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Effects of bisphenol A treatment during pregnancy on kidney development in mice: a stereological and histopathological study

Published online by Cambridge University Press:  06 November 2017

P. Nuñez ,
T. Fernandez ,
M. García-Arévalo ,
P. Alonso-Magdalena ,
A. Nadal ,
C. Perillan  and
J. Arguelles
P. Nuñez*
Affiliation:
Departamento de Biología Funcional (Área de Fisiología), Facultad de Medicina y Ciencias de la Salud, Universidad de Oviedo, Asturias, Spain
T. Fernandez
Affiliation:
Unidad de Histopatología Molecular en Modelos Animales de Cáncer, Facultad de Medicina y Ciencias de la Salud, Universidad de Oviedo, Asturias, Spain
M. García-Arévalo
Affiliation:
Instituto de Bioingeniería. Universidad Miguel Hernández de Elche, 03202-Elche, Spain Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, CIBERDEM. Universidad Miguel Hernández de Elche, 03202-Elche, Spain Department of Structural and Function Biology, Institute of Biology and Obesity and Comorbidities Research Center (OCRC), UNICAMP, Brazil
P. Alonso-Magdalena
Affiliation:
Instituto de Bioingeniería. Universidad Miguel Hernández de Elche, 03202-Elche, Spain Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, CIBERDEM. Universidad Miguel Hernández de Elche, 03202-Elche, Spain
A. Nadal
Affiliation:
Instituto de Bioingeniería. Universidad Miguel Hernández de Elche, 03202-Elche, Spain Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, CIBERDEM. Universidad Miguel Hernández de Elche, 03202-Elche, Spain
C. Perillan
Affiliation:
Departamento de Biología Funcional (Área de Fisiología), Facultad de Medicina y Ciencias de la Salud, Universidad de Oviedo, Asturias, Spain
J. Arguelles
Affiliation:
Departamento de Biología Funcional (Área de Fisiología), Facultad de Medicina y Ciencias de la Salud, Universidad de Oviedo, Asturias, Spain
*
*Address for correspondence: P. Nuñez, Departamento de Biología Funcional, Área de Fisiología, Facultad de Medicina, Universidad de Oviedo, C/Julián Claveria 6, E-33006 Oviedo, Spain. (Email nunezpaula@uniovi.es)
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Abstract

Bisphenol A (BPA) is a chemical found in plastics that resembles oestrogen in organisms. Developmental exposure to endocrine-disrupting chemicals, such as BPA, increases the susceptibility to type 2 diabetes (T2DM) and cardiovascular diseases. Animal studies have reported a nephron deficit in offspring exposed to maternal diabetes. The aim of this study was to investigate the prenatal BPA exposure effects on nephrogenesis in a mouse model that was predisposed to T2DM. This study quantitatively evaluated the renal structural changes using stereology and histomorphometry methods. The OF1 pregnant mice were treated with a vehicle or BPA (10 or 100 μg/kg/day) during days 9–16 of gestation (early nephrogenesis). The 30-day-old offspring were sacrificed, and tissue samples were collected and prepared for histopathological and stereology studies. Glomerular abnormalities and reduced glomerular formation were observed in the BPA offspring. The kidneys of the BPA10 and BPA100 female offspring had a significantly lower glomerular number and density than those of the CONTROL female offspring. The glomerular histomorphometry revealed a significant difference between the female and male CONTROL offspring for the analysed glomerular parameters that disappeared in the BPA10 and BPA100 offspring. In addition, the kidney histopathological examination showed typical male cuboidal epithelial cells of the Bowman capsule in the female BPA offspring. Exposure to environmentally relevant doses of BPA during embryonic development altered nephrogenesis. These structural changes could be associated with an increased risk of developing cardiometabolic diseases later in life.

Keywords

bisphenol Afoetal programingkidneynephrogenesisstereology
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 9 , Issue 2 , April 2018 , pp. 208 - 214
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Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2017 

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References

1. Barker, DJ, Osmond, C, Golding, J, Kuh, D, Wadsworth, ME. Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. Br Med J. 1989; 298, 564–567.CrossRefGoogle ScholarPubMed
2. Barker, DJ, Eriksson, JG, Forsén, T, Osmond, C. Fetal origins of adult disease: strength of effects and biological basis. Int J Epidemiol. 2002; 31, 1235–1239.CrossRefGoogle ScholarPubMed
3. Langley-Evans, SC, McMullen, S. Developmental origins of adult disease. Med Princip Pract. 2010; 19, 87–98.CrossRefGoogle ScholarPubMed
4. Nuñez, P, Arguelles, J, Perillan, C. Offspring’s hydromineral adaptive responses to maternal undernutrition during lactation. J Dev Orig Health Dis. 2015; 6, 520–529.CrossRefGoogle ScholarPubMed
5. You, L, Zhu, X, Shrubsole, MJ, et al. Renal function, bisphenol A, and alkylphenols: results from the National Health and Nutrition Examination Survey (NHANES 2003–2006). Environ Health Perspect. 2011; 119, 527–533.CrossRefGoogle ScholarPubMed
6. Gowder, SJ. Nephrotoxicity of bisphenol A (BPA) – an updated review. Curr Mol Pharmacol. 2013; 6, 163–172.CrossRefGoogle ScholarPubMed
7. Li, M, Bi, Y, Qi, L, et al. Exposure to bisphenol A is associated with low-grade albuminuria in Chinese adults. Kidney Int. 2012; 81, 1131–1139.CrossRefGoogle ScholarPubMed
8. Trasande, L, Attina, TM, Trachtman, H. Bisphenol A exposure is associated with low-grade urinary albumin excretion in children of the United States. Kidney Int. 2013; 83, 741–748.CrossRefGoogle ScholarPubMed
9. Nyengaard, JR, Bendtsen, TF. Glomerular number and size in relation to age, kidney weight, and body surface in normal man. Anat Rec. 1992; 232, 194–201.CrossRefGoogle ScholarPubMed
10. Beeman, SC, Zhang, M, Gubhaju, L, et al. Measuring glomerular number and size in perfused kidneys using MRI. Am J Physiol Renal Physiol. 2011; 300, 1454–1457.CrossRefGoogle ScholarPubMed
11. Bertram, JF. Analyzing renal glomeruli with the new stereology. Int Rev Cytol. 1995; 161, 111–172.CrossRefGoogle ScholarPubMed
12. Hard, GC, Khan, KN. A contemporary overview of chronic progressive nephropathy in the laboratory rat, and its significance for human risk assessment. Toxicol Pathol. 2004; 32, 171–180.CrossRefGoogle ScholarPubMed
13. Bonventre, JV, Vaidya, VS, Schmouder, R, Feig, P, Dieterle, F. Next-generation biomarkers for detecting kidney toxicity. Nat Biotechnol. 2010; 28, 436–440.CrossRefGoogle ScholarPubMed
14. Hughson, MD, Douglas-Denton, R, Bertram, JF, et al. Hypertension, glomerular number, and birth weight in African Americans and white subjects in the southeastern United States. Kidney Int. 2006; 69, 671–678.CrossRefGoogle ScholarPubMed
15. Kataria, A, Trasande, L, Trachtman, H. The effects of environmental chemicals on renal function. Nat Rev Nephrol. 2015; 11, 610–625.CrossRefGoogle ScholarPubMed
16. vom Saal, FS, Welshons, WV. Evidence that bisphenol A (BPA) can be accurately measured without contamination in human serum and urine, and that BPA causes numerous hazards from multiple routes of exposure. Mol Cell Endocrinol. 2014; 398, 101–113.CrossRefGoogle ScholarPubMed
17. Schecter, A, Malik, N, Haffner, D, et al. Bisphenol A (BPA) in U.S. food. Environ Sci Technol. 2010; 44, 9425–9430.CrossRefGoogle ScholarPubMed
18. Martínez-Castelao, A, Navarro-González, JF, Górriz, JL, de Alvaro, F. The concept and the epidemiology of diabetic nephropathy have changed in recent years. J Clin Med. 2015; 4, 1207–1216.CrossRefGoogle ScholarPubMed
19. Alonso-Magdalena, P, Quesada, I, Nadal, A. Endocrine disruptors in the etiology of T2DM mellitus. Nat Rev Endocrinol. 2011; 7, 346–353.CrossRefGoogle Scholar
20. Heindel, JJ, Skalla, LA, Joubert, BR, Dilworth, CH, Gray, KA. Review of developmental origins of health and disease publications in environmental epidemiology. Reprod Toxicol. 2016; 68, 34–48.CrossRefGoogle ScholarPubMed
21. Gore, AC, Chappell, VA, Fenton, SE, et al. EDC-2: the Endocrine Society’s second scientific statement on endocrine-disrupting chemicals. Endocr Rev. 2015; 36, 1–150.CrossRefGoogle ScholarPubMed
22. Firmin, S, Bahi-Jaber, N, Abdennebi-Najar, L. Food contaminants and programming of T2DM: recent findings from animal studies. J Dev Orig Health Dis. 2016; 7, 505–512.CrossRefGoogle Scholar
23. Hu, J, Yang, S, Wang, Y, et al. Serum bisphenol A and progression of type 2 diabetic nephropathy: a 6-year prospective study. Acta Diabetol. 2015; 52, 1135–1141.CrossRefGoogle ScholarPubMed
24. Hu, J, Wang, Y, Xiang, X, et al. Serum bisphenol A as a predictor of chronic kidney disease progression in primary hypertension: a 6-year prospective study. J Hypertens. 2016; 34, 332–337.CrossRefGoogle ScholarPubMed
25. Alonso-Magdalena, P, Vieira, E, Soriano, S, et al. Bisphenol A exposure during pregnancy disrupts glucose homeostasis in mothers and adult male offspring. Environ Health Perspect. 2010; 118, 1243–1250.CrossRefGoogle ScholarPubMed
26. García-Arevalo, M, Alonso-Magdalena, P, Rebelo Dos Santos, J, et al. Exposure to bisphenol-A during pregnancy partially mimics the effects of a high-fat diet altering glucose homeostasis and gene expression in adult male mice. PLoS One. 2014; 9, e100214.CrossRefGoogle ScholarPubMed
27. Liu, XL, Chen, XY, Wang, ZC, Shen, T, Zhao, H. Effects of exposure to bisphenol A during pregnancy and lactation on the testicular morphology and caspase-3 protein expression of ICR pups. Biomed Rep. 2013; 1, 420–424.CrossRefGoogle ScholarPubMed
28. Tran, S, Chen, Y-W, Chenier, I, Chan, JSD, Quaggin, S. Maternal diabetes modulates renal morphogenesis in offspring. J Am Soc Nephrol. 2008; 19, 943–952.CrossRefGoogle ScholarPubMed
29. Chen, YW, Chenier, I, Chang, SY, Tran, S, Ingelfinger, JR. High glucose promotes nascent nephron apoptosis via NF-κB and p53 pathways. Am J Physiol Renal Physiol. 2011; 300, 147–156.CrossRefGoogle ScholarPubMed
30. Kanwar, YS, Nayak, B, Lin, S, Akagi, S, Xie, P. Hyperglycemia: its imminent effects on mammalian nephrogenesis. Pediatr Nephrol. 2005; 20, 858–866.CrossRefGoogle ScholarPubMed
31. Amri, K, Freund, N, Vilar, J, Merlet-Benichou, C, Lelievre-Pegorier, M. (1999) Adverse effects of hyperglycemia on kidney development in rats. Diabetes. 1999; 48, 2240–2245.CrossRefGoogle ScholarPubMed
32. Hokke, SN, Armitage, JA, Puelles, VG, et al. Altered ureteric branching morphogenesis and nephron endowment in offspring of diabetic and insulin-treated pregnancy. PLoS One. 2013; 8, e58243.CrossRefGoogle ScholarPubMed
33. Hokke, S, Arias, N, Armitage, JA, et al. Maternal glucose intolerance reduces offspring nephron endowment and increases glomerular volume in adult offspring. Diabetes Metab Res Rev. 2016; 32, 816–826.CrossRefGoogle ScholarPubMed
34. García-Arévalo, M, Alonso-Magdalena, P, Servitja, JM, et al. Maternal exposure to bisphenol-A during pregnancy increases pancreatic β-cell growth during early life in male mice offspring. Endocrinology. 2016; 157, 4158–4171.CrossRefGoogle ScholarPubMed
35. Fernández García, MT, Núñez Martínez, P, García de la Fuente, V, et al. Practical application of stereological methods in experimental kidney animal models. Nefrologia. 2017; 37, 29–33.CrossRefGoogle ScholarPubMed
36. Sugimoto, H, Shikata, K, Matsuda, M, et al. Increased expression of endothelial cell nitric oxide synthase (ecNOS) in afferent and glomerular endothelial cells is involved in glomerular hyperfiltration of diabetic nephropathy. Diabetologia. 1998; 41, 1426–1434.CrossRefGoogle ScholarPubMed
37. Yamashita, T, Kawashima, S, Miwa, Y, et al. A 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitor reduces hypertensive nephrosclerosis in stroke-prone spontaneously hypertensive rats. J Hypertens. 2002; 20, 2465–2473.CrossRefGoogle ScholarPubMed
38. Hard, GC, Alden, CL, Bruner, RHG, et al. Non-proliferative lesion of the kidney and lower urinary tract in the rat. Guides for Toxicologic Pathology. 1999. STP/ARP/AFIP: Washington, DC.Google Scholar
39. Frazier, KS, Seely, JC, Hard, GC, et al. Proliferative and non-prolferative lesions of the rat and mouse urinary system. Toxicologic Pathol. 2012; 40, 14–86.CrossRefGoogle ScholarPubMed
40. Thornburg, KL. The programming of cardiovascular disease. J Dev Orig Health Dis. 2015; 6, 366–376.CrossRefGoogle ScholarPubMed
41. Kanzaki, G, Tsuboi, N, Haruhara, K, et al. Factors associated with a vicious cycle involving a low nephron number, hypertension and chronic kidney disease. Hypertens Res. 2015; 38, 633–641.CrossRefGoogle ScholarPubMed
42. Moritz, KM, Dodic, M, Wintour, EM. Kidney development and the fetal programming of adult disease. Bioessays. 2003; 25, 212–220.CrossRefGoogle ScholarPubMed
43. Chen, YW, Chenier, I, Tran, S, et al. Maternal diabetes programs hypertension and kidney injury in offspring. Pediatr Nephrol. 2010; 25, 1319–1329.CrossRefGoogle ScholarPubMed
44. Hoy, WE, Ingelfinger, JR, Hallan, S. The early development of the kidney and implications for future health. J Dev Orig Health Dis. 2010; 1, 216–233.CrossRefGoogle ScholarPubMed
45. Zandi-Nejad, K, Luyckx, VA, Brenner, BM. Adult hypertension and kidney disease: the role of fetal programming. Hypertension. 2006; 47, 502–508.CrossRefGoogle ScholarPubMed
46. Fong, D, Denton, KM, Moritz, KM, Evans, R, Singh, RR. Compensatory responses to nephron deficiency: adaptive or maladaptive? Nephrology (Carlton). 2014; 19, 119–128.CrossRefGoogle ScholarPubMed
47. McMullen, S, Langley-Evans, SC. Essential hypertension: defending the contribution of a congenital nephron deficit. Hypertension. 2005; 46, e4.CrossRefGoogle ScholarPubMed
48. Cagampang, FR, Torrens, C, Anthony, FW, Hanson, MA. Developmental exposure to bisphenol A leads to cardiometabolic dysfunction in adult mouse offspring. J Dev Orig Health Dis. 2012; 3, 287–292.CrossRefGoogle ScholarPubMed
49. Johnson, SA, Painter, MS, Javurek, AB, et al. Sex-dependent effects of developmental exposure to bisphenol A and ethinyl estradiol on metabolic parameters and voluntary physical activity. J Dev Orig Health Dis. 2015; 6, 539–552.CrossRefGoogle ScholarPubMed
50. Lemley, KV. A basis for accelerated progression of diabetic nephropathy in Pima Indians. Kidney Int Suppl. 2003; 83, S38–S42.CrossRefGoogle Scholar
51. Chen, HM, Li, SJ, Chen, HP, et al. Obesity-related glomerulopathy in China: a case series of 90 patients. Am J Kidney Dis. 2008; 52, 58–65.CrossRefGoogle Scholar
52. Schmitz, A, Nyengaard, JR, Bendtsen, TF. Glomerular volume in type 2 (noninsulin-dependent) diabetes estimated by a direct and unbiased stereologic method. Lab Invest.. 1990; 62, 108–113.Google ScholarPubMed
53. Keller, G, Zimmer, G, Mall, G, et al. Nephron number in patients with primary hypertension. N Engl J Med. 2003; 348, 101–108.CrossRefGoogle ScholarPubMed
54. Rochester, JR, Bisphenol, A. and human health: a review of the literature. J Steroid Biochem Mol Biol. 2011; 127, 204–215.Google Scholar
55. Frazier, KS, Seely, JC. Urinary system. In Monographs on Pathology of Laboratory Animals, 2nd edn, (eds. Jones TC, Hard GC, Mohr U), 1998; pp. 37–57. Springer: Berlin, Germany.Google Scholar
56. Hard, GC, Alden, CL, Stula, EF, Trump, BF. Proliferative lesions of the kidney in rats. In Guides for Toxicologic Pathology, 1995; pp. 1–19.Google Scholar
57. Sahota, PS, Popp, JA, Hardisty, JF, Gopinath, C, (eds.). Toxicologic Pathology: Nonclinical Safety Assessment. 2013. CRC Press: Boca Raton, USA.CrossRefGoogle Scholar
58. Kilkenny, C, Browne, WJ, Cuthill, IC, et al. Improving biscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol. 2002; 8, e1000412.CrossRefGoogle Scholar