Sex-specific effects of maternal dietary carbohydrate quality on fetal development and offspring metabolic phenotype in mice

ObjectivesIn utero glycemia is an important determinant of fetal growth. Women with gestational diabetes are more likely to deliver large-for-gestational age babies that are at increased risk for obesity. The maternal nutritional state modulates the development of offspring biological systems during the critical periods of gestation and lactation. Carbohydrate typically contributes most of the dietary energy, however, there are very few mechanistic studies investigating the effects of maternal dietary carbohydrate quality on fetal and offspring outcomes. Therefore, we sought to investigate the direct effects of maternal carbohydrate quality on sex-specific offspring metabolic programming. MethodsFemale C57BL/6 mice were fed one of five isocaloric diets: four high-sugar diets based on glucose, sucrose, isomaltulose or fructose (all containing 60% energy as carbohydrate), or a standard, minimally processed, chow diet, and were mated with chow-fed males. Half of the dams were sacrificed for fetus dissection and placental collection, with the remaining giving live birth. All dams were metabolically profiled before and during pregnancy, and pups were similarly profiled at 12 weeks of age. ResultsOverall, glucose-fed dams were heavier and fatter than chow or isomaltulose-fed dams. Female fetuses from glucose and isomaltulose-fed mothers weighed less and had smaller livers, than those from chow-fed mothers, with isomaltulose-fed female fetuses also having decreased placental mass. In contrast, male fetuses responded differently to the maternal diets, with heart mass being significantly increased when their mothers were fed fructose-containing diets, that is, sucrose, isomaltulose and fructose. High-sugar fed female offspring weighed the same, but were significantly fatter, than chow-fed offspring at 12 weeks of age, while glucose and isomaltulose-fed male pups displayed a similar phenotype to their mothers'. ConclusionWhile both glucose and isomaltulose diets constrained fetal growth in females, only placentas from isomaltulose-fed dams were significantly smaller than those from chow-fed mothers, suggesting the mechanisms through which fetal growth is reduced may be different. Female fetuses of isomaltulose-fed mothers were also lighter than sucrose-fed fetuses suggesting the glycemic index, or rate of glucose digestion and absorption, may be an important factor in determining nutrient availability to the growing fetus.