TIMPs Expression as A Maternal Cell Free Plasma Biomarker of Severe Preeclampsia: A Case-Control Study

Document Type : Original Article


1 Medical Nanotechnology and Tissue Engineering Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

2 Obstetrics and Gynecology Department, Tehran University of Medical Science, Tehran, Iran

3 Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

4 Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

5 Department of Epidemiology and Reproductive Health, Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran


Preeclampsia (PE) is a pregnancy related disorder with prevalence of 6-7%. Insufficient trophoblastic
invasion leads to incomplete remodeling of spiral arteries and consequent decrease in feto-placental perfusion. Altered
placental expression of tissue inhibitors of matrix metalloproteinase (TIMPs) is considered to be involved in this process
while the balance between matrix metalloproteinases (MMPs) and TIMPs contributes to remodeling of the placenta
and uterine arteries by degradation and refurbishing of extracellular matrix (ECM). Therefore, TIMPs, fetal expression
pattern was evaluated with the aim of its potential to be used as a determinant for the (early) detection of PE.

Materials and Methods:
In this case-control study, cell free fetal RNA (cffRNA) released by placenta into the maternal
blood was used to determine expression patterns of TIMP1, 2, 3 and 4 in the severe preeclamptic women in comparison
with the normal pregnant women. Whole blood from 20 preeclamptic and 20 normal pregnant women in their 28-32
weeks of gestational age was collected. The second control group consisted of 20 normal pregnant women in either 14
or 28 weeks of gestation (each 10). cffRNA was extracted from plasma and real-time polymerase chain reaction (PCR)
was done to determine the expression levels of TIMP1, 2, 3 and 4 genes.

Statistical analysis of the results showed significant higher expression of TIMP1-4 in the preeclamptic women
in comparison with the control group (P=0.029, 0.037, 0.037 and 0.049, respectively). Also, an increased level of TIMPs
expression was observed by comparing 14 to 28 weeks of gestational age in the normal pregnant women in the second
control group.

An increased cffRNA expression level of TIMPs may be correlated with the intensity of placental vascular
defect and may be used as a determinant of complicated pregnancies with severe preeclampsia.


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