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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



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.


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.


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.


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.

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