Skip to main content Accessibility help

Maternal nutritional restriction during gestation impacts differently on offspring muscular and elastic arteries and is associated with increased carotid resistance and ventricular afterload in maturity

  • Yanina Zócalo (a1), Rodolfo Ungerfeld (a2), Raquel Pérez-Clariget (a3) and Daniel Bia (a1)


Background: Intrauterine undernutrition could impact offspring left ventricle (LV) afterload and arterial function. The changes observed in adulthood could differ depending on the arterial type, pathway and properties studied. Aim: To analyze whether undernutrition during early and mid-gestation is associated with changes in cardiovascular properties in adulthood. Methods: Pregnant ewes were assigned to one of the two treatment groups: (1) standard nutritional offer (high pasture-allowance, HPA; n = 16) or (2) nutritional restriction (50–75% of control intake) from before conception until day 122 of gestation (≈85% term) (low pasture allowance, LPA; n = 17). When offspring reached adult life, cardiovascular parameters were assessed in conscious animals (applanation tonometry, vascular echography). Measurements: Peripheral and aortic pressure, carotid and femoral arteries diameters, intima-media thickness and stiffness, blood flow, local and regional resistances and LV afterload were measured. Blood samples were collected. Parameters were compared before and after adjustment for nutritional characteristics at birth and at the time of the cardiovascular evaluation. Results: Doppler-derived cerebral vascular resistances, mean pressure/flow ratio (carotid resistance) and afterload indexes were higher in descendants from LPA than in descendants from HPA ewes (p < 0.05). Descendants from LPA had lower femoral diameters (p < 0.05). Cardiovascular changes associated with nutritional restriction during pregnancy did not depend on the offsprings’ nutritional conditions at birth and/or in adult life. Conclusion: Pregnant ewes that experienced undernutrition gave birth to female offspring that exhibited increased carotid pathway resistances (cerebral microcirculatory resistances) and LV afterload when they reached the age of 2.5 years. There were differences in the impact of nutritional deficiency on elastic and muscular arteries.


Corresponding author

Address for correspondence: Yanina Zócalo, Departmento de Fisiología, Facultad de Medicina, Núcleo Interdisciplinario CUiiDARTE, Universidad de la República, Montevideo, Uruguay. Email:


Hide All
1. Vorster, HH, Kruger, A. Poverty, malnutrition, underdevelopment and cardiovascular disease: a South African perspective. Cardiovasc J Afr. 2007; 18(5), 321324.
2. Bergmann, R, Bergmann, K, Dudenhausen, J. Undernutrition and growth restriction in pregnancy. In: Barker, DJP, Bergmann, RL, Ogra, PL (eds): The Window of Opportunity: Pre-Pregnancy to 24 Months of Age. NestléNutr Workshop Ser Pediatr Program, vol. 61, pp. 103121. 2008. Nestec Ltd., Vevey/S. Karger AG: Basel.
3. Dodson, RB, Rozance, PJ, Fleenor, BS, et al. Increased arterial stiffness and extracellular matrix reorganization in intrauterine growth-restricted fetal sheep. Pediatr Res. 2013; 73(2), 147154.
4. Dodson, RB, Rozance, PJ, Petrash, CC, Hunter, KS, Ferguson, VL. Thoracic and abdominal aortas stiffen through unique extracellular matrix changes in intrauterine growth restricted fetal sheep. Am J Physiol Heart Circ Physiol. 2014, 306(3), H429H437.
5. Torrens, C, Brawley, L, Barker, AC, et al. Maternal protein restriction in the rat impairs resistance artery but not conduit artery function in pregnant offspring. J Physiol. 2003; 547(Pt 1), 7784.
6. Bubb, KJ, Cock, ML, Black, MJ, et al. Intrauterine growth restriction delays cardiomyocyte maturation and alters coronary artery function in the fetal sheep. J Physiol. 2007; 578(Pt 3), 871881.
7. Symonds, ME, Stephenson, T, Gardner, DS, Budge, H. Long-term effects of nutritional programming of the embryo and fetus: mechanisms and critical windows. Reprod Fertil Dev. 2007; 19(1), 5363.
8. Gardner, DS, Pearce, S, Dandrea, J, et al. Peri-implantation undernutrition programs blunted angiotensin II evoked baroreflex responses in young adult sheep. Hypertension. 2004; 43(6), 12901296.
9. Schlabritz-Loutsevitch, N, Ballesteros, B, Dudley, C, Jenkins, S, Hubbard, G, Burton, GJ, Nathanielsz, P. Moderate maternal nutrient restriction, but not glucocorticoid administration, leads to placental morphological changes in the baboon (Papio sp.). Placenta. 2007; 28, 783793.
10. McDonald, TJ, Wu, G, Nijland, MJ, Jenkins, SL, Nathanielsz, PW, Jansson, T. Effect of 30% nutrient restriction in the first half of gestation on maternal and fetal baboon serum amino acid concentrations. Br J Nutr. 2013; 109(8), 13821388.
11. Nutrition for Health and Development. A global agenda for combating malnutrition. World Health Organization. Nutrition for Health and Development (NHD). Sustainable Development and Healthy Environments (SDE). Progress Report. 2000.
12. Cleal, JK, Poore, KR, Boullin, JP, et al. Mismatched pre- and postnatal nutrition leads to cardiovascular dysfunction and altered renal function in adulthood. Proc Natl Acad Sci USA. 2007; 104, 95299533.
13. Franco, M, Arruda, R, Dantas, A, et al. Intrauterine undernutrition: expression and activity of the endothelial nitric oxide synthase in male and female adult offspring. Cardiovasc Res. 2002; 56, 145153.
14. Nishina, H, Green, LR, McGarrigle, HH, et al. Effect of nutritional restriction in early pregnancy on isolated femoral artery function in mid-gestation fetal sheep. J Physiol. 2003; 553(Pt 2), 637647.
15 Vianna, CA, Horta, BL, Gigante, DP, de Barros, FC. Pulse wave velocity at early adulthood: breastfeeding and nutrition during pregnancy and childhood. PLoS One. 2016; 11(4), e0152501.
16 Vlachopoulos, C, O’Rourke, M, Nichols, W. McDonald’s Blood Flow in Arteries: Theoretical, Experimental and Clinical Principles, 6th edn, 2011. CRC Press: London.
17 Armitage, JA, Khan, IY, Taylor, PD, Nathanielsz, PW, Poston, L. Developmental programming of the metabolic syndrome by maternal nutritional imbalance: how strong is the evidence from experimental models in mammals? J Physiol. 2004; 561(Pt 2), 355377.
18 Sathishkumar, K, Elkins, R, Yallampalli, U, Yallampalli, C. Protein restriction during pregnancy induces hypertension and impairs endothelium-dependent vascular function in adult female offspring. J Vasc Res. 2009; 46(3), 229239.
19 Russel, AJF, Doney, JM, Gunn, RG. Subjective assessment of body fat in live sheep. J Agric Sci. 1969; 72, 451454.
20 Freitas-de-Melo, A, Ungerfeld, R, Hötzel, MJ, et al. Mother–young behaviours at lambing in grazing ewes: effects of lamb sex and food restriction in pregnancy. Appl Anim Behav Sci. 2015; 168, 3136.
21 Freitas-de-Melo, A, Ungerfeld, R, Hötzel, MJ, Orihuela, A, Pérez-Clariget, R. Low pasture allowance until late gestation in ewes: behavioural and physiological changes in ewes and lambs from lambing to weaning. Animal. 2017; 11(2), 285294.
22 Haydock, KP, Shaw, NH. The comparative yield method for estimating dry matter yield of pasture. Aust J Exp Agric Anim Husb. 1975; 15, 663670.
23 Hawkins, P, Steyn, C, McGarrigle, HH, et al. Cardiovascular and hypothalamic-pituitary-adrenal axis development in late gestation fetal sheep and young lambs following modest maternal nutrient restriction in early gestation. Reprod Fertil Dev. 2000; 12, 443456.
24 Trim, CM, Hofmeister, EH, Peroni, JF, Thoresen, M. Evaluation of an oscillometric blood pressure monitor for use in anesthetized sheep. Vet Anaesth Analg. 2013; 40(6), e31e39.
25 Zócalo, Y, Curcio, S, García-Espinosa, V, et al. Comparative analysis of arterial parameters variations associated with inter-individual variations in peripheral and aortic blood pressure: cross-sectional study in healthy subjects aged 2-84 years. High Blood Press Cardiovasc Prev. 2017; 24(4), 437451.
26 Zócalo, Y, Marotta, M, García-Espinosa, V, et al. Children and adolescents macrovascular reactivity level and dynamics, but not the microvascular response, is associated with body mass index and arterial stiffness levels. High Blood Press Cardiovasc Prev. 2017; 24(4), 371386.
27 Santana, DB, Barra, J, Grignola, J, Ginés, F, Armentano, R. Pulmonary artery smooth muscle activation attenuates arterial dysfunction during acute pulmonary hypertension. J Appl Physiol. (1985). 2005; 98(2), 605613.
28 Bude, RO, Rubin, JM. Relationship between the resistive index and vascular compliance and resistance. Radiology. 1999; 211(2), 411417.
29 Li, JK-J. Time domain resolution of forward and reflected waves in the aorta. IEEE Trans Biomed Eng. 1986; 33, 783785.
30 Eng, J. Sample size estimation: how many individuals should be studied? Radiology. 2003; 227(2), 309313.
31 Brawley, L, Poston, L, Hanson, MA. Mechanisms underlying the programming of small artery dysfunction: review of the model using ow protein diet in pregnancy in the rat. Arch Physiol Biochem. 2003; 111, 2335.
32 Ozaki, T, Nishina, H, Hanson, MA,Poston, L. Dietary restriction in pregnant rats causes gender-related hypertension and vascular dysfunction in offspring. J Physiol. 2001; 530, 141152.
33 Ozaki, T, Hawkins, P, Nishina, H, et al. Effects of undernutrition in early pregnancy on systemic small artery function in late-gestation fetal sheep. Am J Obstet Gynecol. 2000; 183(5), 13011307.
34 Faury, G. Function-structure relationship of elastic arteries in evolution: from microfibrils to elastin and elastic fibres. Pathol Biol. 2001; 49, 310325.
35 Peluso, G, García-Espinosa, V, Curcio, S, et al. High central aortic rather than brachial blood pressure is associated with carotid wall remodeling and increased arterial stiffness in childhood. High Blood Press Cardiovasc Prev. 2017; 24(1), 4960.
36 Barker, D. Chapter 8: Fetal origins of adult disease. In: Grace, F., Vivienne, N. (editors), Growing Up in the UK – Ensuring a Healthy Future for Our Children, pp. 149168, 2013. BMA Board of Science.
37 Hanson, MA, Hawkins, P, Ozaki, T, et al. Effects of experimental dietary manipulation during early pregnancy on cardiovascular and endocrine function in fetal sheep. In: O’Brien, PMS, Wheeler, T,Barker, DJP (eds): Fetal Programming: Influences on Development and Disease in Later Life, pp. 365373, 1999. RCOG Press: London.
38 Bloomfield, FH, Oliver, MH, Harding, JE. The late effects of fetal growth patterns. Arch Dis Child Fetal Neonatal Ed. 2006; 91(4), F299F304.
39 Hoet, JJ, Hanson, MA. Intrauterine nutrition: its importance during critical periods for cardiovascular and endocrine development. J Physiol. 1999; 514(Pt 3), 617627.
40 Barry, J, Anthony, R. The pregnant sheep as a model for human pregnancy. Theriogenology. 2008; 69(1), 5567.
41 Bia, D, Zócalo, Y, Armentano, R, et al. Increased reversal and oscillatory shear stress cause smooth muscle contraction-dependent changes in sheep aortic dynamics: role in aortic balloon pump circulatory support. Acta Physiol (Oxf). 2008; 192(4), 487503.
42 Bia, D, Zócalo, Y, Wray, S, Cabrera-Fischer, EI. Comparative in vivo analysis of the role of the adventitia and the endothelium on arterial mechanical function: relevance for aortic counterpulsation. Int J Artif Organs. 2017; 40(6), 286293.
43 Dasinger, JH, Alexander, BT. Gender differences in developmental programming of cardiovascular diseases. Clin Sci (Lond). 2016; 130(5), 337348.
44 Fall, CH. Fetal malnutrition and long-term outcomes. Nestle Nutr Inst Workshop Ser. 2013; 74, 1125.
45 Limones, M, Sevillano, J, Sánchez-Alonso, MG, Herrera, E, Ramos-Álvarez, MDP. Metabolic alterations associated with maternal undernutrition during the first half of gestation lead to a diabetogenic state in the rat. Eur J Nutr. 2018. doi: 10.1007/s00394-018-1805-z.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Journal of Developmental Origins of Health and Disease
  • ISSN: 2040-1744
  • EISSN: 2040-1752
  • URL: /core/journals/journal-of-developmental-origins-of-health-and-disease
Please enter your name
Please enter a valid email address
Who would you like to send this to? *


Type Description Title
Supplementary materials

Zócalo et al. supplementary material
Zócalo et al. supplementary material 1

 Unknown (1.1 MB)
1.1 MB


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed