Mucin (Muc-1) Expression is Differentially Regulated in Uterine Luminal and Glandular Epithelia of the Baboon (Papio Anubis)1

Abstract

Changes in the organization and composition of apical cell surface glycoconjugates accompany the transition of luminal epithelial cells from the prereceptive 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 receptivity. Recent studies in mice demonstrate that the transmembrane mucin glycoprotein, Muc-1, is abundantly expressed at the apical surface of luminal epithelia under most conditions and is invariably reduced in receptive uteri. These and other observations have led to the suggestion that mucins serve an antiadhesive role and function to maintain a nonreceptive uterine state. A pan-species Muc-1 specific antibody recognizing a peptide motif conserved in the cytoplasmic domain of Muc-1 was used to examine the temporal and spatial expression of cell-associated Muc-1 in baboon uteri under a variety of conditions, including the pre- and perimplantation periods. Muc-1 expression was not driven by estrogen influences alone, but required progesterone action. In animals exposed to both steroids, Muc-1 was expressed at low moderate levels in epithelia of the basalis and functionalis regions. The highest expression of Muc-1 was detected in surface epithelium of the preimplantation phase, i.e., up to Day 8 (Day 0 = day of ovulation), or in ovariectomized animals receiving a steroid hormone regime that mimicked this phase (14 days of estrogen priming followed by 7 days of estrogen plus progesterone). Continued exposure to both hormones, i.e., as seen at Days 10-12 or in ovariectomized baboons given 14 days of estrogen plus progesterone treatment after estrogen priming, resulted in marked 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 the prereceptive 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 antiprogestin treatment through to the receptive phase. Furthermore, persistent Muc-1 expression in the functionalis and basalis epithelium correlated with expression of progestin receptors. Thus, Muc-1 expression appeared to be progesterone-dependent rather than estrogen-dependent. It is concluded that Muc-1 expression in surface epithelium serves as a marker of the prereceptive phase in the baboon and that loss of Muc-1 from surface epithelium correlates with generation of a receptive uterine state.

No evidence of association of MUC-1 genetic polymorphism with embryo implantation failure

“…The same observations were made in sheep, pigs and baboons, showing that MUC-1 expression is downregulated during the implantation window (12)(13)(14).…”

Compartmental distinctions in uterine Muc-1 expression during early pregnancy in cynomolgous macaque (Macaca fascicularis) and baboon (Papio anubis)

“…Sections probed with and without antigen retrieval indicated that tissue processed by formalin fixation and paraffin embedding required a retrieval step in order to optimize detection of Muc-1 with the CT-1 antibody. Application of this staining protocol to formalin-fixed, paraffin-embedded sections from cycling baboon uteri produced the same expression pattern for Muc-1 obtained previously when frozen sections were probed with CT-1 antibody and immunoperoxidase detection (Hild-Petito et al, 1996). Controls, which included nonimmune rabbit IgG or buffer in place of primary antibody, displayed a background due to autofluorescence which could not be quenched or blocked.…”

“…Researchers have turned to nonhuman primate models in hopes of explaining the perplexing observation that humans appear to be a rare species in which MUC1, the major transmembrane mucin in uteri of most species, does not seem to be reduced in luminal epithelia of the receptive uterus (Aplin et al, 1998;DeLoia et al, 1998). When the temporal and spacial expression of cell-associated Muc-1 core protein was examined in baboon (Papio anubis) uteri during non-conceptual cycles (Hild-Petito et al, 1996), Muc-1 was upregulated in luminal epithelium of baboon uterus during the early luteal phase in response to progesterone as has been observed in the human uterus (Hey et al, 1994); however, unlike the human, continued exposure to progesterone resulted in loss of both Muc-1 and progesterone receptor from luminal epithelia as the transition to receptivity occurred. In the new world monkey, Cebus apella, Muc-1 was detected on luminal epithelium at day 7 post ovulation (PO) of a non-conceptual cycle .…”

Animal models of implantation

“…In mice, Muc1 expression is stimulated by E2 and repressed by P4 (Surveyor et al 1995). Regulation of Muc1 expression in pigs is similar to mice (Bowen et al 1996) while in baboons and rabbits it is by P4 only (Bowen et al 1996), in baboons and rabbits, by P4 only (Hild-Petito et al 1996, Hoffman et al 1998. However, the expression pattern of Muc1 in the endometrium shows species to species variation.…”