Effects of prostaglandin E2 and F on expression of growth factors and proliferation of bovine endometrial cells and explants in vitro

[Speaker] Shuangyi Zhang:1,2
[Co-author] Takio Kitazawa:1, Jinshan Cao:2
1:Department of Veterinary Medicine, Rakuno Gakuen University, Japan, 2:College of Veterinary Medicine, Inner Mongolia Agricultural University, China

[Background] The uterine endometrium is important for maintaining good performance in reproductive activity as well as for protecting uterine function from infectious diseases caused by bacteria. Therefore, an intact structure and normal function of the endometrium are required in the uterus. The endometrium is well known for its great capacity of degeneration and regeneration in reproductive cycles; however, the underlying mechanisms for maintenance of endometrial function are not well understood. This fact has prompted us to find substances for improving endometrial conditions. In mammals, both prostaglandin E2 (PGE2) and PGF are secreted simultaneously with endometrial regeneration in reproductive cycles, suggesting regulatory roles of PGE2 and PGF in endometrial growth. Although PGE2 and PGF have been reported to regulate tissue growth in the esophagus, stomach, and cornea, the involvement of PGE2 and PGF in endometrial growth has been debated. The aim of this study was to determine the effects of PGE2 and PGF on endometrial growth during reproductive cycles. [Materials and Methods] Isolated bovine endometrial cells and explants were cultured in vitro, and the effects of PGE2 (10-9M-10-5M) and the PGF receptor agonist fluprostenol (10-9M-10-5M) on the expression of growth and proliferation factors (mRNA and protein) were examined using real-time RT-PCR, Western blotting, and immunofluorescence assay. [Results] A method for cultivation of bovine endometrial cells and explants in vitro was established. PGE2 (10-7M-10-5M) and fluprostenol (10-7M-10-5M) increased the mRNA and protein expression levels of connective tissue growth factor (CTGF), fibroblast growth factor-2 (FGF-2), transforming growth factor-β1 (TGF-β1), matrix metalloproteinase-2 (MMP-2), and vascular endothelial growth factor (VEGF) in bovine endometrial cells and explants in culture in a time-dependent manner. PGE2 and fluprostenol (10-7M-10-5M) also induced proliferation of endometrial epithelial cells and stromal cells, whereas apoptosis factor caspase-3 expression was down-regulated. [Conclusion] The results indicated the possible involvement of PGE2 and PGF in the proliferation of cells in the endometrium and endometrial growth. The present study is the first step to explore PGE2 and PGF as potential targets for treatment of an impaired endometrium as well as for therapies for diseases of the uterus.
Applying for IUPHAR Young Investigator Awards.
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