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Effect of high oxygen on placental function in short-term explant cultures

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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-α) 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-α 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.

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Acknowledgments

The authors gratefully acknowledge the contribution made by the clinical research midwives (Val Bryant, Sarah Mitchell, Angie Denning, Melissa Ryan and Ellen Smith) at the Mercy Hospital for Women. They are also grateful to both Daphne Hards and Patricia Ho at the St Vincent’s Institute for Medical Research for time spent on paraffin embedding and performing the PTHrP radioimmunoassay, respectively. Finally, they thank the Medical Research Foundation for Women and Babies for providing funding for the Leica Qwin Image Analysis System.

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Correspondence to Martha Lappas.

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Reti, N.G., Lappas, M., Huppertz, B. et al. Effect of high oxygen on placental function in short-term explant cultures. Cell Tissue Res 328, 607–616 (2007). https://doi.org/10.1007/s00441-006-0375-1

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  • DOI: https://doi.org/10.1007/s00441-006-0375-1

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