Hypoxia-Mediated Soluble Fms-Like Tyrosine Kinase 1 Increase Is Not Attenuated in Interleukin 6-Deficient Mice

Appel, Sarah; Turnwald, Eva-Maria; Ankerne, Janina; Wohlfarth, Maria; Appel, Jan; Rother, Eva; Janoschek, Ruth; Alcázar, Miguel A. Alejandre; Schnare, Markus; Meißner, Udo; Dötsch, Jörg

doi:10.1177/1933719114557898

Cited by 4 publications

(3 citation statements)

References 46 publications

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“…qPCR analysis was performed as described before [22,23]. Briefly, total RNA was isolated from the placenta or egWAT samples with a TriReagent ® solution (Sigma, Steinheim, Germany) and 1 µg was converted into cDNA.…”

Section: Qpcr Analysismentioning

confidence: 99%

Effect of Maternal Obesity in Mice on IL-6 Levels and Placental Endothelial Cell Homeostasis

et al. 2020

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Obesity during pregnancy is a known health risk for mother and child. Since obesity is associated with increased inflammatory markers, our objectives were to determine interleukin-6 (IL-6) levels in obese mice and to examine the effect of IL-6 on placental endothelial cells. Placentas, blood, and adipose tissue of C57BL/6N mice, kept on high fat diet before and during pregnancy, were harvested at E15.5. Serum IL-6 levels were determined and endothelial cell markers and IL-6 expression were measured by qRT-PCR and western blot. Immunostaining was used to determine surface and length densities of fetal capillary profiles and placental endothelial cell homeostasis. Human placental vein endothelial cells were cultured and subjected to proliferation, apoptosis, senescence, and tube formation assays after stimulation with hyperIL-6. Placental endothelial cell markers were downregulated and the percentage of senescent endothelial cells was higher in the placental exchange zone of obese dams and placental vascularization was strongly reduced. Additionally, maternal IL-6 serum levels and IL-6 protein levels in adipose tissue were increased. Stimulation with hyperIL-6 provoked a dose dependent increase of senescence in cultured endothelial cells without any effects on proliferation or apoptosis. Diet-induced maternal obesity led to an IUGR phenotype accompanied by increased maternal IL-6 serum levels. In the placenta of obese dams, this may result in a disturbed endothelial cell homeostasis and impaired fetal vasculature. Cell culture experiments confirmed that IL-6 is capable of inducing endothelial cell senescence.

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Section: Qpcr Analysismentioning

confidence: 99%

Effect of Maternal Obesity in Mice on IL-6 Levels and Placental Endothelial Cell Homeostasis

et al. 2020

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“…[135][136][137][138] The soluble fms-like tyrosine kinase-1 (sFlt-1) acts as a soluble receptor and antagonist against VEGF and PlGF. 150,151 Chronic hypoxia, both in early and late gestation, placental oxidative stress and preeclampsia are all associated with an increased ratio of sFlt-1 to PlGF and VEGF in both the trophoblast and the maternal circulation, and administration of sFlt-1 itself has been found to further increase tissue ROS 137,[152][153][154][155][156][157] ( Figs. 1 and 2).…”

Section: Nitric Oxidementioning

confidence: 99%

Preeclampsia link to gestational hypoxia

Tong

Giussani

2019

J Dev Orig Health Dis

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Complications of pregnancy remain key drivers of morbidity and mortality, affecting the health of both the mother and her offspring in the short and long term. There is lack of detailed understanding of the pathways involved in the pathology and pathogenesis of compromised pregnancy, as well as a shortfall of effective prognostic, diagnostic and treatment options. In many complications of pregnancy, such as in preeclampsia, there is an increase in uteroplacental vascular resistance. However, the cause and effect relationship between placental dysfunction and adverse outcomes in the mother and offspring remains uncertain. In this review, we aim to highlight the value of gestational hypoxia-induced complications of pregnancy in elucidating underlying molecular pathways and in assessing candidate therapeutic options for these complex disorders. Chronic maternal hypoxia not only mimics the placental pathology associated with obstetric syndromes like gestational hypertension at morphological, molecular and functional levels, but it also recapitulates key symptoms that occur as maternal and fetal clinical manifestations of these pregnancy disorders. We propose that gestational hypoxia provides a useful model to study the inter-relationship between placental dysfunction and adverse outcomes in the mother and offspring in a wide array of examples of complicated pregnancy, such as in preeclampsia.

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“…Since IL-6 seems to be able to pass the placenta, it might be able to affect fetal brain development [249,250]. It is noteworthy that not all studies found evidence of IL-6 placental-fetal transport [251]. IL-6 is able to trigger fetal inflammatory processes both directly via placental transfer and indirectly via placental inflammation [252].…”

Section: Activation Of the Fetal Immune System Influences Animal Offsmentioning

confidence: 99%

Gestational Factors throughout Fetal Neurodevelopment: The Serotonin Link

Hanswijk

Spoelder

Shan

et al. 2020

IJMS

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Serotonin (5-HT) is a critical player in brain development and neuropsychiatric disorders. Fetal 5-HT levels can be influenced by several gestational factors, such as maternal genotype, diet, stress, medication, and immune activation. In this review, addressing both human and animal studies, we discuss how these gestational factors affect placental and fetal brain 5-HT levels, leading to changes in brain structure and function and behavior. We conclude that gestational factors are able to interact and thereby amplify or counteract each other’s impact on the fetal 5-HT-ergic system. We, therefore, argue that beyond the understanding of how single gestational factors affect 5-HT-ergic brain development and behavior in offspring, it is critical to elucidate the consequences of interacting factors. Moreover, we describe how each gestational factor is able to alter the 5-HT-ergic influence on the thalamocortical- and prefrontal-limbic circuitry and the hypothalamo-pituitary-adrenocortical-axis. These alterations have been associated with risks to develop attention deficit hyperactivity disorder, autism spectrum disorders, depression, and/or anxiety. Consequently, the manipulation of gestational factors may be used to combat pregnancy-related risks for neuropsychiatric disorders.

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Hypoxia-Mediated Soluble Fms-Like Tyrosine Kinase 1 Increase Is Not Attenuated in Interleukin 6-Deficient Mice

Cited by 4 publications

References 46 publications

Effect of Maternal Obesity in Mice on IL-6 Levels and Placental Endothelial Cell Homeostasis

Effect of Maternal Obesity in Mice on IL-6 Levels and Placental Endothelial Cell Homeostasis

Preeclampsia link to gestational hypoxia

Gestational Factors throughout Fetal Neurodevelopment: The Serotonin Link

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