Effects of taurine depletion on human placental syncytiotrophoblast renewal and susceptibility to oxidative stress.

Taurine is conditionally essential in human pregnancy as fetal tissues do not express the biosynthetic enzyme. Taurine demand by both fetus and placenta must be met by sufficient uptake from maternal blood into syncytiotrophoblast (STB), the transport epithelium of the placenta, via the taurine transporter (TauT). STB TauT activity is reduced in the pregnancy complication pre-eclampsia (PE). This condition is associated with fetal growth restriction (FGR) and placental pathology comprising abnormal STB renewal, mitochondrial dysfunction, and elevated oxidative stress. In non-placental cells intracellular taurine is cytoprotective and regulates proliferation, differentiation, and apoptosis; key events in STB renewal. Here we test the hypothesis that STB taurine deficiency impairs renewal and increases susceptibility to oxidative stress by compromising mitochondrial function.

STB renewal and susceptibility to oxidative stress was assessed in placental villous explants cultured over 7 days in the presence of 10 mM β-alanine to competitively inhibit taurine uptake. During explant culture, STB sheds and thereafter is regenerated by processes resembling those in vivo. Immunohistochemical techniques demonstrated β-alanine significantly reduced the proportion of villi with regenerated STB. In STB of explants treated with 1 mM H2O2 (inducer of oxidative stress), oxidative DNA damage in nuclei and cytoplasm (mitochondrial DNA) was significantly higher following TauT inhibition. Taurine depletion in BeWo cells induced mitochondrial swelling, reduced mitochondrial complex V subunit expression and increased oxidative stress, indicating mitochondrial dysfunction. These data suggest that taurine is important for maintaining STB renewal and protecting against damage caused by oxidative stress, possibly via a mechanism involving regulation of mitochondrial function.