In utero exposure to mixed PAHs causes heart mass reduction in adult male mice

Polycyclic aromatic hydrocarbons (PAHs) are a risk factor for the occurrence of cardiac diseases. The present study was conducted to investigate the influence of prenatal exposure to a mixed PAHs on heart and the underlying mechanism. Pregnant mice were orally administered with a mixture of 8 kinds of PAHs (0, 5, 50, 500 mu g/kg body weight) once every 2 days for a total of 8 dosages. The mixed PAHs contained naphthalene, acenaphthylene, phenanthrene, fluoranthene, pyrene, benzo[a]pyrene, dibenzo[a,h]anthracene and benzo[g,h,i] perylene at a weight ratio of 10: 10: 10: 10: 10: 1: 1: 1. The adult males, not females, showed significantly decreased heart/body weight ratio, which was attributed to the loss of cardiac fiber and the increase of cell apoptosis. The protein expression of transforming growth factor 01 and its downstream transcription factors, Smad3 and Smad4, was significantly downregulated, which caused the loss of cardiac fiber. The downregulated phosphatidylinositol 3-kinase and AKT led to increased expression of caspase3, caspase9, BAX and reduced expression of Bcl-2, which was responsible for the increased cell apoptosis. Different levels of aromatic hydrocarbon receptor and sex hormone receptors between males and females were associated with the distinct effect on heart.

Automated summary

This study found that prenatal exposure to a mixture of PAHs can lead to a decrease in heart/body weight ratio in adult males, resulting in cardiac fiber loss and increased cell apoptosis. The underlying mechanisms involve the downregulation of TF01 and its downstream transcription factors, as well as the downregulation of PI3K and AKT leading to increased expression of apoptosis-related proteins. Differences in aromatic hydrocarbon receptor and sex hormone receptor levels between males and females also contribute to the distinct effects on the heart.