High Fat Diet Impairs Fertility and is Partially Rescued by Coenzyme Q10 — 77p — Mary Sicard, Abigail Klein, Kyle Siemers, Tricia Larsen, Prathapan Ayyappan

Overconsumption of dietary fat is associated with obesity and poorer reproductive outcomes in humans. Our lab used a rat model to show that high-fat (HF) diet causes mitochondria-mediated cardiometabolic disease in offspring. During these studies, we noticed that dams on HF diet took longer to achieve pregnancy. We hypothesize that HF diet causes mitochondrial dysfunction and oxidative stress in the ovary to impair fertility, and that decreasing dietary fat intake and supplementing with Coenzyme Q10 (CoQ10) in the periconceptual period will improve reproductive outcomes. To test this, female rats were fed either a control (CD) or a HF diet for four weeks. After 4 weeks, rats on HF diet were either 1) continued on HF diet, 2) switched to a lower fat diet (HF-S,CD), 3) a CoQ10-supplemented diet (CoQ10) or 4) a combined lower fat + CoQ10 diet (HF-S,CoQ10) for 3 weeks prior to breeding with CD-fed males. Fertility was assessed by daily vaginal swabs for estrus cycling, 3-day post-estrus hormone levels, ovary follicle counts, and 8-oxo-2′-deoxyguanosine (8-oxodG) staining to assess oxidative damage. ANOVA was used for group comparisons with significance set at p<0.05. We found HF-fed dams took longer to achieve pregnancy (p<0.01, n=6-13/group) despite no differences in ovary weights, time spent in estrus, number of follicles or type of follicles. HF-fed dams tended to have more follicular oxidative DNA damage than controls, especially in primary follicles (p=0.11 and p=0.13, n=5-6/group). CoQ10 and combined HF-S,CoQ10 interventions shortened the time to achieve pregnancy (p<0.05, n=6-13/group) but HF-S without CoQ10 did not. Combined HF-S,CoQ10 tended to have fewer primary follicles but similar 8oxodG staining compared to controls (p=0.11, n=5-8/group). Reproductive hormone levels are pending. Our study suggests that periconceptual CoQ10 improves fertility, especially when combined with a lower-fat diet. Additional work is needed to understand the mechanism and effects on offspring.

Sanford Research
Michelle Baack