Immunoregulation and cellular crosstalk in uterine spiral artery remodeling during human pregnancy

Uterine spiral artery (SA) remodeling is essential in human pregnancy to ensure adequate blood perfusion to the maternal-fetal interface and meet the growing demands of the developing fetus. Accumulating evidence underscores the critical role of immunoregulation in this process. In this article, we systematically summarize current advances in this field and propose a compartmentalized framework distinguishing two functionally integrated niches: the intravascular space where endovascular extravillous trophoblasts (enEVTs) interact with maternal immune cells within remodeling SAs, and the perivascular niche where decidual immune cells direct SA remodeling from outside the vessels. By examining the cellular crosstalk among trophoblasts, decidual immune cells, endothelial cells, and vascular smooth muscle cells within and between these niches, we present an integrated model explaining how immune tolerance and vascular transformation are spatiotemporally coordinated. Dysregulation of these finely tuned processes is linked to major pregnancy disorders, highlighting new avenues for pathophysiological research and the development of targeted diagnostic and therapeutic strategies.