Main author: Hallfríður Ingólfsdóttir
Institution or Company: Háskóli Íslands
Co-Authors, Institution or Company:
Guðrún Valdimarsdóttir, Háskóli Íslands.
Introduction: Preeclampsia is a severe pregnancy disease that is highly associated with fetal and maternal morbidity and mortality and occurs in 2-8% of pregnancies. In normal placental development, trophoblast cells invade and replace the endothelial lining of the maternal spiral arteries to allow sufficient flow of nutrients and oxygen to the growing fetus. This artery remodeling is impaired in preeclamptic placentas where these trophoblasts fail to migrate and invade the spiral arteries, leading to insufficient flow of nutrients to the fetus.
Methods: We have assessed the biological role of the catalytic enzymes lysyl oxidases (LOX) in trophoblast cells which play an important role in the ECM. Short hairpin RNA was used to knockdown LOX expression. Trophoblasts were stimulated with TGF-β and BMP9, expression was assessed with western blotting and the trophoblast migration and tube formation assessed with a scratch wound assay and a tube-like formation assay.
Results: We show that the lysyl oxidase-like 1 enzyme plays a pivotal role in the migration and tube formation of trophoblasts. By downregulating the expression of LOXL1, trophoblast migration and tube formation was severely suppressed. We also show that BMP9 has positive effects on the migration and tube formation but TGF-β seemed to have the opposite effect.
Conclusions: These results suggest that LOXL1 is critical for trophoblast invasion and spiral artery remodeling during placental development. They also suggest that TGF-β acts as a suppressor of LOX activity in trophoblasts. Better understanding of this process is a step towards prevention of preeclampsia in early pregnancy.