PS4-5. The Impact of Poor Maternal Nutrition on Mitochondrial Regulatory Factors of Sheep Offspring.

Abstract Poor maternal nutrition, over- and restricted- feeding ewes during gestation detrimentally impact offspring growth and development. We previously demonstrated that poor maternal nutrition in sheep led to offspring with fewer skeletal muscle fibers, smaller cross-sectional areas, and greater intramuscular adiposity. Alterations in skeletal muscle composition and structure may be associated with mitochondrial dysfunction or a decrease in ATP synthesis. Poor maternal nutrition did not impact skeletal mitochondrial cardiolipin content, a phospholipid responsible for mitochondrial structure, however, further understanding of the factors associated with mitochondrial function is important for determining the role of mitochondria in fetal programming. We hypothesized that poor maternal nutrition would reduce gene expression of factors associated with cardiolipin and mitochondrial function and decrease NAD+/NADH content. Ewes (F0; n = 46) were fed a control (CON = 100%), restricted- (RES = 60%), or over-fed (OVER = 140%) diet based on nutrient requirements for ewes pregnant with twins from 31±1.3 of gestation until parturition. Ram offspring (F1; n = 46) were necropsied at d 285 ±- 0.93 of age and longissimus muscle (LM) was collected for gene expression of tafazzin (TAZZ), phospholipid scramblase 3 (PCLRS3), sirtuin 1 (SIRT1), sirtuin 4 (SIRT4), and histone deacetylase 9 (HDAC9). A fluorometric assay kit was utilized to quantify NAD+ and NADH content. Data were analyzed using Proc MIXED in SAS with significance set at P < 0.05 and tendencies considered at 0.05 < P ≤ 0.10. Poor maternal nutrition did not alter NAD + (P = 0.52), NADH (P = 0.43), or NAD+/NADH ratio (P = 0.29) content. Expression of TAZZ tended to be different due to maternal diet (P = 0.07), where TAZZ expression was decreased in RES compared with OVER (P = 0.03) and tended to be decreased compared with CON (P = 0.07). There were no differences in the gene expression of SIRT1 (P = 0.71) SIRT4 (P = 0.71), or PCLRS3 (P = 0.24). Maternal diet tended to alter expression of HDAC9 (P = 0.07), where expression was reduced in RES compared with OVER (P = 0.03). Differences in TAZZ gene expression suggest that the structure of cardiolipin and the mitochondrial membrane are altered in RES offspring. Differences in HDAC9 gene expression suggest that changes in epigenetic regulation may vary between restricted- and over- fed maternal nutrition. In conclusion, poor maternal nutrition during gestation alters factors that influence mitochondrial function in offspring, which may possibly be passed to multiple generations through epigenetic mechanisms.