Observational human data and several lines of animal experimental data indicate that maternal obesity impairs offspring health. Here, we comprehensively tested the model that maternal obesity causes defects in the next three generations of oocytes and embryos. We exposed female F0 mice to a high-fat/high-sugar (HF/HS) diet for 6 weeks before conception until weaning. Sires, F1 offspring and all subsequent generations were fed control chow diet. Oocytes from F1, F2 and F3 offspring of obese mothers had lower mitochondrial mass and less ATP and citrate than oocytes from offspring of control mothers. F0 blastocysts from HF/HS-exposed mice, but not F1 and F2 blastocysts, had lower mitochondrial mass and membrane potential, less citrate and ATP and smaller total cell number than F0 blastocysts from control mothers. Finally, supplementation of IVF media with the anti-oxidant mito-esculetin partially prevented the oocyte mitochondrial effects caused by maternal HF/HS diet. Our results support the idea that maternal obesity impairs offspring oocyte quality and suggest that antioxidant supplementation should be tested as a means to improve IVF outcomes for obese women.
Keywords: HF/HS diet; blastocyst; mito-esculetin; mitochondria; oocytes.
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