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Molecular and Cellular Biochemistry

, Volume 436, Issue 1–2, pp 179–187 | Cite as

Effect of fetal hypothyroidism on MyomiR network and its target gene expression profiles in heart of offspring rats

  • Nasibeh Yousefzadeh
  • Sajad Jeddi
  • Rafighe Ghiasi
  • Mohammad Reza Alipour
Article

Abstract

Thyroid hormone deficiency during fetal life (fetal hypothyroidism) causes intrauterine growth restriction (IUGR). Fetal hypothyroidism (FH) could attenuate normal cardiac functions in the later life of the offspring rats. The aim of this study was to evaluate the contribution of myomiR network and its target gene expression in cardiac dysfunction in fetal hypothyroid rats. Six Pregnant female rats were divided into two groups: Control consumed tap water, and the hypothyroid group received water containing 0.025% 6-propyl-2-thiouracil during gestation. Hearts from male offspring rats in adulthood (month 3) were tested with Langendorff apparatus for measuring hemodynamic parameters. Expressions of miR-208a, -208b, and -499 and its target genes including thyroid hormone receptor 1 (Thrap1), sex-determining region Y-box 6 (Sox6), and purine-rich element-binding protein β (Purβ) were measured by qPCR. FH rats had lower LVDP (%20), +dp/dt (%26), −dp/dt (%20), and heart rate (%21) than controls. FH rats at month 3 had a higher expression of β-MHC (190%), Myh7b (298%), and lower expression of α-MHC (36%) genes in comparison with controls. FH rats at month 3 had a higher expression of miR-499 (520%) and miR-208b (439%) and had lower expression of miR-208a (74%), Thrap1 (47%), Sox6 (49%), and Purβ (45%) compared with controls. Our results showed that thyroid hormone deficiency during fetal life changes the pattern of gene expression of myomiR network and its target genes in fetal heart, which, in turn, resulted in increased β-MHC expression and associated cardiac dysfunction in adulthood.

Keywords

Fetal hypothyroidism myomiR network Hemodynamic parameters Rat 

Notes

Acknowledgements

The Grant of this study was supported by Drug Applied Research Center of Tabriz University of Medical Sciences, Tabriz, Iran. Our data in this work were derived from the thesis of Ms. Nasibeh Yousefzadeh for a Ph.D. degree in physiology (thesis serial number: 94/5-6/1).

References

  1. 1.
    Patel J et al (2011) Thyroid hormones and fetal neurological development. J Endocrinol 209(1):1–8CrossRefPubMedGoogle Scholar
  2. 2.
    de Boo HA, Harding JE (2006) The developmental origins of adult disease (Barker) hypothesis. Aust N Z J Obstet Gynaecol 46(1):4–14CrossRefPubMedGoogle Scholar
  3. 3.
    Fowden AL, Giussani DA, Forhead AJ (2006) Intrauterine programming of physiological systems: causes and consequences. Physiology 21:29–37CrossRefPubMedGoogle Scholar
  4. 4.
    Bourguignon JP, Parent AS (2010) Early homeostatic disturbances of human growth and maturation by endocrine disrupters. Curr Opin Pediatr 22(4):470–477CrossRefPubMedGoogle Scholar
  5. 5.
    Silvestrin SM, Leone C, Leone CR (2017) Detecting congenital hypothyroidism with newborn screening: the relevance of thyroid-stimulating hormone cutoff values. J Pediatr 93(3):274–280CrossRefGoogle Scholar
  6. 6.
    Niwattisaiwong S, Burman KD, Li-Ng M (2017) Iodine deficiency: clinical implications. Cleve Clin J Med 84(3):236–244CrossRefPubMedGoogle Scholar
  7. 7.
    Thornburg KL (2011) Foetal programming reveals the dark side of AT(2)R. Cardiovasc Res 89(2):260–261CrossRefPubMedGoogle Scholar
  8. 8.
    Ghanbari M et al (2015) The effect of maternal hypothyroidism on cardiac function and tolerance to ischemia-reperfusion injury in offspring male and female rats. J Endocrinol Invest 38(8):915–922CrossRefPubMedGoogle Scholar
  9. 9.
    van Rooij E et al (2009) A family of microRNAs encoded by myosin genes governs myosin expression and muscle performance. Dev Cell 17(5):662–673CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Oliveira-Carvalho V, Carvalho VO, Bocchi EA (2013) The emerging role of miR-208a in the heart. DNA Cell Biol 32(1):8–12CrossRefPubMedGoogle Scholar
  11. 11.
    Gupta MP (2007) Factors controlling cardiac myosin-isoform shift during hypertrophy and heart failure. J Mol Cell Cardiol 43(4):388–403CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Izumo S, Nadal-Ginard B, Mahdavi V (1986) All members of the MHC multigene family respond to thyroid hormone in a highly tissue-specific manner. Science 231(4738):597–600CrossRefPubMedGoogle Scholar
  13. 13.
    van Rooij E et al (2007) Control of stress-dependent cardiac growth and gene expression by a microRNA. Science 316(5824):575–579CrossRefPubMedGoogle Scholar
  14. 14.
    Yousefzadeh N, Jeddi S, Alipour MR (2016) Effect of fetal hypothyroidism on cardiac myosin heavy chain expression in male rats. Arq Bras Cardiol 107:147–153PubMedPubMedCentralGoogle Scholar
  15. 15.
    van Rooij E, Olson EN (2007) MicroRNAs: powerful new regulators of heart disease and provocative therapeutic targets. J Clin Invest 117(9):2369–2376CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    van Rooij E, Liu N, Olson EN (2008) MicroRNAs flex their muscles. Trends Genet 24(4):159–166CrossRefPubMedGoogle Scholar
  17. 17.
    Liu N, Olson EN (2010) MicroRNA regulatory networks in cardiovascular development. Dev Cell 18(4):510–525CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Callis TE et al (2009) MicroRNA-208a is a regulator of cardiac hypertrophy and conduction in mice. J Clin Invest 119(9):2772–2786CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Hagiwara N, Yeh M (2007) Sox6 is required for normal fiber type differentiation of fetal skeletal muscle in mice. Dev Dyn 236(8):2062–2076CrossRefPubMedGoogle Scholar
  20. 20.
    Jeddi S, Zaman J, Ghasemi A (2016) Effect of fetal hypothyroidism on tolerance to ischemia-reperfusion injury in aged male rats: role of nitric oxide. Nitric Oxide 55–56:82–90CrossRefPubMedGoogle Scholar
  21. 21.
    Jeddi S et al (2016) Involvement of inducible nitric oxide synthase in the loss of cardioprotection by ischemic postconditioning in hypothyroid rats. Gene 580(2):169–176CrossRefPubMedGoogle Scholar
  22. 22.
    Karbalaei N et al (2013) Comparison of the effect of maternal hypothyroidism on carbohydrate metabolism in young and aged male offspring in rats. Scand J Clin Lab Invest 73(1):87–94CrossRefPubMedGoogle Scholar
  23. 23.
    Samadi R et al (2017) High dose of radioactive iodine per se has no effect on glucose metabolism in thyroidectomized rats. Endocrine 56(2):399–407CrossRefPubMedGoogle Scholar
  24. 24.
    Alipour MR et al (2013) Upregulation of microRNA-146a was not accompanied by downregulation of pro-inflammatory markers in diabetic kidney. Mol Biol Rep 40(11):6477–6483CrossRefPubMedGoogle Scholar
  25. 25.
    Yousefzadeh N, Alipour MR, Soufi FG (2015) Deregulation of NF-small ka, CyrillicB-miR-146a negative feedback loop may be involved in the pathogenesis of diabetic neuropathy. J Physiol Biochem 71(1):51–58CrossRefPubMedGoogle Scholar
  26. 26.
    Newsome CA et al (2003) Is birth weight related to later glucose and insulin metabolism?—A systematic review. Diabet Med 20(5):339–348CrossRefPubMedGoogle Scholar
  27. 27.
    Kuh D et al (2008) Offspring birth weight, gestational age and maternal characteristics in relation to glucose status at age 53 years: evidence from a national birth cohort. Diabet Med 25(5):530–535CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Vincent MA et al (2002) Very low birth weight newborns do not need repeat screening for congenital hypothyroidism. J Pediatr 140(3):311–314CrossRefPubMedGoogle Scholar
  29. 29.
    Morkin E (2000) Control of cardiac myosin heavy chain gene expression. Microsc Res Tech 50(6):522–531CrossRefPubMedGoogle Scholar
  30. 30.
    Lompre AM, Nadal-Ginard B, Mahdavi VIJAK (1984) Expression of the cardiac ventricular α- and β-myosin heavy chain genes is developmentally and hormonally regulated. J Biol Chem 259:6437–6446PubMedGoogle Scholar
  31. 31.
    Patel M et al (2013) Evaluation of acute physiological and molecular alterations in surgically developed hypothyroid Wistar rats. J Pharmacol Pharmacother 4(2):110–115CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Chizzonite RA, Zak R (1984) Regulation of myosin isoenzyme composition in fetal and neonatal rat ventricle by endogenous thyroid hormones. J Biol Chem 259(20):12628–12632PubMedGoogle Scholar
  33. 33.
    Stelzer JE et al (2007) Role of myosin heavy chain composition in the stretch activation response of rat myocardium. J Physiol 579(Pt 1):161–173CrossRefPubMedGoogle Scholar
  34. 34.
    Wibo M et al (1998) Thyroid status and postnatal changes in subsarcolemmal distribution and isoform expression of rat cardiac dihydropyridine receptors. Cardiovasc Res 37(1):151–159CrossRefPubMedGoogle Scholar
  35. 35.
    Meehan J, Kennedy JM (1997) Influence of thyroid hormone on the tissue-specific expression of cytochrome c oxidase isoforms during cardiac development. Biochem J 327(Pt 1):155–160CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Krenz M, Robbins J (2004) Impact of beta-myosin heavy chain expression on cardiac function during stress. J Am Coll Cardiol 44(12):2390–2397CrossRefPubMedGoogle Scholar
  37. 37.
    Rawal S, Manning P, Katare R (2014) Cardiovascular microRNAs: as modulators and diagnostic biomarkers of diabetic heart disease. Cardiovasc Diabetol 13:44CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    McGuigan K, Phillips PC, Postlethwait JH (2004) Evolution of sarcomeric myosin heavy chain genes: evidence from fish. Mol Biol Evol 21(6):1042–1056CrossRefPubMedGoogle Scholar
  39. 39.
    Prado-Uribe MD et al (2013) Role of thyroid hormones and mir-208 in myocardial remodeling in 5/6 nephrectomized rats. Arch Med Res 44(8):616–622CrossRefPubMedGoogle Scholar
  40. 40.
    Bell ML, Buvoli M, Leinwand LA (2010) Uncoupling of expression of an intronic microRNA and its myosin host gene by exon skipping. Mol Cell Biol 30(8):1937–1945CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Shieh JT et al (2013) Elevated miR-499 levels blunt the cardiac stress response. PLoS ONE 6(5):e19481CrossRefGoogle Scholar
  42. 42.
    Li X et al (2013) MiR-499 regulates cell proliferation and apoptosis during late-stage cardiac differentiation via Sox6 and cyclin D1. PLoS One 8(9):e74504CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Yeung F et al (2012) Myh7b/miR-499 gene expression is transcriptionally regulated by MRFs and Eos. Nucleic Acids Res 40(15):7303–7318CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Van Rooij EWA et al (2008) Myosin genes encode a network of microRNAs that control myosin expression and myofiber identity (Abstract). Circulation 118(Pt 2):S305Google Scholar
  45. 45.
    Cook SA et al (2002) Transcriptional effects of chronic Akt activation in the heart. J Biol Chem 277(25):22528–22533CrossRefPubMedGoogle Scholar
  46. 46.
    Lee SJ (2004) Regulation of muscle mass by myostatin. Annu Rev Cell Dev Biol 20:61–86CrossRefPubMedGoogle Scholar
  47. 47.
    Ito M, Roeder RG (2001) The TRAP/SMCC/Mediator complex and thyroid hormone receptor function. Trends Endocrinol Metab 12(3):127–134CrossRefPubMedGoogle Scholar
  48. 48.
    Gulyaeva LF, Kushlinskiy NE (2016) Regulatory mechanisms of microRNA expression. J Transl Med 14(1):143CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Nasibeh Yousefzadeh
    • 1
  • Sajad Jeddi
    • 2
  • Rafighe Ghiasi
    • 1
  • Mohammad Reza Alipour
    • 1
  1. 1.Drug Applied Research CenterTabriz University of Medical SciencesTabrizIran
  2. 2.Endocrine Physiology Research Center, Research Institute for Endocrine SciencesShahid Beheshti University of Medical SciencesTehranIran

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