Granulysin-mediated apoptosis of trophoblasts in blighted ovum and missed abortion

Am J Reprod Immunol. 2018 Sep;80(3):e12978. doi: 10.1111/aji.12978. Epub 2018 May 18.

Abstract

Problem: Granulysin (GNLY) is a cytotoxic molecule mostly present in decidual natural killer (NK) cells. Blighted ovum (BO) and missed abortion (MA) represent the early pathological pregnancies with hindered development of the embryoblast or a dead embryo. We investigated the GNLY-mediated apoptotic mechanism potentially responsible for delayed termination of pregnancy.

Method of study: We performed immunohistological and immunofluorescence labeling of decidual tissues (GNLY, Apaf-1, NF-κB). NKG2A expression was analyzed by flow cytometry and GNLY mRNA by RT-qPCR.

Results: The GNLY labeling intensity (H score) was lower in the nuclei of trophoblast cells in BO and MA. GNLY gene levels were inversely detected in BO and MA. A decreased decidual NK cell percentage was found in MA. NK cells from pathological pregnancies expressed lower NKG2A levels. The highest frequency of Apaf-1 was found in trophoblast cells of MA. NF-kB was highly expressed in decidual cells of BO.

Conclusion: The reduced activation of GNLY-mediated killing might be implicated in the slower rejection of trophoblast cells in BO and MA. A decreased authentic decidual NK cell number could be responsible for low cytotoxicity against trophoblast cells in MA. In BO, trophoblast cells have a higher survival potential due to increased NF-kB expression.

Keywords: Apaf-1; NF-kB; blighted ovum; granulysin; missed abortion; pregnancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Missed / immunology*
  • Antigens, Differentiation, T-Lymphocyte / metabolism*
  • Apoptosis
  • Apoptotic Protease-Activating Factor 1 / metabolism
  • Cells, Cultured
  • Decidua / pathology*
  • Female
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Killer Cells, Natural / immunology*
  • NF-kappa B / metabolism
  • NK Cell Lectin-Like Receptor Subfamily C / metabolism
  • Pregnancy
  • Trophoblasts / immunology*

Substances

  • APAF1 protein, human
  • Antigens, Differentiation, T-Lymphocyte
  • Apoptotic Protease-Activating Factor 1
  • GNLY protein, human
  • KLRC1 protein, human
  • NF-kappa B
  • NK Cell Lectin-Like Receptor Subfamily C