scholarly journals Defective trophoblast invasion underlies fetal growth restriction and preeclampsia-like symptoms in the stroke-prone spontaneously hypertensive rat

2017 ◽  
Vol 23 (7) ◽  
pp. 509-519 ◽  
Author(s):  
G Barrientos ◽  
M Pussetto ◽  
M Rose ◽  
A C Staff ◽  
S M Blois ◽  
...  
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Spontaneously Hypertensive Rat ◽  
Growth Restriction ◽  
Trophoblast Invasion ◽  
Spontaneously Hypertensive ◽  
Hypertensive Rat

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.

The Spontaneously Hypertensive Rat Fetus, Not the Mother, is Responsible for the Reduced Amniotic Fluid PTHrP Concentrations and Growth Restriction

Placenta ◽  
2001 ◽  
Vol 22 (7) ◽  
pp. 646-651 ◽  
Author(s):  
M.E. Wlodek ◽  
K. Koutsis ◽  
K.T. Westcott ◽  
P.W.M. Ho ◽  
R. Di Nicolantonio ◽  
...  
Keyword(s):  
Amniotic Fluid ◽  
Spontaneously Hypertensive Rat ◽  
Growth Restriction ◽  
Rat Fetus ◽  
Spontaneously Hypertensive ◽  
Hypertensive Rat

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 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.

scholarly journals Circulating Maternal sFLT1 (Soluble fms-Like Tyrosine Kinase-1) Is Sufficient to Impair Spiral Arterial Remodeling in a Preeclampsia Mouse Model

Hypertension ◽  
2021 ◽  
Author(s):  
Rebekka Vogtmann ◽  
Jacqueline Heupel ◽  
Florian Herse ◽  
Mahsa Matin ◽  
Henning Hagmann ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Aortic Wall ◽  
Growth Restriction ◽  
Trophoblast Invasion ◽  
Wall Thickening ◽  
Uterine Natural Killer Cells ◽  
Maternal Contribution ◽  
Maternal Hypertension

One driving factor for developing preeclampsia—a pregnancy disorder, often associated with poor spiral artery (SpA)-remodeling and fetal growth restriction—is the anti-angiogenic sFLT1 (soluble fms-like tyrosine kinase-1), which is found to be highly upregulated in preeclampsia patients. The sFLT1-mediated endothelial dysfunction is a common theory for the manifestation of maternal preeclampsia symptoms. However, the influence of sFLT1 on SpA-remodeling and the link between placental and maternal preeclampsia symptoms is less understood. To dissect the hsFLT1 (human sFLT1) effects on maternal and/or fetoplacental physiology in preeclampsia, sFLT1-transgenic mice with systemic hsFLT1 overexpression from midgestation onwards were used. SpA-remodeling was analyzed on histological and molecular level in placental/mesometrial triangle tissues. Maternal kidney and aorta morphology was investigated, combined with blood pressure measurements via telemetry. hsFLT1 overexpression resulted in maternal hypertension, aortic wall thickening, and elastin breakdown. Furthermore, maternal kidneys showed glomerular endotheliosis, podocyte damage, and proteinuria. preeclampsia symptoms were combined with fetal growth restriction already at the end of the second trimester and SpA-remodeling was strongly impaired as shown by persisted vascular smooth muscle cells. This phenotype was associated with shallow trophoblast invasion, delayed presence of uterine natural killer cells, and altered lymphatic angiogenesis. Overall, this study showed that circulating maternal hsFLT1 is sufficient to induce typical maternal preeclampsia-like symptoms in mice and impair the SpA-remodeling independent from the fetoplacental compartment, revealing new insights into the interaction between the placental and maternal contribution of 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.

Fetal growth retardation and increased placental weight in the spontaneously hypertensive rat

1995 ◽  
Vol 7 (3) ◽  
pp. 639 ◽  
Author(s):  
BM Johnston
Keyword(s):  
Birth Weight ◽  
Fetal Growth ◽  
Growth Retardation ◽  
Spontaneously Hypertensive Rat ◽  
Maternal Blood ◽  
Placental Weight ◽  
Fetal Growth Retardation ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Hypertensive Rat

Epidemiological studies have linked low birth weight and increased placental weight with increased risk of hypertension in adult life. It has been proposed that the cardiovascular changes which lead to hypertension are initiated in utero by processes associated with intrauterine growth retardation. The alternative possibility, that hypertension may result from genetic influences which also determine fetal and placental size, has had less support because birth weight is not determined genetically in humans. However, in the spontaneously hypertensive rat (SHR) essential hypertension is known to be transmitted genetically. Fetal and placental weights were, therefore, measured at Day 20 gestation in SHRs and compared with those in the normotensive Wistar Kyoto (WKY) control strain. Fetal weight (1.93 +/- 0.04 g) was significantly (P < 0.001) reduced in SHRs compared with WKY fetuses (2.23 +/- 0.01 g) but placental weight was heavier (P < 0.001) in SHRs (0.347 +/- 0.005 g) than in WKY rats (0.300 +/- 0.006 g) although litter size was not different. As expected, maternal blood pressure recorded under 1% halothane anaesthesia was higher (126 +/- 2.7 mm Hg) in SHR than WKY rats (100 +/- 2.1 mm Hg; 1 mm Hg = 133 Pa). In addition the concentration of maternal blood glucose in SHR was significantly (P < 0.001) higher (4.8 +/- 0.32 mM v. 3.7 +/- 0.11 mM) and the concentration of plasma insulin was significantly (P < 0.05) lower in SHRs (18.8 +/- 3.0 ng mL-1) than in WKY dams (29.4 +/- 3.1 ng mL-1). Thus, the data support human population studies which show an association between adult hypertension and a reduced fetal:placental weight ratio at birth. However, because hypertension in the SHR is genetically determined, these data suggest that fetal growth retardation and increased placental weight may also be determined genetically.

L3. Trophoblast invasion and spiral artery transformation in pre-eclampsia and fetal growth restriction

2011 ◽  
Vol 1 (3-4) ◽  
pp. 239-240
Author(s):  
Fiona Lyall ◽  
Judith Bulmer ◽  
Robert Pijnenborg ◽  
Helen Simpson ◽  
Stephen Robson
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Growth Restriction ◽  
Trophoblast Invasion ◽  
Spiral Artery

Reduced fetal, placental, and amniotic fluid PTHrP in the growth-restricted spontaneously hypertensive rat

2000 ◽  
Vol 279 (1) ◽  
pp. R31-R38 ◽  
Author(s):  
Mary E. Wlodek ◽  
Kerryn T. Westcott ◽  
Patricia W. M. Ho ◽  
Anne Serruto ◽  
Robert Di Nicolantonio ◽  
...  
Keyword(s):  
Amniotic Fluid ◽  
Spontaneously Hypertensive Rat ◽  
Growth Restriction ◽  
Spontaneously Hypertensive ◽  
Fetal Plasma ◽  
Parathyroid Hormone Related Protein ◽  
Hypertensive Rat ◽  
Ionic Calcium ◽  
Near Term ◽  
Wistar Kyoto

Evidence implicates pivotal roles for parathyroid hormone-related protein (PTHrP) in stimulating cell growth and differentiation, placental calcium transport, and placental vasodilatation. As spontaneously hypertensive rat (SHR) fetuses are growth restricted compared with those of its normotensive control, the Wistar Kyoto (WKY) rat, we examined intrauterine PTHrP and total and ionic calcium concentrations in these rats. Fetal plasma PTHrP concentrations, but not total calcium concentrations, were lower in the SHR compared with WKY ( P< 0.05). SHR placental concentrations of PTHrP were lower than in WKY ( P < 0.03) and failed to show the increase observed in WKY near term ( P < 0.05). PTHrP concentrations in amniotic fluid from SHR were not raised near term and were lower compared with WKY ( P < 0.0005). The increased ionic calcium concentrations in amniotic fluid in the WKY near term ( P < 0.05) were not detected in the SHR. Thus SHR fetal plasma, placental, and amniotic fluid PTHrP concentrations were reduced and associated with fetal growth restriction. We suggest that PTHrP may play a role in the etiology of both growth restriction during pregnancy and hypertension later in life.

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