The role of Ca²⁺ signalling and InsP3R in the pathogenesis of intrahepatic cholestasis of pregnancy

In order to contribute new insights for future prevention and treatment of intrahepatic cholestasis of pregnancy (ICP), and to promote positive pregnancy outcomes, we evaluated serum Ca²⁺ levels and inositol 1,4,5-trisphosphate receptor (InsP3R) expression in the liver tissue of a rat ICP model.

After establishing the model by injection of oestradiol benzoate and progesterone into pregnant rats, animals were divided into normal control (n = 5) and ICP model groups (n = 5). The expression of InsP3R protein in the liver, and serum levels of Ca²⁺, glycocholic acid and bile acid were detected.

InsP3R mRNA and protein were significantly lower in the ICP model group compared to the normal group, as determined by qPCR and immunohistochemistry, respectively. Serum enzyme-linked immunosorbent assay results revealed significantly higher levels of glycocholic acid and bile acid in the ICP model group compared to the normal group, while Ca²⁺ levels were significantly lower. The levers of Ca²⁺ were significantly and negatively correlated with the levels of glycocholic acid. The observed decrease in Ca²⁺ was associated with an increase in total bile acids, but there was no significant correlation.

Our results revealed that the expression of InsP3R and serum Ca²⁺ levels was significantly decreased in the liver tissue of ICP model rats. Additionally, Ca²⁺ levels were found to be negatively correlated with the level of glycocholic acid.