Fig. 1

The role of HIF-1α in abnormal glucose metabolism leading to abortion. A. Elevated lactate levels in metaphase macrophages activate the HIF-1α/SRC/LDHA pathway, enhancing INOS expression in a HIF-1α-dependent manner, which in turn promotes their M1 polarization, thereby disrupting immune tolerance and triggering abortion. AZD3965 can reverse. B. Insufficient accumulation of chorionic succinate promotes HIF-1α degradation via the PHD-VHL pathway, leading to a decrease in HIF-1α and thereby inhibiting angiogenesis, trophoblast migration, and glycolysis. C. Downregulation of the TGF-β/mTOR/HTF-1α pathway leads to inhibition of ATP-adenosine metabolism, resulting in a decrease in the number of CD39 + and CD73 + cells at the maternal–fetal interface. This inhibits trophoblast proliferation and invasion and reduces apoptosis and increases toxicity of dNK cells, which in turn leads to RSA. LA lactate, MCT the monocarboxylate transporter protein, AZD3965 MCT-1 inhibitor, HIF-1α the hypoxia-inducible factor 1α, ROS reactive oxygen species, SRC Proto-oncogene tyrosine-protein kinase SRC, LDHA lactate dehydrogenase A, INOS inducible nitric oxide synthase, EVT Extravillous trophoblasts, dNK decidual natural killer cells, TGF-β transforming growth factor-β, mTOR mammalian target of rapamycin, HGF hepatocyte growth factor