title: Abnormal oxidative stress responses in fibroblasts from preeclampsia infants.
abstract: BACKGROUND
  Signs of severe oxidative stress are evident in term placentae of infants born to mothers with preeclampsia (PE), but it is unclear whether this is a cause or consequence of the disease. Here fibroblast lines were established from umbilical cords (UC) delivered by mothers who had experienced early onset PE and from controls with the goal of converting these primary cells to induced pluripotent stem cells and ultimately trophoblast. Contrary to expectations, the oxidative stress responses of these non-placental cells from PE infants were more severe than those from controls.
  
  
  RESULTS
  Three features suggested that UC-derived fibroblasts from PE infants responded less well to oxidative stressors than controls: 1) While all UC provided outgrowths in 4% O2, success was significantly lower for PE cords in 20% O2; 2) PE lines established in 4% O2 proliferated more slowly than controls when switched to 20% O2; 3) PE lines were more susceptible to the pro-oxidants diethylmaleate and tert-butylhydroquinone than control lines, but, unlike controls, were not protected by glutathione. Transcriptome profiling revealed only a few genes differentially regulated between PE lines and controls in 4% O2 conditions. However, a more severely stressed phenotype than controls, particularly in the unfolded protein response, was evident when PE lines were switched suddenly to 20% O2, thus confirming the greater sensitivity of the PE fibroblasts to acute changes in oxidative stress.
  
  
  CONCLUSIONS
  UC fibroblasts derived from PE infants are intrinsically less able to respond to acute oxidative stress than controls, and this phenotype is retained over many cell doublings. Whether the basis of this vulnerability is genetic or epigenetic and how it pertains to trophoblast development remains unclear, but this finding may provide a clue to the basis of the early onset, usually severe, form of PE.
authors: Division of Animal Sciences, University of Missouri, Columbia, Missouri, United States of America; Bond Life Sciences Center, University of Missouri, Columbia, Missouri, United States of America; College of Life Science, Yangtze University, Jingzhou, Hubei, China.
authors: Penghua
authors: P
authors: Yang
authors: Division of Animal Sciences, University of Missouri, Columbia, Missouri, United States of America; Bond Life Sciences Center, University of Missouri, Columbia, Missouri, United States of America.
authors: Aihua
authors: A
authors: Dai
authors: Division of Animal Sciences, University of Missouri, Columbia, Missouri, United States of America; Bond Life Sciences Center, University of Missouri, Columbia, Missouri, United States of America.
authors: Andrei P
authors: AP
authors: Alexenko
authors: Division of Animal Sciences, University of Missouri, Columbia, Missouri, United States of America; Bond Life Sciences Center, University of Missouri, Columbia, Missouri, United States of America; Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, Yangling, Shaanxi, China.
authors: Yajun
authors: Y
authors: Liu
authors: Department of Obstetrics, Gynecology, & Women's Health, University of Missouri, Columbia, Missouri, United States of America.
authors: Amanda J
authors: AJ
authors: Stephens
authors: Department of Obstetrics, Gynecology, & Women's Health, University of Missouri, Columbia, Missouri, United States of America.
authors: Laura C
authors: LC
authors: Schulz
authors: Department of Obstetrics, Gynecology, & Women's Health, University of Missouri, Columbia, Missouri, United States of America.
authors: Danny J
authors: DJ
authors: Schust
authors: Division of Animal Sciences, University of Missouri, Columbia, Missouri, United States of America; Bond Life Sciences Center, University of Missouri, Columbia, Missouri, United States of America; Department of Biochemistry, University of Missouri, Columbia, Missouri, United States of America.
authors: R Michael
authors: RM
authors: Roberts
authors: Division of Animal Sciences, University of Missouri, Columbia, Missouri, United States of America; Bond Life Sciences Center, University of Missouri, Columbia, Missouri, United States of America.
authors: Toshihiko
authors: T
authors: Ezashi
mesh_terms: D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D020869:Gene Expression Profiling; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D010100:Oxygen / Q000494:pharmacology; D011225:Pre-Eclampsia / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011247:Pregnancy; D013312:Stress, Physiological / Q000187:drug effects / Q000235:genetics; D059467:Transcriptome / Q000187:drug effects; D014470:Umbilical Cord / Q000378:metabolism / Q000473:pathology*
chemical_list: D005947:Glucose; D010100:Oxygen