Juan Liu1, Yanyun Ying1, Siwen Wang1, Jingyi Li1, Jinqun Xu1, Pingping Lv1, Jianhua Chen2, Caiyun Zhou2, Yifeng Liu1, Yiqing Wu1, Yun Huang1, Yao Chen1, Lifen Chen3, Shijiong Tu4, Wei Zhao1, Min Yang1, Yanjun Hu1, Runju Zhang5, Dan Zhang6. 1. Key Laboratory of Reproductive Genetics (Ministry of Education) and Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, PR China. 2. Department of Pathology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, PR China. 3. Key Laboratory of Reproductive Genetics (Ministry of Education) and Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, PR China; Huzhou Maternity & Child Care Hospital, PR China. 4. Key Laboratory of Reproductive Genetics (Ministry of Education) and Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, PR China; Ningbo Women & Children's Hospital, PR China. 5. Key Laboratory of Reproductive Genetics (Ministry of Education) and Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, PR China. Electronic address: 5311005@zju.edu.cn. 6. Key Laboratory of Reproductive Genetics (Ministry of Education) and Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, PR China. Electronic address: zhangdan@zju.edu.cn.
Abstract
BACKGROUND: Endometrial injury can result in thin endometrium and subfertility. Granulocyte macrophage colony stimulating factor (GM-CSF) contributes to tissue repair, but its role in endometrial regeneration has not been investigated. METHODS: To determine the effect of GM-CSF on endometrial regeneration, we established a mouse model of thin endometrium by uterine perfusion with 20 μL 90% ethanol. Thin endometrium in mice was featured by lowered endometrial thickness, decreased expression of Ki67 in glandular cells, and a reduced number of implantation sites. To explore the mechanism of GM-CSF on endometrial regeneration, endometrium was obtained from patients undergoing hysterectomy or hysteroscopy and endometrial biopsy. Effects of GM-CSF on primary cultured human endometrial glandular and stromal cells were examined by the 5-bromo-2'-deoxyuridine (BrdU) proliferation assay and transwell migration assay, followed by exploration of the potential signaling pathway. RESULTS: GM-CSF intraperitoneal (i.p.) injection significantly increased endometrial thickness, expression of Ki67 in endometrial glandular cells, and the number of implantation sites. GM-CSF significantly promoted proliferation of primary human endometrial glandular cells and migration of stromal cells. GM-CSF activated p-Akt and increased expressions of p70S6K and c-Jun, which were blocked by LY294002. CONCLUSION: We found that GM-CSF could improve endometrial regeneration, possibly through activating PI3K/Akt signaling pathway.
BACKGROUND:Endometrial injury can result in thin endometrium and subfertility. Granulocyte macrophage colony stimulating factor (GM-CSF) contributes to tissue repair, but its role in endometrial regeneration has not been investigated. METHODS: To determine the effect of GM-CSF on endometrial regeneration, we established a mouse model of thin endometrium by uterine perfusion with 20 μL 90% ethanol. Thin endometrium in mice was featured by lowered endometrial thickness, decreased expression of Ki67 in glandular cells, and a reduced number of implantation sites. To explore the mechanism of GM-CSF on endometrial regeneration, endometrium was obtained from patients undergoing hysterectomy or hysteroscopy and endometrial biopsy. Effects of GM-CSF on primary cultured human endometrial glandular and stromal cells were examined by the 5-bromo-2'-deoxyuridine (BrdU) proliferation assay and transwell migration assay, followed by exploration of the potential signaling pathway. RESULTS:GM-CSF intraperitoneal (i.p.) injection significantly increased endometrial thickness, expression of Ki67 in endometrial glandular cells, and the number of implantation sites. GM-CSF significantly promoted proliferation of primary human endometrial glandular cells and migration of stromal cells. GM-CSF activated p-Akt and increased expressions of p70S6K and c-Jun, which were blocked by LY294002. CONCLUSION: We found that GM-CSF could improve endometrial regeneration, possibly through activating PI3K/Akt signaling pathway.