title: Steroid sulfatase is increased in the placentas and whole blood of women with early-onset preeclampsia.
abstract: Preeclampsia is a serious complication of pregnancy affecting 5% of pregnancies. Our team identified 137 genes highly expressed in placenta relative to other human tissues. Here, we have explored a role for steroid sulfatase (STS) in preeclampsia by characterising STS expression and the functional effects of STS on primary placental trophoblasts.
  
  
  
  Characterisation of STS was performed on preterm preeclamptic and gestation-matched normotensive preterm controls who delivered at <34 weeks gestation. We characterised placental and maternal whole blood STS mRNA and placental protein expression via qRT-PCR, immunohistochemistry and Western Blot. To assess whether STS is involved in sFlt1 secretion and syncytialisation, we administered siRNA to silence STS in primary trophoblasts before measuring sFlt1 and hCG secretion and E-Cadherin expression.
  
  
  
  A custom array containing 45 placental specific genes identified 10 genes significantly altered in the placentas of preeclamptic patients relative to normotensive gestation-matched controls. Of these genes, qRT-PCR and western blot on a larger cohort confirmed that the expression of STS was significantly elevated in preeclamptic placentas (n = 44) relative to gestation matched controls (n = 26). Given placental RNA leaks in to the maternal circulation, we also assessed STS mRNA expression in the whole blood of patients with preeclampsia and found it was significantly increased relative to normotensive controls. siRNA knockdown of STS in primary trophoblast resulted in a modest but significant reduction in sFlt1 secretion, but had no affect on hCG secretion or E-Cadherin protein expression.
  
  
  
  STS is increased in preeclamptic placentas and maternal whole blood. Our data suggests that STS may affect sFlt1 secretion by regulating sFlt1-i13 transcription, and not via alterations in syncytialisation.
authors.affiliation: Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Heidelberg, Victoria, Australia.
authors.forename: Amy M
authors.initials: AM
authors.lastname: Gratton
authors.affiliation: Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Heidelberg, Victoria, Australia.
authors.forename: Louie
authors.initials: L
authors.lastname: Ye
authors.affiliation: Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Heidelberg, Victoria, Australia.
authors.forename: Fiona C
authors.initials: FC
authors.lastname: Brownfoot
authors.affiliation: Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Heidelberg, Victoria, Australia.
authors.forename: Natalie J
authors.initials: NJ
authors.lastname: Hannan
authors.affiliation: Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Heidelberg, Victoria, Australia.
authors.forename: Clare
authors.initials: C
authors.lastname: Whitehead
authors.affiliation: Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Heidelberg, Victoria, Australia.
authors.forename: Ping
authors.initials: P
authors.lastname: Cannon
authors.affiliation: Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Heidelberg, Victoria, Australia.
authors.forename: Minh
authors.initials: M
authors.lastname: Deo
authors.affiliation: The Hudson Institute of Medical Research, Monash Health, Clayton, Victoria, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Fuller
authors.affiliation: Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Heidelberg, Victoria, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Tong
authors.affiliation: Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Heidelberg, Victoria, Australia. Electronic address: t.klino@unimelb.edu.au.
authors.forename: Tu'uhevaha J
authors.initials: TJ
authors.lastname: Kaitu'u-Lino
mesh_terms: D000293:Adolescent; D000328:Adult; D015820:Cadherins / Q000378:metabolism; D005260:Female; D006801:Humans; D010920:Placenta / Q000201:enzymology*; D011225:Pre-Eclampsia / Q000097:blood / Q000378:metabolism*; D011247:Pregnancy; D043266:Steryl-Sulfatase / Q000097:blood / Q000378:metabolism*; D014327:Trophoblasts / Q000201:enzymology*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D055815:Young Adult
chemical_list: D015820:Cadherins; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D043266:Steryl-Sulfatase
keywords: Placental specific genes; Preeclampsia; Steroid sulfatase; sFlt1