Mitochondria-mediated Effects of a Maternal High Fat Diet on Preimplantation Rat Embryos

Abigail Klein, University of South Dakota, Sanford School of Medicine, SD, United States; Ross Lanier, University of South Dakota, Sanford School of Medicine, United States; Tricia Larsen, Sanford Research, United States; Tyler Gandy, Sanford Research/University of South Dakota, United States; Kyle Siemers, University of South Dakota, Sanford School of Medicine, Sioux Falls, SD, United States; Michelle L. Baack, University of South Dakota, Sanford School of Medicine, Sioux Falls, SD, United States

Background: Consuming a high fat (HF) diet not only leads to reproductive consequences for the mother but can also program cardiometabolic disease risk in subsequent generations. Our lab used a rat model to show that a maternal HF diet increases mitochondrial dysfunction and cardiac disease across the lifespan of offspring, especially males exposed to late-gestation diabetes.

Objectives: To understand whether mitochondria-mediated consequences are maternally inherited or acquired during in utero exposure.

Design/Methods: We used a well-described rat model to determine the effect of HF diet on maternal ovaries, fertility, and early embryogenesis, then tested potentially mitigating effects of periconceptual supplementation with mitochondrial antioxidant, Coenzyme Q10 (CoQ10). First generation (F0) female rats were fed a control or HF diet for 28 days, then a subset of each group was switched to a CoQ10-supplemented diet before breeding. Serum, ovaries, and blastocysts were collected on embryonic day 4 for analyses.

Results: Ovaries from F0 dams on HF diet are smaller (p=0.01, n=20/group) and have more oxidized and fragmented mitochondrial DNA (p=0.18, n=4/group and p=0.04, n=2-3/group, respectively) which was associated with increased breeding time before successful pregnancy (p=0.02, n=5-10/group). CoQ10 supplementation increased ovarian mitochondrial CoQ levels and improved fertility in HF-fed dams. Preliminary data from immunofluorescent staining suggests mitochondria content and oxidative damage also differ amongst preimplantation embryos, suggesting baseline inheritable mtDNA damage may play a role in cardiometabolic programming.

Conclusion: Understanding inheritability of mitochondria-mediated perturbations and critical developmental periods to intervene with translatable dietary intervention could improve outcomes of both mothers and babies.
NIH/NHLBI 1R01HL160980-01