Human endometrial mucin MUC1 is up-regulated by progesterone and down-regulated in vitro by the human blastocyst

Expression of MUC1 in endometrial epithelium has been suggested to create a barrier to embryo attachment that must be lifted at the time of implantati on. In this study, we investigated the hormonal regulation of human endomet rial MUC1 in hormone replacement therapy cycles and in the human blastocyst . We also analyzed the embryonic regulation of MUC1 in human endometrial ep ithelial cells (EECs) during the apposition and adhesion phases of human im plantation using two different in vitro models. Our results indicate that e ndometrial MUC1 mRNA and immunoreactive protein increase in receptive endom etrium compared to nonreceptive endometrium. Human blastocysts express MUC1 , as demonstrated by reverse transcription-polymerase chain reaction and im munocytochemistry, localized at the trophectoderm. In vitro, MUC1 was prese nt at the surface of primary cultures of human EEC, and presence of a human blastocyst (i.e., apposition phase) increases EEC MUC1 protein and mRNA co mpared to control EEC lacking embryos. Interestingly, when human blastocyst s were allowed to attach to the EEC monolayer (i.e., adhesion phase), MUC1 was locally removed in a paracrine fashion on EEC at the implantation site. These results demonstrate a coordinated hormonal and embryonic regulation of EEC MUC1. Progesterone combined with estradiol priming induces an up-reg ulation of MUC1 at the receptive endometrium. During the apposition phase, presence of a human embryo increases EEC MUC1. However, at the adhesion pha se, the embryo induces a paracrine cleavage of EEC MUC1 at the implantation site. These findings strongly suggest that MUC1 may act as an endometrial antiadhesive molecule that must be locally removed by the human blastocyst during the adhesion phase.