Register      Login
Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

Mucin 15 is lost but mucin 13 remains in uterine luminal epithelial cells and the blastocyst at the time of implantation in the rat

Connie E. Poon A C , Laura Lecce A , Margot L. Day B and Christopher R. Murphy A
+ Author Affiliations
- Author Affiliations

A School of Medical Sciences (Discipline of Anatomy and Histology) and The Bosch Institute, Anderson Stuart Building, The University of Sydney, Sydney, NSW 2006, Australia.

B School of Medical Sciences (Discipline of Physiology) and The Bosch Institute, The Medical Foundation Building, The University of Sydney, Sydney, NSW 2050, Australia.

C Corresponding author. Email: conniep@anatomy.usyd.edu.au

Reproduction, Fertility and Development 26(3) 421-431 https://doi.org/10.1071/RD12313
Submitted: 2 October 2012  Accepted: 18 February 2013   Published: 22 March 2013

Abstract

The glycocalyx of the uterine luminal epithelium in the rat undergoes considerable reduction before implantation. In particular, the reduction of some mucins is necessary to facilitate blastocyst adhesion and subsequent implantation. The present study investigated the localisation, abundance and hormonal control of two mucin proteins, Muc13 and Muc15, in rat uterine epithelial cells during early pregnancy to determine whether they are likely to play a role in uterine receptivity for implantation. Muc13 and Muc15 are localised to the uterine luminal epithelium but show a presence and an absence, respectively, at the apical cell surface at the time of implantation. This localisation corresponds to changes in the molecular weights of Muc13 and Muc15, as shown with western blotting analysis. Furthermore, the localisation of Muc13 and Muc15 was shown to be controlled by the ovarian hormones, oestrogen and progesterone, and they were also localised in preimplantation rat blastocysts. Our results suggest that Muc15 may operate in an anti-adhesive capacity to prevent implantation while Muc13 potentially functions in either an adhesive or cell-signalling role in the events of implantation.

Additional keywords: hormones, ovariectomy, uterus.


References

Aplin, J. D., and Kimber, S. J. (2004). Trophoblast–uterine interactions at implantation. Reprod. Biol. Endocrinol. 2, 48.
Trophoblast–uterine interactions at implantation.Crossref | GoogleScholarGoogle Scholar | 15236654PubMed |

Aplin, J. D., Meseguer, M., Simon, C., Ortiz, M. E., Croxatto, H., and Jones, C. J. (2001). MUC1, glycans and the cell-surface barrier to embryo implantation. Biochem. Soc. Trans. 29, 153–156.
MUC1, glycans and the cell-surface barrier to embryo implantation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXkslentLY%3D&md5=ce1f23b0c112efedbe0c874aa7d3ae47CAS | 11356144PubMed |

Ardman, B., Sikorski, M. A., and Staunton, D. E. (1992). CD43 interferes with T-lymphocyte adhesion. Proc. Natl. Acad. Sci. USA 89, 5001–5005.
CD43 interferes with T-lymphocyte adhesion.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK38XksVKmsLk%3D&md5=a701e3b35ce910d65ca84a2fb31631aaCAS | 1594606PubMed |

Braga, V. M., and Gendler, S. J. (1993). Modulation of Muc-1 mucin expression in the mouse uterus during the oestrous cycle, early pregnancy and placentation. J. Cell Sci. 105, 397–405.
| 1:CAS:528:DyaK2cXhtlSksbg%3D&md5=639bf6ff6aa71935db4b7351c5dd423bCAS | 7691839PubMed |

Carson, D. D., Bagchi, I., Dey, S. K., Enders, A. C., Fazleabas, A. T., Lessey, B. A., and Yoshinaga, K. (2000). Embryo implantation. Dev. Biol. 223, 217–237.
Embryo implantation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXksFeqs7o%3D&md5=66325f84dc25ef49a070518d604ce87dCAS | 10882512PubMed |

Chauhan, S. C., Kumar, D., and Jaggi, M. (2009a). Mucins in ovarian cancer diagnosis and therapy. J. Ovarian Res. 2, 21.
Mucins in ovarian cancer diagnosis and therapy.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhtlWhu7zP&md5=075636698db3b7ff74aa2cc325ab3df0CAS | 20034397PubMed |

Chauhan, S. C., Vannatta, K., Ebeling, M. C., Vinayek, N., Watanabe, A., Pandey, K. K., Bell, M. C., Koch, M. D., Aburatani, H., Lio, Y., and Jaggi, M. (2009b). Expression and functions of transmembrane mucin MUC13 in ovarian cancer. Cancer Res. 69, 765–774.
Expression and functions of transmembrane mucin MUC13 in ovarian cancer.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhtFOksb8%3D&md5=2bb2439e0af9353b4f45d546292f6b07CAS | 19176398PubMed |

Denker, H. W. (1994). Endometrial receptivity: cell biological aspects of an unusual epithelium. A review. Ann. Anat. 176, 53–60.
Endometrial receptivity: cell biological aspects of an unusual epithelium. A review.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2c7js1Okug%3D%3D&md5=f485d38d30f4b7855c9210045004c016CAS | 8304592PubMed |

Denker, H. W. (2000). Structural dynamics and function of early embryonic coats. Cells Tissues Organs 166, 180–207.
Structural dynamics and function of early embryonic coats.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3c7ps1Wrtw%3D%3D&md5=150a98c817649b765d078f633c58c10dCAS | 10729727PubMed |

DeSouza, M. M., Lagow, E., and Carson, D. D. (1998a). Mucin functions and expression in mammalian reproductive tract tissues. Biochem. Biophys. Res. Commun. 247, 1–6.
Mucin functions and expression in mammalian reproductive tract tissues.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXjsl2qsL0%3D&md5=5e5f4509f45f316bd5f210035abf5442CAS | 9636643PubMed |

DeSouza, M. M., Mani, S. K., Julian, J., and Carson, D. D. (1998b). Reduction of mucin-1 expression during the receptive phase in the rat uterus. Biol. Reprod. 58, 1503–1507.
Reduction of mucin-1 expression during the receptive phase in the rat uterus.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXjsFShtbk%3D&md5=1142a66123bf38f76f1dd243782c8ceaCAS | 9623612PubMed |

Dickmann, Z. (1967). Shedding of the zona pellucida by the rat blastocyst. J. Exp. Zool. 165, 127–137.
Shedding of the zona pellucida by the rat blastocyst.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaF1c%2FgtFCrsg%3D%3D&md5=a9a40dd9f0e2b54fbc2682053dc8f398CAS | 6048476PubMed |

Finn, C. A., and Porter, D. (1975) ‘The uterus’. (Elek: London.)

Gipson, I. K., Blalock, T., Tisdale, A., Spurr-Michaud, S., Allcorn, S., Stavreus-Evers, A., and Gemzell, K. (2008). MUC16 is lost from the uterodome (pinopode) surface of the receptive human endometrium: in vitro evidence that MUC16 is a barrier to trophoblast adherence. Biol. Reprod. 78, 134–142.
MUC16 is lost from the uterodome (pinopode) surface of the receptive human endometrium: in vitro evidence that MUC16 is a barrier to trophoblast adherence.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXlvVQ%3D&md5=17f9769d2b7decc0fdd2a09265a94917CAS | 17942799PubMed |

Hilkens, J., Ligtenberg, M. J., Vos, H. L., and Litvinov, S. V. (1992). Cell membrane-associated mucins and their adhesion-modulating property. Trends Biochem. Sci. 17, 359–363.
Cell membrane-associated mucins and their adhesion-modulating property.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK38Xls1Kjs7s%3D&md5=a5e8dcf77827e336d8fe375ca221b65bCAS | 1412714PubMed |

Huang, J., Che, M. I., Huang, Y. T., Shyu, M. K., Huang, Y. M., Wu, Y. M., Lin, W. C., Huang, P. H., Liang, J. T., Lee, P. H., and Huang, M. C. (2009). Overexpression of MUC15 activates extracellular signal-regulated kinase 1/2 and promotes the oncogenic potential of human colon cancer cells. Carcinogenesis 30, 1452–1458.
Overexpression of MUC15 activates extracellular signal-regulated kinase 1/2 and promotes the oncogenic potential of human colon cancer cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXpsVaktLw%3D&md5=41832127ceb4c2399d0c523dbab6ac4cCAS | 19520792PubMed |

Idris, N., and Carraway, K. L. (2000). Regulation of sialomucin complex/Muc4 expression in rat uterine luminal epithelial cells by transforming growth factor-beta: implications for blastocyst implantation. J. Cell. Physiol. 185, 310–316.
Regulation of sialomucin complex/Muc4 expression in rat uterine luminal epithelial cells by transforming growth factor-beta: implications for blastocyst implantation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXntVygsbs%3D&md5=a8b649b70029e593e5fd900c7048dca9CAS | 11025453PubMed |

Isaacs, J., and Murphy, C. R. (2003). Ultrastructural localisation of Muc-1 on the plasma membrane of uterine epithelial cells. Acta Histochem. 105, 239–243.
Ultrastructural localisation of Muc-1 on the plasma membrane of uterine epithelial cells.Crossref | GoogleScholarGoogle Scholar | 13677617PubMed |

Jones, B. J., and Murphy, C. R. (1994). A high-resolution study of the glycocalyx of rat uterine epithelial cells during early pregnancy with the field-emission gun-scanning electron microscope. J. Anat. 185, 443–446.
| 7961152PubMed |

Kaneko, Y., Lindsay, L. A., and Murphy, C. R. (2008). Focal adhesions disassemble during early pregnancy in rat uterine epithelial cells. Reprod. Fertil. Dev. 20, 892–899.
Focal adhesions disassemble during early pregnancy in rat uterine epithelial cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXht1Oks77E&md5=360f8f3006d062e4dcf237674985b4a6CAS | 19007553PubMed |

Kaneko, Y., Day, M. L., and Murphy, C. R. (2011). Integrin beta3 in rat blastocysts and epithelial cells is essential for implantation in vitro: studies with Ishikawa cells and small interfering RNA transfection. Hum. Reprod. 26, 1665–1674.
Integrin beta3 in rat blastocysts and epithelial cells is essential for implantation in vitro: studies with Ishikawa cells and small interfering RNA transfection.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXnvFantLo%3D&md5=2369e134628d436d042395d1cd910c09CAS | 21531996PubMed |

Kennedy, T. G., Gillio-Meina, C., and Phang, S. H. (2007). Prostaglandins and the initiation of blastocyst implantation and decidualization. Reproduction 134, 635–643.
Prostaglandins and the initiation of blastocyst implantation and decidualization.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXovVCisg%3D%3D&md5=9b20746f5a76e7d1ccbcbf47aa52ad15CAS | 17965253PubMed |

Kerschner, J. E. (2007). Mucin gene expression in human middle-ear epithelium. Laryngoscope 117, 1666–1676.
Mucin gene expression in human middle-ear epithelium.Crossref | GoogleScholarGoogle Scholar | 17667140PubMed |

Kimber, S. J., and Spanswick, C. (2000). Blastocyst implantation: the adhesion cascade. Semin. Cell Dev. Biol. 11, 77–92.
Blastocyst implantation: the adhesion cascade.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXkslChu7o%3D&md5=0bd10c7ee5fdb4c077e43eaf9f588a5eCAS | 10873705PubMed |

Lecce, L., Kaneko, Y., and Murphy, C. R. (2010). CD43 is relocated from the basal to the apical plasma membrane of rat uterine epithelial cells by progesterone. Histochem. Cell Biol. 133, 549–555.
CD43 is relocated from the basal to the apical plasma membrane of rat uterine epithelial cells by progesterone.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXksFahsLk%3D&md5=a98cab855ad2548eeb640c78493fbcc9CAS | 20333395PubMed |

Lopata, A. (1996). Blastocyst–endometrial interaction: an appraisal of some old and new ideas. Mol. Hum. Reprod. 2, 519–525.
Blastocyst–endometrial interaction: an appraisal of some old and new ideas.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2szotlKrsw%3D%3D&md5=97803a59752760b22a0c54ba09c3c49dCAS | 9239662PubMed |

Manjunath, N., Johnson, R. S., Staunton, D. E., Pasqualini, R., and Ardman, B. (1993). Targeted disruption of CD43 gene enhances T lymphocyte adhesion. J. Immunol. 151, 1528–1534.
| 1:CAS:528:DyaK3sXmsVOmsrg%3D&md5=06bc4011d46c5e2ab67e8e85c7c4df8aCAS | 8335945PubMed |

Manjunath, N., Correa, M., Ardman, M., and Ardman, B. (1995). Negative regulation of T-cell adhesion and activation by CD43. Nature 377, 535–539.
Negative regulation of T-cell adhesion and activation by CD43.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2MXoslWltr8%3D&md5=d4603a9c3fd634828b1eec9387d42697CAS | 7566153PubMed |

Murphy, C. R. (2004). Uterine receptivity and the plasma membrane transformation. Cell Res. 14, 259–267.
Uterine receptivity and the plasma membrane transformation.Crossref | GoogleScholarGoogle Scholar | 15353123PubMed |

Murphy, C. R., and Rogers, A. W. (1981). Effects of ovarian hormones on cell membranes in the rat uterus. III. The surface carbohydrates at the apex of the luminal epithelium. Cell Biophys. 3, 305–320.
| 1:CAS:528:DyaL38XhvFeltb4%3D&md5=d21a58bda9075dd1899dd6dba4a5d01fCAS | 6175417PubMed |

Murphy, C. R., and Shaw, T. J. (1994). Plasma membrane transformation: a common response of uterine epithelial cells during the peri-implantation period. Cell Biol. Int. 18, 1115–1128.
Plasma membrane transformation: a common response of uterine epithelial cells during the peri-implantation period.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2M3hvVOnsA%3D%3D&md5=bd0f7a44096bef250cbfdf97f34ffc44CAS | 7703952PubMed |

Nicholson, M. D. O., Lindsay, L. A., and Murphy, C. R. (2010). Ovarian hormones control the changing expression of claudins and occludin in rat uterine epithelial cells during early pregnancy. Acta Histochem. 112, 42–52.
Ovarian hormones control the changing expression of claudins and occludin in rat uterine epithelial cells during early pregnancy.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXksVyksb8%3D&md5=dbc9232fbb5e765495563c14e958bc7cCAS |

Pallesen, L. T., Berglund, L., Rasmussen, L. K., Petersen, T. E., and Rasmussen, J. T. (2002). Isolation and characterization of MUC15, a novel cell membrane-associated mucin. Eur. J. Biochem. 269, 2755–2763.
Isolation and characterization of MUC15, a novel cell membrane-associated mucin.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XkslWku7k%3D&md5=11a9497bf65ddda54f690af3821c7783CAS | 12047385PubMed |

Pallesen, L. T., Pedersen, L. R., Petersen, T. E., and Rasmussen, J. T. (2007). Characterization of carbohydrate structures of bovine MUC15 and distribution of the mucin in bovine milk. J. Dairy Sci. 90, 3143–3152.
Characterization of carbohydrate structures of bovine MUC15 and distribution of the mucin in bovine milk.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXntlClu7o%3D&md5=16a39a42c10746dcbf7790701324e1fcCAS | 17582096PubMed |

Pallesen, L. T., Pedersen, L. R., Petersen, T. E., Knudsen, C. R., and Rasmussen, J. T. (2008). Characterization of human mucin (MUC15) and identification of ovine and caprine orthologs. J. Dairy Sci. 91, 4477–4483.
Characterization of human mucin (MUC15) and identification of ovine and caprine orthologs.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhsVKgtr3I&md5=ebfd0ab18136b7aedea356f86dafc72eCAS | 19038922PubMed |

Psychoyos, A. (1976). Hormonal control of uterine receptivity for nidation. J. Reprod. Fertil. Suppl. 25, 17–28.
| 1:CAS:528:DyaE2sXisl2ntg%3D%3D&md5=6759f8fdddaf60f649e2ffd2893f21b9CAS |

Psychoyos, A. (1986). Uterine receptivity for nidation. Ann. N. Y. Acad. Sci. 476, 36–42.
Uterine receptivity for nidation.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL2s%2FpvVeqtA%3D%3D&md5=d284ea18b4913adf9022891095b00ef1CAS | 3541745PubMed |

Shimamura, T., Ito, H., Shibahara, J., Watanabe, A., Hippo, Y., Taniguchi, H., Chen, Y., Kashima, T., Ohtomo, T., Tanioka, F., Iwanari, H., Kodama, T., Kazui, T., Sugimura, H., Fukayama, M., and Aburatani, H. (2005). Overexpression of MUC13 is associated with intestinal-type gastric cancer. Cancer Sci. 96, 265–273.
Overexpression of MUC13 is associated with intestinal-type gastric cancer.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXlvFSrsL0%3D&md5=2598e7aac5f3d0d047680dbb3c0238f4CAS | 15904467PubMed |

Shyu, M. K., Lin, M. C., Shih, J. C., Lee, C. N., Huang, J., Liao, C. H., Huang, I. F., Chen, H. Y., Huang, M. C., and Hsieh, F. J. (2007). Mucin 15 is expressed in human placenta and suppresses invasion of trophoblast-like cells in vitro. Hum. Reprod. 22, 2723–2732.
Mucin 15 is expressed in human placenta and suppresses invasion of trophoblast-like cells in vitro.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhtlekt77P&md5=1e7ea31c16588936554745cd0902fcf6CAS | 17720698PubMed |

Surveyor, G. A., Gendler, S. J., Pemberton, L., Das, S. K., Chakraborty, I., Julian, J., Pimental, R. A., Wegner, C. C., Dey, S. K., and Carson, D. D. (1995). Expression and steroid hormonal control of Muc-1 in the mouse uterus. Endocrinology 136, 3639–3647.
Expression and steroid hormonal control of Muc-1 in the mouse uterus.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2MXntFKntbg%3D&md5=f9277c319ceae20c938d087ff00a5fbdCAS | 7628404PubMed |

Svalander, P. C., Odin, P., Nilsson, B. O., and Obrink, B. (1987). Trophectoderm surface expression of the cell adhesion molecule cell-CAM 105 on rat blastocysts. Development 100, 653–660.
| 1:STN:280:DyaL1c7ms1CrtA%3D%3D&md5=cebf3ab7c4909308459e409b34053ee8CAS | 3327672PubMed |

Thie, M., Fuchs, P., and Denker, H. W. (1996). Epithelial cell polarity and embryo implantation in mammals. Int. J. Dev. Biol. 40, 389–393.
| 1:STN:280:DyaK28zjslGjsw%3D%3D&md5=17c13c15a46faddbc691581e07df47ebCAS | 8735953PubMed |

Varki, A. (1999) ‘Essentials of glycobiology.’ (Cold Spring Harbor Laboratory Press: Cold Spring Harbor, NY.)

Walsh, M. D., Young, J. P., Leggett, B. A., Williams, S. H., Jass, J. R., and McGuckin, M. A. (2007). The MUC13 cell surface mucin is highly expressed by human colorectal carcinomas. Hum. Pathol. 38, 883–892.
The MUC13 cell surface mucin is highly expressed by human colorectal carcinomas.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXlsFKgsr0%3D&md5=17f5ccd23a458b427c86de503b039427CAS | 17360025PubMed |

Wesseling, J., van der Valk, S. W., and Hilkens, J. (1996). A mechanism for inhibition of E-cadherin-mediated cell–cell adhesion by the membrane-associated mucin episialin/MUC1. Mol. Biol. Cell 7, 565–577.
| 1:CAS:528:DyaK28Xit12qs70%3D&md5=8b7f55fa9a7f83dfe4dc5dfc6eb452aeCAS | 8730100PubMed |

Williams, S. J., Wreschner, D. H., Tran, M., Eyre, H. J., Sutherland, G. R., and McGuckin, M. A. (2001). Muc13, a novel human cell surface mucin expressed by epithelial and hemopoietic cells. J. Biol. Chem. 276, 18 327–18 336.
Muc13, a novel human cell surface mucin expressed by epithelial and hemopoietic cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXktFWmtrc%3D&md5=7500f0acd6a4dc49e9f3df3bccf2ca16CAS |