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Mapping the cord blood transcriptome of pregnancies affected by early maternal anemia to identify signatures of fetal programming

Hatem, Gad LU ; Hjort, Line LU ; Asplund, Olof LU ; Minja, Daniel T R ; Msemo, Omari Abdul ; Møller, Sofie Lykke ; Lavstsen, Thomas ; Groth-Grunnet, Louise ; Lusingu, John P A and Hansson, Ola LU orcid , et al. (2022) In The Journal of clinical endocrinology and metabolism 107(5). p.1303-1316
Abstract

OBJECTIVE: Anemia during early pregnancy (EP) is common in developing countries and is associated with adverse health consequences for both mother and children. Offspring of women with EP anemia often have low birth-weight, the latter being a risk factor for cardiometabolic diseases including type 2 diabetes (T2D) later in life. Mechanisms underlying developmental programming of adult cardiometabolic disease include epigenetic and transcriptional alterations potentially detectable in umbilical cord blood (UCB) at time of birth.

METHODS: We leveraged global transcriptome- and accompanying epigenome-wide changes in 48 UCB from newborns of EP-anemic Tanzanian mothers and 50 controls to identify differentially expressed genes (DEG) in... (More)

OBJECTIVE: Anemia during early pregnancy (EP) is common in developing countries and is associated with adverse health consequences for both mother and children. Offspring of women with EP anemia often have low birth-weight, the latter being a risk factor for cardiometabolic diseases including type 2 diabetes (T2D) later in life. Mechanisms underlying developmental programming of adult cardiometabolic disease include epigenetic and transcriptional alterations potentially detectable in umbilical cord blood (UCB) at time of birth.

METHODS: We leveraged global transcriptome- and accompanying epigenome-wide changes in 48 UCB from newborns of EP-anemic Tanzanian mothers and 50 controls to identify differentially expressed genes (DEG) in UCB exposed to maternal EP-anemia. DEGs were assessed for association with neonatal anthropometry and cord insulin levels. These genes were further studied in expression data from human fetal pancreas and adult islets to understand their role in beta-cell development and/or function.

RESULTS: The expression of 137 genes was altered in UCB of newborns exposed to maternal EP anemia. These putative signatures of fetal programming which included the birth-weight locus LCORL, were potentially mediated by epigenetic changes in 27 genes and associated with neonatal anthropometry. Among the DEGs were P2RX7, PIK3C2B, and NUMBL which potentially influence beta-cell development. Insulin levels were lower in EP anemia exposed UCB, supporting the notion of developmental programming of pancreatic beta-cell dysfunction and subsequently increased risk of T2D in offspring of EP anemic mothers.

CONCLUSIONS: Our data provide proof-of-concept on distinct transcriptional and epigenetic changes detectable in UCB from newborns exposed to maternal EP anemia.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
The Journal of clinical endocrinology and metabolism
volume
107
issue
5
pages
1303 - 1316
publisher
Oxford University Press
external identifiers
  • pmid:35021220
  • scopus:85130069613
ISSN
1945-7197
DOI
10.1210/clinem/dgac010
language
English
LU publication?
yes
additional info
© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.
id
0c545649-8190-425b-a760-b19bf59007f9
date added to LUP
2022-01-17 11:28:48
date last changed
2024-04-18 11:57:55
@article{0c545649-8190-425b-a760-b19bf59007f9,
  abstract     = {{<p>OBJECTIVE: Anemia during early pregnancy (EP) is common in developing countries and is associated with adverse health consequences for both mother and children. Offspring of women with EP anemia often have low birth-weight, the latter being a risk factor for cardiometabolic diseases including type 2 diabetes (T2D) later in life. Mechanisms underlying developmental programming of adult cardiometabolic disease include epigenetic and transcriptional alterations potentially detectable in umbilical cord blood (UCB) at time of birth.</p><p>METHODS: We leveraged global transcriptome- and accompanying epigenome-wide changes in 48 UCB from newborns of EP-anemic Tanzanian mothers and 50 controls to identify differentially expressed genes (DEG) in UCB exposed to maternal EP-anemia. DEGs were assessed for association with neonatal anthropometry and cord insulin levels. These genes were further studied in expression data from human fetal pancreas and adult islets to understand their role in beta-cell development and/or function.</p><p>RESULTS: The expression of 137 genes was altered in UCB of newborns exposed to maternal EP anemia. These putative signatures of fetal programming which included the birth-weight locus LCORL, were potentially mediated by epigenetic changes in 27 genes and associated with neonatal anthropometry. Among the DEGs were P2RX7, PIK3C2B, and NUMBL which potentially influence beta-cell development. Insulin levels were lower in EP anemia exposed UCB, supporting the notion of developmental programming of pancreatic beta-cell dysfunction and subsequently increased risk of T2D in offspring of EP anemic mothers.</p><p>CONCLUSIONS: Our data provide proof-of-concept on distinct transcriptional and epigenetic changes detectable in UCB from newborns exposed to maternal EP anemia.</p>}},
  author       = {{Hatem, Gad and Hjort, Line and Asplund, Olof and Minja, Daniel T R and Msemo, Omari Abdul and Møller, Sofie Lykke and Lavstsen, Thomas and Groth-Grunnet, Louise and Lusingu, John P A and Hansson, Ola and Christensen, Dirk Lund and Vaag, Allan A and Artner, Isabella and Theander, Thor and Groop, Leif and Schmiegelow, Christentze and Bygbjerg, Ib Christian and Prasad, Rashmi B}},
  issn         = {{1945-7197}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{1303--1316}},
  publisher    = {{Oxford University Press}},
  series       = {{The Journal of clinical endocrinology and metabolism}},
  title        = {{Mapping the cord blood transcriptome of pregnancies affected by early maternal anemia to identify signatures of fetal programming}},
  url          = {{http://dx.doi.org/10.1210/clinem/dgac010}},
  doi          = {{10.1210/clinem/dgac010}},
  volume       = {{107}},
  year         = {{2022}},
}