title: Effect of high oxygen on placental function in short-term explant cultures.
abstract: Ex situ culture of human gestational tissues has been routinely used as a model to investigate tissue function. The objective of this study was to determine the effect of varying oxygen concentrations on human term placental explants over a 24-h time period. Specifically, the effect of incubating placental explants in oxygen concentrations of 8%, 21% or 95% on tissue viability, metabolism and cell death was measured by assessing glucose consumption, lactate production, release of lactate dehydrogenase, parathyroid hormone-related protein (PTHrP), tumour necrosis factor-alpha (TNF-alpha) and 8-isoprostane, immunoreactivity for cleaved-caspase-9 and immunohistochemistry for the caspase-3-cleaved cytokeratin-18 neoepitope, M30. Exposure to higher oxygen concentrations significantly increased the rates of glucose consumption and lactate production. Apoptosis was significantly increased under conditions of higher oxygen as evidenced by increased M30 in placental explant sections. Similarly, hyperoxia significantly increased the releases of PTHrP, TNF-alpha and 8-isoprostane. Thus, incubation of placental explants with oxygen concentrations of 95% and, to a lesser extent, 21% oxygen was associated with the modulation of multiple cellular response pathways including those associated with tissue viability and cell death. These data are consistent with the hypothesis that hyperoxia activates pathways and mechanisms involved in cellular metabolism, necrosis and apoptosis, thereby shifting the balance from a steady state towards cell death.
authors.affiliation: Department of Obstetrics and Gynaecology, Mercy Perinatal Research Centre, Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, Victoria, 3084, Australia.
authors.forename: Nicole G
authors.initials: NG
authors.lastname: Reti
authors.forename: Martha
authors.initials: M
authors.lastname: Lappas
authors.forename: Berthold
authors.initials: B
authors.lastname: Huppertz
authors.forename: Clyde
authors.initials: C
authors.lastname: Riley
authors.forename: Mary E
authors.initials: ME
authors.lastname: Wlodek
authors.forename: Phil
authors.initials: P
authors.lastname: Henschke
authors.forename: Michael
authors.initials: M
authors.lastname: Permezel
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Rice
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D002478:Cells, Cultured; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D006801:Humans; D009924:Organ Culture Techniques; D010100:Oxygen / Q000494:pharmacology*; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D011247:Pregnancy; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D044162:Parathyroid Hormone-Related Protein; D014409:Tumor Necrosis Factor-alpha; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D010100:Oxygen