title: Low-Dose Acetylsalicylic Acid Treatment Modulates the Production of Cytokines and Improves Trophoblast Function in an in Vitro Model of Early-Onset Preeclampsia.
abstract: Preeclampsia (PE), a serious hypertensive disorder of pregnancy, remains a leading cause of perinatal morbidity and mortality worldwide. Perturbed trophoblast function and impaired placental development early in pregnancy are key features. Low-dose acetylsalicylic acid (LDA) administered before 16 weeks' gestation significantly reduces the risk for PE. However, the exact mechanisms of action of LDA, particularly on trophoblast function, are unclear. We hypothesized that LDA influences placental trophoblast function and reverses PE-associated abnormalities. This study aimed to determine the effects of serum from normotensive women and from those with PE with or without LDA treatment on a model of placental syncytium. On cytokine profiling, LDA increased placental growth factor production and selectively restored PE serum-induced alterations in levels of cytokines [activated leukocyte cell adhesion molecule, CXCL-16, and ErbB3] to those in normotensive serum-treated cells. PE serum-induced increases in the apoptotic markers P53 mRNA expression, IKBKE mRNA expression, caspase 3 activity, and decreased BIRC8 mRNA expression, were attenuated by LDA treatment. LDA treatment also reduced abnormal differentiation caused by PE serum administration. Possible mechanisms by which LDA influences PE-affected trophoblast cells in vitro are by modulating cytokine secretion, reducing apoptosis to levels seen in normotensive serum-treated cells, and preventing the premature trophoblast differentiation commonly observed in PE.
authors.affiliation: Department of Maternal-Fetal Medicine, Pregnancy Research Centre, The Royal Women's Hospital, Parkville, Victoria, Australia; Department of Obstetrics and Gynaecology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Shanika
authors.initials: S
authors.lastname: Panagodage
authors.affiliation: Department of Maternal-Fetal Medicine, Pregnancy Research Centre, The Royal Women's Hospital, Parkville, Victoria, Australia; Department of Obstetrics and Gynaecology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Hannah E J
authors.initials: HE
authors.lastname: Yong
authors.affiliation: Department of Maternal-Fetal Medicine, Pregnancy Research Centre, The Royal Women's Hospital, Parkville, Victoria, Australia; Department of Obstetrics and Gynaecology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Fabricio
authors.initials: F
authors.lastname: Da Silva Costa
authors.affiliation: Department of Maternal-Fetal Medicine, Pregnancy Research Centre, The Royal Women's Hospital, Parkville, Victoria, Australia.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Borg
authors.affiliation: Department of Maternal-Fetal Medicine, Pregnancy Research Centre, The Royal Women's Hospital, Parkville, Victoria, Australia; Department of Obstetrics and Gynaecology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Bill
authors.initials: B
authors.lastname: Kalionis
authors.affiliation: Department of Maternal-Fetal Medicine, Pregnancy Research Centre, The Royal Women's Hospital, Parkville, Victoria, Australia; Department of Obstetrics and Gynaecology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Shaun P
authors.initials: SP
authors.lastname: Brennecke
authors.affiliation: Department of Maternal-Fetal Medicine, Pregnancy Research Centre, The Royal Women's Hospital, Parkville, Victoria, Australia; Department of Obstetrics and Gynaecology, The University of Melbourne, Parkville, Victoria, Australia; Department of Medicine and the Department of Obstetrics and Gynaecology, School of Clinical Sciences, Monash University, and The Ritchie Centre, Monash Medical Centre, Clayton, Victoria, Australia. Electronic address: padma.murthi@monash.edu.
authors.forename: Padma
authors.initials: P
authors.lastname: Murthi
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001241:Aspirin / Q000008:administration & dosage*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D015726:Giant Cells / Q000378:metabolism; D006801:Humans; D010920:Placenta / Q000378:metabolism; D000072483:Placenta Growth Factor / Q000378:metabolism; D011225:Pre-Eclampsia / Q000188:drug therapy* / Q000378:metabolism; D011247:Pregnancy; D014327:Trophoblasts / Q000378:metabolism*
chemical_list: D016207:Cytokines; C000608036:PGF protein, human; D000072483:Placenta Growth Factor; D001241:Aspirin