Technical noteDecorin expression is decreased in first trimester placental tissue from pregnancies with small for gestation age infants at birth
Introduction
Fetal growth restriction (FGR) is a significant pregnancy disorder that has major consequences for the fetus and neonate as well as an increased risk of long-term morbidity extending into adulthood. Small for gestational age (SGA) is often used as a surrogate for FGR and is defined as a birth weight below the 10th percentile on a birth weight curve [1]. While a number of maternal and fetal factors which contribute to FGR have been identified, the etiologies of the majority of cases remain uncertain [1]. FGR pregnancies are often associated with histological evidence of placental vascular thrombosis, more specifically microvascular thrombosis within the placenta [2], [3], [4].
Recent studies from our laboratory reported that altered placental proteoglycan expression and function may contribute to the coagulation disturbance that leads to maternal-placental vascular thrombosis in third trimester FGR pregnancies. Proteoglycans are macromolecules located within vessel walls that contain a core protein to which sulphated glycosaminoglycan (GAG) chains are covalently linked. There are four types of GAG chains located in the blood vessel wall; chondroitin sulphate, dermatan sulphate, heparan sulphate, and hyaluronan [5]. However, only chondroitin sulphate, dermatan sulphate, and heparan sulphate are covalently linked to a core protein [5]. The placenta contains two major types of proteoglycans; those containing heparan sulphate and those containing chondroitin sulphate or dermatan sulphate [6], [7], [8], [9]. Decorin (DCN) usually has one chondroitin sulphate or dermatan sulphate GAG attached to its core protein.
We previously demonstrated that DCN protein is localised to the stroma surrounding fetal blood vessels of the third trimester placental villi and its expression is decreased in placentae obtained from third trimester FGR-affected pregnancies [10]. Analysis of mice with targeted deletion of the Dcn gene provided conclusive evidence for a role of the Dcn gene in the causal link to preterm birth and reduced birth weight in the offspring [11]. However, determining the cause of human FGR remains a major challenge in human pregnancy research. Uncertainties still exist as to whether the decreased placental DCN expression observed in third trimester human FGR-affected pregnancies is truly causative or rather reflects a response to an altered growth process.
We therefore made use of a unique resource of first trimester tissues obtained via chorionic villus sampling during the first trimester to investigate the temporal relationship between altered decorin expression and any subsequent development of SGA. We hypothesized that placental DCN expression is decreased early in gestation in SGA pregnancies. Early gestation sampling can be accomplished by chorionic villus sampling (CVS), a procedure generally performed between 10 and 14 weeks' gestation. Differentiation of normal from pathological groups is possible, as the eventual maternal and fetal outcomes of ongoing pregnancies are determinable [12], [13]. The aim of this study was to quantify DCN gene expression using real-time PCR in placental tissues collected during CVS performed at first trimester (10–12 weeks' gestation) from on-going pregnancies with known clinical outcomes, i.e. SGA or uncomplicated control pregnancies.
Section snippets
Surplus CVS tissue samples
First-trimester placental villous tissue was obtained from surplus tissue at CVS, which was performed vaginally between 10 and 12 weeks' gestation for maternal age or serum screening related risk for aneuploidy [14]. CVS was performed at the University Medical Centre of Groningen, The Netherlands. Surplus CVS tissue samples were collected from pregnant women with informed consent and in accordance to the guidelines of the Federation of Dutch Medical Scientific Societies regarding surplus
Results and discussion
In this study we used a unique collection of placental tissues to study the expression of DCN proteoglycan in early pregnancy. These placental tissues were collected during routine CVS between 10 and 12 weeks of pregnancy, from ongoing pregnancies that later developed SGA at term, as well as controls. Table 1 depicts the demographic data collected at delivery for both SGA and control pregnancies used in this study. A significant decrease in birth weight was observed in the SGA group compared
Conflict of interest
There is no conflict of interest to declare by the authors.
Disclosures
None.
Acknowledgements
Sources of funding: this work was supported by a National Health and Medical Research Council (NH&MRC) Project Grant, Australia (Application: 1004952 and 75124).
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