Abstract
Background: Down syndrome (DS), which is caused by partial or complete triplication of chromosome 21, may cause a range of clinical features. Although most fetuses with DS exhibit typical characteristics, the molecular pathogenesis underlying DS remains unclear. Wnt signaling is known to play a crucial role in fetal growth and development. However, the link between Wnt signaling and the abnormal development of fetuses with DS remains poorly understood. In this study, our objective was to investigate the dysregulation of the Wnt/β-catenin pathway in the amniocytes of fetuses diagnosed with DS. To this end, we obtained amniocytes from 10 fetuses diagnosed with DS and determined the expression levels of key proteins activated by the Wnt/β-catenin pathway, oxidative stress, cell proliferation, and apoptosis in these amniocytes using western blot and cellular immunofluorescence methods. Subsequently, components of the Wnt/β-catenin pathway were upregulated in amniocytes from fetuses diagnosed with DS and expression of related proteins was detected. The differences were evaluated using Student’s t-test or analysis of variance, followed by Tukey’s test. Results: We found that the Wnt/β-catenin pathway was inhibited in DS fetal amniocytes compared to normal fetal amniocytes, and cell proliferation was reduced, along with increased oxidative stress and apoptosis. In contrast, up-regulation of the Wnt/β-catenin pathway in DS amniocytes increased cell proliferation, decreased oxidative stress and apoptosis, and ultimately improved cell growth. Conclusions: The Wnt/β-catenin pathway mitigates excessive apoptosis caused by oxidative stress, promotes cellular proliferation, and maintains homeostasis in DS amniocytes. These findings reveal a novel molecular mechanism underlying the abnormal regulation of the Wnt/β-catenin pathway during the development of fetuses with DS, thereby suggesting potential targeted therapies for DS. Supplementary Information: The online version contains supplementary material available at 10.1186/s12860-026-00569-9.