Hostname: page-component-8448b6f56d-42gr6 Total loading time: 0 Render date: 2024-04-18T21:08:05.327Z Has data issue: false hasContentIssue false
  • English
  • Français

Intrauterine growth restriction increases circulating mitochondrial DNA and Toll-like receptor 9 expression in adult offspring: could aerobic training counteract these adaptations?

Published online by Cambridge University Press:  22 December 2016

V. Oliveira ,
S. D. Silva Junior ,
M. H. C. de Carvalho ,
E. H. Akamine ,
L. C. Michelini  and
M. C. Franco
V. Oliveira
Affiliation:
School of Medicine, Nephrology Division, Federal University of São Paulo, São Paulo, Brazil
S. D. Silva Junior
Affiliation:
Physiology Department, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
M. H. C. de Carvalho
Affiliation:
Pharmacology Department, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
E. H. Akamine
Affiliation:
Pharmacology Department, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
L. C. Michelini
Affiliation:
Physiology Department, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
M. C. Franco*
Affiliation:
School of Medicine, Nephrology Division, Federal University of São Paulo, São Paulo, Brazil Physiology Department, School of Medicine, Federal University of São Paulo, São Paulo, Brazil
*
*Address for correspondence: M. do Carmo Franco, School of Medicine, Division of Nephrology, Federal University of São Paulo, Rua Botucatu, 703-São Paulo, SP 04023-062, Brazil.(Email maria.franco@unifesp.br)
Get access Rights & Permissions [Opens in a new window]

Abstract

It has been demonstrated that intrauterine growth restriction (IUGR) can program increase cardiometabolic risk. There are also evidences of the correlation between IUGR with low-grade inflammation and, thus can contribute to development of several cardiometabolic comorbidities. Therefore, we investigated the influence of IUGR on circulating mitochondrial DNA (mtDNA)/Toll-like receptor 9 (TLR9) and TNF-α expression in adult offspring. Considering that the aerobic training has anti-inflammatory actions, we also investigated whether aerobic training would improve these inflammatory factors. Pregnant Wistar rats received ad libitum or 50% of ad libitum diet throughout gestation. At 8 weeks of age, male offspring from both groups were randomly assigned to control, trained control, restricted and trained restricted. Aerobic training protocol was performed on a treadmill and after that, we evaluated circulating mtDNA, cardiac protein expression of TLR9, plasma and cardiac TNF-α levels, and left ventricle (LV) mass. We found that IUGR promoted an increase in the circulating mtDNA, TLR9 expression and plasma TNF-α levels. Further, our results revealed that aerobic training can restore mtDNA/TLR9 content and plasma levels of TNF-α among restricted rats. The cardiac TNF-α content and LV mass were not influenced either by IUGR or aerobic training. In conclusion, IUGR can program mtDNA/TLR9 content, which may lead to high levels of TNF-α. However, aerobic training was able to normalize these alterations. These findings evidenced that the association of IUGR and aerobic training seems to exert an important interaction effect regarding pro-inflammatory condition and, aerobic training may be used as a strategy to reduce deleterious adaptations in IUGR offspring.

Keywords

aerobic trainingfetal programmingheartintrauterine growth restriction
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 8 , Issue 2 , April 2017 , pp. 236 - 243
Check for updates
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2016 

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. Barker, DJ, Bull, AR, Osmond, C, Simonds, SJ. Fetal and placental size and risk of hypertension in adult life. BMJ. 1990; 301, 259–262.Google Scholar
2. Gluckman, PD, Hanson, MA, Pinal, C. The developmental origins of adult disease. Matern Child Nutr. 2005; 1, 130–141.Google Scholar
3. Franco, M, Akamine, EH, Di Marco, GS, et al. NADPH oxidase and enhanced superoxide generation in the intrauterine undernourished rats: involvement of the renin-angiotensin system. Cardiovasc Res. 2003; 59, 767–775.Google Scholar
4. Sato, S, Mukai, Y, Norikura, T. Maternal low-protein diet suppresses vascular and renal endothelial nitric oxide synthase phosphorylation in rat offspring independent of a postnatal fructose diet. J Dev Orig Health Dis. 2011; 3, 168–175.CrossRefGoogle Scholar
5. Chandra, RK. Antibody formation in first and second generation offspring of nutritionally deprived rats. Science. 1975; 190, 289–290.CrossRefGoogle ScholarPubMed
6. Moscatelli, P, Bricarelli, FG, Piccinini, A, et al. Defective immunocompetence for foetal malnutrition. Helv Paediatr Acta. 1976; 21, 241–247.Google Scholar
7. Campos, SM, de Oliveira, VL, Lessa, L, et al. Maternal immunomodulation of the offspring’s immunological system. Immunobiology. 2014; 11, 813–821.Google Scholar
8. Guzik, TJ, Hoch, NE, Brown, KA, et al. Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction. J Exp Med. 2007; 10, 2449–2460.Google Scholar
9. Bomfim, GF, Dos Santos, RA, Oliveira, MA, et al. Toll-like receptor 4 contributes to blood pressure regulation and vascular contraction in spontaneously hypertensive rats. Clin Sci (Lond). 2012; 11, 535–543.Google Scholar
10. McCarthy, CG, Wenceslau, CF, Goulopoulou, S, et al. Circulating mitochondrial DNA and toll-like receptor 9 are associated with vascular dysfunction in spontaneously hypertensive rats. Cardiovasc Res. 2015; 1, 119–130.Google Scholar
11. Frantz, S, Ertl, G, Bauersachs, J. Mechanisms of disease: toll-like receptors in cardiovascular disease. Nat Clin Pract Cardiovasc Med. 2007; 4, 444–454.CrossRefGoogle ScholarPubMed
12. Equils, O, Singh, S, Karaburun, S, et al. Intra-uterine growth restriction downregulates the hepatic toll like receptor-4 expression and function. Clin Dev Immunol. 2005; 1, 59–66.CrossRefGoogle Scholar
13. Han, F, Hu, L, Xuan, Y, et al. Effects of high nutrient intake on the growth performance, intestinal morphology and immune function of neonatal intra-uterine growth-retarded pigs. Br J Nutr. 2013; 10, 1819–1827.CrossRefGoogle Scholar
14. Chadio, S, Katsafadou, A, Kotsampasi, B, et al. Effects of maternal undernutrition during late gestation and/or lactation on colostrum synthesis and immunological parameters in the offspring. Reprod Fertil Dev. 2016; 3, 384–393.CrossRefGoogle Scholar
15. Zhang, Q, Raoof, M, Chen, Y, et al. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature. 2010; 7285, 104–107.Google Scholar
16. Berezin, AE. Circulating cell-free mitochondrial DNA as biomarker of cardiovascular risk: new challenges of old findings. Angiology. 2015; 3, 161.Google Scholar
17. Pescatello, LS, Franklin, BA, Fagard, R, et al. American College of Sports Medicine position stand: exercise and hypertension. Med Sci Sports Exerc. 2004; 36, 533–553.CrossRefGoogle ScholarPubMed
18. Moita, L, Lustosa, MF, Silva, AT, et al. Moderate physical training attenuates the effects of perinatal undernutrition on the morphometric of the splenic lymphoid follicles in endotoxemic adult rats. Neuroimmunomodulation. 2011; 2, 103–110.Google Scholar
19. Oliveira, V, Akamine, EH, Carvalho, MHC, et al. Influence of aerobic training on the reduced vasoconstriction to angiotensin II in rats exposed to intrauterine growth restriction: possible role of oxidative stress and AT2 receptor of angiotensin II. PLoS ONE. 2014; 11, e113035.CrossRefGoogle Scholar
20. Reyes, LM, Morton, JS, Kirschenman, R, et al. Vascular effects of aerobic exercise training in rat adult offspring exposed to hypoxia-induced intrauterine growth restriction. J Physiol. 2015; 593, 1913–1929.Google Scholar
21. Romero-Calvo, I, Ocón, B, Martínez-Moya, P, et al. Reversible Ponceau staining as a loading control alternative to actin in Western blots. Anal Biochem. 2010; 2, 318–320.CrossRefGoogle Scholar
22. Liu, J, Cai, X, Xie, L, et al. Circulating cell free mitochondrial DNA is a biomarker in the development of coronary heart disease in the patients with type 2 diabetes. Clin Lab. 2015; 7, 661–667.Google Scholar
23. Park, HK, Jin, CJ, Cho, YM, et al. Changes of mitochondrial DNA content in the male offspring of protein-malnourished rats. Ann N Y Acad Sci. 2004; 1011, 205–216.Google Scholar
24. Beauchamp, B, Ghosh, S, Dysart, MW, et al. Low birth weight is associated with adiposity, impaired skeletal muscle energetics and weight loss resistance in mice. Int J Obes (Lond). 2015; 4, 702–711.Google Scholar
25. Lee, YY, Lee, HJ, Lee, SS, et al. Taurine supplementation restored the changes in pancreatic islet mitochondria in the fetal protein-malnourished rat. Br J Nutr. 2011; 8, 1198–1206.CrossRefGoogle Scholar
26. Miquel, J. An update on the mitochondrial-DNA mutation hypothesis of cell aging. Mutat Res. 1992; 3–6, 209–216.Google Scholar
27. Nasi, M, Cristani, A, Pinti, M, et al. Decreased circulating mtDNA levels in professional male volleyball players. Int J Sports Physiol Perform. 2016; 1, 116–121.Google Scholar
28. Shockett, PE, Khanal, J, Sitaula, A, et al. Plasma cell-free mitochondrial DNA declines in response to prolonged moderate aerobic exercise. Physiol Rep. 2016; 1, pii: e12672.Google Scholar
29. Wang, H, Bei, Y, Lu, Y, et al. Exercise prevents cardiac injury and improves mitochondrial biogenesis in advanced diabetic cardiomyopathy with PGC-1α and Akt activation. Cell Physiol Biochem. 2015; 6, 2159–2168.Google Scholar
30. Jafari, A, Hosseinpourfaizi, MA, Houshmand, M, et al. Effect of aerobic exercise training on mtDNA deletion in soleus muscle of trained and untrained Wistar rats. Br J Sports Med. 2005; 8, 517–520.Google Scholar
31. Ma, Y, He, M, Qiang, L. Exercise therapy downregulates the overexpression of TLR4, TLR2, MyD88 and NF-κB after cerebral ischemia in rats. Int J Mol Sci. 2013; 2, 3718–3733.Google Scholar
32. Oliveira, AG, Carvalho, BM, Tobar, N, et al. Physical exercise reduces circulating lipopolysaccharide and TLR4 activation and improves insulin signaling in tissues of DIO rats. Diabetes. 2011; 3, 784–796.CrossRefGoogle Scholar
33. Landgraf, MA, Landgraf, RG, Silva, RC, et al. Intrauterine undernourishment alters TH1/TH2 cytokine balance and attenuates lung allergic inflammation in Wistar rats. Cell Physiol Biochem. 2012; 3, 552–562.Google Scholar
34. Riddle, ES, Campbell, MS, Lang, BY, et al. Intrauterine growth restriction increases TNF α and activates the unfolded protein response in male rat pups. J Obes. 2014; 2014, 829862.Google Scholar
35. Gleeson, M, McFarlin, B, Flynn, M. Exercise and Toll-like receptors. Exerc Immunol Rev. 2006; 12, 34–53.Google ScholarPubMed
36. Harvey, TJ, Murphy, RM, Morrison, JL, et al. Maternal nutrient restriction alters Ca2+ handling properties and contractile function of isolated left ventricle bundles in male but not female juvenile rats. PLoS ONE. 2015; 9, e0138388.CrossRefGoogle Scholar
37. Muaku, SM, Thissen, JP, Gerard, G, et al. Postnatal catch-up growth induced by growth hormone and insulin-like growth factor-I in rats with intrauterine growth retardation caused by maternal protein malnutrition. Pediatr Res. 1997; 3, 370–377.Google Scholar
38. Menendez-Castro, C, Toka, O, Fahlbusch, F, et al. Impaired myocardial performance in a normotensive rat model of intrauterine growth restriction. Pediatr Res. 2014; 6, 697–706.Google Scholar