Soluble ST2, a preeclampsia-related cytokine receptor, is transported bi-directionally across the placenta

We aimed to elucidate whether soluble ST2 (sST2), a preeclampsia (PE)-related cytokine, in the maternal or fetal circulation could be transported to the other circulatory system across the placenta.

A placental perfusion model in a closed system was established and optimized. HPLC was performed to determine the dynamics of antipyrine levels in the perfusate. Placentas (n = 18) collected from healthy controls and PE patients were perfused without additional treatment or with added sST2 in the maternal or fetal circulation. The concentration of sST2 in the perfusate samples was quantified by ELISA.

Monitoring of the antipyrine levels were used as a quality control and showed each placenta established successfully. In the untreated group, sST2 could be produced by the placenta and enter into both the maternal and fetal circulations, and significantly higher levels were detected in the maternal circulation. In placentas perfused with additional sST2 in the maternal circulation, a similar trend was observed as for the untreated placentas. When sST2 was added to the fetal circulation, increased sST2 was detected in the maternal circulation. Compared with the healthy controls, significantly elevated sST2 in the maternal side of PE patients were detected.

Soluble ST2 could be bi-directionally transported across placentas. It was an active process that maintained a higher level of sST2 in the maternal circulation. Furthermore, the significant increase of sST2 in the maternal blood of PE patients was due to an impaired placental barrier as a result of PE.