Upregulation of Bcl-2 at the foetal-maternal interface from mice undergoing abortion

Scand J Immunol. 2005 Jun;61(6):492-502. doi: 10.1111/j.1365-3083.2005.001625.x.

Abstract

Several burning questions remain unanswered in pregnancy-related research. Pro- and anti-inflammatory cytokines orchestrate an intriguing interaction leading either to the development of a normal individual or to its rejection. Augmented Th1 cytokines' production is involved in immunological rejection of the foetus. Excessive production of Th1 cytokines, particularly of tumour necrosis factor (TNF)-alpha, also triggers apoptosis. Thus, in the present work we investigated the incidence of apoptosis in a well-known experimental model of Th1-induced abortion, characterized by increased local TNF-alpha levels. Apoptosis of lymphocytes as well as their Th1 and Th2 cytokine production were analysed by flow cytometry. TNF-alpha mRNA levels were additionally analysed by real time reverse transcription-polymerase chain reaction (RT-PCR) in placental and decidual samples. Total placental apoptosis activity was investigated by measuring caspase-3 activity and by TdT-mediated dUTP nick end label staining. Immunohistochemistry, Western blot and real time RT-PCR were used to localize and quantify several anti- and pro-apoptotic molecules at the foetal-maternal interface. Despite elevated Th1 levels at the foetal-maternal interface, mice undergoing abortion presented comparable apoptotic rates. Interestingly, we found a significant upregulation of the anti-apoptotic Bcl-2 protein at the foetal-maternal interface from abortion-prone mice, while no changes could be observed for pro-apoptotic molecules. In the light of our results, we conclude that there is no evidence of increased apoptosis in mice undergoing immunological abortion in spite of elevated TNF-alpha levels. This is probably due to a selective upregulation of anti-apoptotic pathways (i.e. Bcl-2) at the foetal-maternal interface as a compensatory and/or protective mechanism.

Publication types

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

MeSH terms

  • Abortion, Spontaneous / immunology
  • Abortion, Spontaneous / metabolism*
  • Animals
  • Decidua / immunology
  • Decidua / metabolism
  • Female
  • Male
  • Mice
  • Mice, Inbred CBA
  • Mice, Inbred DBA
  • Placenta / immunology
  • Placenta / metabolism*
  • Polymerase Chain Reaction
  • Pregnancy
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
  • RNA, Messenger / analysis
  • Th1 Cells / immunology
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / genetics
  • Up-Regulation

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha