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 implantation. In this study, we investigated the hormonal regulation of human endometrial MUC1 in hormone replacement therapy cycles and in the human blastocyst. We also analyzed the embryonic regulation of MUC1 in human endometrial epithelial cells (EECs) during the apposition and adhesion phases of human implantation using two different in vitro models. Our results indicate that endometrial MUC1 mRNA and immunoreactive protein increase in receptive endometrium compared to nonreceptive endometrium. Human blastocysts express MUC1, as demonstrated by reverse transcription-polymerase chain reaction and immunocytochemistry, localized at the trophectoderm. In vitro, MUC1 was present 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 compared to control EEC lacking embryos. Interestingly, when human blastocysts 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-regulation of MUC1 at the receptive endometrium. During the apposition phase, presence of a human embryo increases EEC MUC1. However, at the adhesion phase, 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.
Meseguer
M
M
Fundación Instituto Valenciano de Infertilidad para el Estudio de la Reproducción Humana (FIVIER), C/Guardia Civil 23, 46020 Valencia, Spain.
Aplin
J D
JD
Caballero-Campo
P
P
O'Connor
J E
JE
Martín
J C
JC
Remohí
J
J
Pellicer
A
A
Simón
C
C
D000328:Adult; D001755:Blastocyst / Q000187:drug effects / Q000378:metabolism*; D015152:Blotting, Northern; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D015536:Down-Regulation / Q000502:physiology*; D004717:Endometrium / Q000378:metabolism*; D004846:Epithelial Attachment; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D020249:Hormone Replacement Therapy; D006801:Humans; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D018396:Mucin-1 / Q000096:biosynthesis*; D009077:Mucins / Q000378:metabolism*; D010446:Peptide Fragments / Q000096:biosynthesis*; D011374:Progesterone / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects*
C116055:MUC1 tandem repeat peptide; D018396:Mucin-1; D009077:Mucins; D010446:Peptide Fragments; D011374:Progesterone