Investigating the source of free fetal hemoglobin in preeclampsia. The role of the placenta and the fetus.

Research output: ThesisDoctoral Thesis (compilation)

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Preeclampsia (PE) is an important pregnancy complication that affects 3-8% of women worldwide and is a leading cause of maternal and fetal morbidity and mortality. It is known that PE is associated with placental dysfunction, resulting in hypoxia, oxidative stress, altered metabolism and production of inflammatory cytokines. Hypoxia could enhance erythropoiesis and induce non-erythroid hemoglobin production. Elevated fetal hemoglobin (HbF) levels in term placentas and maternal circulation, as well as higher erythroblast count in the umbilical cord blood (UCB) have been previously described in PE pregnancies. It has been suggested that free HbF damages and leaks through the placental barrier into the maternal circulation and that could trigger inflammation, general endothelial dysfunction and organ damage in the mother. But to date, the source of the increased HbF is unknown.
The aim of this thesis is to elucidate whether altered fetal and placental erythropoiesis and hemolysis could contribute to the excess placental HbF. In addition, the effect of hypoxia-induced oxidative stress on non-erythroid hemoglobin production was analyzed.
Our results indicated an absence of erythropoiesis in term placentas in both PE and normotensive pregnancies. However, hypoxia-triggered oxidative stress induced production of alpha globin protein in non-erythroid cells. Analysis of placental and fetal hematopoietic stem/ progenitor cells (HSPCs) and erythropoiesis (in vitro and in vivo) did not indicate a significant difference in HSPC migration/ homing capacity or erythroid differentiation. However, proteomics and transcriptome analyses of fetal erythroid precursors indicated an imbalance in mammalian target of rapamycin (mTOR)/ AMP-activated protein kinase (AMPK) pathways. Considering that AMPK pathway activation is required for erythroid maturation, this imbalance is therefore suggested to underlie the higher erythroblast count in the UCB.
In summary, our results suggest that hypoxia-induced oxidative stress may lead to non-erythroid globin production in PE placentas. In addition, we propose that PE could lead to an imbalance in mTOR/AMPK pathways in fetal erythroid cells that could hinder their maturation and lead to higher UCB erythroblast count observed in PE. Further analysis is required to indicate the effect of non-erythroid or hemolysisinduced hemoglobin in PE.
Original languageEnglish
Awarding Institution
  • Department of Clinical Sciences, Lund
  • Lund University
  • Catholic University of Leuven
  • Hansson, Stefan, Supervisor
  • Familari, Mary, Assistant supervisor
  • Magnusson, Mattias, Assistant supervisor
  • Erlandsson, Lena, Assistant supervisor
  • Mezey, Eva, Assistant supervisor, External person
  • Vermeesch, Joris R., Assistant supervisor, External person
Thesis sponsors
Award date2018 May 12
Place of PublicationLund
ISBN (Print)978-91-7619-581-9
Publication statusPublished - 2018 May 9

Bibliographical note

Defence details
Date: 2018-05-12
Time: 09:00
Place: Segerfalksalen, BMC A10, Sölvegatan 17 i Lund
External reviewer(s):
Name: Burton, Graham J
Title: Professor
Affiliation: University of Cambridge
ISSN: 1652-8220
Lund University, Faculty of Medicine Doctoral Dissertation Series 2018:14

Subject classification (UKÄ)

  • Medical and Health Sciences


  • Preeclampsia/pregnancy
  • Placenta
  • Umbilical cord blood
  • Fetal erythropoiesis
  • Non-erythroid globin


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