Thyroid hormone does not induce maturation of embryonic chicken cardiomyocytes in vitro

Abstract

Fetal cardiac growth in mammalian models occurs primarily by cell proliferation (hyperplasia). However, most cardiomyocytes lose the ability to proliferate close to term and heart growth continues by increasing cell size (hypertrophy). In mammals, the thyroid hormone triiodothyronine (T3) is an important driver of this process. Chicken cardiomyocytes, however, keep their proliferating ability long after hatching but little information is available on the mechanisms controlling cell growth and myocyte maturation in the chicken heart. Our aim was to study the role of T3 on proliferation and differentiation of embryonic chicken cardiomyocytes (ECCM), enzymatically isolated from 19‐day‐old embryos and to compare the effects to those of insulin‐like growth factor‐1 (IGF‐1) and phenylephrine (PE). Hyperplasia was measured using a proliferation assay (MTS) and hypertrophy/multinucleation was analyzed morphologically by phalloidin staining of F‐actin and nuclear staining with DAPI. We show that IGF‐1 induces a significant increase in ECCM proliferation (30%) which is absent with T3 and PE. PE induced both hypertrophy (61%) and multinucleation (41%) but IGF‐1 or T3 did not. In conclusion, we show that T3 does not induce maturation or proliferation of cardiomyocytes, while IGF‐1 induces cardiomyocyte proliferation and PE induces maturation of cardiomyocytes.

Protective effects of pravastatin on the embryonic cardiovascular system during hypoxic development

“…In humans, cardiomyocyte endowment is set at around the time of birth. In chickens, cardiomyocyte proliferation can continue past hatching 76,77 . In mammals, it has been reported that the timing of exposure to hypoxia during gestation in relation to cardiomyocyte endowment has significant consequences for cardiac function 78 .…”

Synergistic effects of hormones on structural and functional maturation of cardiomyocytes and implications for heart regeneration

“…Of note, in the same study, cardiomyocyte maturation is demonstrated to be epigenetically regulated by RNF20/40, which is reported to be a transcriptional coactivator for PPARγ [ 133 ]. Although another study in chicken embryos could demonstrate neither increased cell size nor elevated binucleation rates of cardiomyocytes treated with T3 for 24 h [ 278 ], other studies support the idea that T3 promotes cardiomyocyte maturation. For example, T3 treatment is reported to foster cardiac differentiation of murine embryonic stem cells (mESCs) [ 164 ] and drive maturation of hPSC-CM influencing basal beating rate, the upstroke of the action potential and mitochondrial metabolism [ 117 ], as well as increasing sarcomere length and force generation [ 319 ].…”

The role of miRNA regulation in fetal cardiomyocytes, cardiac maturation and the risk of heart disease in adults

“…1998) and metabolic stress resulting from periods of starvation between birth and the initiation of nursing or intermittent feeding are also likely to contribute to cardiomyocyte maturation. In addition, chicken cardiomyocytes act counterintuitively to the atmospheric oxygen theory, as they do not undergo binucleation until weeks after hatching and have little difference in oxygen tension between in ovo and post‐hatching (Svensson Holm et al . 2014).…”