Skip to main content Accessibility help

Restricted nutrition-induced low birth weight, low number of nephrons and glomerular mesangium injury in Japanese quail

  • H. Nishimura (a1) (a2), E. Yaoita (a2), M. Nameta (a2), K. Yamaguchi (a3), M. Sato (a4), C. Ihoriya (a4), L. Zhao (a2), H. Kawachi (a2), T. Sasaki (a4), Y. Ikezumi (a5), Y. Ouchi (a6), N. Kashihara (a4) and T. Yamamoto (a2)...


Insufficient nutrition during the perinatal period causes structural alterations in humans and experimental animals, leading to increased vulnerability to diseases in later life. Japanese quail, Coturnix japonica, in which partial (8–10%) egg white was withdrawn (EwW) from eggs before incubation had lower birth weights than controls (CTs). EwW birds also had reduced hatching rates, smaller glomeruli and lower embryo weight. In EwW embryos, the surface condensate area containing mesenchymal cells was larger, suggesting that delayed but active nephrogenesis takes place. In mature EwW quail, the number of glomeruli in the cortical region (mm2) was significantly lower (CT 34.7±1.4, EwW 21.0±1.2); capillary loops showed focal ballooning, and mesangial areas were distinctly expanded. Immunoreactive cell junction proteins, N-cadherin and podocin, and slit diaphragms were clearly seen. With aging, the mesangial area and glomerular size continued to increase and were significantly larger in EwW quail, suggesting compensatory hypertrophy. Furthermore, apoptosis measured by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling analysis was higher in EwWs than in CTs on embryonic day 15 and postnatal day 4 (D4). Similarly, plasma glucocorticoid (corticosterone) was higher (P<0.01) on D4 in EwW quail. These results suggest that although nephrogenic activity is high in low-nutrition quail during the perinatal period, delayed development and increased apoptosis may result in a lower number of mature nephrons. Damaged or incompletely mature mesangium may trigger glomerular injury, leading in later life to nephrosclerosis. The present study shows that birds serve as a model for ‘fetal programming,’ which appears to have evolved phylogenetically early.


Corresponding author

*Address for correspondence: Professor H. Nishimura, Department of Health Informatics, Niigata University of Health and Welfare, 1398 Shimamicho, Kitaku, Niigata City 950-3198, Japan. (Email


Hide All
1. Fowden, AL, Giussani, DA, Forhead, AJ. Intrauterine programming of physiological systems: causes and consequences. Physiology. 2006; 21, 2937.
2. Ingelfinger, JR, Woods, LL. Perinatal programming, renal development, and adult renal function. Am J Hypertens. 2002; 15, 46S49S.
3. Luyckx, VA, Brenner, BM. Low birth weight, nephron number, and kidney disease. Kidney Int Suppl. 2005; 68, S68S77.
4. Baum, M. Role of the kidney in the prenatal and early postnatal programming of hypertension. Am J Physiol Renal Physiol. 2010; 298, F235F247.
5. Manning, J, Vehaskari, VM. Postnatal modulation of prenatally programmed hypertension by dietary Na and ACE inhibition. Am J Physiol Regul Integr Comp Physiol. 2005; 288, R80R84.
6. Moritz, KM, Dodic, M, Wintour, EM. Kidney development and the fetal programming of adult disease. BioEssays. 2003; 25, 212220.
7. Ojeda, NB, Grigore, D, Alexander, BT. Intrauterine growth restriction: fetal programming of hypertension and kidney disease. Adv Chronic Kidney Dis. 2008; 15, 101106.
8. Portha, B, Chavey, A, Movassat, J. Early-life origins of type 2 diabetes: fetal programming of the beta-cell mass. Exp Diabetes Res. 2011; article ID 105076, 16 pages.
9. Burdge, GC, Lillycrop, KA. Nutrition, epigenetics and developmental plasticity: implications for understanding human disease. Annu Rev Nutr. 2010; 30, 315339.
10. Gluckman, PD, Hanson, MA, Buklijas, T, Low, FM, Beedle, AS. Epigenetic mechanisms that underpin metabolic and cardiovascular diseases. Nat Rev Endocrinol. 2009; 5, 401408.
11. Ikezumi, Y, Suzuki, T, Karasawa, T, et al. Low birthweight and premature birth are risk factors for podocytopenia and focal segmental glomerulosclerosis. Am J Nephrol. 2013; 38, 149157.
12. Prelipcean, A (Teusan), Prelipcean, AA, Teusan, V. Investigations on the structure, chemical composition and caloricity of the quail eggs, deposited at the plateau phase of the laying period. Lucrari Stiintifice Seria Zootehnie. 2014; 57, 113120.
13. Miwa, T, Nishimura, H. Diluting segment in avian kidney. II. Water and chloride transport. Am J Physiol Regul Integr Comp Physiol. 1986; 250, R341R347.
14. Nishimura, H, Koseki, C, Imai, M, Braun, EJ. Sodium chloride and water transport in the thin descending limb of Henle of the quail. Am J Physiol Renal Fluid Electrolyte Physiol. 1989; 257, F994F1002.
15. Nishimura, H, Yang, Y, Lau, K, et al. Aquaporin-2 water channel in developing quail kidney: possible role in programming adult fluid homeostasis. Am J Physiol. 2007; 293, R2147R2158.
16. Kihara, I, Yaoita, E, Kawasaki, K, et al. Origin of hyperplastic epithelial cells in idiopathic collapsing glomerulopathy. Histopathology. 1999; 34, 537547.
17. Koda, R, Zhao, L, Yaoita, E, et al. Novel expression of claudin-5 in glomerular podocytes. Cell Tissue Res. 2011; 343, 637648.
18. Yaoita, E, Yao, J, Yoshida, Y, et al. Up-regulation of connexin43 in glomerular podocytes in response to injury. Am J Pathol. 2002; 161, 15971606.
19. Nakatsue, T, Koike, H, Han, GD, et al. Nephrin and podocin dissociate at the onset of proteinuria in experimental membranous nephropathy. Kidney Int. 2005; 67, 22392254.
20. Yaoita, E, Nishimura, H, Nameta, M, et al. Adherens junction proteins in glomerular podocytes of quail kidney. J Histochem Cytochem. 2016; 64, 6776.
21. Satoh, M, Matter, CM, Ogita, H, et al. Inhibition of apoptosis-regulated signaling kinase-1 and prevention of congestive heart failure by estrogen. Circulation. 2007; 115, 31973204.
22. Sugiyama, H, Kashihara, N, Makino, H, Yamasaki, Y, Ota, Z. Apoptosis in glomerular sclerosis. Kidney Int. 1996; 49, 103111.
23. Neese, JW, Duncan, P, Bayse, D, et al. Development and evaluation of a hexokinase/glucose-6-phosphate dehydrogenase procedure for use as a national glucose reference method. HEW Publication No. (CDC) 77-8330. 1976. Center for Disease Control: Atlanta, GA.
24. Dupont, J, Dagou, C, Derouet, M, Simon, J, Taouis, M. Early steps of insulin receptor signaling in chicken and rat: apparent refractoriness in chicken muscle. Domest Anim Endocrinol. 2004; 26, 127142.
25. Nishizono, I, Iida, S, Suzuki, N, et al. Rapid and sensitive chemiluminescent enzyme immunoassay for measuring tumor markers. Clin Chem. 1991; 37, 16391644.
26. Davey, MG, Tickle, C. The chicken as a model for embryonic development. Cytogenet Genome Res. 2007; 117, 231239.
27. Barker, DJP, Eriksson, JG, Forsen, T, Osmond, C. Fetal origins of adult disease: strength of effects and biological basis. Int J Epidemiol. 2002; 31, 12351239.
28. Barker, DJ, Winter, PD, Osmond, C, Margetts, B, Simmonds, SJ. Weight in infancy and death from ischaemic heart disease. Lancet. 1989; 2, 577580.
29. Lau, C, Rogers, JM. Embryonic and fetal programming of physiological disorders in adulthood. Birth Defects Res C Embryo Today. 2004; 72, 300312.
30. Taylor, PD, Poston, L. Developmental programming of obesity in mammals. Exp Physiol. 2007; 92.2, 287298.
31. Coupe’, B, Grit, I, Darmaun, D, Parnet, P. The timing of ‘catch-up growth’ affects metabolism and appetite regulation in male rats born with intrauterine growth restriction. Am J Physiol Regul Integr Comp Physiol. 2009; 297, R813R824.
32. Alexander, B, Dasinger, JH, Intapad, S. Fetal programming and cardiovascular pathology. Comp Physiol. 2015; 5, 9971025.
33. Wu, G, Bazer, FW, Cudd, TA, Meininger, CJ, Spencer, TE. Maternal nutrition and fetal development. J Nutr. 2004; 134, 21692172.
34. Awazu, M, Hida, M. Maternal nutrient restriction inhibits ureteric bud branching but does not affect the duration of nephrogenesis in rats. Pediatr Res. 2015; 77, 633639.
35. Ibáñez, L, Suárez, L, Lopez-Bermejo, A, et al. Early development of visceral fat excess after spontaneous catch-up growth in children with low birth weight. J Clin Endocrinol Metab. 2008; 93, 925928.
36. Sakai, T, Kriz, W. The structural relationship between mesangial cells and basement membrane of the renal glomerulus. Anat Embryol. 1987; 176, 373386.
37. Sakai, T, Lemley, KV, Hackenthal, E, et al. Changes in glomerular structure following acute mesangial failure in the isolated perfused kidney. Kidney Int. 1992; 41, 533541.
38. Nishimura, H, Xi, Z, Zhang, L, et al. Maturation dependent neointima formation in fowl aorta. Comp Biochem Physiol A Mol Integr Physiol. 2001; 30, 3954.
39. Sugizawa, Y. Mesangial injury associated with renal lymph stasis and blood congestion. Nihon Jinzo Gakkai Shi. 1987; 29, 3949.
40. Romano, LA, Ferder, L, Inserra, F, et al. Intraglomerular expression of alpha-smooth muscle actin in aging mice. Hypertension. 1994; 23(Pt 2), 889893.
41. Kriz, W, Lemley, KV. A potential role for mechanical forces in the detachment of podocytes and the progression of CKD. J Am Soc Nephrol. 2015; 26, 258269.
42. Miner, JH. Life without nephrin: It’s for the birds. J Am Soc Nephrol. 2012; 23, 369371.
43. Thornburg, KL, O’Tierney, PF, Louey, S. The placenta is a programming agent for cardiovascular disease. Placenta. 2010; 31, S54S59.
44. Ingelfinger, JR, Schnaper, HW. Renal endowment: developmental origins of adult disease. J Am Soc Nephrol. 2005; 16, 25332536.
45. Moisiadis, VG, Matthews, SG. Glucocorticoids and fetal programming part 1: outcomes. Nat Rev Endocrinol. 2014a; 10, 391402.
46. Moisiadis, VG, Matthews, SG. Glucocorticoids and fetal programming part 2: mechanisms. Nat Rev Endocrinol. 2014b; 10, 403411.
47. Kapoor, A, Dunn, E, Kostaki, A, Andrews, MH, Matthews, SG. Fetal programming of hypothalamo-pituitary-adrenal function: prenatal stress and glucocorticoids. J Physiol. 2006; 572, 3144.
48. Weinstock, M. The potential influence of maternal stress hormone on development and mental health of the offspring. Brain Behav Immun. 2005; 19, 296308.
49. Braun, EJ, Sweazea, KL. Glucose regulation in birds. Comp Biochem Physiol B Biochem Mol Biol. 2008; 151, 19.
50. Srivastava, T. Nondiabetic consequences of obesity on kidney. Pediatr Nephrol. 2006; 21, 463470.
51. Kriz, W, Schiller, A, Kaissling, B, Taugner, R. Comparative and functional aspects of thin loop limb ultrastructure. In Functional Ultrastructure of the Kidney (eds. Maunsbach AB, Olsen TS, Christensen EI), 1980; pp. 241–250. Academic Press, New York.
52. Bailey, JR, Nishimura, H. Renal response of fowl to hypertonic saline infusion into the renal portal system. Am J Physiol. 1984; 246, R624R632.



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