Transmembrane Mucin Expression and Function in Embryo Implantation and Placentation

Abstract

Transmembrane mucins (TMs) are extremely large, complex glycoproteins that line the apical surfaces of simple epithelia including those of the female reproductive tract. TMs provide a physical barrier consistent with their role as part of the innate immune system. This barrier function must be overcome in the context of embryo implantation to permit blastocyst attachment. Three major TMs have been identified in uterine epithelia of multiple species: MUC1, MUC4, and MUC16. MUC1 has been found in all species studied to date, whereas expression of MUC4 and MUC16 have been less well studied and may be species specific. The strategies for removing mucins to permit embryo attachment also vary in a species-specific way and include both hormonal suppression of TM gene expression and membrane clearance via cell surface proteases. Studies emerging from the cancer literature indicate that TMs can modulate a surprisingly wide variety of signal transduction processes. Furthermore, various cell surface proteins have been identified that bind either the oligosaccharide or protein motifs of TMs suggesting that these molecules may support cell attachment in some contexts, including trophoblast interactions with cells of the immune system. The intimate association of TMs at sites of embryo-maternal interaction and the varied functions these complex molecules can play make them key players in embryo implantation and placentation processes.

Human Three-Dimensional Endometrial Epithelial Cell Model To Study Host Interactions with Vaginal Bacteria and Neisseria gonorrhoeae

“…Despite the high levels of expression of cancer-related mucins, our model also produces high levels of the major MAM found in the human endometrium, namely, MUC1 (46). Additionally, the low expression level of secretory mucin MUC5AC in our 3-D EEC model is in accordance with a report showing that MUC5AC is not detectable in the normal endometrial tissues, whereas its levels in pathological tissues are elevated (48).…”

“…The full mucin profile of the human endometrium is still not clearly defined due to the complexity of the tissue and menstrual cycle stages. Previous investigators originally showed that MUC1 is expressed in normal endometrial tissue and plays a role in implantation (45,46). MUC4 expression data differ between laboratories (45,47,48) and have yielded conflicting results.…”

PPARγ Modulation of Cytokine‐Stimulated MUC16 (CA125) Expression in Breast and Ovarian Cancer‐Derived Cells

“…Our preliminary studies indicated a suppressive effect of high concentrations of rosiglitazone on cytokine‐stimulated transmembrane mucin expression in a human female reproductive tract cell line [Constantinou et al, ]. To expand on this observation, we performed rosiglitazone dose response studies on both basal and cytokine‐stimulated MUC16 mRNA levels in MCF‐7 cells.…”

“…Studies from our lab indicate that both progesterone and EGF receptor ligand‐stimulated human MUC1 expression is greatly suppressed by rosiglitazone in a dose‐dependent manner [Wang et al, ; Dharmaraj et al, ] and cytokine‐stimulated MUC1 expression is inhibited by rosiglitazone [Constantinou et al, ]. Additionally, rosiglitazone decreases pro‐inflammatory cytokine production and in vivo studies have shown that it inhibits lung metastasis [Shen et al, ].…”

Comprehensive chromosome screening and gene expression analysis from the same biopsy in human preimplantation embryos

“…Accumulating evidence in both human and mice has shown that the successful development and implantation of embryos may be highly dependent on the stable expression of many genes at the preimplantation stage of development (Constantinou et al ., 2015; Hasegawa et al ., 2015; Cheng et al ., 2016). For example, one recent study identified the expression of C-X-C Motif Chemokine Receptor 4 ( CXCR4 ) in human trophectoderm (TE) cells as a potential biomarker of reproductive competence (Bao et al ., 2016).…”