Novel Regulators of Hemodynamics in the Pregnant Uterus

Clark, Nicole C.; Pru, Cindy A.; Pru, James K.

doi:10.1016/bs.pmbts.2016.12.007

Cited by 9 publications

(8 citation statements)

References 175 publications

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“…Renin-angiotensin signaling regulates systemic blood volume and maternal-fetal blood flow during pregnancy, and has multiple effects in vascular remodeling and reactivity. During pregnancy, estrogen up-regulates renin and angiotensinogen levels leading to increased activity for both systemic and local uteroplacental renin-angiotensin system (RAS) ( Anton and Brosnihan, 2008 ; Clark et al, 2017 ). RAS activity is significantly higher in pre-eclamptic placentas ( Singh et al, 2004 ), which is associated with hypertension, reduced maternal-fetal blood flow, limited nutrient and oxygen supply to the fetus, as well as intrauterine growth restriction ( Clark et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

“…During pregnancy, estrogen up-regulates renin and angiotensinogen levels leading to increased activity for both systemic and local uteroplacental renin-angiotensin system (RAS) ( Anton and Brosnihan, 2008 ; Clark et al, 2017 ). RAS activity is significantly higher in pre-eclamptic placentas ( Singh et al, 2004 ), which is associated with hypertension, reduced maternal-fetal blood flow, limited nutrient and oxygen supply to the fetus, as well as intrauterine growth restriction ( Clark et al, 2017 ). Furthermore, angiotensin II can directly decrease amino acid transporter activities in human placenta ( Shibata et al, 2006 ).…”

Section: Discussionmentioning

confidence: 99%

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Intrauterine Inflammation Alters the Transcriptome and Metabolome in Placenta

et al. 2020

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Placental insufficiency is implicated in spontaneous preterm birth (SPTB) associated with intrauterine inflammation. We hypothesized that intrauterine inflammation leads to deficits in the capacity of the placenta to maintain bioenergetic and metabolic stability during pregnancy ultimately resulting in SPTB. Using a mouse model of intrauterine inflammation that leads to preterm delivery, we performed RNA-seq and metabolomics studies to assess how intrauterine inflammation alters gene expression and/or modulates metabolite production and abundance in the placenta. 1871 differentially expressed genes were identified in LPS-exposed placenta. Among them, 1,149 and 722 transcripts were increased and decreased, respectively. Ingenuity pathway analysis showed alterations in genes and canonical pathways critical for regulating oxidative stress, mitochondrial function, metabolisms of glucose and lipids, and vascular reactivity in LPS-exposed placenta. Many upstream regulators and master regulators important for nutrient-sensing and mitochondrial function were also altered in inflammation exposed placentae, including STAT1, HIF1α, mTOR, AMPK, and PPARα. Comprehensive quantification of metabolites demonstrated significant alterations in the glucose utilization, metabolisms of branched-chain amino acids, lipids, purine and pyrimidine, as well as carbon flow in TCA cycle in LPS-exposed placenta compared to control placenta. The transcriptome and metabolome were also integrated to assess the interactions of altered genes and metabolites. Collectively, significant and biologically relevant alterations in the placenta transcriptome and metabolome were identified in placentae exposed to intrauterine inflammation. Altered mitochondrial function and energy metabolism may underline the mechanisms of inflammationinduced placental dysfunction.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Intrauterine Inflammation Alters the Transcriptome and Metabolome in Placenta

et al. 2020

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“…Sex steroids orchestrate most of the reproductive events in mammals. In particular, progesterone and estradiol are in extremely high concentrations in maternal circulation and have an important role to accomplish proper maternal vascular adaptations during early pregnancy (Clark et al 2017). Although it has been reported that progesterone and estradiol modulate uterine arteries remodeling and placental angiogenesis (Chen et al 2012, Maliqueo et al 2016, their specific role in vascular remodeling at the maternal-fetal interface remains controversial.…”

Section: R63mentioning

confidence: 99%

Novel role for lysophosphatidic acid in vascular remodeling at the maternal–fetal interface

et al. 2020

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Lysophosphatidic acid (LPA) belongs to the group of phosphorylated lipids reported as crucial mediators in the physiology of reproduction. LPA binds to G-protein-coupled receptors and regulates a wide range of female reproductive functions. This bioactive lipid has also been implicated in vascular functions during physiological and pathological conditions. In this regard, the establishment of a successful pregnancy requires proper coordination of vascular processes and remodeling of maternal blood vessels during early gestation. During this process, first trimester cytotrophoblast changes from an invasive to an endovascular phenotype and transforms uterine spiral arteries which are the nutrient supply for placenta and fetus. Here we present an overview of LPA participation in vascular remodeling and highlight the importance of LPA–LPA3 signaling during early gestation at the maternal–fetal interface.

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“…ADM is a negative regulator of MUC1 gene expression in trophoblastic cells. 88 However, due to the hypoxia caused by vascular alterations in the placenta, MUC1 overexpression has been described. 89 The role of ADM in early gestation has also been studied, suggesting that it regulates the optimal expression of MUC1 to promote implantation and facilitate TB invasion.…”

Section: Diabetes During the Third Trimester: From Subtle To Catastro...mentioning

confidence: 99%

The Placental Role in Gestational Diabetes Mellitus: A Molecular Perspective

Calvo,

Parra,

Santeliz

et al. 2024

touchREVIEWS in Endocrinology

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During pregnancy, women undergo several metabolic changes to guarantee an adequate supply of glucose to the foetus. These metabolic modifications develop what is known as physiological insulin resistance. When this process is altered, however, gestational diabetes mellitus (GDM) occurs. GDM is a multifactorial disease, and genetic and environmental factors play a crucial role in its aetiopathogenesis. GDM has been linked to both macroscopic and molecular alterations in placental tissues that affect placental physiology. This review summarizes the role of the placenta in the development of GDM from a molecular perspective, including hormonal and pro-inflammatory changes. Inflammation and hormonal imbalance, the characteristics dominating the GDM microenvironment, are responsible for placental changes in size and vascularity, leading to dysregulation in maternal and foetal circulations and to complications in the newborn. In conclusion, since the hormonal mechanisms operating in GDM have not been fully elucidated, more research should be done to improve the quality of life of patients with GDM and their future children.

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Novel Regulators of Hemodynamics in the Pregnant Uterus

Cited by 9 publications

References 175 publications

Intrauterine Inflammation Alters the Transcriptome and Metabolome in Placenta

Intrauterine Inflammation Alters the Transcriptome and Metabolome in Placenta

Novel role for lysophosphatidic acid in vascular remodeling at the maternal–fetal interface

The Placental Role in Gestational Diabetes Mellitus: A Molecular Perspective

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