Studies on Transgenerational Passage of Programming by the TPLH Group in Collaboration with the University of Wyoming 

There is considerable interest in the transgenerational passage of outcomes of developmental programming. In particular it is necessary to find out whether these changes are due to epigenetic changes in the genome, which likely persist across generations, or just reflect the local changes in the maternal uterus to which the first-generation (or F1 offspring) of obese mothers are exposed. Since the gonads of the F1 generation are also in the uterus in the F1 fetus, local factors may be responsible for the changes. To determine that an effect of developmental programming is truly transgenerational by genetic mechanisms, it is necessary to study the F1, F2, and F3 generations. This has been done in a few studies in rodents where the lifespan is short and it is easy to reach the F3 generation. There are no studies in species more like the human such as the sheep or nonhuman primates. We therefore have developed the ability in our sheep models to maintain the F1 and F2 offspring of obese mothers and then developed the F3 offspring studies to determine whether these changes are truly transgenerational by epigenetic means. To our knowledge these are the only F3 offspring of a programming challenge in a large-bodied species available worldwide.

Publications on transgenerational programming by maternal obesity conducted by TPLH

  1. Maternal obesity and increased nutrient intake before and during gestation in the ewe results in altered growth, adiposity, and glucose tolerance in adult offspring | Journal of Animal Science | Oxford Academic. Available from: https://academic.oup.com/jas/article/88/11/3546/4764170
  2. Long, N. M., S. P. Ford, and P. W. Nathanielsz. 2011. Maternal obesity eliminates the neonatal lamb plasma leptin peak. The Journal of Physiology. 589:1455–1462. doi:10.1113/jphysiol.2010.201681.
  3. Tuersunjiang, N., J. F. Odhiambo, D. R. Shasa, A. M. Smith, P. W. Nathanielsz, and S. P. Ford. 2017. Maternal obesity programs reduced leptin signaling in the pituitary and altered GH/IGF1 axis function leading to increased adiposity in adult sheep offspring. PLOS ONE. 12:e0181795. doi:10.1371/journal.pone.0181795.
  4. Long, N. M., D. C. Rule, N. Tuersunjiang, P. W. Nathanielsz, and S. P. Ford. 2015. Maternal Obesity in Sheep Increases Fatty Acid Synthesis, Upregulates Nutrient Transporters, and Increases Adiposity in Adult Male Offspring after a Feeding Challenge. PLOS ONE. 10:e0122152. doi:10.1371/journal.pone.0122152.
  5. Ghnenis, A. B., J. F. Odhiambo, R. J. McCormick, P. W. Nathanielsz, and S. P. Ford. 2017. Maternal obesity in the ewe increases cardiac ventricular expression of glucocorticoid receptors, proinflammatory cytokines and fibrosis in adult male offspring. PLOS ONE. 12:e0189977. doi:10.1371/journal.pone.0189977.
  6. Yan, X., Y. Huang, J.-X. Zhao, N. M. Long, A. B. Uthlaut, M.-J. Zhu, S. P. Ford, P. W. Nathanielsz, and M. Du. 2011. Maternal Obesity-Impaired Insulin Signaling in Sheep and Induced Lipid Accumulation and Fibrosis in Skeletal Muscle of Offspring. Biol Reprod. 85:172–178. doi:10.1095/biolreprod.110.089649.
  7. Shasa, D. R., J. F. Odhiambo, N. M. Long, N. Tuersunjiang, P. W. Nathanielsz, and S. P. Ford. 2015. Multigenerational impact of maternal overnutrition/obesity in the sheep on the neonatal leptin surge in granddaughters. International Journal of Obesity 39:Up695–701. doi:10.1038/ijo.2014.190.
  8. Pankey, C. L., M. W. Walton, J. F. Odhiambo, A. M. Smith, A. B. Ghnenis, P. W. Nathanielsz, and S. P. Ford. 2017. Intergenerational impact of maternal overnutrition and obesity throughout pregnancy in sheep on metabolic syndrome in grandsons and granddaughters. Domestic Animal Endocrinology. 60:67–74. doi:10.1016/j.domaniend.2017.04.002.