Tissue-specific non-heritable influence drive uterine immune system variation (RNA-seq)

Human twin studies have revealed the combined contribution of heritable and non-heritable (environmental) factors in shaping peripheral blood immune system variability. However, the heterogeneity within tissue immune compartments and the contribution of tissue-specific external factors remain unexplored. The human uterus is a tissue under constant regeneration exposed to distinct environmental factors. To assess uterine immune system variation, we have performed a transcriptomic and epigenetic analysis of uterine and peripheral blood immune cells in monozygotic twins and longitudinal samples in relation to heritable versus non-heritable factors. Overall design: The objective of this study was to investigate immune cell variation in the human uterus and relate the findings to matched peripheral blood immune cells. In collaboration with the Swedish Twin Registry, peripheral and menstrual blood was collected from monozygotic twin pairs (N=3). In addition, we collected a longitudinal cohort of healthy women (N=3). For the longitudinal cohort, we collected samples from two time points, with the long follow-up being four to six years after the initial sampling. All women included in the longitudinal cohort were of fertile age, healthy, not taking any medications, not using contraceptives, and were nulligravida at the first sampling. All human blood and tissue samples were collected after written and oral informed consent was obtained, and the study was approved by the Regional Ethics Review Board, Stockholm, Sweden.