scholarly journals The Role of NFκB in Healthy and Preeclamptic Placenta: Trophoblasts in the Spotlight

2020 ◽  
Vol 21 (5) ◽  
pp. 1775 ◽  
Author(s):  
Brooke Armistead ◽  
Leena Kadam ◽  
Sascha Drewlo ◽  
Hamid-Reza Kohan-Ghadr
Keyword(s):  
Oxidative Stress ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Growth And Development ◽  
Protein Family ◽  
Growth Restriction ◽  
Placental Development ◽  
Critical Organ ◽  
And Oxidative Stress

The NFκB protein family regulates numerous pathways within the cell—including inflammation, hypoxia, angiogenesis and oxidative stress—all of which are implicated in placental development. The placenta is a critical organ that develops during pregnancy that primarily functions to supply and transport the nutrients required for fetal growth and development. Abnormal placental development can be observed in numerous disorders during pregnancy, including fetal growth restriction, miscarriage, and preeclampsia (PE). NFκB is highly expressed in the placentas of women with PE, however its contributions to the syndrome are not fully understood. In this review we discuss the molecular actions and related pathways of NFκB in the placenta and highlight areas of research that need attention

scholarly journals The role of melatonin in pregnancies complicated by placental insufficiency: a systematic review

2021 ◽  
Author(s):  
Ilaria Fantasia ◽  
Sofia Bussolaro ◽  
Tamara Stampalija ◽  
Daniel Rolnik
Keyword(s):  
Oxidative Stress ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Evidence Synthesis ◽  
Placental Insufficiency ◽  
Growth Restriction ◽  
Melatonin Receptors ◽  
Qualitative Evidence Synthesis ◽  
Melatonin Administration

Background: Pregnancies complicated by placental insufficiency are characterised by increased oxidative stress. It has been suggested that melatonin has antioxidant properties and contributes to the maintenance of placental homeostasis. Objective: To systematically review the available literature about melatonin in pregnancies complicated by placental insufficiency, specifically preeclampsia and fetal growth restriction, exploring three different aspects: 1) maternal melatonin levels; 2) expression and activity of melatonin placental receptors; 3) effects of maternal melatonin administration. Search strategy: PubMed (Medline) and Scopus were searched until December 2020. Selection criteria: Published literature in English language describing the role of melatonin in pregnancies complicated by placental insufficiency, with a specific focus on preeclampsia and fetal growth restriction. Data collection and analysis: Identified studies were screened and assessed independently by two authors. Data were extracted and compiled in a qualitative evidence synthesis. Main results: Pregnancies complicated by placental insufficiency show a significant reduction in maternal systemic serum melatonin levels and a significant reduction in the expression of placental melatonin receptors. Melatonin administration in pregnancy seems safe and may reduce oxidative stress. Conclusion: The circadian pattern of melatonin secretion seems to be altered in pregnancies complicated by placental insufficiency. This is reflected by lower production of melatonin, with consequent lower systemic and placental concentrations, and lower expression of melatonin receptors, thus reducing the local release of the indole and its autocrine function. Funding: None Keywords: Melatonin, Preeclampsia, Fetal growth restriction, Placental insufficiency, Review.

scholarly journals DAAM2 is elevated in the circulation and placenta in pregnancies complicated by fetal growth restriction and is regulated by hypoxia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Natasha de Alwis ◽  
Sally Beard ◽  
Natalie K. Binder ◽  
Natasha Pritchard ◽  
Tu’uhevaha J. Kaitu’u-Lino ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mrna Expression ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Linear Regression Analysis ◽  
Growth Restriction ◽  
Oxidative Stress Marker ◽  
Small Interfering Rnas ◽  
Maternal Circulation ◽  
And Oxidative Stress

AbstractPreviously, we identified increased maternal circulating DAAM2 mRNA in pregnancies complicated by preterm fetal growth restriction (FGR). Here, we assessed whether circulating DAAM2 mRNA could detect FGR, and whether the DAAM2 gene, known to play roles in the Wnt signalling pathway is expressed in human placenta and associated with dysfunction and FGR. We performed linear regression analysis to calculate area under the ROC curve (AUC) for DAAM2 mRNA expression in the maternal circulation of pregnancies complicated by preterm FGR. DAAM2 mRNA expression was assessed across gestation by qPCR. DAAM2 protein and mRNA expression was assessed in preterm FGR placenta using western blot and qPCR. DAAM2 expression was assessed in term cytotrophoblasts and placental explant tissue cultured under hypoxic and normoxic conditions by qPCR. Small interfering RNAs were used to silence DAAM2 in term primary cytotrophoblasts. Expression of growth, apoptosis and oxidative stress genes were assessed by qPCR. Circulating DAAM2 mRNA was elevated in pregnancies complicated by preterm FGR [p < 0.0001, AUC = 0.83 (0.78–0.89)]. Placental DAAM2 mRNA was detectable across gestation, with highest expression at term. DAAM2 protein was increased in preterm FGR placentas but demonstrated no change in mRNA expression. DAAM2 mRNA expression was increased in cytotrophoblasts and placental explants under hypoxia. Silencing DAAM2 under hypoxia decreased expression of pro-survival gene, BCL2 and oxidative stress marker, NOX4, whilst increasing expression of antioxidant enzyme, HMOX-1. The increased DAAM2 associated with FGR and hypoxia implicates a potential role in placental dysfunction. Decreasing DAAM2 may have cytoprotective effects, but further research is required to elucidate its role in healthy and dysfunctional placentas.

Maternal Undernourishment in Guinea Pigs Leads to Fetal Growth Restriction with Increased Hypoxic Cells and Oxidative Stress in the Brain

2019 ◽  
Vol 41 (5-6) ◽  
pp. 290-299
Author(s):  
Yohei Maki ◽  
Karen Nygard ◽  
Robert R. Hammond ◽  
Timothy R.H. Regnault ◽  
Bryan S. Richardson
Keyword(s):  
Oxidative Stress ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Guinea Pigs ◽  
Growth Restriction ◽  
The Brain ◽  
And Oxidative Stress

scholarly journals Hypoxia and Oxidative Stress Are Associated with Reduced Fetal Growth in Twin and Undernourished Sheep Pregnancies

Animals ◽  
2018 ◽  
Vol 8 (11) ◽  
pp. 217 ◽  
Author(s):  
Francisco Sales ◽  
Oscar Peralta ◽  
Eileen Narbona ◽  
Sue McCoard ◽  
Mónica De los Reyes ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Birth Weight ◽  
Low Birth Weight ◽  
Cord Blood ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Growth Restriction ◽  
Maternal Undernutrition ◽  
Natural Pasture ◽  
And Oxidative Stress

Low birth weight has profound implications for perinatal mortality and morbidity in lambs, causing higher mortality and lower growth potential. Low birth weight, as a consequence of fetal growth restriction, occurs in undernourished and multiple pregnancies, where hypoxia and oxidative stress could play a critical role. Our aim was to establish the effects of nutritional deprivation and pregnancy rank on fetal growth, oxygenation, and oxidative status in sheep pregnancies under extensive Patagonian conditions. At 30 days after mating, single- and twin-bearing ewes were offered only natural pasture (undernutrition group) or natural pasture plus concentrate supplementation (well-nourished group). At day 140 of gestation, blood gases and redox status were evaluated in venous cord blood, and fetal biometric characteristics were obtained after cesarean section. Both maternal undernutrition and twinning led to decreased oxygen supply to the fetuses (p = 0.016 and p = 0.050, respectively), which was associated with decreased intrauterine growth (r = 0.446, p < 0.01). Moreover, twinning increased oxidative stress in cord blood (p < 0.05), which might also contribute to fetal growth restriction. These results reinforce the importance of maternal nutrition, especially for those ewes bearing multiples, and opens new possibilities for nutritional or antioxidant interventions for preventing fetal hypoxia and oxidative stress.

Diabetes and pre-eclampsia affecting pregnancy: a retrospective cross-sectional study

2017 ◽  
Vol 66 (4) ◽  
pp. 728-732 ◽  
Author(s):  
Ram R Kalagiri ◽  
Niraj Vora ◽  
Jessica L Wilson ◽  
Syeda H Afroze ◽  
Venkata N Raju ◽  
...  
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Cross Sectional Study ◽  
Growth Restriction ◽  
Sectional Study ◽  
Placental Development ◽  
Cross Sectional ◽  
Diabetes Status ◽  
Elevated Glucose ◽  
Post Hoc

The interaction between pre-eclampsia and diabetes mellitus (DM) is far from being completely understood. In this study, we compared normal pregnancies with those complicated with pre-eclampsia, gestational DM, and/or pre-existing diabetes to assess the effects of hyperglycemia on placental development. AnInstitutional Review Board (IRB) approved retrospective cross-sectional study with 621 subjects was performed. Statistical analysis was performed using Duncan’s post hoc test and analysis of variance. Regardless of diabetes status, patients with pre-eclampsia delivered prematurely. Patients in the group with pre-eclampsia and pregestational diabetes delivered much earlier, at 35.0±0.4 weeks, when compared with the patients that had pre-eclampsia with gestational diabetes and pre-eclampsia with no diabetes (*P<0.05 for each). Additionally, patients with pre-existing diabetes who developed pre-eclampsia delivered smaller babies than those with pre-existing diabetes without pre-eclampsia (1.00±0.03, P<0.05 for each). Pre-existing diabetes with added insult of pre-eclampsia led to fetal growth restriction. This outcome validates the understanding that elevated glucose earlier in pregnancy alters placentogenesis and leads to fetal growth restriction.

Development of Structures and Transport Functions in the Mouse Placenta

Physiology ◽  
2005 ◽  
Vol 20 (3) ◽  
pp. 180-193 ◽  
Author(s):  
Erica D. Watson ◽  
James C. Cross
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Cell Biology ◽  
Fetal Death ◽  
Nutrient Transport ◽  
Growth Restriction ◽  
Molecular Pathways ◽  
Placental Development ◽  
Mouse Mutants ◽  
Mouse Placenta

The placenta is essential for sustaining the growth of the fetus during gestation, and defects in its function result in fetal growth restriction or, if more severe, fetal death. Several molecular pathways have been identified that are essential for development of the placenta, and mouse mutants offer new insights into the cell biology of placental development and physiology of nutrient transport.

scholarly journals Effects of antenatal melatonin therapy on lung structure in growth-restricted newborn lambs

2017 ◽  
Vol 123 (5) ◽  
pp. 1195-1203 ◽  
Author(s):  
Graeme R. Polglase ◽  
Jade Barbuto ◽  
Beth J. Allison ◽  
Tamara Yawno ◽  
Amy E. Sutherland ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Lung Development ◽  
Fetal Lung ◽  
Growth Restriction ◽  
Fetal Sheep ◽  
Respiratory Dysfunction ◽  
Melatonin Administration ◽  
Lung Structure

Oxidative stress arising from suboptimal placental function contributes to a multitude of pathologies in infants compromised by fetal growth restriction (FGR). FGR infants are at high risk for respiratory dysfunction after birth and poor long-term lung function. Our objective was to investigate the contribution of oxidative stress to adverse lung development and the effects of melatonin administration, a powerful antioxidant, on lung structure in FGR lambs. Placental insufficiency and FGR was surgically induced in 13 fetal sheep at ∼105 days of gestation by ligation of a single umbilical artery. Maternal intravenous melatonin infusion was commenced in seven of the ewes 4 h after surgery and continued until birth. Lambs delivered normally at term and lungs were collected 24 h after birth for histological assessment of lung structure and injury and compared with appropriately grown control lambs ( n = 8). FGR fetuses were hypoxic and had lower glucose during gestation compared with controls. Melatonin administration prevented chronic hypoxia. Within the lung, FGR caused reduced secondary septal crest density and altered elastin deposition compared with controls. Melatonin administration had no effect on the changes to lung structure induced by FGR. We conclude that chronic FGR disrupts septation of the developing alveoli, which is not altered by melatonin administration. These findings suggest that oxidative stress is not the mechanism driving altered lung structure in FGR neonates. Melatonin administration did not prevent disrupted airway development but also had no apparent adverse effects on fetal lung development. NEW & NOTEWORTHY Fetal growth restriction (FGR) results in poor respiratory outcomes, which may be caused by oxidation in utero. We investigated the contribution of oxidative stress to adverse lung development and the effects of melatonin administration, a powerful antioxidant, on lung structure in FGR lambs. FGR disrupted septation of the developing alveoli, which is not altered by melatonin administration. Oxidative stress may not be the mechanism driving altered lung structure in FGR neonates.

scholarly journals The Role of HLAC and NK Cells in Fetal Growth Restriction

2017 ◽  
pp. 142
Author(s):  
Sri Sulistyawati ◽  
Didon M Trimulya ◽  
Supriyadi H Respati ◽  
Soetrisno Soetrisno
Keyword(s):  
Nk Cells ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Nk Cell ◽  
Normal Pregnancy ◽  
Growth Restriction ◽  
Immunohistochemical Method ◽  
Cross Sectional ◽  
The Mean

Objective: To determine the role of HLA-C and NK cell expressions in fetal growth restriction (FGR). Methods: A cross sectional study design was used. This study was conducted at the Obstetrics and Gynecology Department of Dr. Moewardi General Hospital, Surakarta, its affiliated hospitals, and at the Pathological Anatomy Laboratory of the Faculty of Medicine, University of Sebelas Maret Surakarta. A total of 40 samples were included in this study. The samples consisted of 20 normal pregnancies and 20 pregnancies with FGR. HLA-C expression in the trophoblast and NK cells in decidua of the subjects who met the inclusion and exclusion criteria were examined using immunohistochemical method and statistical analysis with T test. Results: The mean expression of HLA-C in the trophoblast in the pregnant group with FGR was 9.021.30, normal pregnancy was 7.96 ± 0.97, p=0.01 (p<0.05). The mean expression of NK cells in decidua of pregnancy with FGR was 10.59 ± 2.11, normal pregnancy was 0.91 ± 8.18, with p=0.00 (p<0.05). Conclusion: The expressions of HLA-C in trophoblast and NK cells in decidua of pregnancy with FGR were higher compared with those of normal pregnancy. [Indones J Obstet Gynecol 2017; 5-3: 142-148] Keywords: fetal growth restriction, HLA-C, NK cells

scholarly journals Effects of excess thromboxane A2 on placental development and nutrient transporters in a Mus musculus model of fetal growth restriction†

2018 ◽  
Vol 98 (5) ◽  
pp. 695-704 ◽  
Author(s):  
Karen J Gibbins ◽  
Katherine N Gibson-Corley ◽  
Ashley S Brown ◽  
Matthew Wieben ◽  
Richard C Law ◽  
...  
Keyword(s):  
Fetal Growth ◽  
Mus Musculus ◽  
Fetal Growth Restriction ◽  
Thromboxane A2 ◽  
Growth Restriction ◽  
Nutrient Transporters ◽  
Placental Development
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