Human peripheral blood mononuclear cells enhance cell–cell interaction between human endometrial epithelial cells and BeWo‐cell spheroids

BACKGROUND: Previously, it was reported that T-lymphocytes derived from non-pregnant mice promote murine embryo implantation. In order to examine the immunological regulation of endometrial receptivity in humans, the effects of peripheral blood mononuclear cells (PBMCs) on endometrial epithelial cell (EEC) function were monitored by a newly developed attachment assay using primary human EEC culture and BeWo cell-derived spheroids. METHODS AND RESULTS: EECs isolated from 25 women in the mid- and late proliferative and early, mid- and late secretory phases were subjected to monolayer culturing. Spheroids were constructed from BeWo cells, a human choriocarcinoma cell line, by incubation with continuous rolling, after which their interaction with cultured EECs was studied. The mean (6 SEM) number of attached spheroids was significantly higher (P < 0.01) in the EEC culture derived from women in the mid-secretory phase (90 6 2.9%) than the other groups (ranging from 0 to 5.8 6 3.7%), which is in agreement with the existence of a so-called ‘implantation window’. After 72 h co-culture of EECs with PBMCs, the number of attached spheroids significantly increased in the EEC cultures derived from the late proliferative and early secretory phases [65.0 6 6 21.7 versus 5.0 6 2.0% (P < 0.05) and 83.1 6 4.1 versus 4.4 6 1.9% (P < 0.01)]. CONCLUSIONS: This attachment assay appears to be a useful method with which to assess endometrial receptivity. Functional change of EECs induced by PBMCs suggests possible regulation of endometrial receptivity by immune cells.