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Harrison, Matthew James
Languages: English
Types: Unknown
Epidemiological associations between birthweight and cardiovascular disease in adult life are supported by rodent experiments showing that undernutrition in fetal life programmes adult blood pressure. In rats, the feeding of a maternal low protein(MLP) diet during gestation programmes hypertension. Given interest in the mechanistic role of epigenetic modification of gene expression in programming, this study aimed to assess the potential for a nutritional insult to impact across several generations. Pregnant female Wistar (F0) rats were fed a control (n=10) or MLP diet(n=10) throughout gestation. At delivery all animals were fed the same standard laboratory chow diet. At approximately 10 weeks of age, F1 generation offspring were mated to produce a second generation (F2) without any further dietary change. The same procedure was adhered to, to produce the F3 generation. Physiological analysis confirmed F1 generation MLP exposed offspring exhibited raised (P<0.001)systolic blood pressure and reduced nephron number (P<0.001) compared with controls. Raised blood pressure and reduced nephron number were also noted in the F2 generation (P<0.001) and this intergenerational transmission occurred via both the maternal and paternal lines, No effect was noted in the F3 generation. Microarray analysis highlighted a number of genes that were differentially expressed however upon RT-PCR analysis results were not significant. DNA methylation analysis noted in a trend towards hypomethylation in MLP exposed rats and their offspring as described in previous studies. In conclusion, data within this thesis shows for the first time, that fetal protein restriction may play a critical role in determining blood pressure and overall disease risk in a subsequent generation. It is clear from the data that both males and females can transmit their phenotype to a subsequent generation. This finding suggests that maternal diet can influence the nature of epigenetic markers in germ line cells.
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    • Z. Mansano, J. S. Torday and C. C. Nast (2008). "Mechanisms of impaired nephrogenesis with fetal growth restriction: altered renal transcription and growth factor expression." Am J Obstet Gynecol 199(3): 252 e1-7.
    • Almeida, S. S., J. Tonkiss and J. R. Galler (1996). "Prenatal protein malnutrition affects exploratory behavior of female rats in the elevated plusmaze test." Physiol Behav 60(2): 675-80.
    • Antonov, A. N. (1947). "Children Born during the siege of Leningrad in 1942." Journal of Paediatrics 30: 250-259.
    • Anway, M. D., A. S. Cupp, M. Uzumcu and M. K. Skinner (2005).
    • "Epigenetic transgenerational actions of endocrine disruptors and male fertility." Science 308(5727): 1466-9.
    • Anway, M. D., C. Leathers and M. K. Skinner (2006a). "Endocrine disruptor vinclozolin induced epigenetic transgenerational adult-onset disease." Endocrinology 147(12): 5515-23.
    • Anway, M. D., M. A. Memon, M. Uzumcu and M. K. Skinner (2006b).
    • "Transgenerational effect of the endocrine disruptor vinclozolin on male spermatogenesis." J Androl 27(6): 868-79.
    • Anway, M. D., S. S. Rekow and M. K. Skinner (2008). "Transgenerational epigenetic programming of the embryonic testis transcriptome." Genomics 91(1): 30-40.
    • Barker, D. J., P. D. Winter, C. Osmond, B. Margetts and S. J. Simmonds (1989). "Weight in infancy and death from ischaemic heart disease." Lancet 2(8663): 577-80.
    • Barker, D. J. (1992). "The fetal origins of adult hypertension." J Hypertens Suppl 10(7): S39-44.
    • Barker, D. J., P. D. Gluckman, K. M. Godfrey, J. E. Harding, J. A. Owens and J. S. Robinson (1993). "Fetal nutrition and cardiovascular disease in adult life." Lancet 341(8850): 938-41.
    • Barker, D. J., T. Forsen, J. G. Eriksson and C. Osmond (2002a). "Growth and living conditions in childhood and hypertension in adult life: a longitudinal study." J Hypertens 20(10): 1951-6.
    • Barker, D. J., J. G. Eriksson, T. Forsen and C. Osmond (2002b). "Fetal origins of adult disease: strength of effects and biological basis." Int J Epidemiol 31(6): 1235-9.
    • Barker, D. J. P. (1994). Mothers, Babies and Disease in Later Life. London, BMJ Publishing Group.
    • Bartley, M., C. Power, G. Davey-Smith and M. Shipley (1994). "Birthweight and later socio-economic disadvantage: evidence from the 1958 British cohort study." British Medical Journal 309: 1475-1478.
    • Metcalfe, P. Monaghan, H. G. Spencer and S. E. Sultan (2004).
    • "Developmental plasticity and human health." Nature 430(6998): 419-421.
    • Battista, M. C., L. L. Oligny, J. St-Louis and M. Brochu (2002). "Intrauterine growth restriction in rats is associated with hypertension and renal dysfunction in adulthood." Am J Physiol Endocrinol Metab 283(1): E124-31.
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