Treating the Placenta

Reed, Michael D.; Mattison, Donald R.

doi:10.1016/b978-0-12-386007-1.00006-4

Cited by 3 publications

(3 citation statements)

References 47 publications

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“…454 Targeted drug delivery to the placenta itself could also improve therapeutic options for malaria-infected placenta or prevent mother-to-child transmission of HIV. 455 …”

Section: Evolving Technologies For Placental Specific Therapeuticmentioning

confidence: 99%

Placental origins of adverse pregnancy outcomes: potential molecular targets: an Executive Workshop Summary of the Eunice Kennedy Shriver National Institute of Child Health and Human Development

Ilekis

Tsilou

Fisher

et al. 2016

American Journal of Obstetrics and Gynecology

237

167

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Although much progress is being made in understanding the molecular pathways in the placenta involved in the pathophysiology of pregnancy related disorders, a significant gap exists in utilizing this information for developing new drug therapies to improve pregnancy outcome. On March 5–6, 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health sponsored a two day workshop titled Placental Origins of Adverse Pregnancy Outcomes: Potential Molecular Targets to begin to address this gap. Particular emphasis was given in the identification of important molecular pathways that could serve as drug targets and the advantages and disadvantages of targeting these particular pathways. This article is a summary of the proceedings of this workshop. A broad number of topics were covered ranging from basic placental biology to clinical trials. This included research in the basic biology of placentation, such as trophoblast migration and spiral artery remodeling, and trophoblast sensing and response to infectious and non-infectious agents. Research findings in these areas will be critical for formulating developing future treatments and developing therapies for the prevention of a number of pregnancy disorders of placental origin including preeclampsia, fetal growth restriction, and uterine inflammation. Research was also presented summarizing ongoing clinical efforts in the U.S. and in Europe testing novel interventions for preeclampsia and fetal growth restriction, including agents such as oral arginine supplementation, sildenafil, pravastatin, gene therapy using virally-delivered vascular endothelial growth factor, and oxygen supplementation therapy. Strategies were also proposed to improve fetal growth by enhancing nutrient transport to the fetus by modulating their placental transporters, as well as targeting placental mitochondrial dysfunction and oxidative stress to improve placental health. The roles of microRNAs and placental-derived exosomes, as well as messenger RNAs, were also discussed in the context of their use for diagnostics and as drug targets. The workshop discussed the aspect of safety and pharmacokinetic profiles of potential existing and new therapeutics that will need to be determined especially in the context of the unique pharmacokinetic properties of pregnancy, as well as the hurdles and pitfalls of translating research findings into practice. The workshop also discussed novel methods of drug delivery and targeting during pregnancy using macromolecular carriers, such as nanoparticles and biopolymers, to minimize placental drug transfer and hence fetal drug exposure. In closing, a major theme that developed from the workshop was that the scientific community needs to change their thinking of the pregnant women and her fetus as a vulnerable patient population for which drug development should be avoided, but rather thought of as a deprived population in need of more effective therapeutic interventions.

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“…454 Targeted drug delivery to the placenta itself could also improve therapeutic options for malaria-infected placenta or prevent mother-to-child transmission of HIV. 455 …”

Section: Evolving Technologies For Placental Specific Therapeuticmentioning

confidence: 99%

Placental origins of adverse pregnancy outcomes: potential molecular targets: an Executive Workshop Summary of the Eunice Kennedy Shriver National Institute of Child Health and Human Development

Ilekis

Tsilou

Fisher

et al. 2016

American Journal of Obstetrics and Gynecology

237

167

View full text Add to dashboard Cite

show abstract

“…The key events of placental development include differentiation of cytotrophoblasts cells into extravillous trophoblast cells (EVTs) and syncytiotrophoblast, invasion and migration of EVTs, and remodeling of maternal spiral arteries [ 3 , 4 ]. Humans have a hemochorial placenta, where syncytiotrophoblast is in direct contact with maternal blood and is responsible for the exchange of gases, nutrients, metabolites, and wastes between fetal and maternal circulations [ 5 , 6 , 7 ]. During the early stages of placental development, the dynamic turnover of trophoblasts is tightly regulated by complex molecular pathways to ensure normal placental development and function [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA–mRNA Networks in Pregnancy Complications: A Comprehensive Downstream Analysis of Potential Biomarkers

Ali

Hadlich

Abbas

et al. 2021

IJMS

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Pregnancy complications are a major cause of fetal and maternal morbidity and mortality in humans. The majority of pregnancy complications initiate due to abnormal placental development and function. During the last decade, the role of microRNAs (miRNAs) in regulating placental and fetal development has become evident. Dysregulation of miRNAs in the placenta not only affects placental development and function, but these miRNAs can also be exported to both maternal and fetal compartments and affect maternal physiology and fetal growth and development. Due to their differential expression in the placenta and maternal circulation during pregnancy complications, miRNAs can be used as diagnostic biomarkers. However, the differential expression of a miRNA in the placenta may not always be reflected in maternal circulation, which makes it difficult to find a reliable biomarker for placental dysfunction. In this review, we provide an overview of differentially expressed miRNAs in the placenta and/or maternal circulation during preeclampsia (PE) and intrauterine growth restriction (IUGR), which can potentially serve as biomarkers for prediction or diagnosis of pregnancy complications. Using different bioinformatics tools, we also identified potential target genes of miRNAs associated with PE and IUGR, and the role of miRNA-mRNA networks in the regulation of important signaling pathways and biological processes.

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“…Within the first week of treatment, no significant decrease was observed for both doses of WFRE (200 and 400 mg/kg b.w) when compared to the positive control (glibenclamide), p < 0.001. This result indicated that the WFRE may not have a direct action on the main actors involved in blood glucose regulation, unlike glibenclamide, as an oral hypoglycemic drug that directly controls the release of insulin by beta cells [17].…”

Section: Evaluation Of the Antidiabetic Potential Of W Frutescens Root Extractmentioning

confidence: 97%

Glycemic Control Potential of Chemically Characterized Extract from Withania frutescens L. Roots in Severe Diabetes-Induced Mice

et al. 2021

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Diabetes mellitus is a metabolic syndrome that causes impairment, mortality, and many other complications. Insulin and several synthetic medications are currently used in the treatment of diabetes. However, these pharmaceutical drugs are costly, and therefore medicines place priority on alternatives to fight this lethal disease. This modest study aims to investigate the chemical composition, antidiabetic and antihyperglycemic potentials along with subacute toxicity (bodyweight change and biochemical parameters) of hydroethanol extract from Withania frutescens L. roots (WFRE). The chemical analysis was carried out using GC–MS after extract silylation. The chemical analysis identified many potentially active compounds that may determine the antidiabetic results of WFRE. The antidiabetic effect of WFRE was evaluated in mice with severe diabetes using oral administration of doses up to 400 mg/kg for 28 days. The results of the antidiabetic and antihyperglycemic tests indicate that WFRE possesses promising glucose-lowering effects and, as a result, it may serve as an antidiabetic alternative for long-term use. The 4-week treatments with different doses of plant extract did not alter the bodyweight appearance of the diabetic mice nor their biochemical parameters (AST and ALT). The findings obtained indicate that the studied plant extract controlled severe diabetes in mice. Therefore, Withania frutescens L. can serve society as it provides natural agents to control diabetes.

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Treating the Placenta

Cited by 3 publications

References 47 publications

Placental origins of adverse pregnancy outcomes: potential molecular targets: an Executive Workshop Summary of the Eunice Kennedy Shriver National Institute of Child Health and Human Development

Placental origins of adverse pregnancy outcomes: potential molecular targets: an Executive Workshop Summary of the Eunice Kennedy Shriver National Institute of Child Health and Human Development

MicroRNA–mRNA Networks in Pregnancy Complications: A Comprehensive Downstream Analysis of Potential Biomarkers

Glycemic Control Potential of Chemically Characterized Extract from Withania frutescens L. Roots in Severe Diabetes-Induced Mice

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