Defect in lipid rafts results in failed tolerance induction at the maternal-fetal interface: a possible cause for the recurrent spontaneous abortion.

The pregnancy is the successful induction and maintenance of maternal tolerance to semi-allogeneic fetus. As a failure result, recurrent spontaneous abortion occurs in about 1-2% of women of reproductive age, defined as the loss of three or more consecutive pregnancies. The mechanism of recurrent spontaneous abortion is often elusive. Recently, mounting evidence suggests that HLA-G induced suppressive uterine natural killer (uNK) cells play an important role in the maternal-fetal tolerance and their abnormalities are responsible for recurrent spontaneous abortion. However, there are some clinical cases of recurrent spontaneous abortion could not be detected of the HLA-G alterations, while their uNK cells showed considerable cytolytic activities against fetus. Thus we hypothesize that lipid rafts, specialized micro-domains in plasma membrane, is of vital importance in the HLA-G-NK cells interactions and the accompanied suppressive induction process. We further hypothesize that the defect in lipid rafts may result in failed tolerance induction at the maternal-fetal interface, which would be a novel explanation for the occurrence of recurrent spontaneous abortion. The hypothesis can be practically evaluated by in vitro experiments and clinical tests. To sum up, this hypothesis proposes a new mechanism in the NK cells suppressive induction. Also the hypothesis may provide new vision in the drug development and disease control of recurrent spontaneous abortion.