Frequency and distribution of uterine macrophages on days 4.5 and 7 of pregnancy in NMRI mice

 Introduction: Macrophages play a crucial role in appropriate embryo implantation and maintenance of pregnancy. This study was done to evaluate the frequency and distribution of uterine (local changes) and spleen (systemic changes) macrophages on days 4.5 and 7 of NMRI mouse pregnancy which are simultaneous with beginning of implantation and complete establishment of embryo in the uterus.  Materials and methods: The precise day of pregnancy was determined through vaginal plug detection. Blood was collected from pregnant mice on days 4.5 and 7 of gestation and serum 17- β estradiol and progesterone concentrations were measured using the ELISA method. The frequency and localization of macrophages in different regions of uterus and spleen were also investigated by immunohistochemistry staining using anti F4/80 antibody.  Results: The results of this study showed that frequency of uterine macrophages has decreased on day 7 in comparison to day 4.5 of gestation. Macrophages are distributed throughout the whole uterus on day 4.5 while their distribution was restricted to myometrium and stroma beneath the circular muscles on day 7 of pregnancy. The frequency of spleen macrophages as a representative of their systemic changes was not different in studied groups. Serum 17-β estradiol and progesterone concentrations increased significantly on day 7 compared to day 4.5 of pregnancy.  Conclusion: Considering the changes in 17-β estradiol and progesterone concentrations and their indirect effects on macrophages recruitment through regulation of M-CSF and GM-CSF secretion by uterine stromal cells, the differences in frequency and distribution of macrophages in different stages of pregnancy could be explained. While the macrophages chemotactic factors and homing receptors and their sources in spleen are different from uterus and don’t response to ovarian hormones variations. Regarding the role of macrophages in embryo implantation and regulation of feto-maternal immune responses, it seems that the changes in their frequency and localization can be helpful for a successful pregnancy