Mapping the cord blood transcriptome of pregnancies affected by early maternal anemia to identify signatures of fetal programming
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Mapping the cord blood transcriptome of pregnancies affected by early maternal anemia to identify signatures of fetal programming. / Hatem, Gad; Hjort, Line; Asplund, Olof; Minja, Daniel T. R.; Msemo, Omari Abdul; Møller, Sofie Lykke; Lavstsen, Thomas; Groth-Grunnet, Louise; Lusingu, John P A; Hansson, Ola; Christensen, Dirk Lund; Vaag, Allan A; Artner, Isabella; Theander, Thor; Groop, Leif; Schmiegelow, Christentze; Bygbjerg, Ib Christian; Prasad, Rashmi B.
In: The Journal of clinical endocrinology and metabolism, Vol. 107, No. 5, 2022, p. 1303–1316.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Mapping the cord blood transcriptome of pregnancies affected by early maternal anemia to identify signatures of fetal programming
AU - Hatem, Gad
AU - Hjort, Line
AU - Asplund, Olof
AU - Minja, Daniel T. R.
AU - Msemo, Omari Abdul
AU - Møller, Sofie Lykke
AU - Lavstsen, Thomas
AU - Groth-Grunnet, Louise
AU - Lusingu, John P A
AU - Hansson, Ola
AU - Christensen, Dirk Lund
AU - Vaag, Allan A
AU - Artner, Isabella
AU - Theander, Thor
AU - Groop, Leif
AU - Schmiegelow, Christentze
AU - Bygbjerg, Ib Christian
AU - Prasad, Rashmi B
N1 - © The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
U2 - 10.1210/clinem/dgac010
DO - 10.1210/clinem/dgac010
M3 - Journal article
C2 - 35021220
VL - 107
SP - 1303
EP - 1316
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 5
ER -
ID: 290395791