MUCIN (MUC-1) EXPRESSION IS DIFFERENTIALLY REGULATED IN UTERINE LUMINAL AND GLANDULAR EPITHELIA OF THE BABOON (PAPIO-ANUBIS)

Changes in the organization and composition of apical cell surface gly coconjugates accompany the transition of luminal epithelial cells from the prereceptive to the receptive state of the uterus in many species . In spite of the biological and clinical significance of this process , few molecular markers have arisen as useful predictors of uterine re ceptivity. Recent studies in mice demonstrate that the transmembrane m ucin glycoprotein, Muc-1, is abundantly expressed at the apical surfac e of luminal epithelia under most conditions and is invariably reduced in receptive uteri. These and other observations have led to the sugg estion that mucins serve an antiadhesive role and function to maintain a nonreceptive uterine state. A pan-species Muc 1-specific antibody r ecognizing a peptide motif conserved in the cytoplasmic domain of Muc- 1 was used to examine the temporal and spatial expression of cell-asso ciated Muc-1 in baboon uteri under a variety of conditions, including the pre- and periimplantation periods. Muc-1 expression was not driven by estrogen influences alone, but required progesterone action. In an imals exposed to both steroids, Muc-1 was expressed at low to moderate levels in epithelia of the basalis and functionalis regions. The high est expression of Muc-1 was detected in surface epithelium of the prei mplantation phase, i.e., up to Day 8 (Day 0 = day of ovulation), or in ovariectomized animals receiving a steroid hormone regime that mimick ed this phase (14 days of estrogen priming followed by 7 days of estro gen plus progesterone). Continued exposure to both hormones, i.e., as seen at Days 10-12 or in ovariectomized baboons given 14 days of estro gen plus progesterone treatment after estrogen priming, resulted in ma rked reduction of Muc-1 expression in the surface epithelium; however, staining patterns in the glandular epithelium were unchanged by this treatment. The expression of Muc-1 on the surface epithelium during pr ereceptive phase was associated with the presence of both estrogen and progestin receptors in these epithelia. Muc-1 expression was reduced by neither antiestrogen treatment during the prereceptive stage nor an tiprogestin 1 treatment through to the receptive phase. Furthermore, p ersistent Muc-1 expression in the functionalis and basalis epithelium correlated with expression of progestin receptors. Thus, Muc-1 express ion appea red to be progesterone-dependent rather than estrogen-depend ent. It is concluded that Muc-1 expression in surface epithelium serve s as a marker of the prereceptive phase in the baboon and that loss of Muc-1 from surface epithelium correlates with generation of a recepti ve uterine state.