Response to letter regarding article, "elevated placental adenosine signaling contributes to the pathogenesis of preeclampsia"

We appreciate the thoughtful and inquisitive remarks by Escudero et al in response to our recent publication.1 Escudero et al noted that our mouse models of preeclampsia did not show “elevated adenosine concentrations in maternal plasma, which have been reported as a feature of human preeclampsia.” There are several potential explanations for this difference. (1) In our genetic model of preeclampsia, only half of the placentas have elevated adenosine. (2) Because of the relatively short gestation time in mice, there may not be enough time for adenosine to accumulate in maternal plasma. (3) In contrast to humans, mice have high levels of adenosine deaminase (ADA) in the decidua,2 a feature that may prevent the accumulation of adenosine in maternal circulation. Importantly, our findings indicate that a local increase in adenosine in the placenta is sufficient to trigger features of preeclampsia in 2 different mouse models. Escudero et al write “Other factors that could increase local adenosine concentrations, including equilibrative nucleoside transporters …