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Hypoxia Fetal Changes

Maria Violeta Novac, Mihaela Niculescu, Maria Magdalena Manolea, Anda Lorena Dijmărescu, Dominic Gabriel Iliescu, Marius Bogdan Novac, Luciana Teodora Rotaru, Manuela Florica Stoenescu, Maria Carmen Tabacu, Ştefania Tudorache, Cristina Jana Busuioc, Ioana Andreea Gheonea
OBJECTIVE: Placental lesions and placental ischemia are typical elements of intrauterine growth restriction (IUGR). The aim of this study is to analyze histological and immunohistochemical (IHC) changes in the placentas of IUGR fetuses. MATERIALS AND METHODS: In this prospective study, 126 placentas from small for gestational age (SGA) pregnancies (newborns with birth weight <10th percentile) that formed the study group and 31 placentas from pregnancies without SGA representing control group, were included...
2018: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
Bryony V Natale, Prutha Mehta, Priscilla Vu, Christina Schweitzer, Katarina Gustin, Ramie Kotadia, David R C Natale
This study characterized the effect of the reduced utero-placental perfusion pressure (RUPP) model of placental insufficiency on placental morphology and trophoblast differentiation at mid-late gestation (E14.5). Altered trophoblast proliferation, reduced syncytiotrophoblast gene expression, increased numbers of sinusoidal trophoblast giant cells, decreased Vegfa and decreased pericyte presence in the labyrinth were observed in addition to changes in maternal blood spaces, the fetal capillary network and reduced fetal weight...
November 21, 2018: Scientific Reports
Ibrahim Bildirici, W Timothy Schaiff, Baosheng Chen, Mayumi Morizane, Soo-Young Oh, Matthew O'Brien, Christina Sonnenberg-Hirche, Tianjiao Chu, Yaacov Barak, D Michael Nelson, Yoel Sadovsky
Trophoblast hypoxia and injury, key components of placental dysfunction, are associated with fetal growth restriction and other complications of pregnancy. Accumulation of lipid droplets has been found in hypoxic nonplacental cells. Unique to pregnancy, lipid accumulation in the placenta might perturb lipid transport to the fetus. We tested the hypothesis that hypoxia leads to accumulation of lipid droplets in human trophoblasts and that trophoblastic PLIN proteins play a key role in this process. We found that hypoxia promotes the accumulation of lipid droplets in primary human trophoblasts...
December 1, 2018: Endocrinology
Wentao Yu, Wei Gao, Dan Rong, Zhixian Wu, Raouf A Khalil
Preeclampsia is a pregnancy-related disorder characterized by hypertension and often fetal intrauterine growth restriction, but the underlying mechanisms are unclear. Defective placentation and apoptosis of invasive cytotrophoblasts cause inadequate remodeling of spiral arteries, placental ischemia and reduced uterine perfusion pressure (RUPP). RUPP causes imbalance between the anti-angiogenic factors soluble fms-like tyrosine kinase-1 and soluble endoglin and the pro-angiogenic vascular endothelial growth factor and placental growth factor, and stimulates the release of proinflammatory cytokines, hypoxia-inducible factor, reactive oxygen species, and angiotensin AT1 receptor agonistic autoantibodies...
October 19, 2018: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
Jeremy A Sandgren, Guorui Deng, Danny W Linggonegoro, Sabrina M Scroggins, Katherine J Perschbacher, Anand R Nair, Taryn E Nishimura, Shao Yang Zhang, Larry N Agbor, Jing Wu, Henry L Keen, Meghan C Naber, Nicole A Pearson, Kathy A Zimmerman, Robert M Weiss, Noelle C Bowdler, Yuriy M Usachev, Donna A Santillan, Matthew J Potthoff, Gary L Pierce, Katherine N Gibson-Corley, Curt D Sigmund, Mark K Santillan, Justin L Grobe
Copeptin, a marker of arginine vasopressin (AVP) secretion, is elevated throughout human pregnancies complicated by preeclampsia (PE), and AVP infusion throughout gestation is sufficient to induce the major phenotypes of PE in mice. Thus, we hypothesized a role for AVP in the pathogenesis of PE. AVP infusion into pregnant C57BL/6J mice resulted in hypertension, renal glomerular endotheliosis, intrauterine growth restriction, decreased placental growth factor (PGF), altered placental morphology, placental oxidative stress, and placental gene expression consistent with human PE...
October 4, 2018: JCI Insight
Camila Infantosi Vannucchi, Liege Cristina Garcia Silva, Silvana Maria Unruh, Cristina Fátima Lúcio, Gisele Almeida Lima Veiga
Neonatal immediate adaptation to extrauterine life depends mainly on adequate lung function, which is under the influence of previous fetal maturation and obstetrical condition, both acting to stimulate the efficient liquid removal from the pulmonary parenchyma during the immediate transition period. The objective of the present study is to identify chest radiographic changes of neonatal calves born under the influence of different duration of calving and obstetric assistance and correlate with clinical analysis and blood acid-base balance...
2018: PloS One
Adrian C Eddy, Heather Chapman, Eric M George
Preeclampsia is a common obstetrical complication, hallmarked by new-onset hypertension. Believed to result from placental insufficiency and chronic placental ischemia, the symptoms of preeclampsia are caused by release of pathogenic factors from the placenta itself, although the mechanisms of their regulation are in many cases unknown. One potential mechanism is through changes in placental epigenetic chromatin modifications, particularly histone acetylation and DNA methylation. Here, we determined the effects of chronic ischemia on global epigenetic modifications in the rodent placenta in vivo and acute hypoxia in BeWo placental trophoblast cells in vitro...
September 17, 2018: Reproductive Sciences
Long Jin, Silu Hu, Teng Tu, Zhiqing Huang, Qianzi Tang, Jideng Ma, Xun Wang, Xuewei Li, Xuan Zhou, Surong Shuai, Mingzhou Li
Lung tissue plays an important role in the respiratory system of mammals after birth. Early lung development includes six key stages, of which the saccular stage spans the pre- and neonatal periods and prepares the distal lung for alveolarization and gas-exchange. However, little is known about the changes in gene expression between fetal and neonatal lungs. In this study, we performed transcriptomic analysis of messenger RNA (mRNA) and long noncoding RNA (lncRNA) expressed in the lung tissue of fetal and neonatal piglets...
September 5, 2018: Genes
Tania Jacobo-Estrada, Mariana Cardenas-Gonzalez, Mitzi Paola Santoyo-Sánchez, Frank Thevenod, Olivier Barbier
During embryonic development, some hypoxia occurs due to incipient vascularization. Under hypoxic conditions, gene expression is mainly controlled by hypoxia-inducible factor 1 (HIF-1). The activity of this transcription factor can be altered by the exposure to a variety of compounds; among them is cadmium (Cd), a nephrotoxic heavy metal capable of crossing the placenta and reaching fetal kidneys. The goal of the study was to determine Cd effects on HIF-1 on embryonic kidneys. Pregnant Wistar rats were exposed to a mist of isotonic saline solution or CdCl₂ (DDel = 1...
September 3, 2018: Toxics
Dana S Hutchinson, Nadine Brew, Teresa Vu, Jon Merlin, Nadia Hale, David William Walker, Flora Y Wong
Preterm infants frequently suffer cardiovascular compromise, with hypotension and/or low systemic blood flow, leading to tissue hypoxia-ischemia (HI). Many preterm infants respond inadequately to inotropic treatments using adrenergic agonists such as dobutamine or dopamine. This may be due to altered cardiac adrenoceptor expression due to tissue HI, or prolonged exposure to adrenergic agonists. We assessed the effects of severe HI with and without dobutamine/dopamine treatment on cardiac adrenoceptor expression in preterm fetal sheep...
August 23, 2018: Journal of Applied Physiology
Yao-Lung Chang, An-Shine Chao, Hsiu-Huei Peng, Shuenn-Dyh Chang, Kuan-Ju Chen, Po-Jen Cheng, Tzu-Hao Wang
BACKGROUND: We previously reported that fetal plasma erythropoietin (EPO) concentrations are significantly increased in growth-restricted fetuses with abnormal umbilical artery (UA) Doppler. During hypoxia in an ovine model, the primary site of fetal EPO synthesis was switched from the kidneys to the placenta. Therefore, we designed this study to evaluate human placental EPO gene expression and the correlation to fetal serum EPO concentration in growth-restricted fetuses in a monochorionic (MC) twin model...
August 8, 2018: BMC Pregnancy and Childbirth
Bethany R Mordhorst, Stephanie L Murphy, Martin Schauflinger, Shirley Rojas Salazar, Tieming Ji, Susanta K Behura, Kevin D Wells, Jonathan A Green, Randall S Prather
The Warburg effect is characterized by decreased mitochondrial oxidative phosphorylation and increased glycolytic flux in adequate oxygen. The preimplantation embryo has been described to have characteristics of the Warburg effect, including similar changes in gene expression and mitochondria, which are more rudimentary in appearance. We hypothesized hypoxia would facilitate anaerobic glycolysis in fibroblasts thereby promoting gene expression and media metabolite production reflecting the Warburg effect hallmarks in early embryos...
August 2018: Cellular Reprogramming
Chih-Chieh Yang, Pei-Ling Tang, Po-Yen Liu, Wei-Chun Huang, Ying-Yao Chen, Hsiao-Ping Wang, Jenn-Tzong Chang, Li-Te Lin
The utero-placental ischemia induced by pregnancy-induced hypertension (PIH) could lead to fetal hypoxia and proinflammatory cytokine release, which are associated with the development of neonatal necrotizing enterocolitis (NEC). However, a few studies have investigated the relationship between PIH and neonatal NEC and have produced controversial results. Therefore, we attempted to assess the relationship between PIH and the subsequent neonatal NEC risk and identify predictive risk factors.Patients with newly diagnosed PIH were recruited from the Taiwan National Health Insurance Research Database (NHIRD)...
August 2018: Medicine (Baltimore)
David W Sant, Vladimir Camarena, Sushmita Mustafi, Yiwen Li, Zachary Wilkes, Derek Van Booven, Rong Wen, Gaofeng Wang
Purpose: To investigate the impact of ascorbate, via DNA hydroxymethylation, on VEGF expression in retinal pigment epithelial (RPE) cells. Methods: Dot-blot and hydroxymethylated DNA immunoprecipitation sequencing were applied to evaluate the impact of ascorbate on DNA hydroxymethylation in ARPE-19 cells. RNA sequencing (RNA-seq) was carried out to analyze the transcriptome. Quantitative RT-PCR and ELISA were conducted to examine the transcription and secretion of VEGF from cultured cells...
July 2, 2018: Investigative Ophthalmology & Visual Science
Nadine Brew, Shinji Nakamura, Nadia Hale, Aminath Azhan, Grace I Davies, Ilias Nitsos, Suzanne L Miller, David W Walker, Flora Y Wong
BACKGROUND: Impaired cerebral autoregulation in preterm infants makes circulatory management important to avoid cerebral hypoxic-ischemic injury. Dobutamine is frequently used as inotropic treatment in preterm neonates, but its effects on the brain exposed to cerebral hypoxia are unknown. We hypothesized that dobutamine would protect the immature brain from cerebral hypoxic injury. METHODS: In preterm (0.6 gestation) fetal sheep, dobutamine (Dob, 10 μg/kg/min) or saline (Sal) was infused intravenously for 74 h...
July 6, 2018: Pediatric Research
Avery C Rossidis, Heron D Baumgarten, Kendall M Lawrence, Patrick E McGovern, Ali Y Mejaddam, Haiying Li, Grace Hwang, Kathleen Young, William H Peranteau, Marcus G Davey, J William Gaynor, Alan W Flake
INTRODUCTION: We have recently developed an extra-uterine environment for neonatal development (EXTEND) capable of supporting premature fetal lambs and have been able to replicate hypoxic in utero conditions by controlling fetal oxygen delivery. In this study, we investigated the fetal mitochondrial response to hypoxia. METHODS: Eight premature fetal lambs were delivered via hysterotomy and transitioned to extra-uterine support for 3 weeks. The lambs were divided into 2 groups: normoxic fetuses which maintained physiologic oxygen delivery and hypoxic fetuses in which oxygen delivery was significantly reduced...
June 28, 2018: Fetal Diagnosis and Therapy
Miguel A Zarate, Eileen I Chang, Charles E Wood
KEY POINTS: The cerebral response to fetal asphyxia is characterized by an upregulation of nucleic acid and chromatin modification processes, as well as a downregulation of metabolic processes at 1 h post-umbilical cord occlusion (UCO). Twenty-four hours post UCO, there was an upregulation of metabolic processes and protein modifications. UCO did not alter bacterial gene expression levels, nor did it produce a robust inflammatory response compared to maternal hypoxia. The administration of ketamine produced minimal effects on the fetal response to UCO in the cerebral cortex...
December 2018: Journal of Physiology
Roberto V Reyes, Sebastián Castillo-Galán, Ismael Hernandez, Emilio A Herrera, Germán Ebensperger, Aníbal J Llanos
The pulmonary arteries are exquisitely responsive to oxygen changes. They rapidly and proportionally contract as arterial PO2 decrease, and they relax as arterial PO2 is re-established. The hypoxic pulmonary vasoconstriction (HPV) is intrinsic since it does not require neural or endocrine factors, as evidenced in isolated vessels. On the other hand, pulmonary arteries also respond to sustained hypoxia with structural and functional remodeling, involving growth of smooth muscle medial layer and later recruitment of adventitial fibroblasts, secreted mitogens from endothelium and changes in the response to vasoconstrictor and vasodilator stimuli...
2018: Frontiers in Physiology
Ke Lu, Malin Holzmann, Fahrad Abtahi, Kaj Lindecrantz, Pelle G Lindqvist, Lennart Nordstrom
INTRODUCTION: Fetal heart rate short term variation (STV) decreases with severe chronic hypoxia in the antenatal period. However, only limited research has been done on STV during labor. We have tested a novel algorithm for a valid baseline estimation and calculated STV. To explore the value of STV during labor, we compared STV with fetal scalp blood (FBS) lactate concentration, an early marker in the hypoxic process. MATERIAL AND METHODS: Software was developed which estimates baseline frequency using a novel algorithm and thereby calculates STV according to Dawes and Redman in up to four 30-minute blocks prior to each FBS...
October 2018: Acta Obstetricia et Gynecologica Scandinavica
Karel Maršál
The growth-restricted fetus in utero is exposed to a hostile environment and suffers undernutrition and hypoxia. To cope with the stress, the fetus changes its physiological functions. These adaptive changes aid intrauterine survival; however, they can lead to permanent functional and structural changes that can contribute to the development of serious chronic diseases later in life. Epigenetic mechanisms are an important part of the pathophysiological processes behind this "developmental origin of adult diseases...
May 2018: Best Practice & Research. Clinical Obstetrics & Gynaecology
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