期刊
ENDOCRINOLOGY
卷 163, 期 12, 页码 -出版社
ENDOCRINE SOC
DOI: 10.1210/endocr/bqac165
关键词
pregnancy; extracellular vesicles; endometrial stromal cells; decidualization; angiogenesis; hypoxia-inducible transcription factor
资金
- Eunice Kennedy Shriver NICHD/NIH [R01 HD090066]
- NIEHS [T32 ES007326]
The secretion of extracellular vesicles (EVs) plays a crucial role in intercellular communication among the uterine cells to regulate uterine decidualization, neovascularization, and tissue remodeling, ensuring successful establishment of pregnancy.
The mouse decidua secretes many factors that act in a paracrine/autocrine manner to critically control uterine decidualization, neovascularization, and tissue remodeling that ensure proper establishment of pregnancy. The precise mechanisms that dictate intercellular communications among the uterine cells during early pregnancy remain unknown. We recently reported that conditional deletion of the gene encoding the hypoxia-inducible transcription factor 2 alpha (Hif2 alpha) in mouse uterus led to infertility. Here, we report that HIF2 alpha in mouse endometrial stromal cells (MESCs) acts via the cellular trafficking regulator RAB27b to control the secretion of extracellular vesicles (EVs) during decidualization. We also found that Hif2 alpha-regulated pathways influence the biogenesis of EVs. Proteomic analysis of EVs secreted by decidualizing MESCs revealed that they harbor a wide variety of protein cargoes whose composition changed as the decidualization process progressed. The EVs enhanced the differentiation capacity of MESCs and the production of angiogenic factors by these cells. We also established that matrix metalloproteinase-2, a prominent EV cargo protein, modulates uterine remodeling during decidualization. Collectively, our results support the concept that EVs are central to the mechanisms by which the decidual cells communicate with each other and other cell types within the uterus to facilitate successful establishment of pregnancy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据