Chitosan Oligosaccharides Alleviates Maternal Diabetes-Induced Embryonic Neural Tube Defects through Inhibiting the cGAS-STING Pathway
WANG Bingbin1, ZHOU Mei1, CHEN Ran1, NIE Saiqun1, FANG Li1, ZHANG Bingyan1, ZHANG Wenting1, WU Wenjun2, WU Yanqing1*
Maternal diabetes significantly mediates embryonic NTDs (neural tube defects), but the underly ing regulatory mechanisms and therapeutic strategies remain unclear. In this study, a diabetic female mouse model was established using streptozotocin, and on this basis, a embryonic NTDs model was further generated to explore the role and regulatory mechanism of COSs (chitosan oligosaccharides) for the occurrence of embryonic NTDs. Firstly, embryonic tissues were collected at E10.5, and the closure of the embryonic neural tube was examined us ing stereomicroscope and HE staining. The results demonstrated that COSs intervention significantly reduced the incidence of maternal diabetes-induced embryonic NTDs. Moreover, immunofluorescence staining was used to detect the expression levels of cleaved Caspase-1 and NLRP3 in embryonic tissues at E8.5. COSs intervention was found to effectively suppress the pyroptosis of embryonic neuroepithelial cells caused by maternal diabetes. Finally, Western blot and immunofluorescence staining were used to detect the expression levels of cGAS (cyclic GMP AMP synthase), STING (stimulator of interferon gene), and IFN-β1 (interferon-β1). It was found that the aberrant activation of the cGAS-STING signaling pathway and the elevated levels of inflammatory cytokines induced by maternal diabetes were significantly alleviated by COSs intervention. This study indicates that COSs alleviate py roptosis in neuroepithelial cells by inhibiting the cGAS-STING pathway, thus reducing the incidence of maternal diabetes-induced NTDs.
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