Expression Of ADAMTS13 In Normal And Abnormal Placentae And Its Potential Role In Placenta Development

Background ADAMTS13 is primarily synthesized in liver.The biosynthesis and its physiological role in placenta are not known.Objects We aimed to investigate the expression of ADAMTS13 in normal and abnormal human placentae and its association with preeclampsia.Methods Real-time PCR,immunohistochemistry,and Western blotting analyses,as well as proteolytic cleavage of FRETS-VWF73 were employed to determine ADAMTS13 expression in placentae obtained during normal pregnancy and patients with preeclampsia and trophoblasts;the MTT(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)assay,wound scratch assay,transwell migration assay,tube formation assay,and tissue outgrowth assays were used to determine ADAMTS13 functions in extravillous trophoblasts.Results We showed that proteolytically active ADAMTS13 was expressed in normal human placenta,primarily in trophoblasts and villous core fetal vessel endothelium throughout pregnancy;placental ADAMTS13 protein were detected at the highest levels during the first trimester and reduced at the term of gestation;additionally,significantly reduced levels of placental ADAMTS13 expression under hypoxic conditions and in patients with preeclampsia were observed.Moreover,recombinant full-length ADAMTS13 stimulated trophoblasts proliferation,migration,invasion and network formation in culture.Conclusions Our results demonstrate for the first time the expression of ADAMTS13 in normal and abnormal placental tissues and its role in promoting angiogenesis and trophoblastic cell development.These findings suggest a role of ADAMTS13 during pregnancy and likely the pathogenesis of preeclampsia.