Hostname: page-component-78c5997874-m6dg7 Total loading time: 0 Render date: 2024-11-13T07:33:50.884Z Has data issue: false hasContentIssue false
  • English
  • Français

Fetal programming of cardiovascular function through exposure to maternal undernutrition

Published online by Cambridge University Press:  28 February 2007

Simon C. Langley-Evans
Simon C. Langley-Evans*
Affiliation:
Nutritional Biochemistry, University of Nottingham, Sutton Bonington, UK
*
Corresponding Author: Dr Simon Langley-Evans, email simon.langley-evans@nottingham.ac.uk
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

A substantial and robust body of epidemiological evidence indicates that prenatal dietary experience may be a factor determining cardiovascular disease risk. Retrospective cohort studies indicate that low birth weight and disproportion at birth are powerful predictors of later disease risk. This prenatal influence on non-communicable disease in later life has been termed programming. Maternal nutritional status has been proposed to be the major programming influence on the developing fetus. The evidence from epidemiological studies of nutrition, fetal development and birth outcome is, however, often weak and inconclusive. The validity of the nutritional programming concept is highly dependent on experimental studies in animals. The feeding of low-protein diets in rat pregnancy results in perturbations in fetal growth and dimensions at birth. The offspring of rats fed low-protein diets exhibit a number of metabolic and physiological disturbances, and are consistently found to have high blood pressure from early postnatal life. This experimental model has been used to explore potential mechanisms of programming through which maternal diet may programme the cardiovascular function of the fetus. Indications from this work are that fetal exposure to maternally-derived glucocorticoids plays a key role in the programming mechanism. Secondary to this activity, the fetal hypothalamic–pituitary–adrenal axis may stimulate renin–angiotensin system activity, resulting in increased vascular resistance and hypertension.

Keywords

PregnancyFetal programmingHypertension
Type
Symposium on ‘Nutritional adaptation to pregnancy and lactation’
Information
Proceedings of the Nutrition Society , Volume 60 , Issue 4 , November 2001 , pp. 505 - 513
Copyright
Copyright © The Nutrition Society 2001

References

Anguita, RM, Sigulem, DM & Sawaya, AL (1993) Intrauterine food restriction is associated with obesity in young rats. Journal of Nutrition 123, 1421–1428.Google Scholar
Antonov, AN (1947) Children born during the siege of Leningrad in 1942. Journal of Pediatrics 30, 250–259.Google Scholar
Arishima, K, Nakama, K, Monkava, Y, Hashimot, Y & Eguchi, Y (1977) Maternal–fetal interrelations of plasma corticosterone concentrations at the end of gestation in the rat. Journal of Endocrinology 72, 239–240.CrossRefGoogle ScholarPubMed
Barker, DJP (1994) Mothers, Babies and Disease in Later Life. London: BMJ Publishing Group.Google Scholar
Bartley, M, Power, C, Davey-Smith, G & Shipley, M (1994) Birthweight and later socioeconomic disadvantage: evidence from the 1958 British cohort study. British Medical Journal 309, 1475–1478.Google Scholar
Benediktsson, R, Lindsay, RS, Noble, J, Seckl, JR & Edwards, CRW (1993) Glucocorticoid exposure in utero: new model for adult hypertension. Lancet 341, 339–341.Google Scholar
Calder, PC & Yaqoob, P (2000) The level of protein and fat in the diet of pregnant rats both affect lymphocyte function in the offspring. Nutrition Research 20, 995–1005.Google Scholar
Campbell, DM, Hall, MH, Barker, DJP, Cross, J, Shiell, AW & Godfrey, KM (1996) Diet in pregnancy and the offsprings blood pressure 40 years later. British Journal of Obstetrics and Gynaecology 103, 273–280.CrossRefGoogle ScholarPubMed
Celsi, G, Kistner, A, Eklof, AC, Ceccatelli, S, Aizman, R & Jacobson, S (1997) Inhibition of renal growth by prenatal dexamethasone and the programming of blood pressure in the offspring. Journal of the American Society for Nephrology 8, A1360.Google Scholar
Chatelain, J, Dupouy, J-P, & Allaume, P (1980) Fetal-maternal adrenocorticotropin and corticosterone relationships in the rat: effects of maternal adrenalectomy. Endocrinology 106, 1297–1302.Google Scholar
Clark, PM, Hindmarsh, PC, Shiell, AW, Law, CM, Honour, JW & Barker, DJP (1996) Size at birth and adrenocortical function in childhood. Clinical Endocrinology 45, 721–726.CrossRefGoogle ScholarPubMed
Crowe, C, Dandekar, P, Fox, M, Dhingra, K, Bennet, L & Hanson, MA (1995) The effects of anaemia on heart, placenta and body weight, and blood pressure in fetal and neonatal rats. Journal of Physiology 488, 515–519.CrossRefGoogle ScholarPubMed
Doyle, W, Wynn, AHA, Crawford, MA & Wynn, SW (1992) Nutritional counselling and supplementation in the second and third trimester of pregnancy: a study in a London population. Journal of Nutrition and Medicine 3, 249–256.CrossRefGoogle Scholar
Dunn, RL, Langley-Evans, SC, Jackson, AA & Whorwood, CB (2001) Hypertension in the mouse following intrauterine exposure to a maternal low-protein diet. Proceedings of the Nutrition Society 60, 51A.Google Scholar
Edwards, CRW, Benediktsson, R, Lindsay, RS & Seckl, JR (1993) Dysfunction of placental glucocorticoid barrier: link between fetal environment and adult hypertension. Lancet 341, 355–357.CrossRefGoogle ScholarPubMed
Edwards, CRW, Benediktsson, R, Lindsay, RS & Seckl, JR (1996) 11α-hydroxysteroid dehydrogenases: key enzymes in determining tissue-specific glucocorticoid effects. Steroids 61, 263–269.CrossRefGoogle Scholar
Forrester, TE, Wilks, RJ, Bennett, FI, Simeon, D, Osmond, C, Allen, M, Chung, AP & Scott, P (1996) Fetal growth and cardiovascular risk factors in Jamaican schoolchildren. British Medical Journal 312, 156–160.CrossRefGoogle ScholarPubMed
Forsen, T, Eriksson, JG, Tuomilehto, J, Osmond, C & Barker, DJP (1999) Growth in utero and during childhood among women who develop coronary heart disease: longitudinal study. British Medical Journal 319, 1403–1407.CrossRefGoogle ScholarPubMed
Gardner, DS, Jackson, AA & Langley-Evans, SC (1997 a) Maintenance of maternal diet-induced hypertension in the rat is dependent upon glucocorticoids. Hypertension 30, 1525–1530.CrossRefGoogle ScholarPubMed
Gardner, DS, Jackson, AA & Langley-Evans, SC (1997 b) Prenatal undernutrition alters postnatal vascular sensitivity to angiotensin II. Clinical Science 95, Suppl. 39, 14P.CrossRefGoogle Scholar
Godfrey, KM, Forrester, T, Barker, DJP, Jackson, AA, Landman, JP, Hall, JStE, Cox, V & Osmond, C (1994) The relation of maternal nutritional status during pregnancy to blood pressure in childhood. British Journal of Obstetrics and Gynaecology 101, 398–403.Google Scholar
Godfrey, KM, Robinson, S, Barker, DJP, Osmond, C & Cox, V (1996) Maternal nutrition in early and late pregnancy in relation to placental and fetal growth. British Medical Journal 312, 410–414.CrossRefGoogle ScholarPubMed
Hales, CN, Desai, M, Ozanne, SE & Crowther, NJ (1996) Fishing in the stream of diabetes: from measuring insulin to the control of fetal organogenesis. Biochemical Society Transactions 24, 341–350.Google Scholar
Hall, SM & Zeman, FJ (1968) Kidney function of the progeny of rats fed a low protein diet. Journal of Nutrition 95, 49–56.CrossRefGoogle ScholarPubMed
Harrap, SB (1998) Preventing adult disease: windows of opportunity. Clinical Science 94, 337–338.CrossRefGoogle ScholarPubMed
Harrap, SB, Mirakian, C, Datodi, SR & Lever, AF (1994) Blood pressure and lifespan following brief ACE inhibitor treatment in young Spontaneously Hypertensive rats. Clinical and Experimental Pharmacology and Physiology 21, 125–127.CrossRefGoogle ScholarPubMed
Hastings-Roberts, MM & Zeman, FJ (1977) Effects of protein deficiency, pair-feeding, or diet supplementation on maternal, fetal and placental growth in rats. Journal of Nutrition 107, 973–982.CrossRefGoogle ScholarPubMed
Hinchcliffe, SA, Lynch, MRJ, Sargent, PH, Howard, CV & Van Zelzen, D (1992) The effect of intrauterine growth retardation on the development of renal nephrons. British Journal of Obstetrics and Gynaecology 99, 296–301.CrossRefGoogle Scholar
Hoy, WE, Mathews, JD, McCredie, DA, Pugsley, DJ, Hayhurst, BG, Rees, M, Kile, E, Walker, KA & Wang, Z (1998) The multidimensional nature of renal disease: Rates and associations of albuminuria in an Australian Aboriginal community. Kidney International 54, 1296–1304.Google Scholar
Iglesias-Barreira, V, Ahn, M-T,, Reussens, B, Dahri, S, Hoet, JJ & Remacle, C (1996) Pre- and postnatal low protein diet affect pancreatic islet blood flow and insulin release in adult rats. Endocrinology 137, 3797–3801.CrossRefGoogle ScholarPubMed
Jackson, AA, Langley-Evans, SC & McCarthy, HD (1996) Nutritional influences in early life upon obesity and body proportions. In Origins and Consequences of Obesity. CIBA Foundation Symposium no. 201, pp. 407–435 [James, WPT and Shaper, G, editors]. Chichester, West Sussex: John Wiley and Sons.Google Scholar
Kind, KL, Clifton, PM, Katsman, AI, Tsiounis, M, Robinson, JS & Owens, JA (1999) Restricted fetal growth and the response to dietary cholesterol in the guinea pig. American Journal of Physiology 277, R1675–R1682.Google Scholar
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 91, 169–175.CrossRefGoogle ScholarPubMed
Kornel, L, Prancan, AV, Kanamarlapudi, N, Hynes, J & Kuzianik, E (1995) Study on the mechanisms of glucocorticoid-induced hypertension: glucocorticoids increase transmembrane Ca2+ influx in vascular smooth muscle in vivo. Endocrine Research 21, 203–210.CrossRefGoogle Scholar
Kramer, MS & Joseph, KS (1996) Enigma of fetal/infant-origins hypothesis. Lancet 348, 1254–1255.CrossRefGoogle ScholarPubMed
Kwong, WY, Wild, AE, Roberts, P, Willis, AC & Fleming, TP (2000) Maternal undernutrition during the preimplantation period of rat development causes blastocyst abnormalities and programming of postnatal hypertension. Development 127, 4195–4202.CrossRefGoogle ScholarPubMed
Langley, SC, Browne, RF & Jackson, AA (1994 a) Altered glucose tolerance in rats exposed to maternal low protein diets in utero. Comparative Biochemistry and Physiology 109A, 223–229.Google Scholar
Langley, SC & Jackson, AA (1994) Increased systolic blood pressure in adult rats induced by fetal exposure to maternal low protein diet. Clinical Science 86, 217–222.CrossRefGoogle Scholar
Langley, SC, Seakins, M, Grimble, RF & Jackson, AA (1994 b) The acute phase response of adult rats is altered by in utero exposure to maternal low protein diets. Journal of Nutrition 124, 1588–1596.CrossRefGoogle ScholarPubMed
Langley-Evans, SC (1996) Intrauterine programming of hypertension: nutrient interactions. Comparative Biochemistry and Physiology 114A, 327–333.CrossRefGoogle Scholar
Langley-Evans, SC (1997 a) Maternal carbenoxolone treatment lowers birthweight and induces hypertension in the offspring of rats fed a protein-replete diet. Clinical Science 93, 423–429.Google Scholar
Langley-Evans, SC (1997 b) Hypertension induced by fetal exposure to a maternal low protein diet, in the rat, is prevented by pharmacological blockade of glucocorticoid synthesis. Journal of Hypertension 15, 537–544.CrossRefGoogle ScholarPubMed
Langley-Evans, SC (1997 c) Intrauterine programming of hypertension by glucocorticoids. Life Sciences 60, 1213–1221.Google Scholar
Langley-Evans, SC (2000) Critical differences between two low protein diet protocols in the programming of hypertension in the rat. International Journal of Food Sciences and Nutrition 51, 11–17.CrossRefGoogle ScholarPubMed
Langley-Evans, SC, Gardner, DS & Jackson, AA (1996 a) Maternal protein restriction influences the programming of the rat hypothalamic-pituitary-adrenal axis. Journal of Nutrition 126, 1578–1585.CrossRefGoogle ScholarPubMed
Langley-Evans, SC, Gardner, DS & Jackson, AA (1996 b) Association of disproportionate growth of fetal rats in late gestation with raised systolic blood pressure in later life. Journal of Reproduction and Fertility 106, 307–312.Google Scholar
Langley-Evans, SC & Jackson, AA (1995) Captopril normalises systolic blood pressure in rats with hypertension induced by fetal exposure to maternal low protein diets. Comparative Biochemistry and Physiology 110A, 223–228.CrossRefGoogle Scholar
Langley-Evans, SC & Nwagwu, MO (1998) Impaired growth and increased activities of glucocorticoid-sensitive enzymes in tissues of rat fetuses exposed to maternal low protein diets. Life Sciences 63, 605–615.Google Scholar
Langley-Evans, SC, Phillips, GJ, Benediktsson, R, Gardner, DS, Edwards, CRW, Jackson, AA & Seckl, JR (1996 c) Protein intake in pregnancy, placental glucocorticoid metabolism and the programming of hypertension. Placenta 17, 169–172.CrossRefGoogle ScholarPubMed
Langley-Evans, SC, Phillips, GJ, Gardner, DS & Jackson, AA (1996 d) Role of glucocorticoids in programming of maternal diet-induced hypertension in the rat. Journal of Nutritional Biochemistry 7, 173–178.Google Scholar
Langley-Evans, SC, Phillips, GJ & Jackson, AA (1994) In utero exposure to maternal low protein diets induces hypertension in weanling rats, independently of maternal blood pressure changes. Clinical Nutrition 13, 319–324.CrossRefGoogle ScholarPubMed
Langley-Evans, SC, Phillips, GJ & Jackson, AA (1997) Fetal exposure to a maternal low protein diet alters the susceptibility of the young adult rat to sulfur dioxide-induced lung injury. Journal of Nutrition 127, 202–209.Google Scholar
Langley-Evans, SC, Welham, SJM & Jackson, AA (1999) Fetal exposure to maternal low protein diets impairs nephrogenesis and promotes hypertension in the rat. Life Sciences 64, 965–974.CrossRefGoogle ScholarPubMed
Langley-Evans, SC, Welham, SJM, Sherman, RC & Jackson, AA (1996 e) Weanling rats exposed to maternal low protein diets during discrete periods of gestation exhibit differing severity of hypertension. Clinical Science 91, 607–615.Google Scholar
Langley-Evans, SC, Wood, S & Jackson, AA (1995) Enzymes of the gamma-glutamyl cycle are programmed in utero by maternal nutrition. Annals of Nutrition and Metabolism 39, 28–35.CrossRefGoogle ScholarPubMed
Lelievre-Pegorier, M, Euzet, S & Merlet-Benichou, C (1993) Effect of fetal exposure to gentamicin on phosphate transport in young rat kidney. American Journal of Physiology 265, F807–F812.Google ScholarPubMed
Leon, DA (1999) Fetal growth and later disease: epidemiological evidence from Swedish cohorts. In Fetal Programming: Influences on Development and Disease in Later Life, pp. 12–29 [O'Brien, PMS, Wheeler, T and Barker, DJP, editors]. London: RCOG Press.Google Scholar
Levy, L & Jackson, AA (1993) Modest restriction of dietary protein during pregnancy in the rat: fetal and placental growth. Journal of Developmental Physiology 19, 113–118.Google ScholarPubMed
Liggins, GC (1969) Premature delivery of foetal lambs infused with glucocorticoids. Journal of Endocrinology 45, 515–523.CrossRefGoogle ScholarPubMed
Lindsay, RS, Lindsay, RM, Edwards, CRW & Seckl, JR (1996) Inhibition of 11α-hydroxysteroid dehydrogenase in pregnant rats and the programming of blood pressure in the offspring. Hypertension 27, 1200–1204.Google Scholar
Lucas, A (1992) Programming by nutrition in man. In Early Diet, Later Consequences, pp. 24–28 [Conning, D, editor]. London: British Nutrition Foundation.Google Scholar
Mackenzie, HS & Brenner, BM (1995) Fewer nephrons at birth: a missing link in the etiology of essential hypertension? American Journal of Kidney Diseases 26, 91–98.CrossRefGoogle ScholarPubMed
Marchand, MC, Dunn, RL, Jackson, AA & Langley-Evans, SC (2001) Programming of blood pressure and renal structure in rats exposed to nitrogen-supplemented maternal low protein diets. Proceedings of the Nutrition Society 60, 139A.Google Scholar
Mathews, F, Yudkin, P & Neil, A (1999) Influence of maternal nutrition on outcome of pregnancy: prospective cohort study. British Medical Journal 319, 339–343.Google Scholar
Matthes, JWA, Lewis, PA, Davies, DP & Bethel, JA (1994) Relation between birth weight at term and systolic blood pressure in adolescence. British Medical Journal 308, 1074–1077.CrossRefGoogle ScholarPubMed
Mercuri, O, de Tomas, ME & Itarte, H (1979) Prenatal protein depletion and delta 9, delta 6 and delta 5 desaturase. Lipids 14, 822–825.CrossRefGoogle Scholar
Merlet-Benichou, C, Gilbert, T, Muffat-Joly, M, Lelievre-Pegorier, M & Leroy, B (1994) Intrauterine growth retardation leads to a permanent nephron deficit in the rat. Pediatric Nephrology 8, 175–180.CrossRefGoogle ScholarPubMed
Moore, VM, Miller, AG, Boulton, TJC, Cockington, RA, Hamilton Craig, I, Magarey, AM & Robinson, JS (1996) Placental weight, birth measurements and blood pressure at age 8 years. Archives of Disease in Childhood 74, 538–541.CrossRefGoogle ScholarPubMed
Narce, M, Poisson, J-P,, Belleville, J & Chanusot, B (1992) Depletion of delta 9 desaturase (EC 1.14.99.5) enzyme activity in growing rats during dietary protein restriction. British Journal of Nutrition 68, 627–637.CrossRefGoogle ScholarPubMed
Nwagwu, MO, Cook, A & Langley-Evans, SC (2000) Evidence of progressive deterioration of renal function in rats exposed to a maternal low protein diet in utero. British Journal of Nutrition 83, 79–85.CrossRefGoogle ScholarPubMed
Persson, E & Jansson, T (1993) Low birth weight is associated with elevated adult blood pressure in the chronically catheterized guinea-pig. Acta Physiologica Scandinavica 115, 195–196.Google Scholar
Petry, CJ, Ozanne, SE, Wang, CL & Hales, CN (1997) Early protein restriction and obesity independently induce hypertension in year old rats. Clinical Science 93, 147–152.CrossRefGoogle ScholarPubMed
Phillips, DIW, Walker, BR, Reynolds, RM, Flanagan, DEH, Wood, PJ, Osmond, C, Barker, DJP & Whorwood, CB (2000) Low birth weight predicts elevated plasma cortisol concentrations in adults from 3 populations. Hypertension 35, 1301–1306.CrossRefGoogle ScholarPubMed
Pickard, CL, McCarthy, HD, Browne, RF & Jackson, AA (1996) Altered insulin response to a glucose load in rats following exposure to a low protein diet in utero. Proceedings of the Nutrition Society 55, 44A.Google Scholar
Prentice, AM, Cole, TJ, Foord, FA, Lamb, WH & Whitehead, RG (1987) Increased birthweight after prenatal dietary supplementation of rural African women. American Journal of Clinical Nutrition 46, 912–925.CrossRefGoogle ScholarPubMed
Ravelli, ACJ, van der Meulen, JHP, Michels, RPJ, Osmond, C, Barker, DJP, Hales, CN & Bleker, OP (1998) Glucose tolerance in adults after exposure to the Dutch Famine. Lancet 351, 173–177.Google Scholar
Rees, WD & Hay, SM (1998) The effect of maternal protein deficiency on the expression of the growth arrest specific gene 6 (gas6) in the fetal kidney. Biochemical Society Transactions 667, 70.Google Scholar
Rees, WD, Hay, SM, Brown, DS, Antipatis, C & Palmer, RM (2000) Maternal protein deficiency causes hypermethylation of DNA in the livers of rat fetuses. Journal of Nutrition 130, 1821–1826.Google Scholar
Reinisch, JM, Simon, NG & Karwo, WG (1978) Prenatal exposure to prednisone in humans and animals retards intra-uterine growth. Science 202, 436–438.Google Scholar
Rich-Edwards, J, Stampfer, M, Manson, J, Rosner, B, Colditz, G, Willett, W, Speizer, F & Hennekens, C (1995) Birthweight, breastfeeding and the risk of coronary heart disease in the nurses health study. American Journal of Epidemiology 141, S78.Google Scholar
Roach, HI, Langley-Evans, SC & Cooper, C (1999) Protein deficiencies during pregnancy affect skeletal development in the offspring. Journal of Bone and Mineral Research 14, Suppl. 1, S394.Google Scholar
Rush, D, Stein, Z & Susser, M (1980) A randomized controlled trial of prenatal nutritional supplementation in New York City. Pediatrics 65, 683–697.CrossRefGoogle ScholarPubMed
Sayer, AA, Dunn, RL, Langley-Evans, SC & Cooper, C (2001) Intrauterine exposure to a maternal low protein diet shortens lifespan in rats. Gerontology 47, 9–14.CrossRefGoogle Scholar
Sherman, RC (1999) The role of the renin-angiotensin system in the fetal programming of hypertension. PhD Thesis, University of Southampton.Google Scholar
Sherman, RC, Jackson, AA & Langley-Evans, SC (1999) Long term modification of the excretion of prostaglandin E2 by fetal exposure to a maternal low protein diet in the rat. Annals of Nutrition and Metabolism 43, 98–106.CrossRefGoogle ScholarPubMed
Sherman, RC & Langley-Evans, SC (1998) Early administration of angiotensin-converting enzyme inhibitor captopril, prevents the development of hypertension programmed by intrauterine exposure to a maternal low protein diet. Clinical Science 94, 373–381.Google Scholar
Sherman, RC & Langley-Evans, SC (2000) Antihypertensive treatment in early postnatal life modulates prenatal dietary influences upon blood pressure in the rat. Clinical Science 98, 269–275.Google Scholar
Stein, CE, Fall, CHD, Osmond, C, Cox, V & Barker, DJP (1996) Fetal growth and coronary heart disease in South India. Lancet 348, 1269–1273.CrossRefGoogle ScholarPubMed
Stewart, PM, Whorwood, CB & Mason, JI (1995) Type 2 11α-hydroxysteroid dehydrogenase in fetal and adult life. Journal of Steroid Biochemistry and Molecular Biology 55, 465–471.Google Scholar
Tangalakis, K, Lumbers, ER, Moritz, KM, Towstoless, MK & Wintour, EM (1992) Effect of cortisol on blood pressure and vascular reactivity in the ovine fetus. Experimental Physiology 77, 709–717.CrossRefGoogle ScholarPubMed
Thame, M, Wilks, RJ, McFarlane-Anderson, N, Bennett, FI & Forrester, TE (1997) Relationship between maternal nutritional status and infants weight and body proportions at birth. European Journal of Clinical Nutrition 51, 134–138.CrossRefGoogle ScholarPubMed
Willett, WC (1994) Diet and health: What should we eat? Science 264, 532–537.CrossRefGoogle ScholarPubMed
Woodall, SM, Johnston, BM, Breier, BH & Gluckman, PD (1996) Chronic maternal undernutrition in the rat leads to delayed postnatal growth and elevated blood pressure of offspring. Pediatric Research 40, 438–443.Google Scholar
Yajnik, CS, Fall, CHD, Vaidya, U, Pandit, AN, Bavdekar, A, Bhat, DS, Osmond, C, Hales, CN & Barker, DJP (1995) Fetal growth and glucose and insulin metabolism in four-year-old Indian children. Diabetic Medicine 12, 330–336.CrossRefGoogle ScholarPubMed
Zeman, FJ (1968) Effects of maternal protein restriction on the kidney of the newborn young of rats. Journal of Nutrition 94, 111–117.CrossRefGoogle ScholarPubMed
Zeman, FJ & Stanbrough, EC (1969) Effect of maternal protein deficiency on cellular development in the fetal rat. Journal of Nutrition 99, 274–282.CrossRefGoogle ScholarPubMed