Thus, these methods are specialized for detection of open chromatin

one therapy on cardiac function, and showed that the heart to body weight ratio was increased in P7 pups PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/1977615 but decreased in 45-weekold rats. Similar to this study, our results also showed an increase in the heart to body weight ratio in P14 pups. It has been reported that dexamethasone treatment increased cardiomyocyte length, width and volume at 45 week, suggesting neonatal dexamethasone therapy had a long-term effect on the heart and may be responsible for the cardiomyocyte hypertrophy later in life in adulthood. However, the underlying mechanisms at the cellular and molecular levels remain elusive. The present study provided a mechanism in the understanding of this long-term effect of neonatal dexamethasone therapy, and demonstrated that dexamethasone treatment significantly suppressed proliferation and promoted premature maturation of cardiomyocytes, resulting in a decreased total cardiomyocyte number in the developing heart. The finding that dexamethasone-mediated stimulation of premature cardiomyocyte binucleation and inhibition of myocyte proliferation were blocked by Ru486 demonstrates the GR-mediated effects during this critical window of the heart development. In the developing heart, cardiomyocytes are initially mononucleate and proliferative, but proliferation capacity is soon limited as mature cardiomyocytes undergo binucleation and hence are non-proliferative. Fetal exposure to glucocorticoids has been shown to stimulate binucleation in preterm piglets, but has no overall effects in fetal lambs. Because rodent cardiomyocyte terminal differentiation starts and continues within the first two weeks of postnatal life, which is equivalent to human heart development in late fetal stage of third trimester, neonatal rats provide a reasonable animal model to study the effect of glucocorticoid treatment on preterm infants at the critical window of the heart development. The present study demonstrates that dexamethasone treatment of newborn rats stimulates premature cardiomyocyte binucleation in day 4 pups. The transition to binucleation is a critical time in the heart development because of the limited proliferative capacity thereafter. Therefore, premature binucleation can potentially depress cardiomyocyte endowment. Since cardiomyocytes are the functional unit of the heart, Danoprevir adequate numbers are essential for cardiac function in adaption to physiological changes. Indeed, our results showed decreased cardiomyocyte proliferation on P4 and P7 pups, as well as a significantly lower cardiomyocyte number in P14 pups. Since the majority of cardiomyocytes are binucleated and terminally differentiated at this developmental age, it is likely that the dexamethasone-induced reduction of cardiomyocyte number will persist into adulthood and contribute to heart dysfunction later in life. The depressed cardiomyocyte number was also reported with other stressor such as intrauterine growth restriction. This raises a major concern, when cardiomyocyte numbers are lowered in the heart, the remaining cardiomyocytes may undergo cellular hypertrophy to generate sufficient contractile forces. This compensation is not without consequence in increased risk of ischemic heart disease. Although the present study focuses on the effect of glucocorticoid on the PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19776277 critical window of the heart development in cardiomyocyte maturation and binucleation, which is of clinical relevance in the glucocorticoid therapy in preterm infants, the potential effect of glucocorticoid o