Seminal plasma exosome derived miR-26-5p can regulate decidual macrophage polarization via PTEN / PI3K / AKT signaling pathway

The immunomodulatory effects of seminal plasma (SP) on the maternal immune system play an important role in the implantation and development of the embryo. Decidual macrophages (dMΦs) are one of the major immune cells in the maternal-fetal immune microenvironment, and their M2-type polarization facilitates the establishment and maintenance of pregnancy. However, the role of SP on the polarization of dMΦs is unknown. In this study, we investigated the role and mechanism of SP on the polarization of dMΦs by gene chip sequencing as well as in vitro and in vivo experiments. The results revealed that SP promoted dMΦs M2-type polarization. Gene chip sequencing revealed that miR-26-5p was highly expressed in seminal exosomes (SEs) which could act on PTEN/PI3K/AKT signaling pathway and significantly promote MΦs M2 polarization. Moreover, SEs supplementation significantly reduced embryo resorption in spontaneously aborted mice. In conclusion, our study demonstrated that the SEs derived miR-26-5p in SP promoted the M2 polarization of dMΦs by targeting PTEN/PI3K/AKT signaling pathway, which created an immune-tolerant environment conducive to embryo implantation and development. This study provided new ideas for clinical SP-assisted therapy to improve pregnancy outcomes.