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Maternal nutrient restriction alters renal development and blood pressure regulation of the offspring

Published online by Cambridge University Press:  07 March 2007

Kathryn A. Brennan*
Affiliation:
Centre for Reproduction and Early Life, Institute of Clinical Research, University Hospital, Nottingham NG7 2UH, UK Perinatal Research Centre, Departments of Obstetrics and Gynecology, Pediatrics and Physiology, University of Alberta, Edmonton, Alberta T6G 2S2, Canada
David M. Olson
Affiliation:
Perinatal Research Centre, Departments of Obstetrics and Gynecology, Pediatrics and Physiology, University of Alberta, Edmonton, Alberta T6G 2S2, Canada
Michael E. Symonds
Affiliation:
Centre for Reproduction and Early Life, Institute of Clinical Research, University Hospital, Nottingham NG7 2UH, UK
*
*Corresponding author: Kathryn Brennan, fax +44 115 970 9382, email [email protected]
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Abstract

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Studies have shown that the risk of hypertension in adulthood can be affected by the in utero environment. It is established that hypertension is linked to compromised kidney function and that factors affecting organogenesis can increase the risk of later disease. Prostaglandins (PG) and growth factors are known to play an important role in regulating kidney function and renal organogenesis. The extent, however, to which global energy restriction (where all nutrients are reduced) of the mother can programme later blood pressure control or renal PG and growth factor status is unknown. A study is described that aimed to examine the long-term effects of maternal nutrient restriction (NR) and elucidate their relationship with compromised kidney development. First, it was necessary to establish animal models. A sheep model of 50% NR during specific stages of gestation was used to investigate fetal renal development, whilst a rat model of 50% NR throughout pregnancy was used to investigate postnatal kidney development and adult functioning. Molecular analysis has shown that expression of the growth hormone–insulin-like growth factor (GH–IGF) axis is affected by NR in the fetal sheep kidneys, and that changes are dependent on the timing of NR and whether the fetus is a singleton or a twin. Analysis of the kidneys from the rat model has shown nutritional differences in the expression of PG receptors and the enzymes responsible for PG synthesis and degradation that persist into adulthood. In conclusion, NR does affect the GH–IGF and PG axes, and these changes may be important in the nutritional programming of renal functioning and adult blood pressure control.

Type
Postgraduate Symposium
Copyright
Copyright © The Nutrition Society 2006

References

Audoly, LP, Tilley, SL, Goulet, J, Key, M, Nguyen, M, Stock, JL, McNeish, JD, Koller, BH & Coffman, TM (1999) Identification of specific EP receptors responsible for the hemodynamic effects of PGE2. American Journal of Physiology 277 H924H930.Google ScholarPubMed
Barker, DJ (2002) Fetal programming of coronary heart disease. Trends in Endocrinology and Metabolism 13 364368.CrossRefGoogle ScholarPubMed
Barker, DJ, Bull, AR, Osmond, C & Simmonds, SJ (1990) Fetal and placental size and risk of hypertension in adult life. British Medical Journal 301 259262.CrossRefGoogle ScholarPubMed
Bauer, MK, Breier, BB, Bloomfield, FH, Jensen, EC, Gluckman, PD & Harding, JE (2003) Chronic pulsatile infusion of growth hormone to growth-restricted fetal sheep increases circulating fetal insulin-like growth factor-I levels but not fetal growth. Journal of Endocrinology 177 8392.CrossRefGoogle Scholar
Bauer, MK, Harding, JE, Breier, BH & Gluckman, PD (2000) Exogenous GH infusion to late-gestational fetal sheep does not alter fetal growth and metabolism. Journal of Endocrinology 166 591597.CrossRefGoogle Scholar
Bertram, C, Trowern, AR, Copin, N, Jackson, AA & Whorwood, CB (2001) The maternal diet during pregnancy programs altered expression of the glucocorticoid receptor and type 2 11 beta-hydroxysteroid dehydrogenase: Potential molecular mechanisms underlying the programming of hypertension in utero. Endocrinology 142 28412853.CrossRefGoogle Scholar
Bispham, J, Gopalakrishnan, GS, Dandrea, J, Wilson, V, Budge, H, Keisler, DH, Broughton Pipkin, F, Stephenson, T & Symonds, ME (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 35753585.CrossRefGoogle ScholarPubMed
Brameld, JM, Mostyn, A, Dandrea, J, Stephenson, TJ, Dawson, JM, Buttery, PJ & Symonds, ME (2000) Maternal nutrition alters the expression of insulin-like growth factors in fetal sheep liver and skeletal muscle. Journal of Endocrinology 167 429437.CrossRefGoogle ScholarPubMed
Brennan, KA, Gopalakrishnan, GS, Kurlak, L, Rhind, SM, Kyle, CE, Brooks, AN, Rae, MT, Olson, DM, Stephenson, T & Symonds, ME (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 151159.CrossRefGoogle ScholarPubMed
Breyer, MD & Breyer, RM (2000) Prostaglandin E receptors and the kidney. American Journal of Physiology 279 F12F23.Google ScholarPubMed
Budge, H, Dandrea, J, Mostyn, A, Evens, Y, Watkins, R, Sullivan, C, Ingleton, P, Stephenson, T & Symonds, ME (2003) Differential effects of fetal number and maternal nutrition in late gestation on prolactin receptor abundance and adipose tissue development in the neonatal lamb. Pediatric Research 53 302308.CrossRefGoogle Scholar
Campean, V, Theilig, F, Paliege, A, Breyer, M & Bachmann, S (2003) Key enzymes for renal prostaglandin synthesis: site-specific expression in rodent kidney (rat, mouse). American Journal of Physiology 285 F19F32.Google ScholarPubMed
Catella-Lawson, F, McAdam, B, Morrison, B, Kapoor, S, Kujubu, D, Antes, L, Lasseter, K, Quan, H, Gertz, B & FitzGerald, G (1999) Effects of specific inhibition of cyclooxygenase-2 on sodium balance, hemodynamics, and vasoactive eicosanoids. Journal of Pharmacology and Experimental Therapeutics 289 735741.Google ScholarPubMed
Devarajan, P & Benz, EJ (2000) Translational regulation of Na-K-ATPase subunit mRNAs by glucocorticoids. American Journal of Physiology 279 F1132F1138.Google ScholarPubMed
Dilger, K, Herrlinger, C, Peters, J, Seyberth, HW, Schweer, H & Klotz, U (2002) Effects of celecoxib and diclofenac on blood pressure, renal function, and vasoactive prostanoids in young and elderly subjects. Journal of Clinical Pharmacology 42 985994.CrossRefGoogle Scholar
Dinchuk, JE, Car, BD, Focht, RJ, Johnston, JJ, Jaffee, BD, Covington, MB et al. (1995) Renal abnormalities and an altered inflammatory response in mice lacking cyclooxygenase II. Nature 378 406409.CrossRefGoogle Scholar
Dodic, M, Hantzis, V, Duncan, J, Rees, S, Koukoulas, I, Johnson, K, Wintour, EM & Moritz, K (2002) Programming effects of short prenatal exposure to cortisol. FASEB Journal 16 10171026.CrossRefGoogle ScholarPubMed
Edwards, LJ & McMillen, IC (2002) Impact of maternal undernutrition during the periconceptional period, fetal number, and fetal sex on the development of the hypothalamo-pituitary adrenal axis in sheep during late gestation. Biology of Reproduction 66 15621569.CrossRefGoogle ScholarPubMed
Franco, MCP, Arruda, RMMP, Fortes, ZB, Oliveira, SF, Carvalho, MHC, Tostes, RCA & Nigro, D (2002) Severe nutritional restriction in pregnant rats aggravates hypertension, altered vascular reactivity, and renal development in spontaneously hypertensive rats offspring. Journal of Cardiovascular Pharmacology 39 369377.CrossRefGoogle ScholarPubMed
Fulton, M, Adams, W, Lutz, W & Oliver, MF (1978) Regional variations in mortality from ischaemic heart and cerebrovascular disease in Britain. British Heart Journal 40 563568.CrossRefGoogle ScholarPubMed
Gardner, DS, Jackson, AA, Langley-Evans, SC (1997) Maintenance of maternal diet-induced hypertension in the rat is dependent on glucocorticoids. Hypertension 30 15251530.CrossRefGoogle ScholarPubMed
Gardner, DS, Jamall, E, Fletcher, AJ, Fowden, AL & Giussani, DA (2004 a) Adrenocortical responsiveness is blunted in twin relative to singleton ovine fetuses. Journal of Physiology 557 10211032.CrossRefGoogle Scholar
Gardner, DS, Pearce, S, Dandrea, J, Walker, R, Ramsay, MM, Stephenson, T & Symonds, ME (2004 b) Peri-implantation undernutrition programs blunted angiotensin II evoked baroreflex responses in young adult sheep. Hypertension 43 12901296.CrossRefGoogle ScholarPubMed
Gertz, BJ, Krupa, D, Bolognese, JA, Sperling, RS & Reicin, A (2002) A comparison of adverse renovascular experiences among osteoarthritis patients treated with rofecoxib and comparator non-selective non-steroidal anti-inflammatory agents. Current Medical Research and Opinion 18 8291.CrossRefGoogle ScholarPubMed
Gleason, CA (1987) Prostaglandins and the developing kidney. Seminars in Perinatology 11 1221.Google Scholar
Gopalakrishnan, GS, Gardner, DS, Dandrea, J, Langley-Evans, SC, Pearce, S, Kurlak, LO et al. (2005) Influence of maternal pre-pregnancy body composition and diet during early-mid pregnancy on cardiovascular function and nephron number in juvenile sheep. British Journal of Nutrition (In the Press).CrossRefGoogle ScholarPubMed
Gopalakrishnan, GS, Gardner, DS, Rhind, SM, Rae, MT, Kyle, CE, Brooks, AN, Walker, RM, Ramsay, MM, Keisler, DH, Stephenson, T & Symonds, ME (2004) Programming of adult cardiovascular function after early maternal undernutrition in sheep. American Journal of Physiology 287 R12R20.Google ScholarPubMed
GoppeltStruebe, M (1997) Molecular mechanisms involved in the regulation of prostaglandin biosynthesis by glucocorticoids. Biochemical Pharmacology 53 13891395.CrossRefGoogle ScholarPubMed
Hammerman, MR (1989) The growth hormone insulin-like growth-factor axis in kidney. American Journal of Physiology 257 F503F514.Google ScholarPubMed
Hammerman, MR & Miller, SB (1993) The growth-hormone insulin-like growth-factor axis in kidney revisited. American Journal of Physiology 265 F1F14.Google ScholarPubMed
Hinchliffe, SA, Lynch, MR, Sargent, PH, Howard, CV, van Velzen, D (1992) The effect of intrauterine growth retardation on the development of renal nephrons. British Journal of Obstetrics and Gynaecology 99 296301.CrossRefGoogle ScholarPubMed
Hochberg, Z (2002) Mechanisms of steroid impairment of growth. Hormone Research 58 3338.CrossRefGoogle ScholarPubMed
Holt, RIG (2002) Fetal programming of the growth hormone-insulin-like growth factor axis. Trends in Endocrinology and Metabolism 13 392397.CrossRefGoogle ScholarPubMed
Hyatt, MA, Walker, DA, Stephenson, T & Symonds, ME (2004) Ontogeny and nutritional manipulation of the hepatic prolactin-growth hormone-insulin-like growth factor axis in the ovine fetus and in neonate and juvenile sheep. Proceedings of the Nutrition Society 63 127135.CrossRefGoogle ScholarPubMed
Ishibe, Y, Shiokawa, Y, Umeda, T, Uno, H, Nakamura, M & Izumi, T (1998) Prostaglandin E1 antagonizes hypoxic pulmonary vasoconstriction but reduces systemic blood pressure in dogs. Critical Care Medicine 26 126131.CrossRefGoogle ScholarPubMed
Jensen, BL, Stubbe, J, Hansen, PB, Andreasen, D & Skott, O (2001) Localization of prostaglandin E-2 EP2 and EP4 receptors in the rat kidney. American Journal of Physiology 280 F1001F1009.Google ScholarPubMed
Jensen, R, Armitage, JA, Athauda, S, Preston, J, Poston, L & Taylor, PD (2005) Cardiovascular radiotelemetric monitoring and aortic function in adult rats exposed to protein restriction in utero. Journal of the Society for Gynecologic Investigation (In the Press).Google Scholar
Johnson, AG, Nguyen, TV & Day, RO (1994) Do nonsteroidal anti-inflammatory drugs affect blood pressure? A meta-analysis. Annals of Internal Medicine 121 289300.CrossRefGoogle ScholarPubMed
Johnson, RF, Mitchell, CM, Clifton, V & Zakar, T (2004) Regulation of 15-hydroxyprostaglandin dehydrogenase (PGDH) gene activity, messenger ribonucleic acid processing, and protein abundance in the human chorion in late gestation and labor. Journal of Clinical Endocrinology and Metabolism 89 56395648.CrossRefGoogle ScholarPubMed
Kailasam, MT, Lin, MC, Cervenka, JH, Parmer, RJ, Kennedy, BP, Ziegler, MG, O'Connor, DT (1994) Effects of an oral prostaglandin E1 agonist on blood pressure and its determinants in essential hypertension. Journal of Human Hypertension 8 515520.Google ScholarPubMed
Knox, EG (1973) Ischaemic-heart-disease mortality and dietary intake of calcium. Lancet i 14651467.CrossRefGoogle Scholar
Komhoff, M, Wang, JL, Cheng, HF, Langenbach, R, McKanna, JA, Harris, RC & Breyer, MD (2000) Cyclooxygenase-2-selective inhibitors impair glomerulogenesis and renal cortical development. Kidney International 57 414422.CrossRefGoogle ScholarPubMed
Konje, JC, Bell, SC, Morton, JJ, de Chazal, R & Taylor, DJ (1996) Human fetal kidney morphometry during gestation and the relationship between weight, kidney morphometry and plasma active renin concentration at birth. Clinical Science (London) 91 169175.CrossRefGoogle ScholarPubMed
Langley, SC & Jackson, AA (1994) Increased systolic blood pressure in adult rats induced by fetal exposure to maternal low protein diets. Clinical Science (London) 86 217222.CrossRefGoogle ScholarPubMed
Langley-Evans, SC, Welham, SJM & Jackson, AA (1999) Fetal exposure to a maternal low protein diet impairs nephrogenesis and promotes hypertension in the rat. Life Sciences 64 965974.CrossRefGoogle ScholarPubMed
Lemmer, B, Witte, K, Schanzer, A & Findeisen, A (2000) Circadian rhythms in the renin-angiotensin system and adrenal steroids may contribute to the inverse blood pressure rhythm in hypertensive TGR(mREN-2)27 rats. Chronobiology International 17 645658.CrossRefGoogle Scholar
Lesage, J, Blondeau, B, Grino, M, Breant, B & Dupouy, JP (2001) Maternal undernutrition during late gestation induces fetal overexposure to glucocorticoids and intrauterine growth retardation, and disturbs the hypothalamopituitary adrenal axis in the newborn rat. Endocrinology 142 16921702.CrossRefGoogle ScholarPubMed
Lucas, SRR, Silva, VLC, Miraglia, SM & Gil, FZ (1997) Functional and morphometric evaluation of offspring kidney after intrauterine undernutrition. Pediatric Nephrology 11 719723.CrossRefGoogle ScholarPubMed
McMullen, S, Gardner, DS, Langley-Evans, SC (2004) Prenatal programming of angiotensin II type 2 receptor expression in the rat. British Journal of Nutrition 91 133140.CrossRefGoogle ScholarPubMed
Mackenzie, H & Brenner, B (1995) Fewer nephrons at birth: a missing link in the etiology of essential hypertension. American Journal of Kidney Disease 26 9198.CrossRefGoogle ScholarPubMed
Madsen, K, Stubbe, J, Yang, T, Skott, O, Bachmann, S & Jensen, BL (2004) Low endogenous glucocorticoid allows induction of kidney cortical cyclooxygenase-2 during postnatal rat development. American Journal of Physiology 286 F26F37.Google ScholarPubMed
Matson, JR, Stokes, JB & Robillard, JE (1981) Effects of inhibition of prostaglandin synthesis on fetal renal-function. Kidney International 20 621627.CrossRefGoogle ScholarPubMed
Mitchell, EK, Louey, S, Harding, R, Cock, ML & Black, MJ (2003) Growth retardation in utero due to twinning: effect on nephron endowment. Pediatric Research 53 46A.Google Scholar
Moritz, KM, Dodic, M & Wintour, EM (2003) Kidney development and the fetal programming of adult disease. Bioessays 25 212220.CrossRefGoogle ScholarPubMed
Nasjletti, A, Erman, A, Cagen, L & Baer, P (1984) Plasma concentrations, renal excretion, and tissue release of prostaglandins in the rat with dexamethasone-induced hypertension. Endocrinology 114 10331040.CrossRefGoogle ScholarPubMed
Ogawa, T, Tomomasa, T, Hikima, A, Kobayashi, Y, Nakano, K, Fukabori, Y & Morikawa, A (2001) Developmental changes in cyclooxygenase mRNA expression in the kidney of rats. Pediatric Nephrology 16 618622.CrossRefGoogle ScholarPubMed
Osmond, C, Barker, DJ & Slattery, JM (1990) Risk of death from cardiovascular disease and chronic bronchitis determined by place of birth in England and Wales. Journal of Epidemiology and Community Health 44 139141.CrossRefGoogle ScholarPubMed
Ozaki, T, Nishina, H, Hanson, MA & Poston, L (2001) Dietary restriction in pregnant rats causes gender-related hypertension and vascular dysfunction in offspring. Journal of Physiology 530 141152.CrossRefGoogle ScholarPubMed
Parving, H, Noer, I, Mogensen, C & Svendsen, P (1978) Kidney function in normal man during short-term growth hormone infusion. Acta Endocrinologica 89 796800.Google ScholarPubMed
Pocock, SJ, Shaper, AG, Cook, DG, Packham, RF, Lacey, RF, Powell, P & Russell, PF (1980) British Regional Heart Study: geographic variations in cardiovascular mortality, and the role of water quality. British Medical Journal 280 12431249.CrossRefGoogle ScholarPubMed
Pope, JE, Anderson, JJ & Felson, DT (1993) A meta-analysis of the effects of nonsteroidal anti-inflammatory drugs on blood pressure. Archives of Internal Medicine 153 477484.CrossRefGoogle ScholarPubMed
Potter, EL (1972) Normal and Abnormal Development of the Kidney. Chicago, IL: Year Book Medical Publishers.Google Scholar
Rogers, SA, Powell-Braxton, L & Hammerman, MR (1999) Insulin-like growth factor I regulates renal development in rodents. Developmental Genetics 24 293298.3.0.CO;2-S>CrossRefGoogle ScholarPubMed
Schweda, F, Klar, J, Narumiya, S, Nusing, RM & Kurtz, A (2004) Stimulation of renin release by prostaglandin E2 is mediated by EP2 and EP4 receptors in mouse kidneys. American Journal of Physiology 287 F427F433.Google ScholarPubMed
Sherman, RC, Jackson, AA, Langley-Evans, SC (1999) Long-term modification of the excretion of prostaglandin E-2 by fetal exposure to a maternal low protein diet in the rat. Annals of Nutrition and Metabolism 43 98106.CrossRefGoogle ScholarPubMed
Tilley, SL, Audoly, LP, Hicks, EH, Kim, HS, Flannery, PJ, Coffman, TM & Koller, BH (1999) Reproductive failure and reduced blood pressure in mice lacking the EP2 prostaglandin E-2 receptor. Journal of Clinical Investigation 103 15391545.CrossRefGoogle Scholar
Tonkiss, J, Trzcinska, M, Galler, JR, Ruiz-Opazo, N & Herrera, VLM (1998) Prenatal malnutrition-induced changes in blood pressure–Dissociation of stress and nonstress responses using radiotelemetry. Hypertension 32 108114.CrossRefGoogle ScholarPubMed
Vio, CP, Balestrini, C, Recabarren, M & Cespedes, C (1999) Postnatal development of cyclooxygenase-2 in the rat kidney. Immunopharmacology 44 205210.CrossRefGoogle ScholarPubMed
Wada, J, Liu, ZZ, Alvares, K, Kumar, A, Wallner, E, Makino, H & Kanwar, YS (1993) Cloning of cDNA for the alpha-subunit of mouse insulin-like growth factor-I receptor and the role of the receptor in metanephric development. Proceedings of the National Academy of Sciences USA 90 1036010364.CrossRefGoogle ScholarPubMed
Whorwood, CB, Firth, KM, Budge, H & Symonds, ME (2001) Maternal undernutrition during early to midgestation programs tissue-specific alterations in the expression of the glucocorticoid receptor, 11 beta-hydroxysteroid dehydrogenase isoforms, and type 1 angiotensin II receptor in neonatal sheep. Endocrinology 142 28542864.CrossRefGoogle ScholarPubMed
Williams, SJ, McMillen, IC, Zaragoza, DB & Olson, DM (2002) Placental restriction increases the expression of prostaglandin endoperoxide G/H synthase-2 and EP2 mRNA in the fetal sheep kidney during late gestation. Pediatric Research 52 879885.CrossRefGoogle Scholar
Williams, SJ, Olson, DM, Zaragoza, DB, Coulter, CL, Butler, TG, Ross, JT & McMillen, IC (2004) Cortisol infusion decreases renin, but not PGHS-2, EP2, or EP4 mRNA expression in the kidney of the fetal sheep at days 109–116. Pediatric Research 55 637644.CrossRefGoogle ScholarPubMed
Woods, LL, Ingelfinger, JR & Rasch, R (2005) Modest maternal protein restriction fails to program adult hypertension in female rats. American Journal of Physiology (In the Press).Google ScholarPubMed
Woods, LL & Weeks, DA (2005) Prenatal programming of adult blood pressure: role of maternal corticosteroids. American Journal of Physiology (In the Press).Google ScholarPubMed
Yao, B, Harris, RC & Zhang, MZ (2005) Interactions between 11beta-hydroxysteroid dehydrogenase and COX-2 in kidney. American Journal of Physiology 288 R1767R1773.Google ScholarPubMed
Ymer, SI & Herington, AC (1992) Developmental expression of the growth-hormone receptor gene in rabbit-tissues. Molecular and Cellular Endocrinology 83 3949.CrossRefGoogle ScholarPubMed
Zhang, M-H, Harris, RC & McKanna, JA (1999) Regulation of cyclooxygenase-2 (COX-2) in rat renal cortex by adrenal glucocorticoids and mineralocorticoids. Proceedings of the National Academy of Sciences USA 96 1528015285.CrossRefGoogle ScholarPubMed
Zhang, MZ, Hao, CM, Breyer, MD, Harris, RC & McKanna, JA (2002) Mineralocorticoid regulation of cyclooxygenase-2 expression in rat renal medulla. American Journal of Physiology 283 F509F516.Google ScholarPubMed