Mapping the dynamics of human uterine natural killer cells for development of personalized care in female reproductive medicine

Uterine natural killer (uNK) cells are present in the non-pregnant (endometrium) and pregnant (decidua) human uterus. Studies indicate uNK cell properties influence risk for fertility and pregnancy complications including pre-eclampsia. The long-term goal of my work is to develop uNK cell-based personalized medicine methods targeting such conditions.

As a first step towards this the purpose of this proposal is to determine how uNK cells are regenerated each menstrual cycle, and how they are linked to uNK cells in pregnancy.

For this I have developed a non-invasive method using menstrual cups to collect menstrual blood, from which the uNK cells are isolated and frozen for later analysis.

With this and other methods we have collected unique samples from monozygotic twins; women sampled during and after pregnancy (decidua from elective termination, followed by menstrual blood sampling); before and after pregnancy; and from uterus or bone marrow transplanted women.

During years 1-3 we will apply state-of-the-art single-cell methods, and functional analysis, to uterine- and matched blood-NK cells. This will result in an analysis-pipeline and a deep level of knowledge about human uNK cells.

During year 4 we will publish our findings and hope start translating the results in the form of prognostic clinical trial(s).

This ambition represents an important step towards personalized female reproductive medicine, which has great potential to benefit many patient groups.