A novel three-dimensional in vitro system to study trophoblast-endothelium cell interactions.
BACKGROUND
Pregnancy complications have been linked to improper trophoblast migration and failure of spiral artery transformation. Endothelial cells play an essential role in directing trophoblast migration and transformation, although by an unknown mechanism. We describe a novel in vitro model to evaluate endothelial-trophoblast interaction and signaling in a three-dimensional system.


METHODS
Immortalized human endometrial endothelial cell line and first trimester trophoblast cells were co-cultured. Endothelial transformation into vessel-like structures occurred in Matrigel(TM) OpenLab Image Analysis software was used to monitor labeled trophoblast migration and endothelium transformation. Cytokine/chemokine production was determined using Multiplex.


RESULTS
Trophoblast migrates toward endothelial cells in Matrigel, aligns on top of the endothelium within 4-8 hr and achieves complete replacement of the endothelium by 72-96 hr. Lipopolysaccharide treatment damages the endothelium and disrupts endothelium-trophoblast interaction.


CONCLUSIONS
We report a novel three-dimensional in vitro and in vivo system of trophoblast-endothelium cell interaction. Significant changes in endothelial cells' phenotype are observed upon differentiation in Matrigel. These changes may be necessary for endothelium to direct trophoblast migration and transformation.
Aldo
Paulomi B
PB
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, Yale University, New Haven, CT 06520, USA.
Krikun
Graciela
G
Visintin
Irene
I
Lockwood
Charles
C
Romero
Roberto
R
Mor
Gil
G
D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D004717:Endometrium / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D011247:Pregnancy; D014327:Trophoblasts / Q000166:cytology / Q000502:physiology*; D039762:Ulex
D018925:Chemokines