scholarly journals Identifying target sites for placental therapeutics through the comparison of normal term pregnancies and intrauterine growth restricted proteomes

2021 ◽  
Author(s):  
Amanda Bowman ◽  
Heather M Brockway ◽  
Helen Jones
Keyword(s):  
Growth Restriction ◽  
Placental Development ◽  
Maternal Circulation ◽  
Nanoparticle Delivery ◽  
Intrauterine Growth ◽  
In Utero Environment ◽  
Normal Term ◽  
Enhance Efficiency ◽  
And Function ◽  
Development Structure

A variety of pathologies, including intrauterine growth restriction (IUGR), have been linked to placental insufficiencies as important causal factors, however, little has been done to develop therapeutics that may improve placental development, structure and function. The placenta offers the opportunity to manipulate the in-utero environment without directly intervening with the fetus, accessible from the maternal circulation, a vital but temporary organ, the placenta is no longer required after birth. Developing therapeutics must involve multiple aspects of targeting and safety to ensure no off-target impact on the pregnant person or fetus as well as enhance efficiency of delivery. In addition to our studies on nanoparticle delivery to the placenta [1] we are developing targeting strategies to allow peripheral delivery via the maternal circulation. In this study we have performed the isolation of the microvillous membrane from human placental syncytiotrophoblast (the targeting cell) and via proteomic analysis identified potential targeting moieties, we have then compared this to publicly available data from pregnancies complicated by fetal growth restriction to ensure that we do not identify targets which would be reduced in FGR, resulting in less efficient targeting.

scholarly journals Cardiac left heart morphology and function in newborns with intrauterine growth restriction: relevance for long-term assessment

2019 ◽  
Vol 21 (1) ◽  
pp. 62
Author(s):  
Gabriela Corina Zaharie ◽  
Monica Hasmasanu ◽  
Ligia Blaga ◽  
Melinda Matyas ◽  
Daniel Muresan ◽  
...  
Keyword(s):  
Intrauterine Growth Restriction ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Growth Restriction ◽  
Control Group ◽  
Left Heart ◽  
Functional Changes ◽  
Intrauterine Growth ◽  
Cardiac Adaptation ◽  
And Function

Aim: To asses the cardiac morphology and functional changes specific for newborns from intrauterine growth restriction (IUGR) pregnancies.Material and method: A cohort of IUGR infants were evaluated by serial echocardiographies at delivery and at the first and six months follow-ups. IUGR newborn delivery status was compared to that of newborns in the control group according to gestational age (AGA).Results: Left heart measurements were significantly lower in IUGR newborns compared to AGA babies. Left ventricular size increased at follow-up inthe IUGR group (p<0.05). Systolic dysfunction (the myocardial performance index (MPI)> 0.47) was identified in 40% of the neonates in the IUGR group (16/40), respectively 4.76% in the control group. IUGR neonates had a significantly increased proportion of systolic malfunction (p=0.004).Conclusion: IUGR patients had reduced left ventricle dimensions compared to AGA babies. The MPI stands out as a marker of leftheart function in newborns. Systolic dysfunction was a hallmark of the cardiac adaptation in IUGR neonates. 

Influence of Maternal Dietary Intake, Intrauterine Growth Restriction (IUGR), and Estrogen Replacement on Placental Development and Vascularity.

2011 ◽  
Vol 85 (Suppl_1) ◽  
pp. 801-801 ◽  
Author(s):  
Roza D. Yunusova ◽  
Raymond P. Aitken ◽  
John S. Milne ◽  
Pawel Piotr Borowicz ◽  
Lawrence P. Reynolds ◽  
...  
Keyword(s):  
Dietary Intake ◽  
Intrauterine Growth Restriction ◽  
Growth Restriction ◽  
Estrogen Replacement ◽  
Placental Development ◽  
Intrauterine Growth ◽  
Maternal Dietary Intake

scholarly journals Placental Expressions of CDKN1C and KCNQ1OT1 in Monozygotic Twins with Selective Intrauterine Growth Restriction

2017 ◽  
Vol 20 (5) ◽  
pp. 389-394 ◽  
Author(s):  
Chenyu Gou ◽  
Xiangzhen Liu ◽  
Xiaomei Shi ◽  
Hanjing Chai ◽  
Zhi-ming He ◽  
...  
Keyword(s):  
Protein Expression ◽  
Mrna Expression ◽  
Intrauterine Growth Restriction ◽  
Monozygotic Twins ◽  
Growth Restriction ◽  
Control Group ◽  
Placental Development ◽  
Intrauterine Growth ◽  
Immunohistochemical Assay ◽  
Mrna Ratio

CDKN1C and KCNQ1OT1 are imprinted genes that might be potential regulators of placental development. This study investigated placental expressions of CDKN1C and KCNQ1OT1 in monozygotic twins with and without selective intrauterine growth restriction (sIUGR). Seventeen sIUGR and fifteen normal monozygotic(MZ) twin pairs were examined. Placental mRNA expressions of CDKN1C and KCNQ1OT1 were detected by real-time fluorescent quantitative PCR. CDKN1C protein expression was detected by immunohistochemical assay and Western-blotting. In the sIUGR group, smaller fetuses had a smaller share of the placenta, and CDKN1C protein expression was significantly increased while KCNQ1OT1 mRNA expression was significantly decreased. The CDKN1C/KCNQ1OT1 mRNA ratio was lower in the larger fetus than in the smaller fetus (p < .05). In the control group, CDKN1C protein expression showed no difference between larger and smaller fetuses, while KCNQ1OT1 mRNA expression was significantly lower in the larger fetus, and the CDKN1C/KCNQ1OT1 mRNA ratio was higher in the larger fetus than in the smaller fetus (p < .05). Our findings showed that pathogenesis of sIUGR may be related to the co-effect of the up-regulated protein expression of CDKN1C and down-regulated mRNA expression of KCNQ1OT1 in the placenta.

Characterization of fetal monocytes in preeclampsia and fetal growth restriction

2019 ◽  
Vol 47 (4) ◽  
pp. 434-438 ◽  
Author(s):  
Thushari I. Alahakoon ◽  
Heather Medbury ◽  
Helen Williams ◽  
Nicole Fewings ◽  
Xin M. Wang ◽  
...  
Keyword(s):  
Cord Blood ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Normal Pregnancy ◽  
Growth Restriction ◽  
Clinical Group ◽  
Monocyte Subset ◽  
Maternal Circulation ◽  
Cross Sectional ◽  
And Function

AbstractBackgroundThere is little available data on fetal monocyte phenotype and function. A prospective cross-sectional pilot study was conducted to describe the cord blood monocyte subset phenotype in preeclampsia (PE) and fetal growth restriction (FGR) as compared to normal pregnancy and maternal circulation.MethodsMaternal and cord blood samples from 27 pregnancies were collected at delivery from normal pregnancy, PE, FGR and PE+FGR. The distribution of fetal monocyte subtypes was characterized by CD14 and CD16 expression using flow cytometry and compared for each clinical group using a classification of classical, intermediate and non-classical subsets.ResultsThe intermediate monocytes were the dominant monocyte subset in the cord blood of PE and PE+FGR with an increase in the combined inflammatory monocyte subsets intermediate and non-classical in PE compared to normal pregnancy. The non-classical monocyte subset proportion was elevated in all pathological groups PE, FGR and PE+FGR. A significant reduction in the non-classical monocyte subset was observed in the cord blood of the normal pregnancy group as compared to the maternal circulation.ConclusionThis study describes for the first time in the fetal circulation, dominant monocyte intermediate subsets and increased inflammatory subsets in PE as well as increased non-classical subsets in PE and FGR compared to normal pregnancy.

scholarly journals Maternal growth factor regulation of human placental development and fetal growth

2010 ◽  
Vol 207 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Karen Forbes ◽  
Melissa Westwood
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Fetal Growth ◽  
Mechanism Of Action ◽  
Normal Development ◽  
Receptor Interaction ◽  
Placental Development ◽  
Maternal Circulation ◽  
Successful Pregnancy ◽  
And Function

Normal development and function of the placenta is critical to achieving a successful pregnancy, as normal fetal growth depends directly on the transfer of nutrients from mother to fetus via this organ. Recently, it has become apparent from both animal and human studies that growth factors within the maternal circulation, for example the IGFs, are important regulators of placental development and function. Although these factors act via distinct receptors to exert their effects, the downstream molecules activated upon ligand/receptor interaction are common to many growth factors. The expression of numerous signaling molecules is altered in the placentas from pregnancies affected by the fetal growth complications, fetal growth restriction, and macrosomia. Thus, targeting these molecules may lead to more effective treatments for complications of pregnancy associated with altered placental development. Here, we review the maternal growth factors required for placental development and discuss their mechanism of action.

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