Role of extracellular vesicles(EVs) in mediating cell-to-cell signaling during early pregnancy

During establishment of pregnancy in humans and rodents, uterine stromal cells secrete various factors that act in an autocrine/paracrine manner to promote their differentiation into decidual cells and facilitate maternal angiogenesis leading to placentation. Signaling factors produced by the decidual cells are relayed to other cells within the uterine milieu to influence dynamic adaptive processes during pregnancy. A major challenge in reproductive sciences today is to decipher the molecular basis of cell-cell communication during early pregnancy. Here, we indicated that hypoxia-inducible factor Hif2α plays an essential role in embryo implantation and decidualization by regulating the expression of Rab27b, a member of the Rab family of GTPases. Rab27b controls the secretion of extracellular vesicles (EVs) that carry mediators of intercellular communication during many physiological processes. The present study showed that primary mouse and human endometrial stromal cells secrete EVs during decidualization and that this process is controlled by a conserved Hif2α - Rab27b pathway. EVs generated by endometrial stromal cells carry a variety of molecular cargoes that augments decidualization, impacts tissue remodeling, stimulates angiogenesis and modulates trophoblast differentiation upon incorporation into recipient cells. Additionally, we analyzed the individual contributions of the potential cargo, specifically GLUT1 and MMP2, that facilitate cell metabolism and tissue remodeling during pregnancy. To our knowledge, this is the first demonstration of the pleiotropic functions of EVs in supporting communication between various cell types within the uterus that is vital in promoting decidualization, angiogenesis and trophoblast development.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Molecular & Integrative Physi

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2022

Author dc:creator

• Ma, Qiuyan

Contributors dc:contributor

• Bagchi, Milan K
• Bagchi, Indrani C
• Nelson, Erik Russell
• Raetzman, Lori T
• Anakk, Sayeepriyadarsh

• EVs
• Decidualization
• Pregnancy

Statement dc:rights

• Copyright 2022 Qiuyan Ma

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/115904

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F115904