scholarly journals Levels of miR-374 increase in BeWo b30 cells exposed to hypoxia

2021 ◽  
Author(s):  
EN Knyazev ◽  
SYu Paul
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Target Genes ◽  
Expression Profiles ◽  
Growth Restriction ◽  
Trophoblast Invasion ◽  
Placental Development ◽  
Cell Potential ◽  
Bewo B30 ◽  
Next Generation Sequencing Ngs

In humans, trophoblast hypoxia during placental development can be a cause of serious pregnancy complications, such as preeclampsia and fetal growth restriction. The pathogenesis of these conditions is not fully clear and may be associated with changed expression of some genes and regulatory molecules, including miRNA, in trophoblast cells. The aim of this study was to analyze miRNA profiles and measure the expression of their target genes in a model of trophoblast hypoxia. Human choriocarcinoma BeWo b30 cells were used as a trophoblast model. Hypoxia was induced by cobalt chloride (CoCl2) and an oxyquinoline derivative. MRNA and miRNA expression profiles were evaluated by means of next generation sequencing (NGS); the expression of individual genes was analyzed by PCR. We studied the secondary structure of mRNAs of target genes for those miRNAs whose expression had changed significantly and analyzed potential competition between these miRNAs for the binding site. The observed changes in the expression of the key genes involved in the response to hypoxia confirmed the feasibility of using CoCl2 and the oxyquinoline derivative as hypoxia inducers. The analysis revealed an increase in miR-374 levels following the activation of the hypoxia pathway in our trophoblast model. The changes were accompanied by a reduction in FOXM1 mRNA expression; this mRNA is a target for hsa-miR-374a-5p and hsa-miR374b-5p, which can compete with hsa-miR-21-5p for the binding sites on FOXM1 mRNA. The involvement of FOXM1 in the regulation of the invasive cell potential suggests the role of miR-374 and FOXM1 in the pathogenesis of disrupted trophoblast invasion during placental development as predisposing for fetal growth restriction and preeclampsia.

scholarly journals Nutrient sensor signaling pathways and cellular stress in fetal growth restriction

2019 ◽  
Vol 62 (2) ◽  
pp. R155-R165 ◽  
Author(s):  
Bethany Hart ◽  
Elizabeth Morgan ◽  
Emilyn U Alejandro
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Cellular Stress ◽  
Nutrient Sensing ◽  
Growth Restriction ◽  
Trophoblast Invasion ◽  
Supporting Evidence ◽  
Placental Development ◽  
Nutrient Regulation ◽  
Placental Perfusion

Fetal growth restriction is one of the most common obstetrical complications resulting in significant perinatal morbidity and mortality. The most frequent etiology of human singleton fetal growth restriction is placental insufficiency, which occurs secondary to reduced utero-placental perfusion, abnormal placentation, impaired trophoblast invasion and spiral artery remodeling, resulting in altered nutrient and oxygen transport. Two nutrient-sensing proteins involved in placental development and glucose and amino acid transport are mechanistic target of rapamycin (mTOR) and O-linked N-acetylglucosamine transferase (OGT), which are both regulated by availability of oxygen. Impairment in either of these pathways is associated with fetal growth restriction and accompanied by cellular stress in the forms of hypoxia, oxidative and endoplasmic reticulum (ER) stress, metabolic dysfunction and nutrient starvation in the placenta. Recent evidence has emerged regarding the potential impact of nutrient sensors on fetal stress response, which occurs in a sexual dysmorphic manner, indicating a potential element of genetic gender susceptibility to fetal growth restriction. In this mini review, we focus on the known role of mTOR and OGT in placental development, nutrient regulation and response to cellular stress in human fetal growth restriction with supporting evidence from rodent models.

scholarly journals Sex-Biased lncRNA Signature in Fetal Growth Restriction (FGR)

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 921
Author(s):  
Aleksandra Lipka ◽  
Jan Pawel Jastrzebski ◽  
Lukasz Paukszto ◽  
Karol Gustaw Makowczenko ◽  
Elzbieta Lopienska-Biernat ◽  
...  
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Target Genes ◽  
Active Regions ◽  
Bioinformatic Analysis ◽  
Growth Restriction ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Differential Analysis ◽  
Protein Coding

Impaired fetal growth is one of the most important causes of prematurity, stillbirth and infant mortality. The pathogenesis of idiopathic fetal growth restriction (FGR) is poorly understood but is thought to be multifactorial and comprise a range of genetic causes. This research aimed to investigate non-coding RNAs (lncRNAs) in the placentas of male and female fetuses affected by FGR. RNA-Seq data were analyzed to detect lncRNAs, their potential target genes and circular RNAs (circRNAs); a differential analysis was also performed. The multilevel bioinformatic analysis enabled the detection of 23,137 placental lncRNAs and 4263 of them were classified as novel. In FGR-affected female fetuses’ placentas (ff-FGR), among 19 transcriptionally active regions (TARs), five differentially expressed lncRNAs (DELs) and 12 differentially expressed protein-coding genes (DEGs) were identified. Within 232 differentially expressed TARs identified in male fetuses (mf-FGR), 33 encompassed novel and 176 known lncRNAs, and 52 DEGs were upregulated, while 180 revealed decreased expression. In ff-FGR ACTA2-AS1, lncRNA expression was significantly correlated with five DEGs, and in mf-FGR, 25 TARs were associated with DELs correlated with 157 unique DEGs. Backsplicing circRNA processes were detected in the range of H19 lncRNA, in both ff- and mf-FGR placentas. The performed global lncRNAs characteristics in terms of fetal sex showed dysregulation of DELs, DEGs and circRNAs that may affect fetus growth and pregnancy outcomes. In female placentas, DELs and DEGs were associated mainly with the vasculature, while in male placentas, disturbed expression predominantly affected immune processes.

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 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

scholarly journals Phosphorylation of Yes-associated protein impairs trophoblast invasion and migration: implications for the pathogenesis of fetal growth restriction†

2020 ◽  
Vol 103 (4) ◽  
pp. 866-879
Author(s):  
Hao Wang ◽  
Ping Xu ◽  
Xiaofang Luo ◽  
Mingyu Hu ◽  
Yamin Liu ◽  
...  
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Cell Function ◽  
Hippo Pathway ◽  
Growth Restriction ◽  
Growth Potential ◽  
Biomechanical Analysis ◽  
Trophoblast Invasion ◽  
Invasion And Migration ◽  
And Migration

Abstract Fetal growth restriction (FGR) is a condition in which a newborn fails to achieve his or her prospective hereditary growth potential. This condition is associated with high newborn mortality, second only to that associated with premature birth. FGR is associated with maternal, fetal, and placental abnormalities. Although the placenta is considered to be an important organ for supplying nutrition for fetal growth, research on FGR is limited, and treatment through the placenta remains challenging, as neither proper uterine intervention nor its pathogenesis have been fully elucidated. Yes-associated protein (YAP), as the effector of the Hippo pathway, is widely known to regulate organ growth and cancer development. Therefore, the correlation of the placenta and YAP was investigated to elucidate the pathogenic mechanism of FGR. Placental samples from humans and mice were collected for histological and biomechanical analysis. After investigating the location and role of YAP in the placenta by immunohistochemistry, we observed that YAP and cytokeratin 7 have corresponding locations in human and mouse placentas. Moreover, phosphorylated YAP (p-YAP) was upregulated in FGR and gradually increased as gestational age increased during pregnancy. Cell function experiments and mRNA-Seq demonstrated impaired YAP activity mediated by extracellular signal-regulated kinase inhibition. Established FGR-like mice also recapitulated a number of the features of human FGR. The results of this study may help to elucidate the association of FGR development with YAP and provide an intrauterine target that may be helpful in alleviating placental dysfunction.

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 Placental Homeobox Genes in Human Fetal Growth Restriction

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Padma Murthi ◽  
Gayathri Rajaraman ◽  
Shaun Patrick Brennecke ◽  
Bill Kalionis
Keyword(s):  
Pregnancy Outcome ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Transcriptional Control ◽  
Molecular Mechanisms ◽  
Adverse Pregnancy Outcome ◽  
Growth Restriction ◽  
Placental Development ◽  
Increased Risk ◽  
Adverse Pregnancy

Fetal growth restriction (FGR) is an adverse pregnancy outcome associated with significant perinatal and paediatric morbidity and mortality, and an increased risk of chronic disease later in adult life. One of the key causes of adverse pregnancy outcome is fetal growth restriction (FGR). While a number of maternal, fetal, and environmental factors are known causes of FGR, the majority of FGR cases remain idiopathic. These idiopathic FGR pregnancies are frequently associated with placental insufficiency, possibly as a result of placental maldevelopment. Understanding the molecular mechanisms of abnormal placental development in idiopathic FGR is, therefore, of increasing importance. Here, we review our understanding of transcriptional control of normal placental development and abnormal placental development associated with human idiopathic FGR. We also assess the potential for understanding transcriptional control as a means for revealing new molecular targets for the detection, diagnosis, and clinical management of idiopathic FGR.

scholarly journals Inflammation in rat pregnancy inhibits spiral artery remodeling leading to fetal growth restriction and features of preeclampsia

2014 ◽  
Vol 211 (1) ◽  
pp. 165-179 ◽  
Author(s):  
Tiziana Cotechini ◽  
Maria Komisarenko ◽  
Arissa Sperou ◽  
Shannyn Macdonald-Goodfellow ◽  
Michael A. Adams ◽  
...  
Keyword(s):  
Fetal Growth ◽  
Pregnancy Complications ◽  
Fetal Growth Restriction ◽  
Nitrosative Stress ◽  
Growth Restriction ◽  
Trophoblast Invasion ◽  
Spiral Artery ◽  
Transdermal Administration ◽  
Pregnant Rats ◽  
Maternal Inflammation

Fetal growth restriction (FGR) and preeclampsia (PE) are often associated with abnormal maternal inflammation, deficient spiral artery (SA) remodeling, and altered uteroplacental perfusion. Here, we provide evidence of a novel mechanistic link between abnormal maternal inflammation and the development of FGR with features of PE. Using a model in which pregnant rats are administered low-dose lipopolysaccharide (LPS) on gestational days 13.5–16.5, we show that abnormal inflammation resulted in FGR mediated by tumor necrosis factor-α (TNF). Inflammation was also associated with deficient trophoblast invasion and SA remodeling, as well as with altered uteroplacental hemodynamics and placental nitrosative stress. Moreover, inflammation increased maternal mean arterial pressure (MAP) and was associated with renal structural alterations and proteinuria characteristic of PE. Finally, transdermal administration of the nitric oxide (NO) mimetic glyceryl trinitrate prevented altered uteroplacental perfusion, LPS-induced inflammation, placental nitrosative stress, renal structural and functional alterations, increase in MAP, and FGR. These findings demonstrate that maternal inflammation can lead to severe pregnancy complications via a mechanism that involves increased maternal levels of TNF. Our study provides a rationale for the use of antiinflammatory agents or NO-mimetics in the treatment and/or prevention of inflammation-associated pregnancy complications.

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