Enhanced beta-catenin expression and inflammation are associated with human ectopic tubal pregnancy

Hum Reprod. 2013 Sep;28(9):2363-71. doi: 10.1093/humrep/det246. Epub 2013 Jun 19.


Study question: Is there a molecular link between Wnt signaling in fallopian tube inflammation and ectopic tubal implantation?

Summary answer: Enhanced beta-catenin expression, reduced E-cadherin expression and glycogen accumulation in the tubal epithelia and hyperplasia in tubal arteries were found in ectopic tubal pregnancy, consistent with the effects induced by Wnt signaling and inflammation.

What is known already: Chronic inflammation caused by infection can alter gene expression in the fallopian tube cells possibly leading to the development of ectopic pregnancy. Knockout mouse models have shown a relationship between Wnt/beta-catenin signaling and predisposition to tubal ectopic pregnancy.

Study design, size, duration: Women with ectopic tubal pregnancy (n = 18) were included in the case group, while women with chronic salpingitis (n = 13) and non-pregnant women undergoing sterilization procedures or salpingectomy for benign uterine disease (n = 10) were set as the controls. This study was performed between January 2012 and November 2012.

Participants/materials, setting, methods: The ampullary segments of fallopian tubes were collected from patients. Tissues of tubal pregnancy were separated into implantation sites and non-implantation sites. Beta-catenin and E-cadherin expression were determined using immunohistological and immunofluorescence staining. Glycogen production was measured with periodic acid Schiff by staining. The diameter and wall thickness of tubal arteries were evaluated by histological analysis method.

Main results and the role of chance: Immunohistological staining revealed that beta-catenin protein expression was 100% positive in the ectopic pregnant and inflamed tubal tissues, and the staining intensity was significantly higher than in non-pregnant tubal tissues. In contrast, E-cadherin expression was reduced in ectopic pregnant fallopian tubes, possibly as a consequence of increased Wnt signaling. Moreover, glycogen accumulated in the tubal cells, and hyperplasia was observed in the tubal arteries with ectopic pregnancy, which is consistent with the effects induced by Wnt signaling and inflammation. All these changes could create the permissive environment that promotes embryos to ectopically implant into the fallopian tube.

Limitations, reasons for caution: This finding requires a further confirmation about what activates Wnt signaling in ectopic tubal pregnancies. Also, it is generally recognized that Chlamydia infection is associated with ectopic pregnancy, and disturbs tubal epithelia via the Wnt signaling. However, the infection type in the samples used was salpingitis.

Wider implications of the findings: A better understanding of the underlying mechanisms leading to ectopic pregnancies may contribute to our knowledge of the pathogenesis of tubal disorders and infertility and to the prevention of tubal ectopic pregnancy.

Keywords: Wnt-signaling pathway; beta-catenin; ectopic pregnancy; fallopian tube; inflammation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD
  • Arteries / immunology
  • Arteries / pathology
  • Cadherins / metabolism*
  • Case-Control Studies
  • Disease Susceptibility
  • Down-Regulation
  • Fallopian Tube Diseases / immunology
  • Fallopian Tube Diseases / physiopathology
  • Fallopian Tubes / blood supply
  • Fallopian Tubes / immunology
  • Fallopian Tubes / metabolism*
  • Fallopian Tubes / pathology
  • Female
  • Glycogen / biosynthesis
  • Glycogen / metabolism
  • Humans
  • Hyperplasia
  • Models, Biological*
  • Mucous Membrane / blood supply
  • Mucous Membrane / immunology
  • Mucous Membrane / metabolism*
  • Mucous Membrane / pathology
  • Neovascularization, Pathologic / etiology
  • Neovascularization, Pathologic / immunology
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / physiopathology
  • Pregnancy
  • Pregnancy, Tubal / immunology
  • Pregnancy, Tubal / metabolism*
  • Pregnancy, Tubal / pathology
  • Pregnancy, Tubal / physiopathology
  • Up-Regulation*
  • Wnt Signaling Pathway
  • beta Catenin / biosynthesis*
  • beta Catenin / metabolism


  • Antigens, CD
  • CDH1 protein, human
  • CTNNB1 protein, human
  • Cadherins
  • beta Catenin
  • Glycogen