Lithocholic acid-induced placental tumor necrosis factor-α upregulation and syncytiotrophoblast cell apoptosis in intrahepatic cholestasis of pregnancy.

AIM: To investigate tumor necrosis factor (TNF)-α expression and its relationship with serum bile acids in placental trophoblasts from patients with intrahepatic cholestasis of pregnancy (ICP).

METHODS

Human placenta, including normal pregnancies (n = 10) and patients with ICP (n = 10), were collected at term and subject to TNF-α measurements. Bile acid-induced TNF-α expression and cell apoptosis were evaluated in cultured syncytiotrophoblasts in vitro.

RESULTS

ICP placental trophoblasts displayed apoptotic histological abnormalities. TNF-α levels in ICP tissue were significantly greater than those of controls as measured by quantitative polymerase chain reaction and western blot. Levels of placental TNF-α mRNA were positively correlated with serum bile acid concentration in ICP patients. In vitro, lithocholic acid (LCA) significantly enhanced TNF-α mRNA at both doses, by 2.07-fold at 15 μm and by 3.41-fold at 30 μm, whereas deoxycholic acid mildly increased TNF-α mRNA by 1.41-fold at 100 μm only. LCA treatment produced significantly higher percentage of caspase-3 positive cells than vehicle treatment, rescuable by the addition of a TNF-α inhibitor, indicative of apoptosis induced by LCA-TNF-α pathway.

CONCLUSION

This study shows that the increase of TNF-α expression in placental trophoblasts is strongly associated with ICP pathology and is inducible by LCA in vitro, suggesting its potential value in the clinical prevention, diagnosis and treatment of ICP.