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

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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.

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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).

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Authors and Affiliations

  1. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Nasibeh Yousefzadeh, Rafighe Ghiasi & Mohammad Reza Alipour

  2. Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Sajad Jeddi

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  1. Nasibeh Yousefzadeh
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Correspondence to Mohammad Reza Alipour.

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Yousefzadeh, N., Jeddi, S., Ghiasi, R. et al. Effect of fetal hypothyroidism on MyomiR network and its target gene expression profiles in heart of offspring rats. Mol Cell Biochem 436, 179–187 (2017). https://doi.org/10.1007/s11010-017-3089-7

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  • DOI: https://doi.org/10.1007/s11010-017-3089-7

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