Sex-dependent Effects of Developmental Hypoxia on Cardiac Mitochondria from Adult Murine Offspring

Kim Hellgren, Hajani Premanandhan, Callum Quinn, Andrew Trafford, Gina Galli

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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 H 20 2 production) and Western Blot (protein expression). Our data showed that male adult offspring from hypoxic pregnancies possessed mitochondria with increased H 20 2 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 H 20 2 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.

Original languageEnglish
JournalFree Radical Biology and Medicine
Publication statusPublished - 10 Nov 2020


  • Developmental programming
  • Fetal hypoxia
  • Heart
  • Mitochondria
  • Reactive oxygen species


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