Reproduction Abstracts

Background: Uterine natural killer (uNK) cells are a phenotypically distinct population of tissue-resident immune cells that are reported to regulate vascular remodelling within the endometrium. The mechanisms that control accumulation of uNK cells in the endometrium remain unresolved although there is evidence to suggest that homing and differentiation of peripheral blood NK (pbNK) cells may contribute to the rapid increase in cell numbers during the secretory phase of the menstrual cycle. NK cell phenotype is characterised by expression of the surface proteins CD56 and CD16; the majority of pbNK cells are CD56⁺CD16⁺ whereas uNK cells are CD56⁺CD16⁻.

We have previously reported that during the secretory phase, decidualisation is associated with increased biosynthesis of estradiol (E₂) resulting in an estrogen-dominated microenvironment. Given that uNK cells express estrogen receptor (ER)β we hypothesised that E₂ might promote differentiation of pbNK cells recruited to the uterus during preparation for pregnancy.

Methods: PbNK cells were isolated from healthy pre-menopausal female donors by Percoll gradient separation and magnetic sorting for CD56⁺ cells. Purified pbNK cells were treated with E₂ and the impact on expression of NK cell markers was assessed using flow cytometery.

Results and discussion: Analysis of pbNK cells revealed that E₂ altered expression of surface proteins consistent with differentiation towards a uNK cell phenotype. Specifically, the number of CD16 positive NK cells was decreased and the proportion of CD56⁺CD16⁻ cells was increased by treatment with E₂. These data offer novel insight into the regulation of uNK cell differentiation during establishment of pregnancy.