Hypoxia does not reduce HLA-G expression on extravillous cytotrophoblasts

Placental hypoxia following the immature remodeling of spiral arteries by extravillous cytotrophoblasts (CTs) is focused on the pathogenesis of pre-eclampsia. At the same time, the expression of human leukocyte antigen (HLA)-G is decreased at the protein and mRNA levels in the pre-eclamptic placenta. In view of the potential function of HLA-G in immunological tolerance in the feto-maternal interface, we were much concerned to find whether the lowered expression of HLA-G in the pre-eclamptic placenta is a precursor or the result of placental hypoxia. The effect of oxygen on the expression of membrane-bound (mb) and soluble (s) HLA-G was investigated in primary cultures of extravillous CTs. The undifferentiated CTs isolated from the first-trimester placenta were cultured with different concentrations of oxygen (20%, 8% and 2%). The protein expression of mbHLA-G and of sHLA-G was assessed using flow cytometry, and mRNA expression was analyzed using real-time PCR. Expression of mbHLA-G and of sHLA-G protein was intensified with time in culture regardless of the oxygen concentration, and the expression intensities were synchronized between the 20% and the 2% oxygen concentrations at each time point. The mRNA expressions of mbHLA-G1 and sHLA-G1 at 2% oxygen were increased to twice those with 20% oxygen. Our findings demonstrate that no reduction of HLA-G was induced in CTs by short-term exposure to hypoxia, although further study may be required to find the effect of chronic hypoxia.