TY - JOUR
T1 - Galectin-3 deficiency in pregnancy increases the risk of fetal growth restriction (FGR) via placental insufficiency
AU - Freitag, Nancy
AU - Tirado-Gonzalez, Irene
AU - Barrientos, Gabriela
AU - Powell, Katie L.
AU - Boehm-Sturm, Philipp
AU - Koch, Stefan P.
AU - Hecher, Kurt
AU - Staff, Anne C.
AU - Arck, Petra C.
AU - Diemert, Anke
AU - Blois, Sandra M.
N1 - Funding Information:
We thank P. Moschansky and G. Koch (Blois’s lab), L. Øhra Levy (Staff’s lab), and S. Mueller (Boehm-Sturm’s lab) for their excellent technical assistances in generating this work. We are grateful to Dr. Herse and Dr. Dechend for discussion and assistance with PE experiments. This work was supported by grants from the Deutsche Forschungsgemeinschaft (DFG) BL1115/2-1, Heisenberg Program (BL1115/3-1-BL1115/7-1) to S.M.B. MRI studies are supported by the Federal Ministry of Education and Research (grant: 01EO0801-Center for Stroke Research Berlin) and DFG, Excellence Cluster NeuroCure to P.B.S. The PRINCE study was supported by grants of the German Research Foundation within the Clinical Research Unit 296 “Feto-maternal immune cross talk” to A.D. (DI 2103/3-2) and P.C.A. (AR232/25-2). A.D. and P.C. A. would like to thank all the PRINCE participants for allowing us to study them during their pregnancy, Gudula Hansen, Mirja Pagenkemper for their support in recruitment and Thomas Andreas, Christopher Urbschat and Agnes Wiezorek for their technical assistance. Open Access Funding provided by Projekt DEAL.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/7/1
Y1 - 2020/7/1
N2 - Fetal growth restriction (FGR) is the most common pregnancy complication in developed countries. Pregnancies affected by FGR, frequently concur with complications and high risk of neonatal morbidity and mortality. To date, no approved treatment is available for pregnant women affected with FGR. The objective of this study was to investigate the contribution of galectin-3 (gal-3), a β-galactoside binding protein involved in pregnancy, placental function and fetal growth. We demonstrated that lack of gal-3 during mouse pregnancy leads to placental dysfunction and drives FGR in the absence of a maternal preeclampsia syndrome. Analysis of gal-3 deficient dams revealed placental inflammation and malperfusion, as well as uterine natural killer cell infiltration with aberrant activation. Our results also show that FGR is associated with a failure to increase maternal circulating gal-3 levels during the second and third trimester in human pregnancies. Placentas from human pregnancies affected by FGR displayed lower gal-3 expression, which correlated with placental dysfunction. These data highlight the importance of gal-3 in the promotion of proper placental function, as its absence leads to placental disease and subsequent FGR.
AB - Fetal growth restriction (FGR) is the most common pregnancy complication in developed countries. Pregnancies affected by FGR, frequently concur with complications and high risk of neonatal morbidity and mortality. To date, no approved treatment is available for pregnant women affected with FGR. The objective of this study was to investigate the contribution of galectin-3 (gal-3), a β-galactoside binding protein involved in pregnancy, placental function and fetal growth. We demonstrated that lack of gal-3 during mouse pregnancy leads to placental dysfunction and drives FGR in the absence of a maternal preeclampsia syndrome. Analysis of gal-3 deficient dams revealed placental inflammation and malperfusion, as well as uterine natural killer cell infiltration with aberrant activation. Our results also show that FGR is associated with a failure to increase maternal circulating gal-3 levels during the second and third trimester in human pregnancies. Placentas from human pregnancies affected by FGR displayed lower gal-3 expression, which correlated with placental dysfunction. These data highlight the importance of gal-3 in the promotion of proper placental function, as its absence leads to placental disease and subsequent FGR.
UR - http://www.scopus.com/inward/record.url?scp=85088403582&partnerID=8YFLogxK
U2 - 10.1038/s41419-020-02791-5
DO - 10.1038/s41419-020-02791-5
M3 - Article
C2 - 32703931
AN - SCOPUS:85088403582
SN - 2041-4889
VL - 11
JO - Cell Death and Disease
JF - Cell Death and Disease
IS - 7
M1 - 560
ER -