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

SummaryThe 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.