Paracrine communication modulates production of Wnt antagonists and COX1-mediated prostaglandins in a decidual-trophoblast co-culture model

• Both decidua and trophoblast express a wide array of Wnt-related genes.
• Expression of Wnt genes in trophoblast is modulated by decidual paracrine factors.
• Wnt antagonist secretion is increased in decidual-trophoblast co-cultures.
• Co-cultured trophoblasts exhibit increased COX1 expression and PGE2 production.
• Wnt antagonists replicate this effect on COX1 levels and PGE2 production.
• Decidua-trophoblast interactions may modulate placentation via Wnt signalling.

Wnt signalling has important roles in decidualisation, implantation and placentation. We investigated the role of decidua-trophoblast communication and Wnt signalling in the placenta using a co-culture model. Expression of a wide range of Wnt-related genes was observed in both decidual and trophoblast cells using PCR array, with remarkably similar expression profiles. Co-culture induced altered expression of several Wnt-related proteins, with the Wnt inhibitors sFPR4 and DKK1 being among the most differentially expressed genes. Media concentrations of sFRP4 and DKK1 were increased with co-culture, coincident with a decrease in canonical Wnt signalling activity. Expression of PTGS1 mRNA and COX1 protein was also increased with co-culture as were media PGE2 concentrations; these changes were replicated by addition of exogenous DKK1 and sFRP4. Collectively, these data suggest that paracrine interactions between decidua and trophoblast stimulate Wnt antagonist secretion leading to increased placental prostaglandin production. This may be important for implantation and placental function.