Thyroid hormone signaling and consequences for cardiac development

Chattergoon, Natasha N.

doi:10.1530/joe-18-0704

Cited by 34 publications

(28 citation statements)

References 148 publications

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“…TH levels are maintained at low levels during fetal development [ 58 ], which are required for proper cardiomyocyte proliferation. Before birth, the T3 concentration increases (prenatal surge) and contributes to cardiovascular and metabolic adjustment once T3 participates in the maturation of cardiomyocytes and the formation of normal heart physiology (reviewed in [ 59 ] and [ 60 ]).…”

Section: Resultsmentioning

confidence: 99%

Reorganization of Metabolism during Cardiomyogenesis Implies Time-Specific Signaling Pathway Regulation

Barisón

Pereira

Robert

et al. 2021

IJMS

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Understanding the cell differentiation process involves the characterization of signaling and regulatory pathways. The coordinated action involved in multilevel regulation determines the commitment of stem cells and their differentiation into a specific cell lineage. Cellular metabolism plays a relevant role in modulating the expression of genes, which act as sensors of the extra-and intracellular environment. In this work, we analyzed mRNAs associated with polysomes by focusing on the expression profile of metabolism-related genes during the cardiac differentiation of human embryonic stem cells (hESCs). We compared different time points during cardiac differentiation (pluripotency, embryoid body aggregation, cardiac mesoderm, cardiac progenitor and cardiomyocyte) and showed the immature cell profile of energy metabolism. Highly regulated canonical pathways are thoroughly discussed, such as those involved in metabolic signaling and lipid homeostasis. We reveal the critical relevance of retinoic X receptor (RXR) heterodimers in upstream retinoic acid metabolism and their relationship with thyroid hormone signaling. Additionally, we highlight the importance of lipid homeostasis and extracellular matrix component biosynthesis during cardiomyogenesis, providing new insights into how hESCs reorganize their metabolism during in vitro cardiac differentiation.

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Section: Resultsmentioning

confidence: 99%

Reorganization of Metabolism during Cardiomyogenesis Implies Time-Specific Signaling Pathway Regulation

Barisón

Pereira

Robert

et al. 2021

IJMS

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“…When pregnant women have hypothyroidism, abnormal thyroid hormone levels can severely affect the development of neuromotor, auditory, cardiovascular, and respiratory systems [15]. Thyroid hormones can promote the transformation of fetal cardiomyocytes from proliferation to hypertrophy and differentiation during full-term and early pregnancy [16]. Since the thyroid function of pregnant women affects the growth and maturation of fetal organs, the birth weight of the baby can indirectly reflect the level of thyroid function of pregnant women [17].…”

Section: Discussionmentioning

confidence: 99%

Early L-T4 intervention improves fetal heart development in pregnant rats with subclinical hypothyroidism rats by activating BMP4/Smad4 signaling pathway

Xue

Sun

Jun

2020

BMC Cardiovasc Disord

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Background: It is unclear whether the offspring of subclinical hypothyroidism (SCH) pregnant rats still have abnormal cardiac development, and whether early intervention with L-T4 can improve the abnormality of these offspring. Therefore, the aim of this study was to investigate the effect of early L-T4 intervention on the heart development of offspring of SCH pregnant rats and its possible molecular mechanism. Methods: Eighty female Wistar rats were randomly divided into Sham group (placebo control), SCH group, LT4-E10 group (L-T4 treatment started on the 10th day of gestation), and LT4-E13 group (L-T4 treatment started on the 13th day of gestation). Each group was further divided into E16 (16th day of gestation), E18 (18th day of gestation), P5 (5th day postnatal day), and P10 (10th day postnatal day) subgroups. The levels of serum TT4 and TSH, the ratio of heart weight to body weight of offspring rats, the expression of metabolic enzymes, and the histopathology of cardiomyocytes were determined. To elucidate the effects of L-T4 on cardiac development of offspring of SCH pregnant rats, the expression levels of GATA4, Nkx2-5 and proteins involved in BMP4/Smad4 signaling pathway were detected by immunohistochemistry, real time quantitative polymerase chain reaction and Western blotting to elucidate the molecular mechanism of L-T4 regulating the heart development of the offspring of SCH pregnant rats. Results: Compared with Sham group, serum TSH was significantly increased in SCH pregnant rats. Moreover, early L-T4 intervention significantly reduced the levels of serum TSH. Compared with the offspring in the SCH group, early L-T4 intervention significantly increased the heart weight, heart weight to body weight ratio, the activities of succinate dehydrogenase (SDH), Na + /K +-ATPase and Ca 2+-ATPase, but reduced myocardial cell shrinkage and nuclear staining, hyperemia/congestion and vacuolar degeneration. In addition, early L-T4 intervention not only significantly increased the mRNA and protein expression of Gata4 and Nkx2-5, but also increased the protein expression involved in BMP4/Smad4 signal pathway in myocardium of the offspring of SCH pregnant rats.

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“…When pregnant women have hypothyroidism, abnormal thyroid hormone levels can severely affect the development of neuromotor, auditory, cardiovascular, and respiratory systems [15]. Thyroid hormones can promote the transformation of fetal cardiomyocytes from proliferation to hypertrophy and differentiation during full-term and early pregnancy [16]. Since the thyroid function of pregnant women affects the growth and maturation of fetal organs, the birth weight of the baby can indirectly re ect the level of thyroid function of pregnant women [17].…”

Section: Discussionmentioning

confidence: 99%

Early L-T4 intervention improves fetal heart development in pregnant rats with subclinical hypothyroidism rats by activating BMP4/Smad4 signaling pathway

Xue

Sun²,

Yang

2020

Preprint

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Background: It is unclear whether the offspring of subclinical hypothyroidism (SCH) pregnant rats have abnormal cardiac development, and whether early intervention with L-T4 can improve the abnormality of these offspring. Therefore, the aim of this study was to investigate the effect of early L-T4 intervention on the heart development of offspring of SCH pregnant rats and its possible molecular mechanism. Methods: Eighty female Wistar rats were randomly divided into Sham group (placebo control), SCH group, LT4-E10 group (L-T4 treatment started on the 10th day of gestation), and LT4-E13 group (L-T4 treatment started on the 13th day of gestation). Each group was further divided into E16, E18, P5 (postnatal day 5 rats), and P10 (postnatal day 10 rats) subgroups. The levels of serum TT4 and TSH, the ratio of heart weight to body weight of offspring rats, the expression of metabolic enzymes, and the histopathology of cardiomyocytes were determined. To elucidate the effects of L-T4 on cardiac development of offspring of SCH pregnant rats, the expression levels of GATA4, Nkx2-5 and proteins involved in BMP4/Smad4 signaling pathway were detected by immunohistochemistry, real time quantitative polymerase chain reaction and Western blotting to elucidate the molecular mechanism of L-T4 regulating the heart development of the offspring of SCH pregnant rats. Results: Compared with Sham group, serum TSH was significantly increased in SCH pregnant rats. Moreover, early L-T4 intervention significantly reduced the levels of serum TSH. Compared with the offspring in the SCH group, early L-T4 intervention significantly increased the heart weight, heart weight to body weight ratio, the activities of succinate dehydrogenase (SDH), Na + /K + -ATPase and Ca 2+ -ATPase, but reduced myocardial cell shrinkage and nuclear staining, hyperemia/congestion and vacuolar degeneration. In addition, early L-T4 intervention not only significantly increased the mRNA and protein expression of Gata4 and Nkx2-5, but also increased the protein expression involved in BMP4/Smad4 signal pathway in myocardium of the offspring of SCH pregnant rats. Conclusions : Early L-T4 intervention can regulate the cardiac development of the offspring of SCH pregnant rats by activating BMP4/Smad4 signaling pathway and increasing the expression of Gata4 and Nkx2-5 proteins.

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Thyroid hormone signaling and consequences for cardiac development

Cited by 34 publications

References 148 publications

Reorganization of Metabolism during Cardiomyogenesis Implies Time-Specific Signaling Pathway Regulation

Reorganization of Metabolism during Cardiomyogenesis Implies Time-Specific Signaling Pathway Regulation

Early L-T4 intervention improves fetal heart development in pregnant rats with subclinical hypothyroidism rats by activating BMP4/Smad4 signaling pathway

Early L-T4 intervention improves fetal heart development in pregnant rats with subclinical hypothyroidism rats by activating BMP4/Smad4 signaling pathway

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