Role of cathepsin E in decidual macrophage of patients with recurrent miscarriage
Description
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.
Journal
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- Molecular Human Reproduction
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Molecular Human Reproduction 20 (5), 454-462, 2014-01-23
Oxford University Press (OUP)
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Keywords
- Lipopolysaccharides
- proteolysis
- Abortion, Habitual
- Time Factors
- Litter Size
- cathepsin E
- Down-Regulation
- Gestational Age
- macrophage
- Cathepsin E
- recurrent miscarriage
- deciduas
- Interferon-gamma
- Pregnancy
- Decidua
- Animals
- Humans
- Prospective Studies
- Cells, Cultured
- Mice, Knockout
- Macrophages
- Mice, Inbred C57BL
- Case-Control Studies
- Female
Details 詳細情報について
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- CRID
- 1360848659595326208
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- ISSN
- 14602407
- 13609947
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- HANDLE
- 2324/6777136
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- PubMed
- 24464956
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- Data Source
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- Crossref
- KAKEN
- OpenAIRE