The expression profile of Wnt/β-Catenin signalling pathway genes in miscarriages

Abstract

Miscarriage, defined as the spontaneous loss of a fetus before viability, is the most common complication of pregnancy. Among its many causes, genetic factors are thought to play a significant role. One of the key signaling pathways involved in embryonic development is the Wnt/β-catenin pathway, which regulates critical processes such as embryonic cell migration, cell fate determination, proliferation, and differentiation. This pathway is also essential for early developmental events, including preimplantation development and blastocyst implantation. Although numerous animal studies have linked disruptions in Wnt signaling to pregnancy loss, limited data exist on its role in human miscarriage. In this study, we aimed to investigate the expression profiles of genes involved in the Wnt/β-catenin signaling pathway in placental tissues from a total of 23 miscarriage cases, including 15 with normal and 8 with abnormal fetal karyotypes. Our analysis revealed that GSK3B, WNT3A, WNT4, AXIN2, and APC were upregulated in the normal karyotype group, while CTNNB1 (β-catenin) and WNT5A were downregulated. DVL1 expression showed no significant difference between the groups. These findings suggest that upregulation of GSK3B, AXIN2, and APC, together with downregulation of β-catenin, may lead to inhibition of the Wnt/β-catenin signaling pathway. Such disruption could impair key cellular processes—including proliferation, migration, and blastocyst implantation—that are essential for early pregnancy maintenance.