Compromised adenosine-A2AR axis contributes to recurrent spontaneous abortion by promoting proinflammatory macrophage polarization

This study investigates the association between recurrent spontaneous abortion (RSA) and macrophage polarization, exploring adenosine (Ado) as a potential biomarker and therapeutic target. By analyzing decidual tissues from RSA patients and normal pregnancies, we found reduced CD39 expression and lower adenosine levels in RSA, accompanied by increased M1 macrophage polarization and decreased M2 macrophage expression. In vitro experiments demonstrated that adenosine inhibited M1 polarization while promoting M2 polarization, an effect reversed by adenosine deaminase (ADA). Single-cell RNA sequencing revealed decreased adenosine receptor A2aR expression in M1 macrophages of RSA patients, while glycolysis-related enzyme hexokinase 2 (HK2) was overexpressed. These findings suggest that adenosine plays a key role in macrophage polarization and immune homeostasis at the maternal-fetal interface, with glycolysis potentially contributing to this process, highlighting its potential as a target for RSA diagnosis and treatment.