Prenatal EGCG exposure-induced heart mass reduction in adult male mice and underlying mechanisms

• DOI: 10.1016/j.fct.2021.112588
• Publication Date: 2021-09-30T07:15:24Z
• Authors: Shenli Zhang; Kunlin Ou; Jie Huang; Lu Fang; Chonggang Wang; Qin Wang
• Keywords: Male; 0303 health sciences; Caspase 3; Myocardium; Apoptosis; Heart; Organ Size; Caspase 9; Catechin; 3. Good health; Mice, Inbred C57BL; Mice; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; Pregnancy; Prenatal Exposure Delayed Effects; Animals; Female; Smad3 Protein; Proto-Oncogene Proteins c-akt; Signal Transduction; Smad4 Protein

Epigallocatechin-3-gallate (EGCG), which is a major polyphenol in tea, has an unclear effect on cardiac development. In the present study, mice (C57BL/6) were exposed in utero to EGCG dissolved in drinking water (3 μg/ml) for 16 days. A significant decrease in the heart/body weight ratio was observed in adult males but not in adult females. The protein expression levels of TGF-β1 and its downstream transcription factors SMAD3 and SMAD4 were significantly decreased in male hearts. The PI3K/AKT signaling pathway was inhibited, the expression of proapoptotic proteins, such as BAX, Cleaved Caspase3 and Cleaved Caspase9, was elevated, and the level of antiapoptotic proteins, such as BCL-2, was decreased. A reduced heart/body weight ratio may be associated with the loss of cardiac fibers and an increase in myocardial apoptosis. The cardiac levels of aromatic hydrocarbon receptor and androgen receptor were elevated only in males, which may explain the sexual dimorphism in the effects. The promoter methylation levels of pik3r1, tgf-β, smad4 were elevated, and those of ahr were reduced, explaining the mechanism underlying the cardiac histological alteration caused by prenatal exposure to EGCG. The results suggest that ingestion of EGCG during pregnancy may be a risk factor for cardiac development in offspring.