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Preeclampsia is Associated with Sex-Specific Transcriptional and Proteomic Changes in Fetal Erythroid Cells

Masoumi, Zahra LU ; Maes, Gregory E. ; Herten, Koen ; Cortés-Calabuig, Álvaro ; Alattar, Abdul Ghani LU ; Hanson, Eva LU ; Erlandsson, Lena LU ; Mezey, Eva LU ; Magnusson, Mattias LU and Vermeesch, Joris R. , et al. (2019) In International Journal of Molecular Sciences 20(8).
Abstract

Preeclampsia (PE) has been associated with placental dysfunction, resulting in fetal hypoxia, accelerated erythropoiesis, and increased erythroblast count in the umbilical cord blood (UCB). Although the detailed effects remain unknown, placental dysfunction can also cause inflammation, nutritional, and oxidative stress in the fetus that can affect erythropoiesis. Here, we compared the expression of surface adhesion molecules and the erythroid differentiation capacity of UCB hematopoietic stem/progenitor cells (HSPCs), UCB erythroid profiles along with the transcriptome and proteome of these cells between male and female fetuses from PE and normotensive pregnancies. While no significant differences were observed in UCB HSPC... (More)

Preeclampsia (PE) has been associated with placental dysfunction, resulting in fetal hypoxia, accelerated erythropoiesis, and increased erythroblast count in the umbilical cord blood (UCB). Although the detailed effects remain unknown, placental dysfunction can also cause inflammation, nutritional, and oxidative stress in the fetus that can affect erythropoiesis. Here, we compared the expression of surface adhesion molecules and the erythroid differentiation capacity of UCB hematopoietic stem/progenitor cells (HSPCs), UCB erythroid profiles along with the transcriptome and proteome of these cells between male and female fetuses from PE and normotensive pregnancies. While no significant differences were observed in UCB HSPC migration/homing and in vitro erythroid colony differentiation, the UCB HSPC transcriptome and the proteomic profile of the in vitro differentiated erythroid cells differed between PE vs. normotensive samples. Accordingly, despite the absence of significant differences in the UCB erythroid populations in male or female fetuses from PE or normotensive pregnancies, transcriptional changes were observed during erythropoiesis, particularly affecting male fetuses. Pathway analysis suggested deregulation in the mammalian target of rapamycin complex 1/AMP-activated protein kinase (mTORC1/AMPK) signaling pathways controlling cell cycle, differentiation, and protein synthesis. These results associate PE with transcriptional and proteomic changes in fetal HSPCs and erythroid cells that may underlie the higher erythroblast count in the UCB in PE.

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published
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keywords
erythropoiesis, hematopoietic stem/progenitor cells, preeclampsia, umbilical cord blood
in
International Journal of Molecular Sciences
volume
20
issue
8
article number
2038
publisher
MOLECULAR DIVERSITY PRESERVATION INT
external identifiers
  • pmid:31027199
  • scopus:85065329410
ISSN
1422-0067
DOI
10.3390/ijms20082038
language
English
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yes
id
e7bcbd70-d5dc-4ebd-9eda-fdecc5187dc2
date added to LUP
2019-05-21 14:36:35
date last changed
2019-08-21 03:00:33
@article{e7bcbd70-d5dc-4ebd-9eda-fdecc5187dc2,
  abstract     = {<p>Preeclampsia (PE) has been associated with placental dysfunction, resulting in fetal hypoxia, accelerated erythropoiesis, and increased erythroblast count in the umbilical cord blood (UCB). Although the detailed effects remain unknown, placental dysfunction can also cause inflammation, nutritional, and oxidative stress in the fetus that can affect erythropoiesis. Here, we compared the expression of surface adhesion molecules and the erythroid differentiation capacity of UCB hematopoietic stem/progenitor cells (HSPCs), UCB erythroid profiles along with the transcriptome and proteome of these cells between male and female fetuses from PE and normotensive pregnancies. While no significant differences were observed in UCB HSPC migration/homing and in vitro erythroid colony differentiation, the UCB HSPC transcriptome and the proteomic profile of the in vitro differentiated erythroid cells differed between PE vs. normotensive samples. Accordingly, despite the absence of significant differences in the UCB erythroid populations in male or female fetuses from PE or normotensive pregnancies, transcriptional changes were observed during erythropoiesis, particularly affecting male fetuses. Pathway analysis suggested deregulation in the mammalian target of rapamycin complex 1/AMP-activated protein kinase (mTORC1/AMPK) signaling pathways controlling cell cycle, differentiation, and protein synthesis. These results associate PE with transcriptional and proteomic changes in fetal HSPCs and erythroid cells that may underlie the higher erythroblast count in the UCB in PE.</p>},
  author       = {Masoumi, Zahra and Maes, Gregory E. and Herten, Koen and Cortés-Calabuig, Álvaro and Alattar, Abdul Ghani and Hanson, Eva and Erlandsson, Lena and Mezey, Eva and Magnusson, Mattias and Vermeesch, Joris R. and Familari, Mary and Hansson, Stefan R.},
  issn         = {1422-0067},
  language     = {eng},
  month        = {04},
  number       = {8},
  publisher    = {MOLECULAR DIVERSITY PRESERVATION INT},
  series       = {International Journal of Molecular Sciences},
  title        = {Preeclampsia is Associated with Sex-Specific Transcriptional and Proteomic Changes in Fetal Erythroid Cells},
  url          = {http://dx.doi.org/10.3390/ijms20082038},
  doi          = {10.3390/ijms20082038},
  volume       = {20},
  year         = {2019},
}