Ethinylestradiol and bisphenol A exposure leads to dysregulation of bile acid homeostasis in chicken embryos and LMH spheroids

Bile acids (BAs) are important for cholesterol metabolism and the secretion of xenobiotic compounds. This study examined the effects of 17α-ethinylestradiol (EE2) and bisphenol A (BPA) on bile salt export pump (BSEP) inhibition in chicken embryos and the LMH cell line. BA-related genes and BA concentrations were measured at embryonic day (ED) 11 and 20, and in LMH spheroids at 24 and 48 h. EE2 and BPA altered BA-related gene expression, including downregulation of BSEP, with greater changes at ED11 and 24 h. EE2 and BPA increased BA concentrations at ED20 and 48 h. EE2 (25, 50 µg/g) and BPA (50 µg/g) decreased gallbladder mass and increased liver mass at ED20. These findings suggest that EE2 and BPA may induce cholestasis in birds and that LMH 3D spheroids could be useful as an animal-free model for screening chemicals that alter BA homeostasis.