Background
Decorin, a leucine-rich proteoglycan that is produced by decidual cells, limits invasion
and endovascular differentiation of extravillous trophoblast cells during early placentation
by binding to multiple tyrosine kinase receptors, in particular, vascular endothelial
growth factor receptor-2.
Objective
Because many studies have reported an association between poor trophoblast invasion
and endovascular differentiation with preeclampsia, the studies reported here tested
(1) whether decorin over-expression in the chorionic villi and/or basal decidua is
associated with preeclampsia and, if so, (2) whether this association results in a
hypoinvasive placenta, and (3) whether elevated plasma decorin concentration in the
second trimester is a predictive biomarker for preeclampsia.
Study Design
Decorin messenger RNA expression was measured with quantitative polymerase chain reaction
at the tissue level and with in situ hybridization at the cellular level using 35S-labeled antisense complimentary RNA probe in placentas from healthy control subjects
and subjects with preeclampsia (14 each, 23-40 weeks of gestation). Tissue sections
of the same placentas were also immunostained for decorin protein. A decorin over-expressing
human endometrial stromal cell line was tested for invasion-regulatory effects on
an invasive first-trimester extravillous trophoblast cell line HTR-8/SVneo plated
in cocultures that were separated by a semipermeable membrane. Furthermore, we conducted
retrospective measurements of plasma decorin levels during the second trimester (15-18
weeks of gestation) in a cohort of 28 body mass index–matched pairs of control subjects
and subjects with preeclampsia before the onset of clinical disease.
Results
First, decorin messenger RNA expression at the cellular level measured with in situ
hybridization exhibited profoundly higher expression levels in basal plate decidual
cells within the placentas from preeclamptic subjects than those from control subjects
at all gestational ages, whereas no difference between the 2 subject groups was noted
in villus mesenchymal cells. Similarly decorin messenger RNA expression at the tissue
level in chorionic villi (primarily resulting from fetally derived mesenchymal cells)
did not differ significantly between control and preeclampsia placentas. These findings
were validated with immunostaining for decorin protein. Second, knocking down decorin gene in a decorin over-expressing endometrial cell line (used as an in vitro surrogate
of decorin over-expressing decidual cells) in cocultures with extravillous trophoblast
cells abrogated its invasion-restraining actions on trophoblast cells, which indicated
paracrine contribution of decorin over-expressing decidua to the poor trophoblast
invasiveness in situ. Finally, retrospective measurement of plasma decorin levels
during the second trimester in 28 body mass index–matched pairs of control subjects
and subjects with preeclampsia revealed elevated plasma decorin levels in all subjects
with preeclampsia in all body mass index groups. A receiver operating characteristic
curve analysis revealed strong diagnostic performance of plasma decorin in the prediction
of preeclampsia status. Although there was no significant gestational age-related
change in decorin levels during the second trimester in control or subjects with preeclampsia,
we found that plasma decorin had a significant inverse relationship with body mass
index or bodyweight.
Conclusion
We conclude that decorin over-expression by basal decidual cells is associated with
hypoinvasive phenotype and poor endovascular differentiation of trophoblast cells
in preeclampsia and that elevated plasma decorin concentration is a potential predictive
biomarker for preeclampsia before the onset of clinical signs.
Key words
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Article info
Publication history
Published online: March 19, 2016
Accepted:
March 11,
2016
Received in revised form:
March 10,
2016
Received:
December 23,
2015
Footnotes
Supported by operating grants from the Canadian Institutes of Health Research (P.K.L. and V.K.M. H.), a Translational Research Grant of the Children's Health Research Institute (P.K.L. and G.E.), and a Lawson Health Research Institute Internal Research Fund grant (B.deV.).
The authors report no conflict of interest.
Cite this article as: Siddiqui MF, Nandi P, Girish GV, et al. Decorin over-expression by decidual cells in preeclampsia: a potential blood biomarker. Am J Obstet Gynecol 2016;215:361.e1-15.
Identification
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© 2016 Elsevier Inc. All rights reserved.
