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

Shinobu Goto, Yasuhiko Ozaki, Nobuhiro Suzumori, Atsushi Yasukochi, Tomoyo Kawakubo, Tadahide Furuno, Mamoru Nakanishi, Kenji Yamamoto, Mayumi Sugiura-ogasawara

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15 Citations (Scopus)


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.

Original languageEnglish
Article numbergau008
Pages (from-to)454-462
Number of pages9
JournalMolecular Human Reproduction
Issue number5
Publication statusPublished - Jan 2014

All Science Journal Classification (ASJC) codes

  • Reproductive Medicine
  • Embryology
  • Molecular Biology
  • Genetics
  • Obstetrics and Gynaecology
  • Developmental Biology
  • Cell Biology


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