Dysregulation of CD44v6 may lead to recurrent spontaneous abortion by inhibiting the proliferation and migration of trophoblast cells.

In the establishment and continuation of a successful pregnancy, the proliferation, migration, and invasion of trophoblast cells play essential roles. Impaired trophoblast function has been reported to be involved in recurrent spontaneous abortion (RSA) but the potential mechanisms are still unknown. CD44 variant domain 6 (CD44v6) is a transmembrane glycoprotein that has been known for decades to be expressed in the placenta. In this study, we investigated the effect of CD44v6 on proliferation and migration of trophoblast cells. Our results show that CD44v6 expression in the villi is lower in RSA patients than in women with normal pregnancies. Furthermore, downregulation of CD44v6 leads to a reduction in proliferation and migration in the human trophoblast cell line HTR-8/SVneo, along with decreased expression and nuclear translocation of NF-κB. These results suggest that decreased expression of CD44v6 may cause miscarriage by downregulating trophoblast cell proliferation via the NF-κB pathway.