Increased D ickkopf‐1 expression in patients with unexplained recurrent spontaneous miscarriage

Summary Wnt pathways play an important role in pre‐implantation embryo development, blastocyst implantation, and post‐implantation uterine decidualisation. However, little is known about the potential role that Wnt signaling plays in patients with unexplained recurrent spontaneous miscarriage ( URSM ), and no single biomarker with a high predictive value of maternally caused URSM has been identified. We aim to study the molecular mechanisms by which the Wnt pathway controls the progression of early pregnancy by investigating the expression of D ickkopf‐1 ( DKK 1), one of the Wnt agonists, in URSM patients. Plasma and fresh decidual tissues samples were collected from 59 subjects (29 patients with URSM and 30 patients with normal, early pregnancy). Time‐resolved immunofluorometric assay system and quantitative real‐time RT‐PCR were used to determine the serum levels of DKK 1 and DKK 1 m RNA in the deciduas, respectively. Western blot and immunohistochemistry were used to measure DKK 1 protein levels in the deciduas. Serum DKK 1 levels were significantly higher in URSM patients compared to the control group ( P  < 0·001); the expression of DKK 1 m RNA and protein in URSM patients were higher relative to healthy controls ( P  = 0·013). Glandular epithelium from decidual tissues demonstrated cytoplasmic signals for DKK 1 in URSM patients, and DKK 1 did not stain in healthy controls. Furthermore, serum DKK 1 levels significantly correlated with those in the decidual tissues. Our study suggests that DKK 1 may be a valuable biomarker of URSM ; it can be reliably and conveniently detected in serum, thus obviating the need for decidual tissue analysis.