A growing body of evidence supports the concept that changes in the intrauterine milieu during “sensitive” periods of embryonic development or in infant diet after birth affect the developing individual, resulting in general health alterations later in life. This phenomenon is referred to as “developmental programming” or “developmental origins of health and disease.” The risk of developing late-onset diseases such as hypertension, chronic kidney disease (CKD), obesity or type 2 diabetes is increased in infants born prematurely at <37 weeks of gestation or in low birth weight (LBW) infants weighing <2,500？g at birth. Both genetic and environmental events contribute to the programming of subsequent risks of CKD and hypertension in premature or LBW individuals. A number of observations suggest that susceptibility to subsequent CKD and hypertension in premature or LBW infants is mediated, at least in part, by reduced nephron endowment. The major factors influencing in utero environment that are associated with a low final nephron number include uteroplacental insufficiency, maternal low-protein diet, hyperglycemia, vitamin A deficiency, exposure to or interruption of endogenous glucocorticoids, and ethanol exposure. This paper discusses the effect of premature birth, LBW, intrauterine milieu, and infant feeding on the development of hypertension and renal disease in later life as well as examines the role of the kidney in developmental programming of hypertension and CKD. 1. Introduction Despite the availability of a number of treatment options for hypertension, cardiovascular, and renal disease, the prevalence, morbidity, and mortality of these diseases in children and adults remain very high [1]. Therefore, elucidation of the causality and pathogenesis of these diseases is critical. Studies by Widdowson and McCance in the 1960s demonstrated that acceleration or retardation of the rate of growth induced by malnutrition during early postnatal life in rats led to distinct and different effects on anatomical, physiological, and chemical development [2]. In the 1980s, studies by Barker demonstrated that systolic blood pressure in older children is inversely related to their birth weight [3]. Around the same time, Brenner hypothesized that early loss of nephron mass results in hyperfiltration of remaining nephrons leading to subsequent hypertension, proteinuria, and progressive kidney injury [4]. These and subsequent studies have provided initial evidence that a suboptimal in utero environment may predispose or “program” an individual to an increased risk of
M. M. Mitsnefes, “Cardiovascular disease in children with chronic kidney disease,” Journal of the American Society of Nephrology, vol. 23, no. 4, pp. 578–585, 2012.
E. M. Widdowson and R. A. McCance, “Some effects of accelerating growth—I. General somatic development,” Proceedings of the Royal Society of London. Series B, vol. 152, pp. 188–206, 1960.
D. J. P. Barker, C. Osmond, J. Golding, D. Kuh, and M. E. J. Wadsworth, “Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease,” British Medical Journal, vol. 298, no. 6673, pp. 564–567, 1989.
B. M. Brenner, D. L. Garcia, and S. Anderson, “Glomeruli and blood pressure. Less of one, more the other?” American Journal of Hypertension, vol. 1, no. 4, pp. 335–347, 1988.
V. A. Luyckx and B. M. Brenner, “The clinical importance of nephron mass,” Journal of the American Society of Nephrology, vol. 21, no. 6, pp. 898–910, 2010.
K. M. Moritz, M. Dodic, and E. M. Wintour, “Kidney development and the fetal programming of adult disease,” BioEssays, vol. 25, no. 3, pp. 212–220, 2003.
A. F. Duncan, R. J. Heyne, J. S. Morgan, N. Ahmad, and C. R. Rosenfeld, “Elevated systolic blood pressure in preterm very-low-birth-weight infants ≤3 years of life,” Pediatric Nephrology, vol. 26, no. 7, pp. 1115–1121, 2011.
F. de Jong, M. C. Monuteaux, R. M. van Elburg, et al., “Systematic review and meta-analysis of preterm birth and later systolic blood pressure,” Hypertension, vol. 59, no. 2, pp. 226–234, 2012.
S. L. White, V. Perkovic, A. Cass et al., “Is low birth weight an antecedent of CKD in later life? A systematic review of observational studies,” American Journal of Kidney Diseases, vol. 54, no. 2, pp. 248–261, 2009.
F. Costantini and R. Kopan, “Patterning a complex organ: branching morphogenesis and nephron segmentation in kidney development,” Developmental Cell, vol. 18, no. 5, pp. 698–712, 2010.
W. E. Hoy, R. N. Douglas-Denton, M. D. Hughson, A. Cass, K. Johnson, and J. F. Bertram, “A stereological study of glomerular number and volume: preliminary findings in a multiracial study of kidneys at autopsy,” Kidney International, vol. 63, no. 83, supplement, pp. S31–S37, 2003.
M. L. Sequeira Lopez and R. A. Gomez, “Development of the renal arterioles,” Journal of the American Society of Nephrology, vol. 22, no. 12, pp. 2156–2165, 2011.
R. Manalich, L. Reyes, M. Herrera, C. Melendi, and I. Fundora, “Relationship between weight at birth and the number and size of renal glomeruli in humans: a histomorphometric study,” Kidney International, vol. 58, no. 2, pp. 770–773, 2000.
C. C. Hoppe, R. G. Evans, K. M. Moritz et al., “Combined prenatal and postnatal protein restriction influences adult kidney structure, function, and arterial pressure,” American Journal of Physiology, vol. 292, no. 1, pp. R462–R469, 2007.
L. A. Ortiz, A. Quan, A. Weinberg, and M. Baum, “Effect of prenatal dexamethasone on rat renal development,” Kidney International, vol. 59, no. 5, pp. 1663–1669, 2001.
A. Drougia, V. Giapros, E. Hotoura, F. Papadopoulou, M. Argyropoulou, and S. Andronikou, “The effects of gestational age and growth restriction on compensatory kidney growth,” Nephrology Dialysis Transplantation, vol. 24, no. 1, pp. 142–148, 2009.
E. Hotoura, M. Argyropoulou, F. Papadopoulou et al., “Kidney development in the first year of life in small-for-gestational-age preterm infants,” Pediatric Radiology, vol. 35, no. 10, pp. 991–994, 2005.
I. M. Schmidt, M. Chellakooty, K. A. Boisen et al., “Impaired kidney growth in low-birth-weight children: distinct effects of maturity and weight for gestational age,” Kidney International, vol. 68, no. 2, pp. 731–740, 2005.
M. Basioti, V. Giapros, A. Kostoula, V. Cholevas, and S. Andronikou, “Growth restriction at birth and kidney function during childhood,” American Journal of Kidney Diseases, vol. 54, no. 5, pp. 850–858, 2009.
S. A. Hinchliffe, M. R. J. Lynch, P. H. Sargent, C. V. Howard, and D. Van Velzen, “The effect of intrauterine growth retardation on the development of renal nephrons,” British Journal of Obstetrics and Gynaecology, vol. 99, no. 4, pp. 296–301, 1992.
C. P. M. Leeson, M. Kattenhorn, R. Morley, A. Lucas, and J. E. Deanfield, “Impact of low birth weight and cardiovascular risk factors on endothelial function in early adult life,” Circulation, vol. 103, no. 9, pp. 1264–1268, 2001.
J. Goodfellow, M. F. Bellamy, S. T. Gorman et al., “Endothelial function is impaired in fit young adults of low birth weight,” Cardiovascular Research, vol. 40, no. 3, pp. 600–606, 1998.
A. Fattal-Valevski, J. Bernheim, Y. Leitner, B. Redianu, H. Bassan, and S. Harel, “Blood pressure values in children with intrauterine growth retardation,” Israel Medical Association Journal, vol. 3, no. 11, pp. 805–808, 2001.
S. P. Walker, P. Gaskin, C. A. Powell, F. I. Bennett, T. E. Forrester, and S. Grantham-McGregor, “The effects of birth weight and postnatal linear growth retardation on blood pressure at age 11-12 years,” Journal of Epidemiology and Community Health, vol. 55, no. 6, pp. 394–398, 2001.
S. Shankaran, A. Das, C. R. Bauer et al., “Fetal origin of childhood disease: intrauterine growth restriction in term infants and risk for hypertension at 6 years of age,” Archives of Pediatrics and Adolescent Medicine, vol. 160, no. 9, pp. 977–981, 2006.
M. R. J？rvelin, U. Sovio, V. King et al., “Early life factors and blood pressure at age 31 years in the 1966 Northern Finland birth cohort,” Hypertension, vol. 44, no. 6, pp. 838–846, 2004.
M. Mu, S. F. Wang, J. Sheng, et al., “Birth weight and subsequent blood pressure: a meta-analysis,” Archive of Cardiovascular Disease, vol. 105, no. 2, pp. 99–113, 2012.
C. M. Law, M. De Swiet, C. Osmond et al., “Initiation of hypertension in utero and its amplification throughout life,” British Medical Journal, vol. 306, no. 6869, pp. 24–27, 1993.
M. G. Keijzer-Veen, M. Schrevel, M. J. J. Finken et al., “Microalbuminuria and lower glomerular filtration rate at young adult age in subjects born very premature and after intrauterine growth retardation,” Journal of the American Society of Nephrology, vol. 16, no. 9, pp. 2762–2768, 2005.
B. E. Vikse, L. M. Irgens, T. Leivestad, S. Hallan, and B. M. Iversen, “Low birth weight increases risk for end-stage renal disease,” Journal of the American Society of Nephrology, vol. 19, no. 1, pp. 151–157, 2008.
J. B. Hodgin, M. Rasoulpour, G. S. Markowitz, and V. D. D'Agati, “Very low birth weight is a risk factor for secondary focal segmental glomerulosclerosis,” Clinical Journal of the American Society of Nephrology, vol. 4, no. 1, pp. 71–76, 2009.
B. M. Brenner and H. S. Mackenzie, “Nephron mass as a risk factor for progression of renal disease,” Kidney International, vol. 51, no. 63, supplement, pp. S124–S127, 1997.
C. Stelloh, K. P. Allen, and D. L. Mattson, “Prematurity in mice leads to reduction in nephron number, hypertension, and proteinuria,” Translational Research, vol. 159, no. 2, pp. 80–89, 2012.
H. Bassan, L. Leider Trejo, N. Kariv et al., “Experimental intrauterine growth retardation alters renal development,” Pediatric Nephrology, vol. 15, no. 3-4, pp. 192–195, 2000.
V. M. Vehaskari, D. H. Aviles, and J. Manning, “Prenatal programming of adult hypertension in the rat,” Kidney International, vol. 59, no. 1, pp. 238–245, 2001.
L. L. Woods, J. R. Ingelfinger, J. R. Nyengaard, and R. Rasch, “Maternal protein restriction suppresses the newborn renin-angiotensin system and programs adult hypertension in rats,” Pediatric Research, vol. 49, no. 4, pp. 460–467, 2001.
M. M. Rodríguez, A. H. Gómez, C. L. Abitbol, J. J. Chandar, S. Duara, and G. E. Zilleruelo, “Histomorphometric analysis of postnatal glomerulogenesis in extremely preterm infants,” Pediatric and Developmental Pathology, vol. 7, no. 1, pp. 17–25, 2004.
M. G. Keijzer-Veen, A. S. Devos, M. Meradji, F. W. Dekker, J. Nauta, and B. J. Van Der Heijden, “Reduced renal length and volume 20 years after very preterm birth,” Pediatric Nephrology, vol. 25, no. 3, pp. 499–507, 2010.
M. R. Sutherland, L. Gubhaju, L. Moore et al., “Accelerated maturation and abnormal morphology in the preterm neonatal kidney,” Journal of the American Society of Nephrology, vol. 22, no. 7, pp. 1365–1374, 2011.
L. Gubhaju, M. R. Sutherland, B. A. Yoder, A. Zulli, J. F. Bertram, and M. J. Black, “Is nephrogenesis affected by preterm birth? Studies in a non-human primate model,” American Journal of Physiology, vol. 297, no. 6, pp. F1668–F1677, 2009.
M. G. Keijzer-Veen, M. J. J. Finken, J. Nauta et al., “Is blood pressure increased 19 years after intrauterine growth restriction and preterm birth? A prospective follow-up study in the Netherlands,” Pediatrics, vol. 116, no. 3, pp. 725–731, 2005.
A. Singhal, M. Kattenhorn, T. J. Cole, J. Deanfield, and A. Lucas, “Preterm birth, vascular function, and risk factors for atherosclerosis,” Lancet, vol. 358, no. 9288, pp. 1159–1160, 2001.
D. A. Leon, M. Johansson, and F. Rasmussen, “Gestational age and growth rate of fetal mass are inversely associated with systolic blood pressure in young adults: an epidemiologic study of 165,136 Swedish men aged 18 years,” American Journal of Epidemiology, vol. 152, no. 7, pp. 597–604, 2000.
A. Kistner, G. Celsi, M. Vanpée, and S. H. Jacobson, “Increased systolic daily ambulatory blood pressure in adult women born preterm,” Pediatric Nephrology, vol. 20, no. 2, pp. 232–233, 2005.
Y. F. Cheung, K. Y. Wong, C. C. Barbara, B. C. C. Lam, and N. S. Tsoi, “Relation of arterial stiffness with gestational age and birth weight,” Archives of Disease in Childhood, vol. 89, no. 3, pp. 217–221, 2004.
J. Bacchetta, J. Harambat, L. Dubourg et al., “Both extrauterine and intrauterine growth restriction impair renal function in children born very preterm,” Kidney International, vol. 76, no. 4, pp. 445–452, 2009.
T. J. Mathews, A. M. Mini？o, M. J. K. Osterman, D. M. Strobino, and B. Guyer, “Annual summary of vital statistics: 2008,” Pediatrics, vol. 127, no. 1, pp. 146–157, 2011.
F. B. Stapleton, D. P. Jones, and R. S. Green, “Acute renal failure in neonates: incidence, etiology and outcome,” Pediatric Nephrology, vol. 1, no. 3, pp. 314–320, 1987.
M. F. Schreuder, R. R. Bueters, M. C. Huigen, F. G. M. Russel, R. Masereeuw, and L. P. Van Den Heuvel, “Effect of drugs on renal development,” Clinical Journal of the American Society of Nephrology, vol. 6, no. 1, pp. 212–217, 2011.
M. E. Wlodek, A. Mibus, A. Tan, A. L. Siebel, J. A. Owens, and K. M. Moritz, “Normal lactational environment restores nephron endowment and prevents hypertension after placental restriction in the rat,” Journal of the American Society of Nephrology, vol. 18, no. 6, pp. 1688–1696, 2007.
M. F. Schreuder, J. R. Nyengaard, F. Remmers, J. A. E. Van Wijk, and H. A. Delemarre-Van De Waal, “Postnatal food restriction in the rat as a model for a low nephron endowment,” American Journal of Physiology, vol. 291, no. 5, pp. F1104–F1107, 2006.
L. Larsson, A. Aperia, and P. Wilton, “Effect of normal development on compensatory renal growth,” Kidney International, vol. 18, no. 1, pp. 29–35, 1980.
S. J. M. Welham, P. R. Riley, A. Wade, M. Hubank, and A. S. Woolf, “Maternal diet programs embryonic kidney gene expression,” Physiological Genomics, vol. 22, pp. 48–56, 2005.
C. Bertram, A. R. Trowern, N. Copin, A. A. Jackson, and C. B. Whorwood, “The maternal diet during pregnancy programs altered expression of the glucocorticoid receptor and type 2 11β-hydroxysteroid dehydrogenase: potential molecular mechanisms underlying the programming of hypertension in utero,” Endocrinology, vol. 142, no. 7, pp. 2841–2853, 2001.
R. A. Augustyniak, K. Singh, D. Zeldes, M. Singh, and N. F. Rossi, “Maternal protein restriction leads to hyperresponsiveness to stress and salt-sensitive hypertension in male offspring,” American Journal of Physiology, vol. 298, no. 5, pp. R1375–R1382, 2010.
Y. L. Tain, C. S. Hsieh, I. C. Lin, C. C. Chen, J. M. Sheen, and L. T. Huang, “Effects of maternal l-citrulline supplementation on renal function and blood pressure in offspring exposed to maternal caloric restriction: the impact of nitric oxide pathway,” Nitric Oxide, vol. 23, no. 1, pp. 34–41, 2010.
H. Bakker and V. W. Jaddoe, “Cardiovascular and metabolic influences of fetal smoke exposure,” European Journal of Epidemiology, vol. 26, no. 10, pp. 763–770, 2011.
E. W. Harville, R. Boynton-Jarrett, C. Power, and E. Hypp？nen, “Childhood hardship, maternal smoking, and birth outcomes: a prospective cohort study,” Archives of Pediatrics and Adolescent Medicine, vol. 164, no. 6, pp. 533–539, 2010.
C. Power, K. Atherton, and C. Thomas, “Maternal smoking in pregnancy, adult adiposity and other risk factors for cardiovascular disease,” Atherosclerosis, vol. 211, no. 2, pp. 643–648, 2010.
S. P. Gray, K. Kenna, J. F. Bertram et al., “Repeated ethanol exposure during late gestation decreases nephron endowment in fetal sheep,” American Journal of Physiology, vol. 295, no. 2, pp. R568–R574, 2008.
C. J. Calvano, R. LeFevre, R. F. Mankes et al., “The incidence of renal anomalies at full term in fetal rats is synergistically increased by estradiol (but not testosterone) supplementation on day 18 of alcoholic gestation,” Journal of Pediatric Surgery, vol. 32, no. 9, pp. 1302–1306, 1997.
J. C. Gage and K. K. Sulik, “Pathogenesis of ethanol-induced hydronephrosis and hydroureter as demonstrated following in vivo exposure of mouse embryos,” Teratology, vol. 44, no. 3, pp. 299–312, 1991.
R. Rodrigo, L. Vergara, and E. Oberhauser, “Effect of chronic ethanol consumption on postnatal development of renal (Na + K)-ATPase in the rat,” Cell Biochemistry and Function, vol. 9, no. 3, pp. 215–222, 1991.
G. Celsi, A. Kistner, R. Aizman et al., “Prenatal dexamethasone causes oligonephronia, sodium retention, and higher blood pressure in the offspring,” Pediatric Research, vol. 44, no. 3, pp. 317–322, 1998.
L. A. Ortiz, A. Quan, F. Zarzar, A. Weinberg, and M. Baum, “Prenatal dexamethasone programs hypertension and renal injury in the rat,” Hypertension, vol. 41, no. 2, pp. 328–334, 2003.
N. Connors, N. K. Valego, L. C. Carey, J. P. Figueroa, and J. C. Rose, “Fetal and postnatal renin secretion in female sheep exposed to prenatal betamethasone,” Reproductive Sciences, vol. 17, no. 3, pp. 239–246, 2010.
C. S. Wyrwoll, P. J. Mark, and B. J. Waddell, “Developmental programming of renal glucocorticoid sensitivity and the renin-angiotensin system,” Hypertension, vol. 50, no. 3, pp. 579–584, 2007.
M. Lelièvre-Pégorier, J. Vilar, M. L. Ferrier et al., “Mild vitamin A deficiency leads to inborn nephron deficit in the rat,” Kidney International, vol. 54, no. 5, pp. 1455–1462, 1998.
R. M. Lewis, C. J. Petry, S. E. Ozanne, and C. N. Hales, “Effects of maternal iron restriction in the rat on blood pressure, glucose tolerance, and serum lipids in the 3-month-old offspring,” Metabolism, vol. 50, no. 5, pp. 562–567, 2001.
S. J. M. Lisle, R. M. Lewis, C. J. Petry, S. E. Ozanne, C. N. Hales, and A. J. Forhead, “Effect of maternal iron restriction during pregnancy on renal morphology in the adult rat offspring,” British Journal of Nutrition, vol. 90, no. 1, pp. 33–39, 2003.
G. D. Simonetti, L. Raio, D. Surbek, M. Nelle, F. J. Frey, and M. G. Mohaupt, “Salt sensitivity of children with low birth weight,” Hypertension, vol. 52, no. 4, pp. 625–630, 2008.
N. Koleganova, G. Piecha, E. Ritz et al., “Both high and low maternal salt intake in pregnancy alter kidney development in the off spring,” American Journal of Physiology, vol. 301, no. 2, pp. F344–F354, 2011.
S. K. Chan, P. R. Riley, K. L. Price et al., “Corticosteroid-induced kidney dysmorphogenesis is associated with deregulated expression of known cystogenic molecules, as well as indian hedgehog,” American Journal of Physiology, vol. 298, no. 2, pp. F346–F356, 2010.
H. Dickinson, D. W. Walker, E. M. Wintour, and K. Moritz, “Maternal dexamethasone treatment at midgestation reduces nephron number and alters renal gene expression in the fetal spiny mouse,” American Journal of Physiology, vol. 292, no. 1, pp. R453–R461, 2007.
A. Dagan, J. Gattineni, V. Cook, and M. Baum, “Prenatal programming of rat proximal tubule Na+/H+ exchanger by dexamethasone,” American Journal of Physiology, vol. 292, no. 3, pp. R1230–R1235, 2007.
J. Bernstein, A. L. Werner, and R. Verani, “Nonsteroidal anti-inflammatory drug fetal nephrotoxicity,” Pediatric and Developmental Pathology, vol. 1, no. 2, pp. 153–156, 1998.
M. Zaffanello, P. P. Bassareo, L. Cataldi, R. Antonucci, P. Biban, and V. Fanos, “Long-term effects of neonatal drugs on the kidney,” Journal of Maternal-Fetal and Neonatal Medicine, vol. 23, no. 3, pp. 87–89, 2010.
O. Gribouval, M. Gonzales, T. Neuhaus et al., “Mutations in genes in the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis,” Nature Genetics, vol. 37, no. 9, pp. 964–968, 2005.
F. Sáez, V. Reverte, F. Salazar, M. T. Castells, M. T. Llinás, and F. J. Salazar, “Hypertension and sex differences in the age-related renal changes when cyclooxygenase-2 activity is reduced during nephrogenesis,” Hypertension, vol. 53, no. 2, pp. 331–337, 2009.
V. Reverte, A. Tapia, J. M. Moreno et al., “Renal effects of prolonged high protein intake and COX2 inhibition on hypertensive rats with altered renal development,” American Journal of Physiology, vol. 301, no. 2, pp. F327–F333, 2011.
M. J. Finken, I. Meulenbelt, F. W. Dekker, et al., “Abdominal fat accumulation in adults born preterm exposed antenatally to maternal glucocorticoid treatment is dependent on glucocorticoid receptor gene variation,” Journal of Clinical Endocrinology Metabolism, vol. 96, no. 10, pp. E1650–E1655, 2011.
L. Manenschijn, E. L. T. Van Den Akker, S. W. J. Lamberts, and E. F. C. Van Rossum, “Clinical features associated with glucocorticoid receptor polymorphisms: an overview,” Annals of the New York Academy of Sciences, vol. 1179, pp. 179–198, 2009.
M. J. J. Finken, I. Meulenbelt, F. W. Dekker et al., “The 23K variant of the R23K polymorphism in the glucocorticoid receptor gene protects against postnatal growth failure and insulin resistance after preterm birth,” Journal of Clinical Endocrinology and Metabolism, vol. 92, no. 12, pp. 4777–4782, 2007.
A. Loria, V. Reverte, F. Salazar, F. Saez, M. T. Llinas, and F. J. Salazar, “Sex and age differences of renal function in rats with reduced ANG II activity during the nephrogenic period,” American Journal of Physiology, vol. 293, no. 2, pp. F506–F510, 2007.
D. Grigore, N. B. Ojeda, E. B. Robertson et al., “Placental insufficiency results in temporal alterations in the renin angiotensin system in male hypertensive growth restricted offspring,” American Journal of Physiology, vol. 293, no. 2, pp. R804–R811, 2007.
M. Baserga, A. L. Bares, M. A. Hale et al., “Uteroplacental insufficiency affects kidney VEGF expression in a model of IUGR with compensatory glomerular hypertrophy and hypertension,” Early Human Development, vol. 85, no. 6, pp. 361–367, 2009.
T. D. Pham, N. K. MacLennan, C. T. Chiu, G. S. Laksana, J. L. Hsu, and R. H. Lane, “Uteroplacental insufficiency increases apoptosis and alters p53 gene methylation in the full-term IUGR rat kidney,” American Journal of Physiology, vol. 285, no. 5, pp. R962–R970, 2003.
C. M. Lynch, R. O'Kelly, B. Stuart, A. Treumann, R. Conroy, and C. L. Regan, “The role of thromboxane A2 in the pathogenesis of intrauterine growth restriction associated with maternal smoking in pregnancy,” Prostaglandins and Other Lipid Mediators, vol. 95, no. 1–4, pp. 63–67, 2011.
A. M. Nuyt, “Mechanisms underlying developmental programming of elevated blood pressure and vascular dysfunction: evidence from human studies and experimental animal models,” Clinical Science, vol. 114, no. 1-2, pp. 1–17, 2008.
L. Marpeau, J. Bouillie, J. Barrat, and J. Milliez, “Obstetrical advantages and perinatal risks of indomethacin: a report of 818 cases,” Fetal Diagnosis and Therapy, vol. 9, no. 2, pp. 110–115, 1994.
A. J. van der Heijden, A. P. Provoost, J. Nauta, E. D. Wolff, and P. J. Sauer, “Indomethacin as an inhibitor of preterm labor. Effect on postnatal renal function,” Contributions to Nephrology, vol. 67, pp. 152–154, 1988.
M. P. R. Walker, T. R. Moore, and R. A. Brace, “Indomethacin and arginine vasopressin interaction in the fetal kidney: a mechanism of oliguria,” American Journal of Obstetrics and Gynecology, vol. 171, no. 5, pp. 1234–1241, 1994.
S. C. Langley-Evans, S. J. M. Welham, and A. A. Jackson, “Fetal exposure to a maternal low protein diet impairs nephrogenesis and promotes hypertension in the rat,” Life Sciences, vol. 64, no. 11, pp. 965–974, 1999.
H. Gao, U. Yallampalli, and C. Yallampalli, “Maternal protein restriction reduces expression of angiotensin I-converting enzyme 2 in rat placental labyrinth zone in late pregnancy,” Biology of Reproduction, vol. 86, no. 2, pp. 1–8, 2012.
H. Gao, U. Yallampalli, and C. Yallampalli, “Protein restriction to pregnant rats increases the plasma levels of angiotensin II and expression of angiotensin II receptors in uterine arteries,” Biology of Reproduction, vol. 86, no. 3, pp. 1–8, 2012.
S. H. Alwasel, I. Kaleem, V. Sahajpal, and N. Ashton, “Maternal protein restriction reduces angiotensin II AT1 and AT2 receptor expression in the fetal rat kidney,” Kidney and Blood Pressure Research, vol. 33, no. 4, pp. 251–259, 2010.
A. J. Watkins, E. S. Lucas, C. Torrens et al., “Maternal low-protein diet during mouse pre-implantation development induces vascular dysfunction and altered renin-angiotensin-system homeostasis in the offspring,” British Journal of Nutrition, vol. 103, no. 12, pp. 1762–1770, 2010.
Z. Zhang, J. Quinlan, W. Hoy et al., “A common RET variant is associated with reduced newborn kidney size and function,” Journal of the American Society of Nephrology, vol. 19, no. 10, pp. 2027–2034, 2008.
J. Quinlan, M. Lemire, T. Hudson et al., “A common variant of the PAX2 gene is associated with reduced newborn kidney size,” Journal of the American Society of Nephrology, vol. 18, no. 6, pp. 1915–1921, 2007.
T. Lloyd, P. Foster, P. Rhodes, et al., “Protein-energy malnutrition during early gestation in sheep blunts fetal renal vascular and nephron development and compromises adult renal function,” Journal of Physiology, vol. 590, no. 2, pp. 377–393, 2012.
P. Pladys, F. Sennlaub, S. Brault et al., “Microvascular rarefaction and decreased angiogenesis in rats with fetal programming of hypertension associated with exposure to a low-protein diet in utero,” American Journal of Physiology, vol. 289, no. 6, pp. R1580–R1588, 2005.
S. Wesseling, M. P. Koeners, and J. A. Joles, “Salt sensitivity of blood pressure: developmental and sex-related effects,” American Journal of Clinical Nutrition, vol. 94, no. 6, pp. 1928S–1932S, 2011.
S. H. Alwasel, D. J. Barker, and N. Ashton, “Prenatal programming of renal salt wasting resets postnatal salt appetite, which drives food intake in the rat,” Clinical Science, vol. 122, no. 6, pp. 281–288, 2012.
J. Li, G. R. Khodus, M. Kruusm？gi et al., “Ouabain protects against adverse developmental programming of the kidney,” Nature Communications, vol. 1, no. 4, pp. 1–7, 2010.
G. R. Khodus, M. Kruusm？gi, J. Li, X. L. Liu, and A. Aperia, “Calcium signaling triggered by ouabain protects the embryonic kidney from adverse developmental programming,” Pediatric Nephrology, vol. 26, no. 9, pp. 1479–1482, 2011.
T. Stewart, F. F. Jung, J. Manning, and V. M. Vehaskari, “Kidney immune cell infiltration and oxidative stress contribute to prenatally programmed hypertension,” Kidney International, vol. 68, no. 5, pp. 2180–2188, 2005.
J. L. Tarry-Adkins, J. H. Chen, R. H. Jones, N. H. Smith, and S. E. Ozanne, “Poor maternal nutrition leads to alterations in oxidative stress, antioxidant defense capacity, and markers of fibrosis in rat islets: potential underlying mechanisms for development of the diabetic phenotype in later life,” FASEB Journal, vol. 24, no. 8, pp. 2762–2771, 2010.
V. Muller, Y. L. Tain, B. Croker, and C. Baylis, “Chronic nitric oxide deficiency and progression of kidney disease after renal mass reduction in the C57Bl6 mouse,” American Journal of Nephrology, vol. 32, no. 6, pp. 575–580, 2010.
Y. L. Tain, S. Ghosh, R. J. Krieg, and C. Baylis, “Reciprocal changes of renal neuronal nitric oxide synthase-α and -β associated with renal progression in a neonatal 5/6 nephrectomized rat model,” Pediatrics and Neonatology, vol. 52, no. 2, pp. 66–72, 2011.
G. Cambonie, B. Comte, C. Yzydorczyk et al., “Antenatal antioxidant prevents adult hypertension, vascular dysfunction, and microvascular rarefaction associated with in utero exposure to a low-protein diet,” American Journal of Physiology, vol. 292, no. 3, pp. R1236–R1245, 2007.
J. P. Figueroa, J. C. Rose, G. A. Massmann, J. Zhang, and G. Acu？a, “Alterations in fetal kidney development and elevations in arterial blood pressure in young adult sheep after clinical doses of antenatal glucocorticoids,” Pediatric Research, vol. 58, no. 3, pp. 510–515, 2005.
D. Grigore, N. B. Ojeda, and B. T. Alexander, “Sex differences in the fetal programming of hypertension,” Gender Medicine, vol. 5, no. 1, pp. S121–S132, 2008.
N. B. Ojeda, D. Grigore, E. B. Robertson, and B. T. Alexander, “Estrogen protects against increased blood pressure in postpubertal female growth restricted offspring,” Hypertension, vol. 50, no. 4, pp. 679–685, 2007.
S. J. Swenson, R. C. Speth, and J. P. Porter, “Effect of a perinatal high-salt diet on blood pressure control mechanisms in young Sprague-Dawley rats,” American Journal of Physiology, vol. 286, no. 4, pp. R764–R770, 2004.
S. S. El-Dahr, L. M. Harrison-Bernard, S. Dipp, I. V. Yosipiv, and S. Meleg-Smith, “Bradykinin B2 null mice are prone to renal dysplasia: gene-environment interactions in kidney development,” Physiological Genomics, vol. 2000, no. 3, pp. 121–131, 2000.
K. Bonamy, K. K？llén, and M. Norman, “High blood pressure in 2.5-year-old children born extremely preterm,” Pediatrics, vol. 129, no. 5, pp. e1199–e1220, 2012.
A. Kistner, L. Jacobson, S. H. Jacobson, E. Svensson, and A. Hellstrom, “Low gestational age associated with abnormal retinal vascularization and increased blood pressure in adult women,” Pediatric Research, vol. 51, no. 6, pp. 675–680, 2002.
M. B. Belfort, S. L. Rifas-Shiman, J. Rich-Edwards, K. P. Kleinman, and M. W. Gillman, “Size at birth, infant growth, and blood pressure at three years of age,” Journal of Pediatrics, vol. 151, no. 6, pp. 670–674, 2007.
J. L. Tarry-Adkins, M. S. Martin-Gronert, J. H. Chen, R. L. Cripps, and S. E. Ozanne, “Maternal diet influences DNA damage, aortic telomere length, oxidative stress, and antioxidant defense capacity in rats,” FASEB Journal, vol. 22, no. 6, pp. 2037–2044, 2008.
P. Rossi, L. Tauzin, E. Marchand, A. Boussuges, J. Gaudart, and Y. Frances, “Respective roles of preterm birth and fetal growth restriction in blood pressure and arterial stiffness in adolescence,” Journal of Adolescent Health, vol. 48, no. 5, pp. 520–522, 2011.
M. Vento, M. Asensi, J. Sastre et al., “Hyperoxemia caused by resuscitation with pure oxygen may alter intracellular redox status by increasing oxidized glutathione in asphyxiated newly born infants,” Seminars in Perinatology, vol. 26, no. 6, pp. 406–410, 2002.
T. M. Asikainen, P. Heikkil, R. Kaarteenaho-Wiik, V. L. Kinnula, and K. O. Raivio, “Cell-specific expression of manganese superoxide dismutase protein in the lungs of patients with respiratory distress syndrome, chronic lung disease, or persistent pulmonary hypertension,” Pediatric Pulmonology, vol. 32, no. 3, pp. 193–200, 2001.
C. M. Law, A. W. Shiell, C. A. Newsome et al., “Fetal, infant, and childhood growth and adult blood pressure: a longitudinal study from birth to 22 years of age,” Circulation, vol. 105, no. 9, pp. 1088–1092, 2002.
G. M. Hermann, R. L. Miller, G. E. Erkonen et al., “Neonatal catch up growth increases diabetes susceptibility but improves behavioral and cardiovascular outcomes of low birth weight male mice,” Pediatric Research, vol. 66, no. 1, pp. 53–58, 2009.
H. Russcher, P. Smit, E. L. T. Van Den Akker et al., “Two polymorphisms in the glucocorticoid receptor gene directly affect glucocorticoid-regulated gene expression,” Journal of Clinical Endocrinology and Metabolism, vol. 90, no. 10, pp. 5804–5810, 2005.
E. F. van Rossum and S. W. Lamberts, “Polymorphisms in the glucocorticoid receptor gene and their associations with metabolic parameters and body composition,” Recent Progress in Hormone Research, vol. 59, pp. 333–357, 2004.
A. H. Hemachandra, P. P. Howards, S. L. Furth, and M. A. Klebanoff, “Birth weight, postnatal growth, and risk for high blood pressure at 7 years of age: results from the Collaborative Perinatal Project,” Pediatrics, vol. 119, no. 6, pp. e1264–e1270, 2007.
L. Yvan-Charvet and A. Quignard-Boulangé, “Role of adipose tissue renin-angiotensin system in metabolic and inflammatory diseases associated with obesity,” Kidney International, vol. 79, no. 2, pp. 162–168, 2011.
J. C. Jimenez-Chillaron and M. E. Patti, “To catch up or not to catch up: is this the question? Lessons from animal models,” Current Opinion in Endocrinology, Diabetes and Obesity, vol. 14, no. 1, pp. 23–29, 2007.
F. Boubred, L. Daniel, C. Buffat et al., “Early postnatal overfeeding induces early chronic renal dysfunction in adult male rats,” American Journal of Physiology, vol. 297, no. 4, pp. F943–F951, 2009.
W. D. Rees, S. M. Hay, D. S. Brown, C. Antipatis, and R. M. Palmer, “Maternal protein deficiency causes hypermethylation of DNA in the livers of rat fetuses,” Journal of Nutrition, vol. 130, no. 7, pp. 1821–1826, 2000.
M. Suter, J. Ma, A. S. Harris, et al., “Maternal tobacco use modestly alters correlated epigenome-wide placental DNA methylation and gene expression,” Epigenetics, vol. 6, no. 11, pp. 1284–1294, 2011.
S. R. Patel, D. Kim, I. Levitan, and G. R. Dressler, “The BRCT-domain containing protein PTIP links PAX2 to a histone H3, lysine 4 methyltransferase complex,” Developmental Cell, vol. 13, no. 4, pp. 580–592, 2007.
G. M. Lefevre, S. R. Patel, D. Kim, L. Tessarollo, and G. R. Dressler, “Altering a histone H3K4 methylation pathway in glomerular podocytes promotes a chronic disease phenotype,” PLoS Genetics, vol. 6, no. 10, Article ID e1001142, 2010.
Z. Saifudeen, S. Dipp, J. Stefkova, X. Yao, S. Lookabaugh, and S. S. El-Dahr, “p53 regulates metanephric development,” Journal of the American Society of Nephrology, vol. 20, no. 11, pp. 2328–2337, 2009.
S. Chen, C. Bellew, X. Yao, et al., “Histone deacetylase (HDAC) activity is critical for embryonic kidney gene expression, growth, and differentiation,” Journal of Biological Chemistry, vol. 286, no. 37, pp. 32775–32789, 2011.
J. Ho and J. A. Kreidberg, “The long and short of microRNAs in the kidney,” Journal of the American Society of Nephrology, vol. 23, no. 3, pp. 400–404, 2012.
L. M. Pastorelli, S. Wells, M. Fray et al., “Genetic analyses reveal a requirement for Dicer1 in the mouse urogenital tract,” Mammalian Genome, vol. 20, no. 3, pp. 140–151, 2009.
H. Tamura, L. Schild, N. Enomoto et al., “Liddle disease caused by a missense mutation of β subunit of the epithelial sodium channel gene,” Journal of Clinical Investigation, vol. 97, no. 7, pp. 1780–1784, 1996.
W. Zhang, X. Xia, D. I. Jalal et al., “Aldosterone-sensitive repression of ENaCα transcription by a histone H3 lysine-79 methyltransferase,” American Journal of Physiology, vol. 290, no. 3, pp. C936–C946, 2006.
H. M. Cho, H. A. Lee, H. Y. Kim, H. S. Han, and I. K. Kim, “Expression of Na+-K+-2Cl- cotransporter 1 is epigenetically regulated during postnatal development of hypertension,” American Journal of Hypertension, vol. 24, no. 12, pp. 1286–1293, 2011.
J. W. Meyer, M. Flagella, R. L. Sutliff et al., “Decreased blood pressure and vascular smooth muscle tone in mice lacking basolateral Na+-K+-2Cl- cotransporter,” American Journal of Physiology, vol. 283, no. 5, pp. H1846–H1855, 2002.
M. P. Vélez, I. S. Santos, A. Matijasevich et al., “Maternal low birth weight and adverse perinatal outcomes: the 1982 Pelotas Birth Cohort Study, Brazil,” Revista Panamericana de Salud Publica, vol. 26, no. 2, pp. 112–119, 2009.
P. D. Gluckman, M. A. Hanson, C. Cooper, and K. L. Thornburg, “Effect of in utero and early-life conditions on adult health and disease,” New England Journal of Medicine, vol. 359, no. 1, pp. 61–73, 2008.
