Procr-expressing progenitor cells are responsible for murine ovulatory rupture repair of ovarian surface epithelium

Jingqiang Wang,Daisong Wang,Yi Arial Zeng,Kun Chu,Wen Li

doi:10.1038/s41467-019-12935-7

Abstract

Ovarian surface epithelium (OSE) undergoes recurring ovulatory rupture and repair. The OSE replenishing mechanism post ovulation remains unclear. Here we report that the expression of Protein C Receptor (Procr) marks a progenitor population in adult mice that is responsible for OSE repair post ovulation. Procr+ cells are the major cell source for OSE repair. The mechanism facilitating the rapid re-epithelialization is through the immediate expansion of Procr+ cells upon OSE rupture. Targeted ablation of Procr+ cells impedes the repairing process. Moreover, Procr+ cells displayed robust colony-formation capacity in culture, which we harnessed and established a long-term culture and expansion system of OSE cells. Finally, we show that Procr+ cells and previously reported Lgr5+ cells have distinct lineage tracing behavior in OSE homeostasis. Our study suggests that Procr marks progenitor cells that are critical for OSE ovulatory rupture and homeostasis, providing insight into how adult stem cells respond upon injury.

Highlights

Ovarian surface epithelium (OSE) undergoes recurring ovulatory rupture and repair
We found that a subset of OSE cells express Protein C Receptor (Procr), including those in the hilum and other OSE areas (Fig. 1a, b)
Procr-rtTA;tetO-H2B-GFP mice were generated by genetic crosses that result in the stable expression of histone 2B-GFP fusion protein in Procr+ cells after doxycycline (DOX) treatment

Summary

Introduction

Ovarian surface epithelium (OSE) undergoes recurring ovulatory rupture and repair. The OSE replenishing mechanism post ovulation remains unclear. We report that the expression of Protein C Receptor (Procr) marks a progenitor population in adult mice that is responsible for OSE repair post ovulation. Considering the short estrus cycle (every 4–5 days) in mouse, the repair mechanism of the OSE is highly robust and efficient, with complete closure of the wound achieved within 12 h to 3 days following rupture[7,8]. This recurring process suggests the existence of stem/progenitor cells in the OSE. We compare the contribution of Procr+ cells and Lgr5+ cells in adult OSE homeostasis

Methods

Results

Conclusion