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Stress and uteroplacental

Hannah L Morgan, Elaine Butler, Shona Ritchie, Florian Herse, Ralf Dechend, Elisabeth Beattie, Martin W McBride, Delyth Graham
Hypertensive disorders of pregnancy are the second leading cause of maternal deaths worldwide. Superimposed preeclampsia is an increasingly common problem and often associated with impaired placental perfusion. Understanding the underlying mechanisms and developing treatment options are crucial. The pregnant stroke-prone spontaneously hypertensive rat has impaired uteroplacental blood flow and abnormal uterine artery remodeling. We used Ang II (angiotensin II) infusion in pregnant stroke-prone spontaneously hypertensive rats to mimic the increased cardiovascular stress associated with superimposed preeclampsia and examine the impact on the maternal cardiovascular system and fetal development...
May 29, 2018: Hypertension
Nga Ling Ko, Liam John, Aaron Gelinne, Maurizio Mandala, George Osol
Although expansive remodeling of the maternal uterine circulation during pregnancy is essential for maintaining uteroplacental perfusion and normal fetal growth, the underlying physiological mechanisms are not well understood. Using a rat model, surgical approaches were used to alter uterine hemodynamics and wall shear stress (WSS) in order to evaluate the effects of WSS and venoarterial communication (e.g. transfer of placentally derived growth signals from post-placental veins to pre-placental arteries) on gestational uterine vascular remodeling...
May 18, 2018: American Journal of Physiology. Heart and Circulatory Physiology
Charles A Ducsay, Ravi Goyal, William J Pearce, Sean Wilson, Xiang-Qun Hu, Lubo Zhang
Hypoxia is one of the most common and severe challenges to the maintenance of homeostasis. Oxygen sensing is a property of all tissues, and the response to hypoxia is multidimensional involving complicated intracellular networks concerned with the transduction of hypoxia-induced responses. Of all the stresses to which the fetus and newborn infant are subjected, perhaps the most important and clinically relevant is that of hypoxia. Hypoxia during gestation impacts both the mother and fetal development through interactions with an individual's genetic traits acquired over multiple generations by natural selection and changes in gene expression patterns by altering the epigenetic code...
July 1, 2018: Physiological Reviews
Laura M Reyes, Margie H Davenport
The Developmental Origins of Health and Disease suggest the in utero environment programs offspring obesity and cardiovascular disease. Therefore, there is a need to implement safe therapeutic interventions that do not involve the intake of medications or biological products during pregnancy that can improve maternal and fetal health. Prenatal exercise is established to promote maternal and fetal health. It is generally recommended that women accumulate at least 150 min per week of moderate-intensity exercise...
June 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Aamod Nawathe, Anna L David
Foetal growth restriction (FGR) and associated placental pathologies such as pre-eclampsia and stillbirth arise in early pregnancy when inadequate remodelling of maternal spiral arteries leads to persistent high-resistance low-flow uteroplacental circulation. Current interventions concentrate on targeting the placental ischaemia-reperfusion injury and oxidative stress associated with an imbalance in angiogenic/anti-angiogenic factors. Recent meta-analyses confirm that aspirin modestly reduces the risk for small-for-gestational-age pregnancy in high-risk women...
May 2018: Best Practice & Research. Clinical Obstetrics & Gynaecology
Graham J Burton, Eric Jauniaux
Placental-related fetal growth restriction arises primarily due to deficient remodeling of the uterine spiral arteries supplying the placenta during early pregnancy. The resultant malperfusion induces cell stress within the placental tissues, leading to selective suppression of protein synthesis and reduced cell proliferation. These effects are compounded in more severe cases by increased infarction and fibrin deposition. Consequently, there is a reduction in villous volume and surface area for maternal-fetal exchange...
February 2018: American Journal of Obstetrics and Gynecology
Katie M Groom, Anna L David
Fetal growth restriction and related placental pathologies such as preeclampsia, stillbirth, and placental abruption are believed to arise in early pregnancy when inadequate remodeling of the maternal spiral arteries leads to persistent high-resistance and low-flow uteroplacental circulation. The consequent placental ischaemia, reperfusion injury, and oxidative stress are associated with an imbalance in angiogenic/antiangiogenic factors. Many interventions have centered on the prevention and/or treatment of preeclampsia with results pertaining to fetal growth restriction and small-for-gestational-age pregnancy often included as secondary outcomes because of the common pathophysiology...
February 2018: American Journal of Obstetrics and Gynecology
Alberto Borges Peixoto, Liliam Cristine Rolo, Luciano Marcondes Machado Nardozza, Edward Araujo Júnior
Pregnancy is known to induce rapid, progressive, and substantial changes to the cardiovascular system, ultimately facilitating successful pregnancy outcomes. Women who develop hypertensive disorders during pregnancy are considered to have "failed" the cardiovascular stress test of pregnancy and likely represent a subpopulation with inadequate cardiovascular accommodation. Preeclampsia is a serious complication with a myriad of manifestations in both mother and offspring. This pregnancy syndrome is a polygenic disease and has now been linked to a greater incidence of cardiovascular disease...
2018: Methods in Molecular Biology
Natalie Cureton, Iana Korotkova, Bernadette Baker, Susan Greenwood, Mark Wareing, Venkata R Kotamraju, Tambet Teesalu, Francesco Cellesi, Nicola Tirelli, Erkki Ruoslahti, John D Aplin, Lynda K Harris
Fetal growth restriction (FGR) in pregnancy is commonly caused by impaired uteroplacental blood flow. Vasodilators enhance uteroplacental perfusion and fetal growth in humans and animal models; however, detrimental maternal and fetal side effects have been reported. We hypothesised that targeted uteroplacental delivery of a vasodilator would enhance drug efficacy and reduce the risks associated with drug administration in pregnancy. Phage screening identified novel peptides that selectively accumulated in the uteroplacental vasculature of pregnant mice...
2017: Theranostics
Horacio Figueroa, Cristobal Alvarado, Jorge Cifuentes, Mauricio Lozano, Jocelyn Rocco, Claudia Cabezas, Sebastian E Illanes, Elisenda Eixarch, Edgar Hernández-Andrade, Eduard Gratacós, Carlos E Irarrazabal
OBJECTIVE: This study investigated the role of oxidative damage and nitric oxide (NO) synthases in the fetal heart using a model of intrauterine growth restriction induced by uteroplacental circulation restriction (UCR). METHODS: New Zealand white rabbits kept under 12-h light cycles, with food and water provided ad libitum, were subjected at day 25 of pregnancy to 40-50% uteroplacental artery ligation. We analyzed the gene expression of enzymes linked to nitric oxide synthesis (iNOS, eNOS, HO-1, and ARG-2), hypoxia inducible factor 1 alpha (HIF-1α), and the state of oxidative stress (protein carbonyl levels) in fetal heart homogenates...
May 2017: Prenatal Diagnosis
S R Giannubilo, A Pasculli, E Tidu, A Biagini, V Boscarato, A Ciavattini
OBJECTIVE: A proper maternal cardiovascular adaptation to the pregnancy plays a key role for promoting an adequate uteroplacental perfusion, for ensuring normal fetal development and for preventing gestational hypertensive complications such as preeclampsia. This study aims to evaluate hemodynamic measurements obtained by noninvasive methods among preclamptic women with and without fetal growth restriction (FGR) and the relationship with plasma levels of natriuretic peptides. STUDY DESIGN: The study compared 98 pregnant women (n=48 with preeclampsia; n=50 normotensive pregnant women) and 50 nonpregnant normotensive control subjects undergoing anultrasonic cardiac output monitor (USCOM) and plasma assessment of atrial N-terminal pro B-type natriuretic peptide (NT-proBNP)...
May 2017: Journal of Perinatology: Official Journal of the California Perinatal Association
Christian J Roth, Eva Haeussner, Tanja Ruebelmann, Franz V Koch, Christoph Schmitz, Hans-Georg Frank, Wolfgang A Wall
Ischemic placental disease is a concept that links intrauterine growth retardation (IUGR) and preeclampsia (PE) back to insufficient remodeling of uterine spiral arteries. The rheological consequences of insufficient remodeling of uterine spiral arteries were hypothesized to mediate the considerably later manifestation of obstetric disease. However, the micro-rheology in the intervillous space (IVS) cannot be examined clinically and rheological animal models of the human IVS do not exist. Thus, an in silico approach was implemented to provide in vivo inaccessible data...
January 19, 2017: Scientific Reports
Jean N Cheong, James S M Cuffe, Andrew J Jefferies, Kristina Anevska, Karen M Moritz, Mary E Wlodek
Low birth weight increases adult metabolic disease risk in both the first (F1) and second (F2) generation. Physiological stress during pregnancy in F1 females that were born small induces F2 fetal growth restriction, but the long-term metabolic health of these F2 offspring is unknown. Uteroplacental insufficiency (restricted) or sham (control) surgery was performed in F0 rats. F1 females (control, restricted) were allocated to unstressed or stressed pregnancies. F2 offspring exposed to maternal stress in utero had reduced birth weight...
November 2016: Endocrinology
Shi-Bin Cheng, Surendra Sharma
Pregnancy represents a period of physiological stress, and although this stress is experienced for a very modest portion of life, it is now recognized as a window to women's future health, often by unmasking predispositions to conditions that only become symptomatic later in life. In normal pregnancy, the mother experiences mild metabolic syndrome-like condition through week 20 of gestation. A pronounced phenotype of metabolic syndrome may program pregnancy complications such as preeclampsia. Preeclampsia is a serious complication with a myriad of manifestations for mother and offspring...
November 2016: Seminars in Immunopathology
O R Vaughan, K L Davies, J W Ward, M J de Blasio, A L Fowden
KEY POINTS: Fetal nutrient supply is dependent, in part, upon the transport capacity and metabolism of the placenta. The stress hormone, cortisol, alters metabolism in the adult and fetus but it is not known whether cortisol in the pregnant mother affects metabolism of the placenta. In this study, when cortisol concentrations were raised in pregnant sheep by infusion, proportionately more of the glucose taken up by the uterus was consumed by the uteroplacental tissues while less was transferred to the fetus, despite an increased placental glucose transport capacity...
November 1, 2016: Journal of Physiology
Larry G Thaete, Saira Khan, Mark G Neerhof
Fetal growth restriction (FGR) is a common cause of perinatal morbidity and mortality. Suboptimal uteroplacental perfusion is the most commonly identified cause of FGR, and ischemic lesions are often observed in placentas from pregnancies complicated by FGR. Ischemia followed by reperfusion is a strong stimulus to the production of the vasoconstrictor endothelin 1 (ET-1) which has been implicated in several models of FGR. We sought to investigate oxidative stress and placental morphology in a rat model of ischemia-reperfusion (I/R)-induced FGR and to evaluate the role of ET-1 in the observed pathology...
November 2016: Reproductive Sciences
Horacio Figueroa, Jorge Cifuentes, Mauricio Lozano, Cristobal Alvarado, Claudia Cabezas, Elisenda Eixarch, Ellio Fernández, Luis Contreras, Sebastian E Illanes, Edgar Hernández-Andrade, Eduard Gratacós, Carlos E Irarrazabal
OBJECTIVE: This work aimed to study the effect of uteroplacental circulation restriction on endothelial kidney damage in a fetal rabbit model. METHODS: New Zealand rabbits were subjected to 40% to 50% of uteroplacental artery ligation at day 25 of pregnancy. After 5 days, surviving fetuses were harvested by cesarean section. The gene and protein expressions of selected enzymes associated with nitric oxide production and oxidative stress were analyzed in fetal kidney homogenates...
July 2016: Prenatal Diagnosis
Victoria H J Roberts, Jamie O Lo, Jennifer A Salati, Katherine S Lewandowski, Jonathan R Lindner, Terry K Morgan, Antonio E Frias
BACKGROUND: The uteroplacental vascular supply is a critical determinant of placental function and fetal growth. Current methods for the in vivo assessment of placental blood flow are limited. OBJECTIVE: We demonstrate the feasibility of the use of contrast-enhanced ultrasound imaging to visualize and quantify perfusion kinetics in the intervillous space of the primate placenta. STUDY DESIGN: Pregnant Japanese macaques were studied at mid second trimester and in the early third trimester...
March 2016: American Journal of Obstetrics and Gynecology
Heather Y Small, Hannah Morgan, Elisabeth Beattie, Sinead Griffin, Marie Indahl, Christian Delles, Delyth Graham
INTRODUCTION: The stroke prone spontaneously hypertensive rat (SHRSP) is an established model of human cardiovascular risk. We sought to characterise the uteroplacental vascular response to pregnancy in this model and determine whether this is affected by the pre-existing maternal hypertension. METHODS: Doppler ultrasound and myography were utilised to assess uterine artery functional and structural changes pre-pregnancy and at gestational day 18 in SHRSP (untreated and nifedipine treated) and in the normotensive Wistar-Kyoto (WKY) rat...
January 2016: Placenta
Xiaoyu Tian, Suling Ma, Yaqi Wang, Lianguo Hou, Yun Shi, Min Yao, Xiaoning Wang, Huifeng Zhang, Lingling Jiang
We evaluated the effects of administration of 1,25-dihydroxyvitamin D (1,25(OH)2D) during pregnancy on relieving adverse outcomes of preeclampsia and the pathologic and biochemical changes in reduction in uteroplacental perfusion (RUPP) model of rats. On day 1, 7, and 14 of pregnancy, rats in pregnant RUPP plus 1,25(OH)2D (RUPP+VD) group (n = 15) received 120 ng/100 g body weight/week of 1,25(OH)2D by subcutaneous injection, while rats in normal pregnant (n = 12) and the RUPP group (n = 14) received 1,25(OH)2D vehicle (saline solution)...
February 2016: DNA and Cell Biology
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