Metformin Alleviates Endometriosis and Potentiates Endometrial Receptivity via Decreasing VEGF and MMP9 and Increasing Leukemia Inhibitor Factor and HOXA10

doi:10.3389/fphar.2022.750208

科研成果详情

题名	Metformin Alleviates Endometriosis and Potentiates Endometrial Receptivity via Decreasing VEGF and MMP9 and Increasing Leukemia Inhibitor Factor and HOXA10
作者	Cheng, Jing1,2; Li, Chunyang3; Ying, Yingfen1; Lv, Jieqiang1; Qu, Xianqin 2; McGowan, Eileen 2; Lin, Yiguang 2; Zhu, Xueqiong1
发表日期	2022-02-22
发表期刊	Frontiers in pharmacology 影响因子和分区
语种	英语
原始文献类型	Article
关键词	HOXA10 endometrial receptivity endometriosis leukemia inhibitor factor matrix metalloproteinase-9 metformin vascular endothelial growth factor.
其他关键词	CLOMIPHENE CITRATE ; MOLECULAR-MECHANISMS ; FACTOR EXPRESSION ; INFERTILE WOMEN ; GENE-EXPRESSION ; RESISTANT WOMEN ; MESSENGER-RNA ; IMPLANTATION ; CELLS ; INFLAMMATION
摘要	Background: Endometriosis affects endometrial receptivity, a key factor for successful embryo implantation. Metformin treatment is associated with alleviating the symptoms of endometriosis; however the mechanism of metformin action is unclear. Neoangiogenesis plays an important role in the development and recurrence of endometriosis. In addition, the leukemia inhibitor factor (LIF) and HOXA10 genes are also distinguishing markers of endometriosis (decrease) and endometrial receptivity (increase). This study investigated the therapeutic potentials of metformin and the underlying mechanism using an in vivo rat endometriosis model. Methods: Female Wistar albino mature rats with experimentally induced endometriosis were used in this study. Metformin was administered at doses of 100 mg/kg/d and 200 mg/kg/d. The volume of endometriotic implants was assessed. The protein and mRNA expression of the vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), the endometrial receptivity markers, LIF and HOXA10, were measured in the endometrium of rats with endometriosis. Results: Metformin treatment significantly suppressed the growth of endometriotic implants. Further, the expression of VEGF and MMP-9 protein and mRNA in endometriotic implants were significantly reduced. Metformin also significantly upregulated LIF and HOXA10 expression in endometrium from rats with endometriosis. The inhibitory effect of metformin on the growth of endometriotic implants, VEGF and MMP-9, and upregulating effect on LIF and HOXA10, was optimal at a dose of 100 mg/kg/d. Conclusion: Our in vivo data demonstrates that metformin treatment alleviates endometriosis and potentiates endometrial receptivity. The underlying mechanisms are associated with decreased expression of VEGF and MMP-9 genes and upregulation of the LIF and HOXA10 genes. The effect of metformin was optimal at 100 mg/kg/d. These findings provide a potential alternative for women with endometriosis with the potential to increase fertility. Metformin is an approved drug by FDA for diabetes and this study may add another potential clinical use for metformin.
资助项目	Wenzhou Municipal Science and Technology Bureau[2011R50013];
出版者	FRONTIERS MEDIA SA
出版地	LAUSANNE
ISSN	1663-9812
EISSN	1663-9812
卷号	13 页码:750208
DOI	10.3389/fphar.2022.750208
页数	11
WOS类目	Pharmacology & Pharmacy
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:000772575500001
收录类别	PUBMED ; SCOPUS ; SCIE
URL	查看原文
PubMed ID	35273494
PMC记录号	PMC8902464
SCOPUSEID	2-s2.0-85125997519
通讯作者地址	[Zhu, Xueqiong]Department of Obstetrics and Gynaecology,The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University,Wenzhou,China ; [Lin, Yiguang]School of Life Sciences,University of Technology Sydney,Sydney,Australia
Scopus学科分类	Pharmacology;Pharmacology (medical)
引用统计	被引频次：3[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/34401
专题	第二临床医学院，附属第二医院、育英儿童医院基础医学院（机能实验教学中心）_生物科学系_生物化学与分子生物学
通讯作者	Lin, Yiguang; Zhu, Xueqiong
作者单位	1.Department of Obstetrics and Gynaecology,The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University,Wenzhou,China; 2.School of Life Sciences,University of Technology Sydney,Sydney,Australia; 3.Department of Biochemistry,School of Basic Sciences,Wenzhou Medical University,Wenzhou,China
第一作者单位	第二临床医学院，附属第二医院、育英儿童医院
通讯作者单位	第二临床医学院，附属第二医院、育英儿童医院
第一作者的第一单位	第二临床医学院，附属第二医院、育英儿童医院
推荐引用方式 GB/T 7714	Cheng, Jing,Li, Chunyang,Ying, Yingfen,et al. Metformin Alleviates Endometriosis and Potentiates Endometrial Receptivity via Decreasing VEGF and MMP9 and Increasing Leukemia Inhibitor Factor and HOXA10[J]. Frontiers in pharmacology,2022,13:750208.
APA	Cheng, Jing., Li, Chunyang., Ying, Yingfen., Lv, Jieqiang., Qu, Xianqin., ... & Zhu, Xueqiong. (2022). Metformin Alleviates Endometriosis and Potentiates Endometrial Receptivity via Decreasing VEGF and MMP9 and Increasing Leukemia Inhibitor Factor and HOXA10. Frontiers in pharmacology, 13, 750208.
MLA	Cheng, Jing,et al."Metformin Alleviates Endometriosis and Potentiates Endometrial Receptivity via Decreasing VEGF and MMP9 and Increasing Leukemia Inhibitor Factor and HOXA10".Frontiers in pharmacology 13(2022):750208.