Effect of hyperglycemia on tbx5a and nppa gene expression and its correlation to structural and functional changes in developing zebrafish heart.

Abstract

The objective of the current study is to analyze the effects of gestational diabetes on structural and functional changes in correlation with these two essential regulators of developing hearts in vivo using zebrafish embryos. We employed fertilized zebrafish embryos exposed to a hyperglycemic condition of 25 mM glucose for 96 h postfertilization. The embryos were subjected to various structural and functional analyses in a time-course manner. The data showed that exposure to high glucose significantly affected the embryo's size, heart length, heart rate, and looping of the heart compared to the control. Further, we observed an increased incidence of ventricular standstill and valvular regurgitation with a marked reduction of peripheral blood flow in the high glucose-exposed group compared to the control. In addition, the histological data showed that the high-glucose exposure markedly reduced the thickness of the wall and the number of cardiomyocytes in both atrium and ventricles. We also observed striking alterations in the pericardium like edema, increase in diameter with thinning of the wall compared to the control group. Interestingly, the expression of tbx5a and nppa was increased in the early development and found to be repressed in the later stage of development in the hyperglycemic group compared to the control. In conclusion, the developing heart is more susceptible to hyperglycemia in the womb, thereby showing various developmental defects possibly by altering the expression of crucial gene regulators such as tbx5a and nppa.