The hypothesis that in preeclampsia SPHK1 pathway can be down-regulated in the early phases of placentation process is supported by our in vitro and ex vivo placental models of hypoxia, (JAR cells and term placental explants), in which we observed strong up-regulation of SPHK1 in the presence of very low oxygen content (1% O2), but not at the physiological hypoxia (8% O2). Here, SPHK1 is linked to preeclampsia.