Free Standard AU & NZ Shipping For All Book Orders Over $80!
Register      Login
Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
Shopping Cart: ( empty )
You are here: Home > Journals > RD > RD09163
RESEARCH ARTICLE
Contents Vol 22(4)

Spatiotemporal expression of α1, α3 and β1 integrin subunits is altered in rat myometrium during pregnancy and labour

S. J. Williams A C , O. Shynlova B C , S. J. Lye B and D. J. MacPhee A D
+ Author Affiliations
- Author Affiliations

A Division of BioMedical Sciences, Faculty of Medicine, Health Sciences Centre, Memorial University of Newfoundland, St John’s, NL A1B 3V6, Canada.

B Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada.

C These authors contributed equally to this work.

D Corresponding author. Email: dmacphee@mun.ca

Reproduction, Fertility and Development 22(4) 718-732 https://doi.org/10.1071/RD09163
Submitted: 13 July 2009  Accepted: 20 October 2009   Published: 25 March 2010

Abstract

Integrins are transmembrane extracellular matrix (ECM) receptors composed of α- and β-subunits. Integrins can cluster to form focal adhesions and, because there is significant ECM remodelling and focal adhesion turnover in the rat myometrium during late pregnancy, we hypothesised that the expression of α1, α3 and β1 integrin subunits in the rat myometrium would be altered at this time to accommodate these processes. Expression of α1 and β1 integrin subunit mRNA was significantly increased on Days 6–23 of pregnancy compared with non-pregnant (NP) and postpartum (PP) time points (P < 0.05). In contrast, α3 integrin subunit mRNA expression was significantly increased on Days 14, 21 and 22 compared with NP, Day 10, 1 day PP and 4 days PP (P < 0.05). A relative gene expression study revealed that, of the integrins studied, the expression of β1 integrin mRNA was highest in pregnant rat myometrium. The α1, α3 and β1 integrin subunit proteins became immunolocalised to myocyte membranes in situ by late pregnancy and labour in both myometrial muscle layers. Increased α1, α3 and β1 integrin gene expression during gestation and the specific detection of these subunits in myocyte membranes during late pregnancy and labour may contribute to the cell–ECM interactions required for the development of a mechanical syncytium.

Additional keywords: female reproductive tract, gene expression, parturition, uterus.


Acknowledgements

The authors acknowledge the assistance of Anna Dorogin and Bryan G. White (tissue collection) and Judy Foote and Art Taylor (tissue processing and sectioning of rat myometrial tissue for immunofluorescence analyses). This work was funded by the Natural Sciences and Engineering Research Council of Canada (grant no. 250218–02 to D.J.M) and the Canadian Institutes of Health Research (to S.J.L.).


References

Applied Biosystems (2001). User bulletin #2: ABI prism 7700 sequence detection system. Available at http://www3.appliedbiosystems.com/cms/groups/mcb_support/documents/generaldocuments/cms_040980.pdf

Asakura, S. , Niwa, K. , Tomozawa, T. , Jin, Y. , and Madoiwa, S. , et al. (1997). Fibroblasts spread on immobilized fibrin monomer by mobilizing a beta1-class integrin, together with a vitronectin receptor alphavbeta3 on their surface. J. Biol. Chem. 272, 8824–8829.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS | Challis J. R. G., and Lye S. J. (2004). Characteristics of parturition. In ‘Maternal–Fetal Medicine: Principles and Practice’, 5th edn. (Eds R. K. Creasy and R. Resnik.) pp. 79–87. (Saunders: Philadelphia.)

Chan, W.-L. , Holstein-Rathlou, N.-H. , and Yip, K.-P. (2001). Integrin mobilizes intracellular Ca2+ in renal vascular smooth muscle cells. Am. J. Physiol. Cell Physiol. 280, C593–C603.
| PubMed |  CAS | Gibb W., Lye S. J., and Challis J. R. G. (2006). Parturition. In ‘Knobil and Neil’s Physiology of Reproduction’. (Eds P. Wassarman and J. Neil.) pp. 2925–2974. (Academic Press: New York.)

Goldspink, D. F. , and Douglas, A. J. (1988). Protein turnover in gravid and nongravid horns of uterus in pregnant rats. Am. J. Physiol. Endocrinol. Metab. 254, E549–E554.
| PubMed |  CAS |

Hynes, R. O. (2002). Integrins: bidirectional, allosteric signaling machines. Cell 110, 673–687.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |

Ivaska, J. , Whelan, R. D. , Watson, R. , and Parker, P. J. (2002). PKCϵ controls the traffic of β1 integrins in motile cells. EMBO J. 21, 3608–3619.
| Crossref | GoogleScholarGoogle Scholar | CAS | PubMed |

Kawarabayashi, T. , and Osa, T. (1976). Comparative investigations of alpha- and beta-effects on the longitudinal and circular muscles of the pregnant rat myometrium. Jpn. J. Physiol. 26, 403–416.
| PubMed |  CAS |

Kitsiou, P. V. , Tzinia, A. K. , Stetler-Stevenson, W. G. , Michael, A. F. , Fan, W. W. , and Zhou, B. (2003). Glucose-induced changes in integrins and matrix-related functions in cultured human glomerular epithelial cells. Am. J. Physiol. Renal Physiol. 284, F671–F679.
| PubMed |  CAS |

Kramer, R. H. , and Marks, N. (1989). Identification of integrin collagen receptors on human melanoma cells. J. Biol. Chem. 264, 4684–4688.
| PubMed |  CAS |

MacPhee, D. J. , and Lye, S. J. (2000). Focal adhesion signalling in the rat myometrium is abruptly terminated with the onset of labour. Endocrinology 141, 274–283.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |

Martinez-Lemus, L. A. , Wu, X. , Wilson, E. , Hill, M. A. , Davis, G. E. , Davis, M. J. , and Meininger, G. A. (2003). Integrins as unique receptors for vascular control. J. Vasc. Res. 40, 211–233.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |

Nishinaka, K. , and Fukuda, Y. (1991). Changes in extracellular matrix materials in the uterine myometrium of rats during pregnancy and postparturition. Acta Pathol. Jpn. 41, 122–132.
| PubMed |  CAS |

Osa, T. , and Katase, T. (1975). Physiological comparison of the longitudinal and circular muscles of the pregnant rat uterus. Jpn. J. Physiol. 25, 153–164.
| PubMed |  CAS |

Reddy, K. V. R. , and Mangale, S. S. (2003). Integrin receptors: the dynamic modulators of endometrial function. Tissue Cell 35, 260–273.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |

Shynlova, O. , Mitchell, J. A. , Tsampalieros, A. , Langille, B. L. , and Lye, S. J. (2004). Progesterone and gravidity differentially regulate expression of extracellular matrix components in pregnant rat myometrium. Biol. Reprod. 70, 986–992.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |

Shynlova, O. , Tsui, P. , Dorogin, A. , Chow, M. , and Lye, S. J. (2005). Expression and localization of alpha-smooth muscle and gamma-actins in the pregnant rat myometrium. Biol. Reprod. 73, 773–780.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |

Shynlova, O. , Oldenhof, A. , Dorogin, A. , Xu, Q. , Mu, J. , Nashman, N. , and Lye, S. J. (2006). Myometrial apoptosis: activation of the caspase cascade in the pregnant rat myometrium at midgestation. Biol. Reprod. 74, 839–849.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |

Shynlova, O. , Williams, S. J. , Draper, H. , White, B. G. , MacPhee, D. J. , and Lye, S. J. (2007). Uterine stretch regulates temporal and spatial expression of fibronectin protein and its α5 integrin receptor in myometrium of unilaterally pregnant rats. Biol. Reprod. 77, 880–888.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |

Shynlova, O. , Tsui, P. , Jaffer, S. , and Lye, S. J. (2009a). Integration of endocrine and mechanical signals in the regulation of myometrial functions during pregnancy and labour. Eur. J. Obstet. Gynecol. Reprod. Biol. 144(Suppl. 1), S2–S10.
| Crossref | GoogleScholarGoogle Scholar | CAS | PubMed |

Shynlova, O. , Chow, M. , and Lye, S. J. (2009b). Expression and organization of basement membranes and focal adhesion proteins in pregnant myometrium is regulated by uterine stretch. Reprod. Sci. 16, 960–969.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |

Taylor, C. V. , Letarte, M. , and Lye, S. J. (1996). The expression of integrins and cadherins in normal human uterus and uterine leiomyomas. Am. J. Obstet. Gynecol. 175, 411–419.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |

Thibault, G. (2000). Sodium dodecyl sulfate-stable complexes of echistatin and RGD-dependent integrins: a novel approach to study integrins. Mol. Pharmacol. 58, 1137–1145.
| PubMed |  CAS |

Wayner, E. A. , and Carter, W. G. (1987). Identification of multiple cell adhesion receptors for collagen and fibronectin in human fibrosarcoma cells possessing unique α and common β subunits. J. Biol. Chem. 105, 1873–1884.
|  CAS |

White, B. G. , Williams, S. J. , Highmore, K. , and MacPhee, D. J. (2005). Small heat shock protein 27 (Hsp27) expression is highly induced in rat myometrium during late pregnancy and labour. Reproduction 129, 115–126.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |

Wiesner, S. , Legate, K. R. , and Fassler, R. (2005). Integrin–actin interactions. Cell. Mol. Life Sci. 62, 1081–1099.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |

Williams, S. J. , White, B. G. , and MacPhee, D. J. (2005). Expression of alpha5 integrin (Itga5) is elevated in the rat myometrium during late pregnancy and labor: implications for development of a mechanical syncytium. Biol. Reprod. 72, 1114–1124.
| Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |

Wozniak, M. A. , Modzelewska, K. , Kwong, L. , and Keely, P. J. (2004). Focal adhesion regulation of cell behaviour. Biochim. Biophys. Acta 1692, 103–119.
| PubMed |  CAS |

Zhang, W. , and Gunst, S. J. (2006). Dynamic association between alpha-actinin and beta integrin regulates contraction of canine tracheal smooth muscle. J. Physiol. 572, 659–676.
| PubMed |  CAS |