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Open Access Research

The development of endometrial hyperplasia in aged PD-1-deficient female mice

Guoning Guo1, Hong Li2, Dayan Cao3 and Yongwen Chen3*

Author Affiliations

1 Department of Emergency, South-West Hospital, Third Military Medical University, Chongqing 400038, China

2 Department of Otorhinolaryngology and Head-Neck Surgery, Xinqiao Hospital, PLA, Third Military Medical University, Chongqing 400037, PR China

3 Institute of Immunology, PLA, Third Military Medical University, Chongqing 400038, People’s Republic of China

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Diagnostic Pathology 2014, 9:97  doi:10.1186/1746-1596-9-97

Published: 26 May 2014

Abstract

Background

Programmed death-1 (PD-1, Pdcd1)-deficient mice develop different types of autoimmune diseases depending on the mouse strain but its role in uterus development has not been reported.

Methods

In this study, the expression of PD-1 and its ligands, PD-L1 and PD-L2, in uterine tissues from aged WT mice in a 129svEv-Brd background was analyzed by immunohistochemistry and the uterine morphology between WT and PD-1-/- mice was compared by hematoxylin and eosin staining.

Results

The aged PD-1-/- female mice in a 129svEv-Brd rather than Balb/c background develop endometrial hyperplasia. H&E staining showed an increase in the number of glands, neovascularization and an extremely large luminal cavity in aged PD-1-/- uteri. Immunohistochemical assay showed that the expression of PD-1 was observed in glandular/luminal epithelium and cells infiltrating the stroma. Fluorescent double staining demonstrated that PD-1 expresses on CD68+ macrophages, CD3+ T cells, CD16+ monocytes, CD56+ NK cells and CK-18+ epithelial cells, respectively. Additionally, PD-1 co-expresses with vascular endothelial growth factor (VEGF), and PD-1 deficiency resulted in an accumulation of glandular/luminal epithelium derived VEGF, which accelerates the expression of the proliferation-associated protein, proliferating cell nuclear antigen (PCNA), and thus potentially lead to epithelial proliferation in aged PD-1-/- uteri.

Conclusions

These findings showed that PD-1 deficiency augments luminal epithelial cell proliferation probably through induced VEGF secretion, suggesting PD-1 plays an important role in controlling the growth and differentiation of the uterine epithelium.

Virtual Slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5809067461223905 webcite

Keywords:
PD-1; Endometrial hyperplasia; VEGF; PCNA; Uterus