The effects and mechanisms of GM-CSF on endometrial regeneration

被引:16
作者
Liu, Juan [1 ,2 ]
Ying, Yanyun [1 ,2 ]
Wang, Siwen [1 ,2 ]
Li, Jingyi [1 ,2 ]
Xu, Jinqun [1 ,2 ]
Lv, Pingping [1 ,2 ]
Chen, Jianhua [3 ]
Zhou, Caiyun [3 ]
Liu, Yifeng [1 ,2 ]
Wu, Yiqing [1 ,2 ]
Huang, Yun [1 ,2 ]
Chen, Yao [1 ,2 ]
Chen, Lifen [1 ,2 ,4 ]
Tu, Shijiong [1 ,2 ,5 ]
Zhao, Wei [1 ,2 ]
Yang, Min [1 ,2 ]
Hu, Yanjun [1 ,2 ]
Zhang, Runju [1 ,2 ]
Zhang, Dan [1 ,2 ]
机构
[1] Zhejiang Univ, Minist Educ, Sch Med, Key Lab Reprod Genet, Hangzhou 310006, Zhejiang, Peoples R China
[2] Zhejiang Univ, Womens Hosp, Sch Med, Dept Reprod Endocrinol, Hangzhou 310006, Zhejiang, Peoples R China
[3] Zhejiang Univ, Womens Hosp, Sch Med, Dept Pathol, Hangzhou 310006, Zhejiang, Peoples R China
[4] Huzhou Matern & Child Care Hosp, Huzhou, Peoples R China
[5] Ningbo Women & Childrens Hosp, Ningbo, Zhejiang, Peoples R China
基金
中国国家自然科学基金;
关键词
GM-CSF; Regeneration; Thin endometrium; Endometrial glandular and stromal cells; PI3K/Akt; COLONY-STIMULATING FACTOR; IN-VITRO FERTILIZATION; THIN ENDOMETRIUM; ALPHA-RECEPTOR; STROMAL CELLS; BETA-RECEPTOR; PREGNANCY; THICKNESS; STEM; EXPRESSION;
D O I
10.1016/j.cyto.2019.154850
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 mu L 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.
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页数:10
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