The role of Dickkopf-1 protein, an antagonist of the Wnt/β-catenin signaling pathway, in endometriosis

Endometriosis is a benign gynecologic disease characterized by endometrial-like tissue (epithelium and stroma) outside the uterus. It affects primarily women of reproductive age and presents with pelvic pain and infertility. As such, it has significant socio-economic implications for individuals and society as a whole. The pathophysiology of endometriosis is likely to be multifactorial and to involve interplay between several factors including factors involved in cell adhesion. The Wnt genes and the Wnt signal transduction pathways are evolutionarily conserved and play a crucial role in cell proliferation, differentiation, and adhesion. Several studies suggested that the Wnt/β-catenin signaling pathway may be aberrantly activated in endometriosis tissues and in the endometrium of patients with endometriosis. The activation of Wnt/β-catenin signaling pathway is regulated by a variety of effectors including the Dickkopf (Dkk) family secreted proteins. Given the role of Dkk1 as an essential antagonist of the Wnt-signalling, we aim in our present study to investigate whether Dkk1 is involved in regulating the cellular and molecular mechanisms in endometriosis.

Dkk1 serum levels were measured in 37 normal subjects (mean age, 31 years) and in 44 endometriosis patients (mean age, 32 years) using the Human Dkk-1 Quantikine ELISA Kit from R&D According to the Manufacturer's Handbook.

The mean level of Dkk1 was significantly higher in patients with endometriosis than in healthy controls (3057 ± 739 [SD] vs. 2458 ± 777 pg/ml; p = 0.015).

In patients with endometriosis, serum levels of Dkk1 are significantly increased comparing to the healthy subjects. This data indicates that Dkk1 may play a role in the pathophysiology of endometriosis via its role as an essential antagonist of the Wnt-signalling. Depending on this observation, our research will continue to test further the plausible role of Dkk1 in endometriosis. Dkk1 protein and gene expression will be tested in endometriosis tissues using immunohistochemistry and RT-PCR respectively. In addition, other components of the Wnt/β-catenin signaling pathway will be tested such as the protein expression of β-catenin in the endometriosis tissues. Although endometriosis is an estrogen-dependent disease, deep infiltrating endometriosis usually does not respond well to hormonal suppressive therapy. Adequate surgical excision of the lesions provides the best long-term results and symptomatic relief. Despite this knowledge, the cellular and molecular mechanisms of endometriosis remain to be clarified. Knowledge of these mechanisms is indispensable for the development of new treatment strategies.