Introduction: Preeclampsia is a serious complication of pregnancy affecting 5% of pregnancies worldwide. The placenta is central to preeclampsia. Our team identified 137 genes highly expressed in placenta relative to other human tissues. A custom microarray of 45 these placental specific genes identified Steroid Sulfatase (STS) as one of twelve genes significantly increased in a cohort of preeclamptic placentas relative to gestation-matched normotensive controls. We explored a role for STS in preeclampsia by characterising STS expression in placenta and maternal whole blood and investigating the functional role of STS in primary placental trophoblasts.
Methods: STS characterisation was performed on severe early-onset preeclamptic (n= 29) and gestation-matched normotensive controls (n=15). We characterised placental and maternal whole blood STS mRNA and placental protein expression via qRT-PCR, immunohistochemistry and Western Blot. To assess the functional contribution to sFlt1 secretion, primary placental trophoblasts were isolated from term placentas and siRNA targeting STS administered. sFlt1 secretion and sFlt1 variant (sFlt1-e15a and sFlt1-i13) expression was assessed after treatment via ELISA and qRT-PCR. The effect of STS on trophoblast differentiation (syncytialisation) was assessed via hCG ELISA and Western Blot for E-Cadherin.
Results: STS mRNA expression was significantly elevated in preeclamptic placentas (p≤0.0001). STS protein localises to the placental syncytiotrophoblast. Functional analysis showed significantly (p≤0.05) reduced sFlt1 secretion when STS was silenced. sFlt1 variant analysis showed a significant (p≤0.01) decrease in sFlt1-i13 expression, but no change in membrane-bound Flt1 or sFlt1-e15a mRNA expression. Silencing STS had no affect on hCG secretion or E-cadherin expression in treated trophoblasts.
Discussion: This study has confirmed that STS is increased in preeclamptic placentas and that this increase is detectable in maternal whole blood. Functional analysis suggests that STS may affect placental sFlt1 secretion in preeclampsia by regulating sFlt1-i13 expression and not via mechanisms related to syncytialisation of the placenta.