. However, there is interindividual variability in the response to antiplatelet drugs, leaving some patients at increased risk of recurrent atherothrombotic events. Several risk factors associated with high on-treatment platelet reactivity (HTPR), including elevated platelet turnover, have been identified. Platelet turnover is adequately estimated from the fraction of reticulated platelets. Reticulated platelets are young platelets, characterised by residual messenger RNA. They are larger, haemostatically more active and there is evidence that platelet turnover is a causal and prognostic factor in atherothrombotic disease. Whether platelet turnover per se represents a key factor in pathogenesis, progression and prognosis of atherothrombotic diseases (with focus on acute coronary syndromes) or whether it merely facilitates insufficient platelet inhibition will be discussed in this state-of-the art review.

scholarly journals NAD(P)H quinone oxidoreductase (NQO1): an enzyme which needs just enough mobility, in just the right places

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Angel L. Pey ◽  
Clare F. Megarity ◽  
David J. Timson
Keyword(s):  
Active Sites ◽  
Physiological Role ◽  
Polymorphic Form ◽  
Normal Function ◽  
Enzyme Mechanism ◽  
Quinone Oxidoreductase ◽  
Lower Stability ◽  
Increased Risk ◽  
Wide Range ◽  
The Right

AbstractNAD(P)H quinone oxidoreductase 1 (NQO1) catalyses the two electron reduction of quinones and a wide range of other organic compounds. Its physiological role is believed to be partly the reduction of free radical load in cells and the detoxification of xenobiotics. It also has non-enzymatic functions stabilising a number of cellular regulators including p53. Functionally, NQO1 is a homodimer with two active sites formed from residues from both polypeptide chains. Catalysis proceeds via a substituted enzyme mechanism involving a tightly bound FAD cofactor. Dicoumarol and some structurally related compounds act as competitive inhibitors of NQO1. There is some evidence for negative cooperativity in quinine oxidoreductases which is most likely to be mediated at least in part by alterations to the mobility of the protein. Human NQO1 is implicated in cancer. It is often over-expressed in cancer cells and as such is considered as a possible drug target. Interestingly, a common polymorphic form of human NQO1, p.P187S, is associated with an increased risk of several forms of cancer. This variant has much lower activity than the wild-type, primarily due to its substantially reduced affinity for FAD which results from lower stability. This lower stability results from inappropriate mobility of key parts of the protein. Thus, NQO1 relies on correct mobility for normal function, but inappropriate mobility results in dysfunction and may cause disease.

scholarly journals Genetic Association of ERAP1 and ERAP2 With Eclampsia and Preeclampsia in Northeastern Brazilian Women

2021 ◽  
Author(s):  
LEONARDO CAPISTRANO FERREIRA ◽  
CARLOS EDUARDO MAIA GOMES ◽  
PRIYA DUGGAL ◽  
INGRID DE PAULA HOLANDA ◽  
AMANDA SAMARA DE LIMA ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Genetic Variants ◽  
Antigen Processing ◽  
P Value ◽  
Chronic Hypertension ◽  
Ang Ii ◽  
Small Peptides ◽  
Increased Risk ◽  
Genotype C ◽  
Risk Of Preeclampsia

Abstract The clinical spectrum of hypertensive disorders of pregnancy (HDP) is determined by the interplay between environmental and genetic factors, most of which remains unknown. ERAP1, ERAP2 and LNPEP genes code for multifunctional aminopeptidases involved with antigen processing and degradation of small peptides such as angiotensin II (Ang II), vasopressin and oxytocin. We aimed to test for associations between genetic variants in aminopeptidases and HDP. A total of 1282 pregnant women (normotensive controls, n=693; preeclampsia, n=342; chronic hypertension with superimposed preeclampsia, n=61; eclampsia, n=74; and HELLP syndrome, n=112) were genotyped for variants in LNPEP (rs27300, rs38034, rs2303138), ERAP1 (rs27044, rs30187) and ERAP2 (rs2549796 rs2927609 rs11135484). We also evaluated the effect of ERAP1 rs30187 on plasma Ang II levels in an additional cohort of 65 pregnant women. The genotype C/C, in ERAP1 rs30187 variant (c.1583T>C, p.Lys528Arg), was associated with increased risk of eclampsia (OR=1.85, p=0.019) whereas ERAP2 haplotype rs2549796(C)-rs2927609(C)-rs11135484(G) was associated with preeclampsia (OR=1.96, corrected p-value=0.01). Ang II plasma levels did not differ across rs30187 genotypic groups (p=0.895). In conclusion, ERAP1 gene is associated with eclampsia whereas ERAP2 is associated with preeclampsia, although the mechanism by which genetic variants in ERAPs influence the risk of preeclampsia and eclampsia remain to be elucidated.

scholarly journals The Dynamics of Cullin-1 Expression in Preeclamptic Placenta and its Association with Pregnancy Termination Time

2020 ◽  
Vol 8 (B) ◽  
pp. 210-215
Author(s):  
Makbruri Makbruri ◽  
Isabella Kurnia Liem ◽  
Ahmad Aulia Jusuf ◽  
Tantri Hellyanti
Keyword(s):  
Gestational Age ◽  
Pregnancy Termination ◽  
Age Groups ◽  
Trophoblast Invasion ◽  
Age Group ◽  
Placental Development ◽  
Very Preterm ◽  
Significant Difference ◽  
Cellular Factors ◽  
Termination Time

BACKGROUND: Preeclampsia is a systemic syndrome occurring in 3–5% of pregnancies, caused by disorders of cellular factors resulting in the disruption of trophoblast differentiation and invasion which is important for the placental development and maintaining pregnancy. Cullin-1 is a protein that plays a role in the process of maintaining pregnancy, development, and trophoblast invasion in the placenta. Until now, there have been no studies linking the expression of cullin-1 in preeclamptic patients with the timing of pregnancy termination. AIM: This study analyzed cullin-1 expression in preeclamptic patients and their relationship to the timing of pregnancy termination was carried out. METHODS: Placental samples were taken from preeclampsia patients consisting of three gestational age groups, then immunohistochemical staining was performed to see the dynamics of expression and distribution in each age group of pregnancy and to find out their relationship with the timing of pregnancy termination. RESULTS: Cullin-1 was expressed in syncytiotrophoblasts and cytotrophoblasts. The lowest cullin-1 level was obtained in the very preterm age group, and the highest was found in the moderate preterm gestational age group. There was a significant difference between cullin-1 optical density (OD) expression and termination time of pregnancy, and there was a significant difference (OD) in cullin-1 preeclamptic patients with very preterm gestational age with moderate preterm gestational age. CONCLUSION: Cullin-1 was expressed both in syncytiotrophoblasts and cytotrophoblasts and was associated with the timing of pregnancy termination.

scholarly journals Vitamin and mineral nutrition for the health and development of the children of Europe

2001 ◽  
Vol 4 (1a) ◽  
pp. 91-99 ◽  
Author(s):  
Andrew Tomkins
Keyword(s):  
Nutritional Status ◽  
Adult Health ◽  
Future Health ◽  
Childhood Nutrition ◽  
Nutritional Interventions ◽  
Childhood Diet ◽  
Structure Of Communities ◽  
Increased Risk ◽  
Key Factor ◽  
And Function

AbstractMost European countries are now affected by demographic transition and changing epidemiology of disease; the nutrition of children is increasingly recognised as crucial for present and future health. Adequate dietary intake and nutritional status among children are important for their own growth, development and function but there is now increasing evidence that childhood nutrition also influences adult health. Intrauterine nutrition influences adult morbidity and mortality, but the childhood diet and nutritional status modify the increased risk of being born small. Thus, childhood diet needs to be taken more seriously in order to improve a nation's health as well as producing bright, active children. A key factor is the recognition that nutritional interventions at different stages of the life cycle are necessary if childhood nutrition is to improve. The mosaic pattern of the geography and social structure of communities in Europe produces ‘poverty’ and ‘consumer’ related nutrition patterns - often side by side. At one extreme, there is an urgent need to prevent obesity; while at the other extreme serious attention is required towards the prevention of deficiency disorders, mostly related to poverty and social exclusion. Few European governments take childhood nutrition at all seriously. This paper reviews a number of micronutrient issues and makes the case for the development of evidence-based policies and programmes for improving the nutrition of children in Europe.

Sign in / Sign up

Export Citation Format

Share Document