Objective To explore the molecular mechanism of transcription factor SOX2 regulating trophoblast cell damage through targeting the γ-aminobutyric acid A receptor π subunit (GABRP) under high glucose conditions, and analyze its potential role in the development of gestational diabetes mellitus (GDM).

Methods The in vitro model was established by inducing human chorionic trophoblast cells HTR-8/SVneo with high glucose (25 mmol/L glucose, HG). The negative control plasmid (oe-NC) or SOX2 (oe-SOX2) overexpression plasmid was transfected into HTR-8/SVneo cells, and the cells were divided into the control group, HG group, HG + oe-NC group and HG + oe-SOX2 group. The mRNA expressions of SOX2 and GABRP genes in each group were detected by real-time fluorescence quantitative PCR (RT-qPCR). Cell viability was detected by the CCK-8 method. The levels of inflammatory factors (IL-18, IL-6, TNF-α) were determined by ELISA, and the levels of ferroptosis-related markers such as superoxide dismutase (SOD), malondialdehyde (MDA), reactive oxygen species (ROS) and iron ions were detected using the corresponding kits. The enrichment degree of SOX2 at the GABRP gene promoter was detected by chromatin immunoprecipitation.

Results Compared with the control group, the expressions levels of SOX2 and GABRP mRNA, cell viability, SOD level and enrichment degree of SOX2 in the promoter region of GABRP gene in the HG group decreased (P ＜ 0.05), while the levels of IL-18, IL-6, TNF-α, MDA, ROS and iron content increased (P ＜ 0.05). Compared with the HG + oe-NC group, the expression levels of SOX2 and GABRP mRNA, cell viability, SOD level and enrichment degree of SOX2 in the promoter region of the GABRP gene in the HG + oe-SOX2 group increased (P ＜ 0.05), while the levels of IL-18, IL-6, TNF-α, MDA, ROS and iron content decreased (P ＜ 0.05).

Conclusions SOX2 inhibits the inflammatory response and ferroptosis of trophoblast cells induced by high glucose by regulating GABRP.