Evidence for similar changes in offspring phenotype following either maternal undernutrition or overnutrition: potential impact on fetal epigenetic mechanisms
S. P. Ford A B C and N. M. Long A B
+ Author Affiliations
- Author Affiliations
A Center for the Study of Fetal Programming, University of Wyoming, Laramie, WY 82071, USA.
B Department of Animal Science, University of Wyoming, Laramie, WY 82071, USA.
C Corresponding author. Email: spford@uwyo.edu
Reproduction, Fertility and Development 24(1) 105-111 https://doi.org/10.1071/RD11911
Published: 6 December 2011
Abstract
The goal of this review is to shed light on the role of maternal malnutrition in inducing epigenetic changes in gene expression, leading to alterations in fetal growth and development, and to altered postnatal phenotype and the development of metabolic disease. We present evidence supporting the concept that both maternal undernutrition and overnutrition can induce the same cadre of fetal organ and tissue abnormalities and lead to the same postnatal metabolic changes in the resulting offspring. Furthermore, we present evidence that in both overnourished and undernourished ovine pregnancies, fetuses experience a period of nutrient restriction as a result of alterations in placental delivery of maternal nutrients into the fetal compartment. We argue that this bout of reduced fetal nutrition in undernourished and overnourished pregnancies leads to the development of a thrifty phenotype in which the fetus attempts to alter the function of its tissues and organs to maximise its chances of survival in a postnatal environment that is deficient in nutrients. Importantly, we present evidence to support the concept that these phenotypic changes in offspring quality resulting from maternal malnutrition are transmitted to subsequent generations, independent of their maternal nutritional inputs.
Additional keywords: maternal nutrition, transgenerational effects.
References
Aitken, R. J., Koopman, P., and Lewis, S. E. (2004). Seeds of concern. Nature 432, 48–52.| Seeds of concern.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXpt1eitrc%3D&md5=1f710ef0e18acda8e829acfa120d6995CAS |
Attig, L., Djiane, J., Gertler, A., Rampin, O., Larcher, T., Boukthir, S., Anton, P.M., Madec, J.Y., Gourdou, I., and Abdennebi-Najar, L. (2008). Study of hypothalamic leptin receptor expression in low-birth-weight piglets and effects of leptin supplementation on neonatal growth and development. Am. J. Physiol. Endocrinol. Metab. 295, E1117–E1125.
| Study of hypothalamic leptin receptor expression in low-birth-weight piglets and effects of leptin supplementation on neonatal growth and development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhsVWkurfE&md5=fd8c049f892935bc1826e3cb42991773CAS |
Barker, D. J. P. (1995). Fetal origins of coronary heart disease. BMJ 331, 171–174.
Barker, D. J. P. (1999). Fetal programming and public health. In ‘Fetal Programming: Influences on Development and Disease in Later Life’. (Eds P. M. S. O’Brien, T. Wheeler, D. J. P. Barker.) pp. 3–11. (TCOG Press: London.)
Barker, D. J., and Osmond, C. (1986). Infant mortality, childhood nutrition, and ischemic heart disease in England and Wales. Lancet 1, 1235–1239.
Barker, D. J., Winter, P. D., Osmond, C., Margetts, B., and Simmons, S. J. (1989). Weight in infancy and death from ischemic heart disease. Lancet 334, 577–580.
| Weight in infancy and death from ischemic heart disease.Crossref | GoogleScholarGoogle Scholar |
Barker, D. J., Eriksson, J. G., Forsen, T., and Osmond, C. (2002). Fetal origins of adult disease: strength of effects and biological basis. Int. J. Epidemiol. 31, 1235–1239.
| Fetal origins of adult disease: strength of effects and biological basis.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3s%2FosVOksw%3D%3D&md5=5957d32bc59b05f8a2b89afdbfb5125eCAS |
Barton, T. S., Robaire, B., and Hales, B. F. (2007). DNA damage recognition in the rat zygote following chronic paternal cyclophosphamide exposure. Toxicol. Sci. 100, 495–503.
| DNA damage recognition in the rat zygote following chronic paternal cyclophosphamide exposure.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhtlaqurbN&md5=5557cb8b4a55d978e0f4f43124638413CAS |
Bateson, P. (2001). Fetal experience and good adult design. Int. J. Epidemiol. 30, 928–934.
| Fetal experience and good adult design.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3MnjvFyisQ%3D%3D&md5=8ce5078f45229159562946776aa319e6CAS |
Bernstein, E., and Allis, C. D. (2005). RNA meets chromatin. Genes Dev. 19, 1635–1655.
| RNA meets chromatin.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXmslGhtbk%3D&md5=7a7b477c467803a36bca856c094ff841CAS |
Boney, C. M., Verma, A., Tucher, R., and Vohr, B. R. (2005). Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics 115, e290–e296.
| Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus.Crossref | GoogleScholarGoogle Scholar |
Bouret, S. G. (2009). Early life origins of obesity: role of hypothalamic programming. J. Pediatr. Gastroenterol. Nutr. 48, 531–538.
Burt, B. E., Hess, B. W., Nathanielsz, P. W., and Ford, S. P. (2007). Flock differences in the impact of maternal dietary restriction on offspring growth and glucose tolerance in female offspring. Soc. Reprod. Fertil. Suppl. 64, 411–424.
| 1:CAS:528:DC%2BD1cXpvVyrsb0%3D&md5=ead440e1ef581337e280eaf887a874d3CAS |
Delahaye, F., Breton, C., Risold, P. Y., Enache, M., Dutriez-Casteloot, I., Laborie, C., Lesage, J., and Vieau, D. (2008). Maternal perinatal undernutrition drastically reduces postnatal leptin surge and affects the development of the arquate nucleus proopiomelanocortin neurons in neonatal male rat pups. Endocrinology 149, 470–475.
| Maternal perinatal undernutrition drastically reduces postnatal leptin surge and affects the development of the arquate nucleus proopiomelanocortin neurons in neonatal male rat pups.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXht1yqsb8%3D&md5=23d55de5c17826ecb4d71500abe79271CAS |
Dong, F., Ford, S. P., Nijland, M. J., Nathanielsz, M. J., and Ren, J. (2008). Influence of maternal undernutrition and overfeeding on cardiac ciliary neurotrophic factor receptor and ventricular size in fetal sheep. J. Nutr. Biochem. 19, 409–414.
| Influence of maternal undernutrition and overfeeding on cardiac ciliary neurotrophic factor receptor and ventricular size in fetal sheep.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXmsValtLw%3D&md5=691a16a72766e56e08b23a9c20246722CAS |
Du Plessis, S. S., Cabler, S., McAlister, D. A., Sabanegh, E., and Agarwal, A. (2010). The effect of obesity on sperm disorders and male infertility. Nat. Rev. Urol. 7, 153–161.
| The effect of obesity on sperm disorders and male infertility.Crossref | GoogleScholarGoogle Scholar |
Dunn, G. A., and Bale, T. L. (2009). Maternal high-fat diet promotes body length increases and insulin insensitivity in second-generation mice. Endocrinology 150, 4999–5009.
| Maternal high-fat diet promotes body length increases and insulin insensitivity in second-generation mice.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhsVCht7bI&md5=2e3ca363ca23e06a50facce234170c99CAS |
Ergaz, Z., Avgil, M., and Ornoy, A. (2005). Intrauterine growth restriction: etiology and consequences: what do we know about the human situation and experimental animal models. Reprod. Toxicol. 20, 301–322.
| Intrauterine growth restriction: etiology and consequences: what do we know about the human situation and experimental animal models.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXlvFKgtLs%3D&md5=322c0b264611ba7424b245da814c89fbCAS |
Fan, X., Turdi, S., Ford, S. P., Hua, Y., Nijland, M. J., Zhu, M., Nathanielsz, P. W., and Ren, J. (2011). Influence of gestational overfeeding on cardiac morphometry and hypertrophic protein markers in fetal sheep. J. Nutr. Biochem. 22, 30–37.
| Influence of gestational overfeeding on cardiac morphometry and hypertrophic protein markers in fetal sheep.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhsFGhtbvJ&md5=3bb405cf4a7597d4d3d5cca39fae9345CAS |
Ford, S. P., Hess, B. W., Schwope, M. M., Nijland, M. J., Gilbert, J. S., Vonnahme, K. A., Means, W. J., Han, H., and Nathanielsz, P. W. (2007). Maternal undernutrition during early to mid-gestation in the ewe results in altered growth, adiposity, and glucose tolerance in male offspring. J. Anim. Sci. 85, 1285–1294.
| Maternal undernutrition during early to mid-gestation in the ewe results in altered growth, adiposity, and glucose tolerance in male offspring.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXksF2hur8%3D&md5=3d5273743cc7b88256f531053243f1f7CAS |
Ford, S. P., Zhang, L., Zhu, M., Miller, M. M., Smith, D. T., Hess, B. W., Moss, G. E., Nathanielsz, P. W., and Nijland, M. J. (2009). Maternal obesity accelerates fetal pancreatic beta-cell but not alpha-cell development in sheep: prenatal consequences. Am. J. Physiol. Regul. Integr. Comp. Physiol. 297, R835–R843.
| 1:CAS:528:DC%2BD1MXhtFGrtbbJ&md5=54477f170fccbae91db8c282d495baf8CAS |
Ford, S. P., Shasa, D. R., Nathanielsz, P. W., and Long, N. M. (2011). The impact of maternal obesity on eliminating the postnatal leptin spike and increasing adiposity of offspring across multiple generations in the sheep: Direct evidence for developmental programming. Proc. Soc. Study. Reprod., Portland, OR. , .
Gilbert, J. S., Lang, A. L., Grant, A. R., and Nijland, M. J. (2005). Maternal nutrient restriction in sheep: Hypertension and decreased nephron number in offspring at 9 months of age. J. Physiol. 565, 137–147.
| Maternal nutrient restriction in sheep: Hypertension and decreased nephron number in offspring at 9 months of age.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXkslyru7c%3D&md5=9600bcba1d3743db95ff0edfc70e94f9CAS |
Gluckman, P. D., and Hanson, M. A. (2004). Developmental origins of disease paradigm: a mechanistic and evolutionary perspective. Pediatr. Res. 56, 311–317.
| Developmental origins of disease paradigm: a mechanistic and evolutionary perspective.Crossref | GoogleScholarGoogle Scholar |
Gluckman, P. D., Hanson, M. A., and Spencer, H. G. (2005). Predictive Adaptive Response and human evolution. Trends Ecol. Evol. 20, 527–533.
| Predictive Adaptive Response and human evolution.Crossref | GoogleScholarGoogle Scholar |
Godfrey, K., and Robinson, S. (1998). Maternal nutrition, placental growth and fetal programming. Proc. Nutr. Soc. 57, 105–111.
| Maternal nutrition, placental growth and fetal programming.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK1c3jtlajtA%3D%3D&md5=4751e65232621334a2acc00bea34b7eaCAS |
Goldberg, A. D., Allis, C. D., and Bernstein, E. C. (2007). Epigenetics: a landscape takes shape. Cell 128, 635–638.
| Epigenetics: a landscape takes shape.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXis12ju74%3D&md5=c3ed7c57f1ac83d6936477fb9717e5e5CAS |
Guerrero-Bosagna, C., Settles, M., Lucker, B., and Skinner, M. K. (2010). Epigenetic transgenerational actions of vinclozolin on promoter regions of the sperm epigenome. PLoS ONE 5, e13100.
| Epigenetic transgenerational actions of vinclozolin on promoter regions of the sperm epigenome.Crossref | GoogleScholarGoogle Scholar |
Hales, C. N., and Barker, D. J. (2001). The thrifty phenotype hypothesis. Br. Med. Bull. 60, 5–20.
| The thrifty phenotype hypothesis.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD38%2Fot12mug%3D%3D&md5=b4e075a13f4dba5fbaca60f45a8f40b0CAS |
Huang, Y., Yan, X., Zhao, J. X., Zhu, M. J., McCormick, R. J., Ford, S. P., Nathanielsz, P. W., Ren, J., and Du, M. (2010). Maternal obesity induces fibrosis in fetal myocardium of sheep. Am. J. Physiol. Endocrinol. Metab. 299, E968–E975.
| Maternal obesity induces fibrosis in fetal myocardium of sheep.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhs1aisbfK&md5=adf811748c916c39694ba8e440983d14CAS |
Jaenisch, R., and Bird, A. (2003). Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat. Genet. 33, 245–254.
| Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXhsV2kt7s%3D&md5=6ebd2e42d07f171871b0af010b8c8223CAS |
Jammes, H,, Junien, C., and Chavatte-Palmer, P. (2011). Epigenetic control of development and expression of quantitative traits. Reprod. Fertil. Dev. 23, 64–74.
| Epigenetic control of development and expression of quantitative traits.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhvVyqsLY%3D&md5=9aa819f22ffe49aa9847e15afc04d208CAS |
Jobgen, W. S., Ford, S. P., Jobgen, S. C., Feng, C. P., Hess, B. W., Nathanielsz, P. W., Li, P., and Wu, G. (2008). Baggs ewes adapt to maternal undernutrition and maintain conceptus growth by maintaining fetal plasma concentrations of amino acids. J. Anim. Sci. 86, 820–826.
| Baggs ewes adapt to maternal undernutrition and maintain conceptus growth by maintaining fetal plasma concentrations of amino acids.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXjvFertbk%3D&md5=aafadbc1691c3fbf058b63a1b8a9f6feCAS |
Lande-Diner, L., and Cedar, H. (2005). Silence of the genes – mechanisms of long-term repression. Nat. Rev. Genet. 6, 648–654.
| Silence of the genes – mechanisms of long-term repression.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXntFeqtbg%3D&md5=e2cfa84d4eb45e1d6528efbda6ff7721CAS |
Li, E. (2002). Chromatin modification and epigenetic reprogramming in mammalian development. Nat. Rev. Genet. 3, 662–673.
| Chromatin modification and epigenetic reprogramming in mammalian development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38Xmslagt7w%3D&md5=468ca8458130f5649dd6de500ac113ddCAS |
Lillycrop, K. A., Phillips, E. S., Jackson, A. A., Hanson, M. A., and Burdge, G. C. (2005). Dietary protein restriction of pregnant rats induces and folic acid supplementation prevents epigenetic modification of hepatic gene expression in the offspring. J. Nutr. 135, 1382–1386.
| 1:CAS:528:DC%2BD2MXltFaiu7Y%3D&md5=e5c3c173afac974fa833973481802e19CAS |
Long, N. M., George, L. A., Uthlaut, A. B., Smith, D. T., Nijland, S. M., Nathanielsz, P. W., and Ford, S. P. (2010). Maternal obesity and increased nutrient intake before and during gestation in the ewe results in altered growth, adiposity, and glucose tolerance in adult offspring. J. Anim. Sci. 88, 3546–3553.
| Maternal obesity and increased nutrient intake before and during gestation in the ewe results in altered growth, adiposity, and glucose tolerance in adult offspring.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtlGlsL7J&md5=98778acba3ac3e7b58580bc563e5bf6fCAS |
Long, N. M., Ford, S. P., and Nathanielsz, P. W. (2011). Maternal obesity eliminates the neonatal lamb plasma leptin peak. J. Physiol. 589, 1455–1462.
| Maternal obesity eliminates the neonatal lamb plasma leptin peak.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXksFOrsLg%3D&md5=d85884961842317c40089e07e792e134CAS |
Ma, Y., Zhu, M. J., Zhang, L., Hein, S. M., Nathanielsz, P. W., and Ford, S. P. (2010). Maternal obesity and overnutrition alter fetal growth rate and cotyledonary vascularity and angiogenic factor expression in the ewe. Am. J. Physiol. Regul. Integr. Comp. Physiol. 299, R249–R258.
| 1:CAS:528:DC%2BC3cXpsVOrt7k%3D&md5=20b0be1d84a874277f772cfa2b9a062fCAS |
Ma, Y., Zhu, M. J., Uthlaut, A. B., Nijland, M. J., Nathanielsz, P. W., Hess, B. W., and Ford, S. P. (2011). Upregulation of growth signaling and nutrient transporters in the cotyledons of early to mid-gestational nutrient restricted ewes. Placenta 32, 255–263.
| Upregulation of growth signaling and nutrient transporters in the cotyledons of early to mid-gestational nutrient restricted ewes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXit1WmtLk%3D&md5=66beb306677e173a1105cf62f67c38deCAS |
McMillen, I. C., and Robinson, J. S. (2005). Developmental origins of the metabolic syndrome: prediction, plasticity, and programming. Physiol. Rev. 85, 571–633.
| Developmental origins of the metabolic syndrome: prediction, plasticity, and programming.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXjt12lsLw%3D&md5=30fe31ba18db36d905badebc689dee4dCAS |
Mingrone, G., Manco, M., Mora, M. E., Guidone, C., Iaconelli, A., Gnuili, D., Leccesi, L., Chiellini, C., and Ghirlanda, G. (2008). Influence of maternal obesity on insulin sensitivity and secretion in offspring. Diabetes Care 31, 1872–1876.
| Influence of maternal obesity on insulin sensitivity and secretion in offspring.Crossref | GoogleScholarGoogle Scholar |
Morgan, H. D., Sutherland, H. G., Martin, D. I., and Whitelaw, E. (1999). Epigenetic inheritance at the agouti locus in the mouse. Nat. Genet. 23, 314–318.
| Epigenetic inheritance at the agouti locus in the mouse.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXnt1Gns7w%3D&md5=788953fe9224aa9217e7d5284821a2a5CAS |
Morgan, H.D., Santos, F., Green, G., Dean, W., and Reik, W. (2005). Epigenetic reprogramming in mammals. Hum. Mol. Genet. 14, R47–R58.
| Epigenetic reprogramming in mammals.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXjsFeksb4%3D&md5=e05605cb13d90a91ba2717ce31de5fb4CAS |
Ng, S. F., Lin, R. C., Laybutt, D. R., Barres, R., Owens, J. A., and Morris, M. J. (2010). Chronic high-fat diet in fathers programs β-cell dysfunction in female rat offspring. Nature 467, 963–966.
| Chronic high-fat diet in fathers programs β-cell dysfunction in female rat offspring.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtlWlsr%2FF&md5=2e25e65e017d1d9fab58f4ec3d143ae6CAS |
Niculescu, M. D., Craciunescu, C. N., and Zeisel, S. H. (2006). Dietary choline deficiency alters global and gene-specific DNA methylation in the developing hippocampus of mouse fetal brains. FASEB J. 20, 43–49.
| Dietary choline deficiency alters global and gene-specific DNA methylation in the developing hippocampus of mouse fetal brains.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XislSntA%3D%3D&md5=670b12f5da897eadc57d070679f196eaCAS |
Park, J. H., Stoffers, D. A., Nichols, R. D., and Simmons, R. A. (2008). Development of type 2 diabetes following intrauterine growth retardation in rats in associated with progressive epigenetic silencing of Pdx1. J. Clin. Invest. 118, 2316–2324.
| 1:CAS:528:DC%2BD1cXntVClsrY%3D&md5=777d430a8d45baceafe8298b94d16a81CAS |
Pembrey, M. E., Bygren, L. O., Kaati, G., Edvinsson, S., Northstone, K., Sjostrom, M., and Golding, J. (2006). Sex-specific male-line transgenerational responses in humans. Eur. J. Hum. Genet. 14, 159–166.
| Sex-specific male-line transgenerational responses in humans.Crossref | GoogleScholarGoogle Scholar |
Pinney, S. E., and Simmons, R. A. (2010). Epigenetic mechanisms in the development of type 2 diabetes. Trends Endocrinol. Metab. 21, 223–229.
| Epigenetic mechanisms in the development of type 2 diabetes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXksVejtb4%3D&md5=9148e325c5fe8d079a139ba1e85e2bb7CAS |
Proulx, K., Clavel, S., Nault, G., Richard, D., and Walker, C. D. (2001). High neonatal leptin exposure enhances brain BR expression and feedback efficiency on the adrenocortical axis of developing rats. Endocrinology 142, 4607–4616.
| High neonatal leptin exposure enhances brain BR expression and feedback efficiency on the adrenocortical axis of developing rats.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXnslGqt7c%3D&md5=38bfbb7c4fd3159c2a2837f69c694160CAS |
Rakyan, V. K., Blewitt, M. E., Druker, R., Preis, J. I., and Whitelaw, E. (2002). Metastable epialleles in mammals. Trends Genet. 18, 348–351.
| Metastable epialleles in mammals.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XlsVOlsrs%3D&md5=9f060b8d50f6e01464c2f960b3f3c987CAS |
Reaven, C. N. (1988). Role of insulin resistance in human disease. Diabetes 37, 1595–1607.
| Role of insulin resistance in human disease.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL1M%2Flt12msQ%3D%3D&md5=916e6f98600c258d7ede088fe4378cf1CAS |
Reik, W., and Walter, J. (2001). Genomic imprinting: parental influences on the genome. Nat. Rev. Genet. 2, 21–32.
| Genomic imprinting: parental influences on the genome.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXisVGjs70%3D&md5=fb50dcf8914567facca990bd63bbd5eaCAS |
Reik, W., Romer, I., Barton, S. C., Surani, M. A., Howlett, S. K., and Klose, J. (1993). Adult phenotype in the mouse can be affected by epigenetic events in the early embryo. Development 119, 933–942.
| 1:CAS:528:DyaK2cXisVWjt74%3D&md5=d7a28d36687920f95645927febbfa28cCAS |
Reik, W., Dean, W., and Walter, J. (2001). Epigenetic reprogramming in mammalian development. Science 293, 1089–1093.
| Epigenetic reprogramming in mammalian development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXmtVWltL8%3D&md5=678eba65c9b79bdddcea70604c8784caCAS |
Richards, E. J. (2006). Inherited epigenetic variation-revisiting soft inheritance. Nat. Rev. Genet. 2, 21–32.
Riggs, A. D., Martienssen, R. A., and Russo, V. E. (1996). Introduction. In ‘Epigenetic Mechanisms of Gene Regulation’. (Eds V. E. Russo, R. A. Martienssen and A. D. Riggs.) pp. 1–4. (Cold Spring Harbor Laboratory: Plainview, NY.)
Sharpe, R. M. (2010). Environmental/lifestyle effects on spermatogenesis. Phil. Trans. R Soc. Lond. B Biol. Sci. 365, 1697–1712.
| Environmental/lifestyle effects on spermatogenesis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtVaisrrE&md5=dc2133c214634c0b28df4bf3f52bee39CAS |
Simmons, R. A. (2007). Developmental origins of diabetes: the role of epigenetic mechanisms. Curr. Opin. Endocrinol. Diabetes Obes. 14, 13–16.
| Developmental origins of diabetes: the role of epigenetic mechanisms.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXitVenu78%3D&md5=c6285c29804073e7572b2bd3eab129a6CAS |
Sinclair, K. D., Lea, R. G., and Rees, W. D. (2007). The developmental origins of health and disease: current theories and epigenetic mechanisms. Soc. Reprod. Fertil. Suppl. 64, 424–443.
Skinner, M. K., Manikkam, M., and Guerro-Bosagna, C. (2010). Epigenetic transmissional actions of environmental factors in disease etiology. Trends Endocrinol. Metab. 21, 214–222.
| Epigenetic transmissional actions of environmental factors in disease etiology.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXksVejtLc%3D&md5=6dc11df88fa0b239925d765802673fe2CAS |
Stocker, C., O’Dowd, J., Morton, M. N., Wargent, E., Sennitt, M. V., Hislop, D., Glund, S., Seckl, J. R., Arch, J. R., and Cawthorne, M. A. (2004). Modulation of susceptibility to weight gain and insulin resistance in low birth weight rats by treatment of their mothers with leptin during pregnancy and lactation. Int. J. Obes. Relat. Metab. Disord. 28, 129–136.
| Modulation of susceptibility to weight gain and insulin resistance in low birth weight rats by treatment of their mothers with leptin during pregnancy and lactation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXhtFKlsw%3D%3D&md5=ae2d06a5250ec1a8c860082461995efcCAS |
Susser, M., and Stein, Z. (1994). Timing in postnatal nutrition: a reprise of the Dutch Famine Study. Nutr. Rev. 52, 84–94.
| Timing in postnatal nutrition: a reprise of the Dutch Famine Study.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2c3os1WktA%3D%3D&md5=35638b5b1c38dea451aa6e5654ad938cCAS |
Ulrey, C. L., Liu, L., Andrews, L. G., and Tollefsbol, T. O. (2005). The impact of metabolism on DNA methylation. Hum. Mol. Genet. 14, R139–R147.
| The impact of metabolism on DNA methylation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXjsFektr4%3D&md5=5d4d70970e7f73c6d61f6872f276ad85CAS |
Vickers, M. H., Gluckman, P. D., Coveny, A. H., Hofman, P. L., Cutfield, W. S., Gertler, A., Breier, B. H., and Harris, M. (2005). Neonatal leptin treatment reverses developmental programming. Endocrinology 146, 4211–4216.
| Neonatal leptin treatment reverses developmental programming.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXhtVGmurnM&md5=eaa6cadb3593f2ee49de9a9db0b7de9bCAS |
Vickers, M. H., Gluckman, P. D., Coveny, A. H., Hofman, P. L., Cutfield, W. S., Gertler, A., Breier, B. H., and Harris, M. (2008). The effect of neonatal leptin treatment on postnatal weight gain in male rats is dependent on maternal nutritional status during pregnancy. Endocrinology 149, 1906–1913.
| The effect of neonatal leptin treatment on postnatal weight gain in male rats is dependent on maternal nutritional status during pregnancy.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXktVeqsb4%3D&md5=9d1aa0f976f1a6722750b69b88b69633CAS |
Vonnahme, K. A., Hess, B. W., Hansen, T. R., McCormick, R. J., Rule, D. C., Moss, G. E., Murdock, W. J., Skinner, D. C., Nathanielsz, P. W., and Ford, S. P. (2003). Maternal undernutrition from early to mid-gestation leads to growth retardation, cardiac ventricular hypertrophy, and increased liver weight in the fetal sheep. Biol. Reprod. 69, 133–140.
| Maternal undernutrition from early to mid-gestation leads to growth retardation, cardiac ventricular hypertrophy, and increased liver weight in the fetal sheep.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXkvFCnt7o%3D&md5=388187830bb3846cb7b958d23226f9b8CAS |
Vonnahme, K. A., Hess, B. W., Nijland, M. J., Nathanielsz, P. W., and Ford, S. P. (2006). Placentomal differentiation may compensate for maternal nutrient restriction in ewes adapted to harsh range conditions. J. Anim. Sci. 84, 3451–3459.
| Placentomal differentiation may compensate for maternal nutrient restriction in ewes adapted to harsh range conditions.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xht1CnurfO&md5=3345e857ee764bb08c32bee498db3119CAS |
Waddington, C. H. (1968). The basic ideas of biology. In ‘Towards a Theoretical Biology’. (Ed C. H. Waddington.) pp. 1–31. (Edinburgh University Press: Edinburgh.)
Walterland, R. A., and Garza, C. (1999). Potential mechanisms of metabolic imprinting that lead to chronic disease. Am. J. Clin. Nutr. 69, 179–197.
Wang, J., Ma, H., Tong, C., Zhang, H., Lawlis, G. B., Li, Y., Zang, M., Ren, J., Nijland, M. J., Ford, S. P., Nathanielsz, P. W., and Li, J. (2010). Overnutrition and maternal obesity in sheep pregnancy alter the JNK-IRS-1 signaling cascades and cardiac function in the fetal heart. FASEB J. 24, 2066–2076.
| Overnutrition and maternal obesity in sheep pregnancy alter the JNK-IRS-1 signaling cascades and cardiac function in the fetal heart.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXnt1Ois70%3D&md5=58b764f856e4fe02777665c4a71c9c89CAS |
Waterland, R. A., and Michels, K. B. (2007). Epigenetic epidemiology of the developmental origins hypothesis. Annu. Rev. Nutr. 27, 363–388.
| Epigenetic epidemiology of the developmental origins hypothesis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhsVWisLvN&md5=c308e5ad267b5cdeec8cc92964fe90a3CAS |
Waterland, R. A., Lin, J. R., Smith, C. A., and Jirtle, R. L. (2006). Post-weaning diet affects genomic imprinting at the insulin-like growth factor 2 (Igf2) locus. Hum. Mol. Genet. 15, 705–716.
| Post-weaning diet affects genomic imprinting at the insulin-like growth factor 2 (Igf2) locus.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XhsF2mtb0%3D&md5=e5dc01a52ee1975ab4296c2bf4d84d32CAS |
Wells, J. C. K. (2011). The thrifty phenotype: An adaptation in growth or metabolism? Am. J. Hum. Biol. 23, 65–75.
| The thrifty phenotype: An adaptation in growth or metabolism?Crossref | GoogleScholarGoogle Scholar |
Whitaker, R. C. (2004). Predicting preschooler obesity at birth: the role of maternal obesity in early pregnancy. Pediatrics 114, e29–e36.
| Predicting preschooler obesity at birth: the role of maternal obesity in early pregnancy.Crossref | GoogleScholarGoogle Scholar |
Yura, S., Itoh, H., Sawaga, N., Yamamoto, H., Masuzaki, H., Nahao, K., Kawamura, M., Takemura, M., Ogawa, Y., and Fujii, S. (2005). Role of premature leptin surge in obesity resulting from intrauterine undernutrition. Cell Metab. 1, 371–378.
| Role of premature leptin surge in obesity resulting from intrauterine undernutrition.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXlslajsL8%3D&md5=40be90748c53482a9592f10bd7584914CAS |
Zamenhof, S., van Marthens, E., and Grauel, L. (1971). DNA (cell number) in neonatal brain: second generation (F2) alteration by maternal (F0) dietary protein restriction. Science 172, 850–851.
| DNA (cell number) in neonatal brain: second generation (F2) alteration by maternal (F0) dietary protein restriction.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaE3MXks1Slt7g%3D&md5=b2e8b2e100df764fb574b5152c29cfadCAS |
Zhang, L., George, L. A., Ford, S. P., and Nathanielsz, P. W. (2010). Maternal nutrient restriction (NR) from early to mid-gestation increases pancreatic β-cell numbers at midgestation, but pancreatic weight and β-cell numbers are reduced by late gestation. J. Anim. Sci. , 870..
Zhang, L., Long, N. M., Hein, S. M., Ma, Y., Nathanielsz, P. W., and Ford, S. P. (2011). Maternal obesity in ewes results in reduced fetal pancreatic β-cell numbers in late gestation and decreased circulating insulin concentration at term. Domest. Anim. Endocrinol. 40, 30–39.
| Maternal obesity in ewes results in reduced fetal pancreatic β-cell numbers in late gestation and decreased circulating insulin concentration at term.Crossref | GoogleScholarGoogle Scholar |
