In the present study, we also observed a significant reduction in SPHK1 expression and So-1-P content in E17.5 Phd2−/− cKO placentae, which aligns with previous findings showing that SPHK1 expression and So-1-P levels are downregulated in placentae from preeclamptic patients (22, 45), suggesting that the placental SPHK1/So-1-P pathway is compromised in preeclampsia. This evidence concerns the gene SPHK1 and preeclampsia.