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. 2019 Nov 30;25(11):717-728.
doi: 10.1093/molehr/gaz049.

The effect of maternal high-fat/high-sugar diet on offspring oocytes and early embryo development

E Andreas  1 , M Reid  1 , W Zhang  1 , K H Moley  1
Affiliations

The effect of maternal high-fat/high-sugar diet on offspring oocytes and early embryo development

E Andreas et al. Mol Hum Reprod. .

Abstract

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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Figures

Figure 1
Figure 1
Effect of F0 diet on mitochondrial mass and membrane potential and Oma1 protein expression in offspring oocytes. (A and E) Representative images of oocytes derived from chow and HF/HS groups. Quantification of mitochondrial mass (MTDR), mitochondrial membrane potential (MTRC/MTDR) and lipid droplets (BODIPY 409/503) in oocytes derived from F1 (B), F2 (C) and F3 (D) generations (n = 29–30 oocytes derived from five mice/diet/generation). Quantification of Oma1 protein expression in F1 (F), F2 (G) and F3 (H) oocytes (n = 28–30 oocytes derived from five mice/diet/generation). Scale bar = 10 μm. Data are represented as mean ± SEM. **P < 0.01, ***P < 0.001, ****P < 0.0001.
Figure 2
Figure 2
Effect of F0 diet (chow versus HF/HS) on ATP and citrate in offspring oocytes. Quantification of ATP and citrate in oocytes derived from F1 (A), F2 (B) and F3 (C) mice (n = 29–30 oocytes derived from five mice/diet/generation). Data are represented as mean ± SEM. *P < 0.05, ****P < 0.0001.
Figure 3
Figure 3
Effect of F0 diet (chow versus HF/HS) on H3K9me2/3 and 5mC in offspring oocytes. (A) Representative images of oocytes derived from chow and HF/HS groups. Quantification of H3K9me2/3 and 5mC in oocytes derived from F1 (B), F2 (C) and F3 (D) generations (n = 29–32 oocytes derived from five mice/diet/generation). Scale bar = 10 μm. Data are represented as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001.
Figure 4
Figure 4
Effect of F0 diet (chow versus HF/HS) on mitochondria and lipid in offspring blastocysts. (A and E) Representative images of blastocysts derived from chow and HF/HS groups. Quantification of mitochondrial mass (MTDR), mitochondrial membrane potential (MTRC/MTDR) and lipid droplets (BODIPY 409/503) in blastocysts derived from F0 (B), F1 (C) and F2 (D) oocytes (n = 29–30 blastocysts derived from five mice/diet/generation). Quantification of Oma1 protein expression in blastocysts derived from F0 (F), F1 (G) and F2 (H) oocytes (n = 25–30 blastocysts derived from five mice/diet/generation). Scale bar = 10 μm. Data are represented as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.
Figure 5
Figure 5
Effect of F0 (chow versus HF/HS) diet on ATP and citrate in offspring blastocysts. Quantification of ATP and citrate in blastocysts derived from F0 (A), F1 (B) and F2 (C) oocytes (n = 27–30 blastocysts derived from five mice/diet/generation). Data are represented as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.
Figure 6
Figure 6
Effect of F0 diet (chow versus HF/HS) on H3K9 me2/3 and 5mC in offspring blastocysts. (A) Representative images of blastocysts derived from chow and HF/HS groups. Quantification of H3K9me2/3 and 5mC in blastocysts derived from F0 (B), F1 (C) and F2 (D) oocytes (n = 28–30 blastocysts derived from five mice/diet/generation). Scale bar = 10 μm. Data are represented as mean ± SEM. **P < 0.01.
Figure 7
Figure 7
Effect of F0 diet (chow versus HF/HS) on cell number and apoptosis in IVF-derived offspring blastocysts. (A) Representative images of blastocysts derived from chow and HF/HS groups. Total cell number, apoptotic cell number and apoptosis rate in blastocysts derived from F0 (B), F1 (C) and F2 (D) oocytes (n = 29–30 blastocysts derived from five mice/diet/generation). Scale bar = 10 μm. Data are represented as mean ± SEM. **P < 0.01, ***P < 0.001, ****P < 0.0001.
Figure 8
Figure 8
Effect of F0 diet (chow versus HF/HS) on blastocyst mitochondrial parameters and fat content with 1 μM mito-esculetin supplementation during IVF. (A and D) Representative images of blastocysts derived from chow and HF/HS groups. (B) Quantification of mitochondrial mass (MitoTracker Deep Red), mitochondrial membrane potential (MitoTracker CMXRos) and lipid droplets (BODIPY 409/503) in blastocysts derived from chow (n = 27 blastocysts from five mice) and HF/HS (n = 30 blastocysts from five mice) groups. (C) Quantification of ATP and citrate in blastocysts derived from F0 oocytes (n = 30 blastocysts derived from five mice/treatment). (E) Total cell number, apoptotic cell number and apoptosis rate in blastocysts derived F0 oocytes (n = 28–31 blastocysts derived from five mice/treatment). Scale bar = 10 μm. Data are represented as mean ± SEM. *P < 0.05, **P < 0.01, ****P < 0.0001.
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