Successful pregnancy depends on the mother's immune tolerance towards the semi-allogeneic fetus, primarily facilitated by the intricate interaction between endometrial epithelial cells, stromal cells, and decidual immune cells at the fetal-maternal interface. The secretion of the endometrial gland is crucial for decidualization, implantation, and placental development, which ultimately determines the pregnancy outcome. Dysregulated endometrial gland function is widely considered as a significant factor contributing to pregnancy loss and complications during human gestation (Spencer, 2014). However, there is limited research on whether gland secretion impacts the functions of decidual immune cells.

Decidual macrophages (dMs) serve as the primary phagocytic cells in the maternal-fetal interface. They play a crucial role in creating a maternal tolerance environment and regulating tissue remodeling during blastocyst implantation and placental development. The dMs originate from monocytes that migrate from blood vessels and infiltrate the endometrium, where they subsequently differentiate into decidual macrophages. The high plasticity of these cells enables them to swiftly respond to signals from their surrounding decidua microenvironment.

The objective of this study was to investigate the regulatory effects of endometrial gland secretome on macrophage polarization and activities. A three-dimensional (3D) endometrial epithelial organoid (EEO) model, which simulates human endometrial glands (Turco et al., 2017), was employed in this study. These self-renewing EEOs are hormone-responsive and exhibit the molecular and functional characteristics of their original tissue, therefore make them a suitable model for investigating their communication with decidual immune cells (Dong et al., 2023, Turco et al., 2017). Since the EEO contains a small population of endometrial luminal epithelial cells, its secretome would include basal secretions from the luminal epithelium. These secretions may also contribute to the regulation of macrophage differentiation.