Immune Status in the Mouse Oviduct and Uterine Lumen Across Early Embryogenesis to Embryo Implantation

Abstract In manmalian early pregnancy, maternal immune cells are critical during early pregnancy for initiating embryogenesis and maintaining implantation. However, the preimplantation immune environment within the reproductive tract is largely uncharacterized. Here, we detected a massive influx of immune cells into the lumen of the oviduct and uterusafter mating in mice. In immune cells, CD11b+ cells up to about 38.1% in the oviduct and 59.5% in the uterus, of which neutrophils accounted for 81.7% and 97.7%, respectively. Neutrophils presented a antigen-presenting cells like phenotype (nAPCs), a specialized population expressing Ly6G and MHCII. We followed the dynamic changes and fate of neutrophils, and found that these cells rapidly disappeared from the lumen of the reproductive tract from 0.5 days post-coitus (dpc) to 1.5 dpc. Instead of apoptosis, they migrated from the oviduct to the uterus and infiltrated the endometrium at 1.0-1.5 dpc. At 3.5 dpc, the number of immune cells decreased and natural killer cells became the predominant population. The cytokines involved in modulating immune cell responses (GM-CSF, IFN-γ and IL17A), pro-inflammation (IL-1β, IL-6, IL-12p70, TNF-α), and anti-inflammation (IL-10) were detected in luminal fluid, in which GM-CSF and IL-6 decreased, IL-10 increased in 3.5 dpc uterus. However, spontaneous abortion mice (CBA/J×DBA/2) exhibited altered immune patterns at the stage of embryogenesis and implantation. Our findings reveal a dynamic and finely tuned immune state in the lumen of the oviduct and uterus, which provide a microenvironment for early embryo development, and provide insights into pre-implantation embryo-uterine cross-talk in mice.