Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Mol Cell Biochem. 2017 Dec;436(1-2):179-187. doi: 10.1007/s11010-017-3089-7. Epub 2017 Jun 28.
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.
胎儿期甲状腺激素缺乏（胎儿甲状腺功能减退症）可导致宫内生长受限（IUGR）。胎儿甲状腺功能减退症（FH）可减弱后代大鼠生命后期的正常心脏功能。本研究旨在评估心肌 microRNA 网络及其靶基因表达在 FH 大鼠心脏功能障碍中的作用。6 只妊娠雌性大鼠分为两组：对照组饮用自来水，甲状腺功能减退组在妊娠期饮用含 0.025%6-丙基-2-硫代尿嘧啶的水。成年雄性仔鼠（3 月龄）的心脏用 Langendorff 仪器进行检测，以测量血流动力学参数。通过 qPCR 检测 miR-208a、-208b 和 -499 及其靶基因甲状腺激素受体 1（Thrap1）、性别决定区 Y 盒 6（Sox6）和嘌呤丰富元件结合蛋白 β（Purβ）的表达。FH 大鼠的 LVDP（%20）、+dp/dt（%26）、-dp/dt（%20）和心率（%21）均低于对照组。与对照组相比，FH 大鼠在 3 月龄时β-MHC（190%）、Myh7b（298%）的表达升高，α-MHC（36%）的表达降低。与对照组相比，FH 大鼠在 3 月龄时 miR-499（520%）和 miR-208b（439%）的表达升高，miR-208a（74%）、Thrap1（47%）、Sox6（49%）和 Purβ（45%）的表达降低。我们的结果表明，胎儿期甲状腺激素缺乏改变了胎儿心脏中肌源性 microRNA 网络及其靶基因的表达模式，进而导致β-MHC 表达增加，并与成年期的心脏功能障碍有关。
