Hellgren 2020 Free Radic Biol Med

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Hellgren KT, Premanandhan H, Quinn CJ, Trafford AW, Galli GLJ (2020) Sex-dependent effects of developmental hypoxia on cardiac mitochondria from adult murine offspring . Free Radic Biol Med [Epub ahead of print].

» PMID: 33186741

Hellgren Kim T, Premanandhan Hajani, Quinn Callum J, Trafford Andrew W, Galli Gina L J (2020) Free Radic Biol Med

Abstract: Insufficient oxygen supply (hypoxia) during fetal and embryonic development can lead to latent phenotypical changes in the adult cardiovascular system, including altered cardiac function and increased susceptibility to ischemia reperfusion injury. While the cellular mechanisms underlying this phenomenon are largely unknown, several studies have pointed towards metabolic disturbances in the heart of offspring from hypoxic pregnancies. To this end, we investigated mitochondrial function in the offspring of a mouse model of prenatal hypoxia. Pregnant C57 mice were subjected to either normoxia (21%) or hypoxia (14%) during gestational days 6-18. Offspring were reared in normoxia for up to 8 months and mitochondrial biology was assessed with electron microscopy (ultrastructure), spectrophotometry (enzymatic activity of electron transport chain complexes), microrespirometry (oxidative phosphorylation and H202 production) and Western Blot (protein expression). Our data showed that male adult offspring from hypoxic pregnancies possessed mitochondria with increased H202 production and lower respiratory capacity that was associated with reduced protein expression of complex I, II and IV. In contrast, females from hypoxic pregnancies had a higher respiratory capacity and lower H202 production that was associated with increased enzymatic activity of complex IV. From these results, we speculate that early exposure to hypoxia has long term, sex-dependent effects on cardiac metabolic function, which may have implications for cardiovascular health and disease in adulthood.

Keywords: Developmental programming, Fetal hypoxia, Heart, Mitochondria, Reactive oxygen species Bioblast editor: Plangger M O2k-Network Lab: UK Manchester Galli GL


Labels: MiParea: Respiration, Developmental biology 

Stress:Hypoxia  Organism: Mouse 




HRR: Oxygraph-2k 

2020-11