Submitted September 21, 2004
Returned for revision October 14, 2004
Accepted February 23, 2005
Pregnancy
Trophoblast Migration Under Flow Is Regulated by
Endothelial Cells
Arlen Soghomonians ,
Abdul I. Barakat ,
Twanda L. Thirkill ,
and
Gordon C. Douglas *
* To whom correspondence should be addressed. E-mail: gcdouglas{at}ucdavis.edu.
Abstract
During pregnancy, trophoblasts enter the uterine
vasculature and are found in spiral arteries far upstream
of uterine capillaries. It is unknown whether trophoblasts
reach the spiral arteries by migration within blood
vessels against blood flow or by intravasation directly
into spiral arteries after interstitial migration. We have
developed an in vitro system consisting of early gestation
macaque monkey trophoblasts co-cultured with uterine
endothelial cells and have exposed the cells in a parallel
plate flow chamber to physiological levels of shear
stress. Videomicroscopy followed by quantitative image
analysis revealed that the migratory activity (expressed
as average displacement and average migration velocity) of
trophoblasts cultured on top of endothelial cells remained
unchanged between shear stresses of 1-30
dyne/cm2 whereas
activity of trophoblasts alone increased with increasing
shear stress. When the direction of migration was assessed
at 1 and 7.5 dyne/cm2, the extent of migration
against and
with flow was roughly equal for both trophoblasts alone
and co-cultured trophoblasts. At shear stress levels of 15
and 30 dyne/cm2, trophoblasts incubated alone
showed a
significant decrease in migration against flow and
corresponding increased migration in the direction of
flow. In contrast, trophoblasts co-cultured with uterine
endothelial cells maintained the same extent of migration
against flow at all shear stress levels. Migration against
flow was also maintained when trophoblasts were cultured
with endothelial cell-conditioned medium or fixed
endothelial cells. The results indicate that factors
expressed on the surface of uterine endothelial cells and
factors released by endothelial regulate trophoblast
migration under flow.
Key words:
Pregnancy •
Placenta •
Trophoblast •
Uterus
