Knockdown of CCNB1 alleviates high glucose-triggered trophoblast dysfunction during gestational diabetes via Wnt/β-catenin signaling pathway.

Gestational diabetes mellitus (GDM), defined as glucose intolerance occurring or first detected during pregnancy, affects approximately 8% of pregnancies worldwide. The dysfunction of trophoblasts in pregnancies complicated by GDM is associated with changes in trophoblast cell functions, resulting in compromised proliferation and regulation of the cell cycle. Cyclin B1 (CCNB1), a pivotal controller of the start of mitosis, is crucial in these mechanisms. Nevertheless, the precise function of CCNB1 in trophoblast dysfunction related to GDM has not been extensively investigated. The aim of this study was to investigate CCNB1's role in high glucose (HG)-triggered trophoblast. Herein, we revealed that in HG-stimulated HTR8/SVneo cells, CCNB1 is highly expressed. Knockdown of CCNB1 significantly promotes the growth of HG-stimulated HTR8/SVneo cells and suppresses inflammation (p < 0.05). Additionally, reducing CCNB1 expression significantly improves glucose uptake and inhibits the Wnt/β-catenin pathway in HG-stimulated HTR8/SVneo cells (p < 0.05). In conclusion, our study demonstrated that the deletion of CCNB1 can alleviate trophoblast dysfunction induced by HG in GDM through the Wnt/β-catenin pathway. This suggests that CCNB1 may be a potential target for managing GDM. Although our results underscore the potential therapeutic benefits of reducing CCNB1 in mitigating trophoblast dysfunction, it is important to note that the study is limited by its reliance on a single cell line and the absence of in vivo validation.