Poor Maternal Nutrition During Gestation Alters Mesenchymal Stem Cell (MSC) Metabolism in Offspring

Poor maternal diet refers to either a nutritional excess or deficiency in the mother during gestation (Reed et al. 2014). It has been well-studied that poor maternal gestational nutrition limits bone and muscle development while increasing adipose development in the offspring (Oreffo et al. 2003; Reed et al. 2014). There is also evidence that suggests poor maternal diet during gestation impairs mesenchymal stem cell (MSC) function (Oreffo et al. 2003). Tissues including bone, muscle, and adipose are derived from this fetal MSC pool (Lawrence et al. 2012). It was hypothesized that poor maternal diet during gestation would negatively alter MSC metabolism in offspring. Eighteen ewes were bred, confirmed pregnant, and individually housed. At d 31 ± 1.3 of gestation, ewes were randomly assigned to one of three diets: 100% (CON), 60% (RES), or 140% (OVER) of NRC requirements for TDN. The diet was maintained until parturition, after which one lamb per ewe was euthanized within 24 h. MSC (n = 6/treatment group) were isolated from the left tibia and femur of the lamb. Cells were plated at 30,000 cells/well and incubated for 48 h at 37oC. Glycolytic and mitochondrial function of the MSC were evaluated using Glycolysis Stress and Cell Mito Stress Test Kits. The assays were performed in the Seahorse XFe24 Extracellular Flux Analyzer. Data were normalized for total cellular DNA content and statistical analysis was performed using PROC MIXED in SAS. Basal respiration was reduced in RES and OVER, compared with CON (127.4 ± 7.48, 90.17 ± 9.75, and 87.51 ± 8.48 ρmol O2-1·minute-1·μg; CON, RES, and OVER, respectively; P ≤ 0.008). Compared with CON, RES and OVER had reduced ATP production (121.09 ± 6.08, 84.86 ± 11.05, and 77.7 ± 6.44 ρmol O2-1·minute-1·μg; CON, RES, and OVER, respectively; P ≤ 0.006) and reduced maximal respiration (149.29 ± 17.05, 90.64 ± 23.81, and 67.93 ± 10.15 ρmol O2-1·minute-1·μg; CON, RES, and OVER, respectively; P ≤ 0.03). Spare respiratory capacity was reduced in OVER compared with CON (P = 0.02) while RES were intermediate (21.9 ± 10.8, 0.47 ± 12.3, and -19.56 ± 9.24 ρmol O2-1·minute-1·μg; CON, RES, and OVER, respectively; P ≤ 0.25). There were no significant differences between groups for proton leak, non-mito-derived OCR, coupling efficiency, glycolysis, glycolytic reserve, non-glucose-derived extracellular acidification rate, and glycolytic reserve capacity (P ≥ 0.18). In conclusion, poor maternal diet during gestation reduces the basal metabolic state of MSC and restricts the ability to produce ATP during energetic demands. This could possibly contribute to the observed differences in muscle, bone, and adipose development of offspring born to over-fed or under-fed mothers