Low Expression of LEFTY1 in Placental Villi Is Associated with Early Unexplained Miscarriage.

ABSTRACT

OBJECTIVE: To investigate the function and underlying mechanism of transforming growth factor­beta (TGF-ß)/bone morphogenetic protein (BMP) signaling pathway in early unexplained miscarriage. STUDY DESIGN: Expression profiles of genes involved in TGF-ß/BMP signaling pathway were compared between placental villous tissue samples from 2 women with missed abortion and those from 2 women with induced abortion by microarray assay. The protein expression level of the most downregulated gene­LEFTY1­was further measured using western blotting in another 8 women with missed abortion and 7 women with induced abortion. RESULTS: A total of 24 genes showed differential expression level between the 2 groups. Their functions were further investigated, of which 6 of 13 upregulated genes were TGF-ß responsive genes. The most reduced gene is LEFTY1, an antagonist of TGF-ß ligand. The protein expression level of LEFTY1 was confirmed to show the same trend as microarray using western blotting. CONCLUSION: A reduced expression of LEFTY1 in women with missed abortion was identified as com-pared with women with induced abortion, which may result in a dysregulation of TGF-ß signaling and may be the underlying mechanism of missed abortion.