Estradiol can promote the differentiation of hepatoblasts into cholangiocytes and the development of intrahepatic bile ducts during embryogenesis, a new mouse model study found.
These findings could help better understand and, in the future, even prevent diseases characterized by intrahepatic bile duct dysplasia such as Alagille syndrome.
The authors of the study published in the Journal of Cellular and Molecular Medicine wrote, “based on our findings, regulating the estradiol level during the embryo period may provide a new approach for the prevention and treatment of ductopenia.” They added, “The regulation may even prevent Alagille syndrome.”
Read more about Alagille syndrome therapies
The aim of the study was to investigate the effects of estradiol on the development of intrahepatic bile ducts.
The researchers conducted a number of experiments in hepatoblasts extracted from fetal inbred mice. They divided the cells into 4 groups. They treated the cells in the first 3 groups with 1, 10, and 100 nM of estradiol, respectively. They treated the cells in the last group with 10 nM of estradiol plus DAPT, an inhibitor of Notch signaling.
The researchers also conducted experiments on the animals themselves. In this case, they divided pregnant mice into 4 groups. They treated the animals in the first group with a peritoneal injection of estradiol. Those in the second group received estradiol plus a subcutaneous injection of DAPT. Those in the third group were treated with tamoxifen, and those in the fourth group were kept as controls.
The results showed that estradiol promoted the differentiation of hepatoblasts into cholangiocytes and induced intrahepatic bile duct development during the embryonic period. It did this via the expression of genes and proteins associated with the Notch signaling pathway in both cell cultures and live animals.
The addition of DAPT inhibited the effects of estradiol, and the antiestrogenic drug tamoxifen inhibited the differentiation of hepatoblasts and the development of intrahepatic bile ducts.
Future research should focus on the effects of estradiol on intrahepatic bile duct development in Alagille syndrome mice, according to the authors.
Dong C, Zhang BP, Ying YQ, et al. Oestradiol promotes the intrahepatic bile duct development of C57BL/6CrSlc mice during embryonic period via Notch signalling pathway. J Cell Mol Med. 2021;25(19):9447-9459. doi:10.1111/jcmm.16888