High repetitive frequency pulsed magnetic fields modulate macrophage M2 polarization and ameliorate inflammation-induced murine abortion

The clinical management of unexplained recurrent pregnancy loss (URPL) poses significant challenges. Due to its unclear etiology, current treatment approaches exhibit limited therapeutic efficacy. Aberrant macrophage polarization towards the pro-inflammatory M1 phenotype at the maternal-fetal interface has been recognized as a pivotal factor contributing to the pathogenesis of URPL. However, therapies aimed at modulating macrophage polarization remain scarce. In this study, a high repetitive frequency pulsed magnetic field (HRFPMF) was employed as an alternative approach to optimize the biophysical parameters for inducing macrophage polarization, elucidate the underlying molecular mechanisms, and evaluate the therapeutic potential of HRFPMF-treated macrophages in abortion-prone mice. The findings demonstrated that HRFPMF effectively promoted the polarization of a diverse range of M2 macrophages in vitro. Mechanistic investigations revealed that HRFPMF-induced calcium influx coordinated cytoskeletal reorganization, thereby driving the phenotypic switch of macrophages. Functionally, HRFPMF-treated macrophages promoted the proliferation, migration, invasion and secretory capacity of trophoblasts. More importantly, adoptive transfer of HRFPMF-treated macrophages significantly improved pregnancy outcomes in abortion-prone mice. This was achieved through enhanced M2 polarization at the maternal-fetal interface and promotion of placental vascular remodeling. Collectively, this study highlights HRFPMF as a promising alternative, drug-free immunomodulatory strategy for the management of URPL, offering a novel approach to address this complex and challenging clinical condition.