Tissue Specific Adaptations to Nutrient Supply: More than Just Epigenetics?
Changes in the maternal diet either throughout pregnancy, or at defined stages therein, can have pronounced effects on organogenesis in conjunction with endocrine sensitivity. These processes can be brought about by either maternal consumption of an imbalanced diet and/or a global reduction in macro or micro-nutrient intake. The magnitude of adaptation in the fetus or offspring is dependent on which organ is most rapidly growing and developing at that particular stage of the life cycle. For a majority of organs, the period of developmental plasticity extends beyond the fetal period, continuing through lactation and into the juvenile period. During lactation, enhanced growth of the offspring appears to be a primary determinant of the magnitude of adverse cardiovascular outcome. Consequently, a change in organ development during pregnancy may not necessarily equate with compromised function in later life. In the kidney, for example, adaptations in its endocrine sensitivity to maternal nutrient restriction through fetal development can be protective against the adverse consequences of later obesity. Such adaptations do not simply represent epigenetic modifications but a plethora of responses that, taken together, can prevent, or delay, at least in the kidney, the onset of apoptosis and later glomerulosclerosis.
KeywordsBlood pressure glucocorticoid receptor kidney obesity
Unable to display preview. Download preview PDF.
- Bispham, J., G. S. Gopalakrishnan, J. Dandrea, V. Wilson, H. Budge, D. H. Keisler, F. Broughton Pipkin, T. Stephenson and M. E. Symonds (2003). “Maternal endocrine adaptation throughout pregnancy to nutritional manipulation: consequences for maternal plasma leptin and cortisol and the programming of fetal adipose tissue development.” Endocrinology 144: 3575 – 3585.PubMedCrossRefGoogle Scholar
- Brennan, K. A., G. S. Gopalakrishnan, L. Kurlak, S. M. Rhind, C. E. Kyle, A. N. Brooks, M. T. Rae, D. M. Olson, T. Stephenson and M. E. Symonds (2005). “Impact of maternal undernutrition and fetal number on glucocorticoID, growth hormone and insulin-like growth factor receptor mRNA abundance in the ovine fetal kIDney.” Reproduction 129(2): 151 – 159.PubMedCrossRefGoogle Scholar
- Brennan, K. A., S. Kaufman, S. W. Reynolds, B. T. McCook, G. Kan, I. Christiaens, M. E. Symonds and D. Olson (2008). “Differential the effects of maternal nutrient restriction through pregnancy on kIDney development and later blood pressure control in the resulting offspring.” Am J Physiol295, R197 – R205.Google Scholar
- Gnanalingham, M. G., A. Mostyn, M. E. Symonds and T. Stephenson (2005b). “Ontogeny and nutritional programming of adiposity: potential role of glucocorticoID sensitivity and uncoupling protein-2.” Am J Physiol 289: R1407 – R1415.Google Scholar
- Gnanalingham, M. G., A. Mostyn, D. S. Gardner, T. Stephenson and M. E. Symonds (2006). “Developmental regulation of the lung in preparation for life after birth: nutritional manipulation of local glucocorticoID action and uncoupling protein 2.” J Endocrinol 188: 375 – 386.PubMedCrossRefGoogle Scholar
- Gopalakrishnan, G., D. S. Gardner, J. Dandrea, S. C. Langley-Evans, S. Pearce, L. O. Kurlak, R. M. Walker, I. Sweetho, D. H. Keisler, M. M. Ramsay, T. Stephenson and M. E. Symonds (2005). “Influence of maternal pre-pregnancy body composition and diet during early-mID pregnancy on cardiovascular function and nephron number in juvenile sheep.” Brit J Nutr 94: 938 – 947.PubMedCrossRefGoogle Scholar
- Hoppe, C. C., R. G. Evans, K. M. Moritz, L. A. Cullen-McEwen, S. M. Fitzgerald, J. Dowling and J. F. Bertram (2007). “Combined prenatal and postnatal protein restriction influences adult kIDney structure, function, and arterial pressure.” Am J Physiol 292(1): R462 – R469.Google Scholar
- Rajah, R., B. Valentinis and P. Cohen (1997). “Insulin-like growth factor (IGF)-binding protein-3 induces apoptosis and mediates the effects of transforming growth factor-beta1 on programmed cell death through a p53- and IGF-independent mechanism.” J Biol Chem 272(18): 12181 – 12188.PubMedCrossRefGoogle Scholar
- Whorwood, C. B., K. M. Firth, H. Budge and M. E. Symonds (2001). “Maternal undernutrition during early- to mID-gestation programmes tissue-specific alterations in the expression of the glucocorticoID receptor, 11β-hydroxysteroID dehydrogenase isoforms and type 1 angiotensin II receptor in neonatal sheep.” Endocrinology 142: 2854 – 2864.PubMedCrossRefGoogle Scholar
- Wintour, E. M. and K. M. Moritz (1997). “Comparative aspects of fetal renal development.” Equine Vet J 24: 51 – 58.Google Scholar