We have investigated whether maternal obstructive
cholestasis during pregnancy (OCP) causes oxidative stress and apoptosis in rat placenta and whether treatment with
ursodeoxycholic acid (UDCA, i.g., 60 microg/100 g b.wt./day, following complete biliary obstruction on day 14 of pregnancy) has protective effects on this organ. In rats with OCP, increased (15-fold) serum
bile acid concentrations (BAs) together with signs of placental oxidative stress (lipid peroxidation and protein carbonylation) were found. The latter were partly prevented by UDCA, even though hypercholanemia was not corrected. Some elements of the
antioxidant system (total
glutathione content, GSH/
GSSG ratio and
catalase,
glutathione peroxidase, and
glutathione-S-transferase--but not
glutathione reductase--activities) were impaired in placentas from the OCP group. UDCA treatment partly prevented changes in the
antioxidant system. OCP induced an increase in Bax-alpha/Bcl-2
mRNA ratio, as determined by real-time quantitative PCR, suggesting enhanced susceptibility to apoptosis activation through the mitochondria-mediated pathway. Accordingly, the activity of
caspase-3, but not
caspase-8, was increased in OCP placentas, in which
DNA-ladder analysis and TUNEL confirmed the existence of apoptosis. UDCA prevented changes in the Bax-alpha/Bcl-2
mRNA ratio and
caspase-3 activity. In conclusion, OCP causes oxidative stress and apoptosis in rat placenta, which can be prevented by treatment with UDCA.