title: FOXO1 expression in villous trophoblast of preeclampsia and fetal growth restriction placentas.
abstract: Oxidative stress and increased apoptosis are implicated in the pathogenesis of many disorders of pregnancy, including preeclampsia (PE) and fetal growth restriction (FGR). Since the transcription factor FOXO1 (forkhead box protein O1) is implicated in the regulation of a variety of cellular processes, including resistance to oxidative stress, apoptosis and morphogenesis of the placenta, we examined whether FOXO1 expression is abnormal in placentas from patients with PE or FGR. Paracentral sections from grossly unremarkable areas of 9 or 10 placentas each from early third trimester patients (31.7±5.0 weeks) with mild PE, severe PE, FGR and a gestational age-matched comparison group (GA controls) were double immunostained for FOXO1 and E-cadherin, the latter distinguishing villous cytotrophoblast cells (CTB) from syncytiotrophoblast (STB). The numbers of FOXO1-positive and FOXO1 negative STB and CTB nuclei were determined on ten 20x objective fields of each placenta section by three observers who were blinded to the clinical outcome. The results were evaluated by a generalized linear mixed model. In mild PE, FOXO1-positive STB nuclei were significantly decreased in number and FOXO1-negative STB nuclei were increased as compared to GA controls. However, the number of FOXO1-positive and FOXO1-negative CTB nuclei were not significantly changes as compared to GA controls. In severe PE and FGR, the numbers of FOXO-positive and FOXO1-negative STB and CTB were not statistically different from GA controls. Since FOXO1 is critical for placental cellular morphogenesis, abnormal FOXO1 expression may contribute in part to the abnormal trophoblast differentiation in mild PE. The differences in FOXO1 expression in mild and severe PE are consistent with other studies suggesting that the two forms of PE are different disease processes.
authors.affiliation: Division of Pathology, Department of Pediatrics, University of Cincinnati Medical College, Cincinnati, Ohio, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Sheridan
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Cincinnati Medical College, Cincinnati, Ohio, USA.
authors.forename: Chethan
authors.initials: C
authors.lastname: Belludi
authors.affiliation: Department of Biostatistics and Epidemiology, Cincinnati Children's Medical Center, Cincinnati, Ohio, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Khoury
authors.affiliation: Division of Pathology, Department of Pediatrics, University of Cincinnati Medical College, Cincinnati, Ohio, USA.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Stanek
authors.affiliation: Department of Endocrinology, Cincinnati Children's Medical Center3, Cincinnati, Ohio, USA. stuart.handwerger@cchmc.org.
authors.forename: Stuart
authors.initials: S
authors.lastname: Handwerger
mesh_terms: D000328:Adult; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics* / Q000378:metabolism*; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000235:genetics* / Q000378:metabolism*; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D014327:Trophoblasts / Q000378:metabolism* / Q000473:pathology
chemical_list: C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors