TY - JOUR
T1 - Pulmonary maternal immune activation does not cross the placenta but leads to fetal metabolic adaptation
AU - Hansen, Signe Schmidt Kjølner
AU - Krautz, Robert
AU - Rago, Daria
AU - Havelund, Jesper
AU - Stigliani, Arnaud
AU - Færgeman, Nils J.
AU - Prézelin, Audrey
AU - Rivière, Julie
AU - Couturier-Tarrade, Anne
AU - Akimov, Vyacheslav
AU - Blagoev, Blagoy
AU - Elfving, Betina
AU - Neess, Ditte
AU - Vogel, Ulla
AU - Khodosevich, Konstantin
AU - Hougaard, Karin Sørig
AU - Sandelin, Albin
N1 - Publisher Copyright:
© 2024. The Author(s).
PY - 2024
Y1 - 2024
N2 - The fetal development of organs and functions is vulnerable to perturbation by maternal inflammation which may increase susceptibility to disorders after birth. Because it is not well understood how the placenta and fetus respond to acute lung- inflammation, we characterize the response to maternal pulmonary lipopolysaccharide exposure across 24 h in maternal and fetal organs using multi-omics, imaging and integrative analyses. Unlike maternal organs, which mount strong inflammatory immune responses, the placenta upregulates immuno-modulatory genes, in particular the IL-6 signaling suppressor Socs3. Similarly, we observe no immune response in the fetal liver, which instead displays metabolic changes, including increases in lipids containing docosahexaenoic acid, crucial for fetal brain development. The maternal liver and plasma display similar metabolic alterations, potentially increasing bioavailability of docosahexaenoic acid for the mother and fetus. Thus, our integrated temporal analysis shows that systemic inflammation in the mother leads to a metabolic perturbation in the fetus.
AB - The fetal development of organs and functions is vulnerable to perturbation by maternal inflammation which may increase susceptibility to disorders after birth. Because it is not well understood how the placenta and fetus respond to acute lung- inflammation, we characterize the response to maternal pulmonary lipopolysaccharide exposure across 24 h in maternal and fetal organs using multi-omics, imaging and integrative analyses. Unlike maternal organs, which mount strong inflammatory immune responses, the placenta upregulates immuno-modulatory genes, in particular the IL-6 signaling suppressor Socs3. Similarly, we observe no immune response in the fetal liver, which instead displays metabolic changes, including increases in lipids containing docosahexaenoic acid, crucial for fetal brain development. The maternal liver and plasma display similar metabolic alterations, potentially increasing bioavailability of docosahexaenoic acid for the mother and fetus. Thus, our integrated temporal analysis shows that systemic inflammation in the mother leads to a metabolic perturbation in the fetus.
U2 - 10.1038/s41467-024-48492-x
DO - 10.1038/s41467-024-48492-x
M3 - Journal article
C2 - 38830841
AN - SCOPUS:85195014674
VL - 15
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 4711
ER -