Following mating, leukocytes are recruited to the uterine epithelium where they phagocytose spermatozoa and mediate maternal immune tolerance as well as a mild inflammatory response. However, the precise mechanisms of antigen presentation to establish tolerance in the uterus are not yet known. In this study we utilised array tomography, a high-resolution volume scanning electron microscopy technique to 3D reconstruct the cellular relationships formed by leukocytes in the uterus after mating.
We discovered for the first time that 12 h post fertilisation in the rat, recruited neutrophils are internalised within uterine epithelial cells (UECs). We generated a 3D model from 200 serial SEM images which confirmed that neutrophils are internalised within a large vacuole contained wholly within the cytoplasm of UECs. This is the first description of cell-in-cell structures forming in the endometrium after mating. Material from the uterine lumen appears to be transported into these structures via UEC transcytosis, where it is phagocytosed by the neutrophils. This is suggested to represent a key mechanism of antigen presentation to the maternal immune system at the beginning of pregnancy.
While cell-in-cell structures have previously been observed to occur in vivo and in vitro in normal and pathological conditions, this observation represents the first evidence of the formation of cell-in-cell structures within the uterine epithelium during normal pregnancy. This is also the first confirmed description of heterotypic cell-in-cell interaction between neutrophils and epithelial cells. This novel observation of neutrophils internalised within uterine epithelial cells may represent the site of antigen presentation that occurs as part of the mediated maternal immune response to semen, which is essential for the development of maternal tolerance to paternal antigens and successful pregnancy.