Role of cathepsin E in decidual macrophage of patients with recurrent miscarriage

Mol Hum Reprod. 2014 May;20(5):454-62. doi: 10.1093/molehr/gau008. Epub 2014 Jan 23.


In a previous study, we reported that the cathepsin-cystatin system caused endometrial dysfunction in early pregnancy. Here, we investigated the existence and contribution of cathepsin E in early pregnancy in patients with recurrent miscarriage (RM). The effect of cathepsin deficiency on fertility and female reproductive organs were also analyzed in CatE(-/-) mice. Human studies were conducted in a hospital setting, with informed consent. Cervical mucus was collected from RM patients in early pregnancy (4-6 gestational weeks, n = 21), and the pregnancy outcome was compared prospectively. The cathepsin E expression in decidua of RM patients (n = 49) and normal pregnant women undergoing elective surgical abortion (n = 24) was measured using SDS-PAGE, and western blot analysis. Decidual macrophages were isolated from RM patients (n = 6) and stimulated by lipopolysaccharide (LPS) and interferon gamma (IFN-γ). Results from the mouse model showed that CatE(-/-) mice were fertile, but the litter number was significantly smaller. The uterus of CatE(-/-) mice showed granulation tissue. In human samples, protease activity of cathepsin E measured with Fluorescence-Quenching Substrate (KYS-1) in cervical mucus of patients who developed miscarriage was markedly decreased compared with patients without RM. The expression of cathepsin E in decidua, semi-quantified by SDS-PAGE, western blot analysis was significantly lower in RM patients compared with patients without RM. By double staining immunofluorescence, the staining of cathepsin E was observed in CD14 or CD68 positive cells in all deciduas. Upon stimulation with LPS and IFN-γ, the expression of cathepsin E in cell lysate of decidual macrophages was markedly reduced in RM patients compared with controls. The results suggested that decreased activity of cathepsin E produced by decidual macrophages might be responsible for the induction of miscarriages in some RM patients.

Keywords: cathepsin E; deciduas; macrophage; proteolysis; recurrent miscarriage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Habitual / enzymology*
  • Abortion, Habitual / genetics
  • Abortion, Habitual / pathology
  • Animals
  • Case-Control Studies
  • Cathepsin E / deficiency
  • Cathepsin E / genetics
  • Cathepsin E / metabolism*
  • Cells, Cultured
  • Decidua / drug effects
  • Decidua / enzymology*
  • Decidua / pathology
  • Down-Regulation
  • Female
  • Gestational Age
  • Humans
  • Interferon-gamma / pharmacology
  • Lipopolysaccharides / pharmacology
  • Litter Size
  • Macrophages / drug effects
  • Macrophages / enzymology*
  • Macrophages / pathology
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pregnancy
  • Prospective Studies
  • Time Factors


  • Lipopolysaccharides
  • Interferon-gamma
  • Cathepsin E
  • Ctse protein, mouse
  • CTSE protein, human