Hostname: page-component-76fb5796d-22dnz Total loading time: 0 Render date: 2024-04-27T03:09:09.224Z Has data issue: false hasContentIssue false
  • English
  • Français

Diabetes and pregnancy in Wistar rats: renal effects for mothers in the postpartum period

Part of: Advancing the DOHaD Agenda in Africa

Published online by Cambridge University Press:  14 August 2017

N. França-Silva ,
N. G. Reis ,
P. F. Santos  and
A. P. C. Balbi
N. França-Silva
Affiliation:
Area of Physiological Sciences, Federal University of Uberlândia, Uberlândia, Brazil
N. G. Reis
Affiliation:
Physiological Department, Faculty of Medicine, University of São Paulo, Ribeirão Preto, Brazil
P. F. Santos
Affiliation:
Department of Biomedicine, Federal University of Uberlândia, Uberlândia, Brazil
A. P. C. Balbi*
Affiliation:
Area of Physiological Sciences, Federal University of Uberlândia, Uberlândia, Brazil
*
*Address for correspondence: A. P. C. Balbi, Avenida Pará, 1720 Campus Umuarama, Bloco 2 A, Uberlândia, MG 38400-902, Brazil. (Email paulabalb@icbim.ufu.br; paulabalb@yahoo.com.br)
Get access Rights & Permissions [Opens in a new window]

Abstract

In this study, diabetes mellitus (DM) was induced in Wistar rats during pregnancy and maintained in the postpartum period (PP) and we evaluated systolic blood pressure (SBP), glomerular filtration rate (GFR) and renal immunohistochemical and morphometric studies from different groups: G1 (non-pregnant control rats), G2 (non-pregnant diabetic rats), G3 (control mothers) and G4 (diabetic mothers). We found that there were no differences in relation to SBP, but there was a tendency for reduction in GFR from G4 compared with the other groups (G). There was increased total kidney weight/body weight ratio of G4 compared with other G. There were increase in glomerular tuft area in G3 and G4 compared with G1 and G2. G2 and G4 showed even higher percentage of cortical collagen. G3 showed increased glomerular proliferating cells compared with G1 and G2, while in G4 this number was smaller than G3. Cell proliferation was higher in the tubulointerstitial (TBI) compartment from G4. Glomerular and TBI α-smooth muscle actin expression was increased in G4 compared with other G. The glomerular p-p38 expression showed a pattern similar to proliferation cell nuclear antigen, with a reduction of p-p38 in G4 relative to other G. The immunoreactivity of p-JNK was higher in both the glomeruli and TBI compartment in G4 compared with G1, G2 and G3. The DM induced during pregnancy and maintained in the PP resulted in renal structural and functional changes to mothers. In addition, altered mitogen-activated protein kinase expression in association with these changes may play an important role in renal damage observed in the present investigation.

Keywords

postpartum periodpregnancyrenal functiontype 1 diabetes mellitus
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 9 , Issue 1: Themed Issue: DOHaD AFRICA , February 2018 , pp. 77 - 86
Check for updates
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2017 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Bramham, K, Rajasingham, D. Pregnancy in diabetes and kidney disease. J Ren Care. 2012; 38, 78–89.Google Scholar
2. Milne, JE, Lindheimer, MD, Davison, JM. Glomerular heteroporous membrane modeling in third trimester and postpartum before and during amino acid infusion. Am J Physiol Renal Physiol. 2002; 282, F170–F175.Google Scholar
3. August, P, Sealy, JE. The renin-angiotensin system in normal and hypertensive pregnancy and in ovarian function. In Hypertension: Pathology, Diagnosis and Management (eds. Laragh JH, Brenner BM), 1990; pp. 1761–1778. Raven Press: New York.Google Scholar
4. Skinner, S. The renin system in fertility and normal human pregnancy. In The Renin-Angiotensin System (eds. Robertson JIS, Nicolls MG), 1993; pp. 1–16. Gower Medical Publishing: London.Google Scholar
5. Reece, EA, Coustan, ER, Hayslett, JP. Diabetic nephropathy: pregnancy performance and fetomaternal outcome. Am J Obstet Gynecol. 1988; 59, 56–66.Google Scholar
6. Tramonti, G, Kanwar, YS. Review and discussion of tubular biomarkers in the diagnosis and management of diabetic nephropathy. Endocrine. 2012; 43, 494–503.CrossRefGoogle ScholarPubMed
7. Brezniceanu, ML, Liu, F, Wei, CC, et al. Attenuation of interstitial fibrosis and tubular apoptosis in db/db transgenic mice overexpressing catalase in renal proximal tubular cells. Diabetes. 2008; 57, 451–459.Google Scholar
8. Liu, F, Brezniceanu, ML, Wei, CC, et al. Overexpression of angiotensinogen increases tubular apoptosis in diabetes. J Am Soc Nephrol. 2008; 19, 269–280.Google Scholar
9. Remuzzi, A, Perico, N, Amuchastegui, CS, et al. Short- and long-term effect of angiotensin II receptor blockade in rats with experimental diabetes. J Am Soc Nephrol. 1993; 4, 40–49.CrossRefGoogle Scholar
10. Volpini, RA, da Silva, CG, Costa, RS, et al. Effect of enalapril and losartan on the events that precede diabetic nephropathy in rats. Diabetes Metab Res Rev. 2003; 19, 43–51.Google Scholar
11. Zatz, R, Dunn, BR, Meyer, TW, et al. Prevention of diabetic glomerulopathy by pharmacological amelioration of glomerular capillary hypertension. J Clin Invest. 1986; 77, 1925–1930.Google Scholar
12. Taylor, R, Davison, JM. Type 1 diabetes and pregnancy. BMJ. 2007; 334, 742–745.Google Scholar
13. Galindo, A, Burguillo, AG, Azriel, S, et al. Outcome of fetuses in women with pregestational diabetes mellitus. J Perinat Med. 2006; 34, 323–331.Google Scholar
14. Remsberg, KE, McKeown, RE, McFarland, KF, et al. Diabetes in pregnancy and caesarean delivery. Diabetes Care. 1999; 22, 1561–1567.Google Scholar
15. Purdy, LP, Hantsch, CE, Molitch, ME, et al. Effect of pregnancy on renal function in patients with moderate to severe diabetic renal insufficiency. Diabetes Care. 1996; 19, 1067–1074.CrossRefGoogle ScholarPubMed
16. Jones, DC, Hayslett, JP. Outcome of pregnancy in women with moderate or severe renal insufficiency. N Engl J Med. 1996; 335, 226–232.Google Scholar
17. Irfan, S, Arain, TM, Shaukat, A, et al. Effect of pregnancy on diabetic nephropathy and retinopathy. J Coll Physicians Surg Pak. 2004; 14, 75–78.Google Scholar
18. Yan, J, Li, X, Su, R, et al. Long-term effects of maternal diabetes on blood pressure and renal function in rat male offspring. PLoS One. 2014; 9, e88269.Google Scholar
19. Kliem, V, Johnson, RJ, Alpers, CE, et al. Mechanism involved in the pathogenesis of tubulointerstitial fibrosis in 5/6 nephrectomized rats. Kidney Int. 1996; 49, 666–678.CrossRefGoogle ScholarPubMed
20. Miodovnik, M, Rosenn, BM, Khoury, JC, et al. Does pregnancy increase the risk for development and progression of diabetic nephropathy. Am J Obstet Gynecol. 1996; 174, 1180–1189.CrossRefGoogle ScholarPubMed
21. Biesenbach, G, Stoger, H, Zazgornik, J. Influence of pregnancy on progression of diabetic nephropathy and subsequent requirement of renal replacement therapy in female type 1 diabetic patients with impaired renal function. Nephrol Dial Transplant. 1992; 7, 105–109.CrossRefGoogle ScholarPubMed
22. Golbert, A, Campos, MAA. Diabetes melito tipo 1 e gestação. Arq Bras Endrocrinol Metabol. 2008; 52, 307–314.Google Scholar
23. Valenzuela, FJ. Pathogenesis of preeclampsia: the genetic component. J Pregnancy. 2012; 2012, 1–8.Google Scholar
24. Han, L, Yang, Z, Li, K, et al. Antepartum or immediate postpartum renal biopsies in preeclampsia/eclampsia of pregnancy; new morphologic and clinical findings. Int J Clin Exp Pathol. 2014; 7, 5129–5143.Google Scholar
25. van Dijk, DJ, Boner, G, Giler, S, et al. Increased serum angiotensin-converting enzyme activity and plasma angiotensin II levels during pregnancy and postpartum in the diabetic rat. J Renin Angiotensin Aldosterone Syst. 2001; 2, 193–198.Google Scholar
26. Silveira, LA, Bacchi, CE, Pinto, GA, et al. The genetics of hypertension modifies the renal cell replication response induced by experimental diabetes. Diabetes. 2002; 51, 1529–1534.Google Scholar
27. Maeda, M, Yabuki, A, Suzuki, S, et al. Renal lesions in spontaneous insulin-dependent diabetes mellitus in the nonobese diabetic mouse: acute phase of diabetes. Vet Pathol. 2003; 40, 187–195.Google Scholar
28. Alpers, CE, Seifert, RA, Hudkins, KL, et al. Developmental patterns of PDGF B chain, PDGF receptor and α-actin expression in human glomerulogenesis. Kidney Int. 1992; 42, 390–399.CrossRefGoogle ScholarPubMed
29. Johnson, RJ, Iida, H, Alpers, CE, et al. Expression of smooth muscle cell phenotype by rat mesangial cells in immune complex nephritis. Alpha-smooth muscle actin is a marker of mesangial cell proliferation. J Clin Invest. 1991; 87, 847–858.CrossRefGoogle ScholarPubMed
30. Makino, H, Kashihara, N, Sugiyama, H, et al. Phenotypic modulation of the mesangium reflected by contractile proteins in diabetes. Diabetes. 1996; 45, 488–495.CrossRefGoogle ScholarPubMed
31. Naruse, K, Ito, H, Moriki, T, et al. Mesangial cell activation in the collagenofibrotic glomerulonephropathy: case report and review of the literature. Virchows Arch. 1998; 433, 183–188.Google Scholar
32. Naruse, K, Fujieda, M, Miyazaki, E, et al. CD34 expression as a novel marker of transformed mesangial cells in biopsied glomerular diseases. J Pathol. 1999; 189, 105–111.Google Scholar
33. Gabbiani, G. The biology of the myofibroblast. Kidney Int. 1992; 41, 530–532.CrossRefGoogle ScholarPubMed
34. Tang, WW, Ulich, TR, Lacey, DL, et al. Platelet-derived growth factor-BB induces renal tubule interstitial myofibroblast formation and tubulointerstitial fibrosis. Am J Pathol. 1996; 148, 1169–1180.Google Scholar
35. Darby, I, Skalli, O, Gabbiani, G. α-Smooth muscle actin is transiently expressed by myofibroblasts during experimental wound healing. Lab Invest. 1990; 63, 21–29.Google Scholar
36. Li, J, Qu, X, Bertram, JF. Endothelial-myofibroblast transition contributes to the early development of diabetic renal intersticial fibrosis in streptozotocin-induced diabetic mice. Am J Pathol. 2009; 175, 1380–1388.Google Scholar
37. Pedagogos, E, Hewitson, T, Fraser, I, et al. Myofibroblasts and arteriolar sclerosis in human diabetic nephopathy. Am J Kidney Dis. 1997; 29, 912–918.CrossRefGoogle Scholar
38. Yonemoto, S, Machiguchi, T, Nomura, K, et al. Correlations of tissue macrophages and cytoskeletal protein expression with renal fibrosis in patients with diabetes mellitus. Clin Exp Nephrol. 2006; 10, 186–192.CrossRefGoogle ScholarPubMed
39. Young, BA, Johnson, RJ, Alpers, CE, et al. Cellular events in the evolution of experimental diabetic nephropathy. Kidney Int. 1995; 47, 935–944.CrossRefGoogle ScholarPubMed
40. Geleilete, TJ, Costa, RS, Dantas, M, et al. α-Smooth muscle actin and proliferating cell nuclear antigen expression in focal segmental glomerulosclerosis: functional and structural parameters of renal disease progression. Braz J Med Biol Res. 2001; 34, 985–991.CrossRefGoogle ScholarPubMed
41. Komers, R, Lindsley, JN, Oyama, TT, et al. Renal p-38 MAP quinase activity in experimental diabetes. Lab Invest. 2007; 87, 548–558.CrossRefGoogle Scholar
42. Iwata, Y, Wada, T, Furuichi, K, et al. p38 mitogen-activated protein kinase contributes to autoimmune renal injury in MRL-Faslpr mice. J Am Soc Nephrol. 2003; 14, 57–67.Google Scholar
43. Cassidy, H, Radford, R, Slyne, J, et al. The role of MAPK in drug-induced kidney injury. J Signal Transduct. 2012; 2012, 1–15.CrossRefGoogle ScholarPubMed
44. Kanellis, J, Ma, FY, Kandane-Rathnayake, R, et al. JNK signaling in human and experimental renal ischaemia/reperfusion injury. Nephrol Dial Transplant. 2010; 25, 2898–2908.CrossRefGoogle ScholarPubMed