title: A role for the mitochondrial-associated protein p32 in regulation of trophoblast proliferation.
abstract: p32 is a conserved eukaryotic protein which is primarily expressed in the mitochondria and regulates cell proliferation, migration and metabolism in various tissues. In this study, we sought to examine the expression and function of p32 in the human placenta. p32 was highly expressed in the syncytiotrophoblast, the underlying cytotrophoblast (CTB), the vascular endothelium and by a proportion of cells in the villous stroma in first trimester and term placenta. p32 mRNA and protein expression was significantly higher in the first trimester of pregnancy than at term, and expression in the trophoblast was significantly reduced in placentas from women with fetal growth restriction (FGR). Small interfering RNA (siRNA)-mediated knockdown of p32 in term placental explants significantly reduced the number of Ki67-positive CTB, but did not alter CTB apoptosis or necrosis. p32 knockdown increased lactate production, reduced glucose extraction from culture medium and was associated with reduced MitoTracker dye accumulation in trophoblast mitochondria. p32 knockdown was also associated with a significant reduction in expression of the mitochondrial respiratory complexes I and IV. These data suggest that p32 expression is important for CTB proliferation, via a mechanism involving regulation of normal mitochondrial function. As p32 expression is reduced in FGR placentas, this may contribute to some of the observed placental pathology, such as reduced CTB proliferation and mitochondrial dysfunction.
authors.affiliation: Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, Manchester M13 9WL, UK Maternal and Fetal Health Research Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, UK.
authors.forename: P
authors.initials: P
authors.lastname: Matos
authors.affiliation: Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, Manchester M13 9WL, UK Maternal and Fetal Health Research Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, UK.
authors.forename: J A
authors.initials: JA
authors.lastname: Horn
authors.affiliation: Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, Manchester M13 9WL, UK Maternal and Fetal Health Research Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, UK.
authors.forename: F
authors.initials: F
authors.lastname: Beards
authors.affiliation: Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, Manchester M13 9WL, UK Maternal and Fetal Health Research Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, UK.
authors.forename: S
authors.initials: S
authors.lastname: Lui
authors.affiliation: Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, Manchester M13 9WL, UK Maternal and Fetal Health Research Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, UK.
authors.forename: M
authors.initials: M
authors.lastname: Desforges
authors.affiliation: Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, Manchester M13 9WL, UK Maternal and Fetal Health Research Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, UK lynda.k.harris@manchester.ac.uk.
authors.forename: L K
authors.initials: LK
authors.lastname: Harris
mesh_terms: D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D014327:Trophoblasts / Q000166:cytology* / Q000378:metabolism*
chemical_list: C087299:C1QBP protein, human; D002352:Carrier Proteins; D024101:Mitochondrial Proteins; D034741:RNA, Small Interfering
keywords: fetal growth restriction; mitochondria; p32; proliferation; trophoblast