title: PAPPA2 is increased in severe early onset pre-eclampsia and upregulated with hypoxia.
abstract: Severe early onset pre-eclampsia is a serious pregnancy complication, believed to arise as a result of persistent placental hypoxia due to impaired placentation. Pregnancy-associated plasma protein A2 (PAPPA2) is very highly expressed in the placenta relative to all other tissues. There is some evidence that PAPPA2 mRNA and protein are increased in association with pre-eclampsia. The aim of the present study was to characterise the mRNA and protein expression, as well as localisation, of PAPPA2 in an independent cohort of severe early onset pre-eclamptic placentas. We also examined whether exposing placental explants to hypoxia (1% oxygen) changed the expression of PAPPA2. Expression of PAPPA2 mRNA and protein was upregulated in severe early onset pre-eclamptic placentas compared with preterm controls and localised to the syncytiotrophoblast. Interestingly, protein localisation was markedly reduced in term placenta. Syncytialisation of BeWo cells did not change PAPPA2 expression. However, hypoxia upregulated PAPPA2 mRNA and protein expression in primary placental explants. Together, our data suggest that PAPPA2 may be upregulated in severe pre-eclampsia and, functionally, this may be mediated via increased placental hypoxia known to occur with this pregnancy disorder.
authors.affiliation: Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, Vic. 3084, Australia.
authors.forename: Kate
authors.initials: K
authors.lastname: Macintire
authors.affiliation: Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, Vic. 3084, Australia.
authors.forename: Laura
authors.initials: L
authors.lastname: Tuohey
authors.affiliation: Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, Vic. 3084, 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, 163 Studley Road, Heidelberg, Vic. 3084, Australia.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Palmer
authors.affiliation: Monash Institute of Medical Research, Monash University, 27-31 Wright Street, Clayton, Vic. 3168, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Gantier
authors.affiliation: Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, Vic. 3084, 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, 163 Studley Road, Heidelberg, Vic. 3084, Australia.
authors.forename: Tu'uhevaha J
authors.initials: TJ
authors.lastname: Kaitu'u-Lino
mesh_terms: D016022:Case-Control Studies; D015687:Cell Hypoxia; D002460:Cell Line; D005260:Female; D005865:Gestational Age; D006801:Humans; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D011266:Pregnancy-Associated Plasma Protein-A / Q000235:genetics / Q000378:metabolism*; D012720:Severity of Illness Index; D013997:Time Factors; D046509:Tissue Culture Techniques; D014327:Trophoblasts / Q000378:metabolism; D015854:Up-Regulation; D014739:Victoria
chemical_list: C430889:PAPPA2 protein, human; D011266:Pregnancy-Associated Plasma Protein-A