Background: Gestational diabetes mellitus (GDM), a common complication during pregnancy, is associated with impaired metabolism and endocrine dysfunction, thereby compromising maternal and fetal health. LIM and SH3 protein 2 (LASP2) has been reported to play regulatory roles in several diseases and has been found to be upregulated in the placental tissues of preeclampsia. However, the specific role of LASP2 and underlying signaling pathways in the progression of GDM largely remains uninvestigated. Therefore, this study aims to assess the impact of LASP2 on the high glucose-induced suppression of trophoblast cell proliferation and migration in GDM patients.

Methods: Placental tissue samples were obtained from women with normal pregnancies (n = 15) and those diagnosed with GDM (n = 15). The GDM cell model was successfully established by exposing HTR-8/SVneo cells to high glucose (30 mM). Furthermore, HTR-8/SVneo cells were transfected with siRNAs targeting LASP2 (si-LASP2#1 and si-LASP2#2), along with a negative control (si-NC). The expression levels of LASP2 were evaluated using RT-qPCR and Western blot analysis, and cell proliferation was determined using Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays. Additionally, cell migratory capability was evaluated using wound healing and Transwell assays, and their angiogenic ability was assessed using the tube formation assay.

Results: LASP2 was upregulated in the placental tissues of patients with GDM (p < 0.001). Moreover, the cell viability of HTR-8/SVneo cells was significantly alleviated under high glucose conditions, an effect that was counteracted by LASP2 knockdown (p < 0.05). Similarly, cell migration ability was substantially suppressed under high glucose treatment; this impairment was effectively rescued by LASP2 silencing (p < 0.01). Additionally, angiogenic ability significantly decreased after high glucose treatment, an effect that was neutralized by LASP2 suppression (p < 0.001). LASP2 knockdown effectively provoked the Wingless-related integration site (Wnt)/β-catenin signaling pathway.

Conclusion: LASP2 knockdown effectively reverses high glucose-induced suppression of proliferation and migration in trophoblast cells by modulating the Wnt/β-catenin signaling pathway, providing novel insights into the role of LASP2 in GDM.