{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/130194"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/130194","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Endometrial extracellular vesicles during pregnancy: their regulation by transcription factor RUNX1 and dysregulation by phthalate exposure","abstract":"Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2027-08-01","abstract_html":"Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2027-08-01","abstract_has_math":false,"creators":["Beal, Jacob Reed"],"institution":"University of Illinois Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Molecular & Integrative Physi","degree_department":null,"school":null,"contributors":["Bagchi, Milan","Bagchi, Indrani","Raetzman, Lori","Flaws, Jodi","Nelson, Erik"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-07-17","date_published":"2025-07-17","updated_at":"2026-07-22T22:25:06Z","subjects":["Extracellular Vesicles","Phthalates","Pregnancy","Placentation"],"languages":["en","eng"],"rights":["Copyright 2025 Jacob Beal"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2142/130194","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Bagchi, Milan","Bagchi, Indrani","Raetzman, Lori","Flaws, Jodi","Nelson, Erik"]},{"key":"dc:creator","label":"Author","values":["Beal, Jacob Reed"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2025-07-17","2025-08"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Molecular & Integrative Physi"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Extracellular Vesicles","Phthalates","Pregnancy","Placentation"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en","eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2025 Jacob Beal"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2142/130194"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2027-08-01","The student, Jacob Beal, accepted the attached license on 2025-07-16 at 14:47.","The student, Jacob Beal, submitted this Dissertation for approval on 2025-07-16 at 14:54.","This Dissertation was approved for publication on 2025-07-17 at 16:33.","DSpace SAF Submission Ingestion Package generated from Vireo submission #22587 on 2025-10-25 at 15:54:09","During early pregnancy, endometrial stromal cells in the maternal uterus play a crucial role in coordinating significant events necessary for reproductive success by secreting paracrine factors, including extracellular vesicles (EVs) that contain diverse molecular cargo, facilitating critical processes such as embryo implantation, uterine neoangiogenesis, and trophoblast differentiation. The secretion of EVs from endometrial stromal cells is regulated by a conserved pathway involving hypoxia-inducible factor HIF2α, which controls the expression of RAB27B, a vesicular trafficking protein necessary for the release of EVs into the extracellular space. In human endometrial stromal cells (HESCs), runt-related transcription factor RUNX1 has been identified to act upstream of HIF2α to facilitate proper EV secretion and the inclusion of specific protein cargoes, including insulin-like growth factor IGF2. Consequently, EVs collected from HESCs with reduced RUNX1 or IGF2 expression were less effective in promoting angiogenesis or trophoblast differentiation. In a conditional knockout mouse model in which the gene encoding IGF2 was ablated in the maternal uterus, we observed a reduction in litter size and smaller offspring, attributed to defective placental development. Understanding the regulation of the EV signaling pathway and how it can be disrupted is critical, as impairment of cell-to-cell communication within the uterus during early pregnancy can significantly affect placental development and fetal growth. Our study demonstrated that exposure to an environmentally relevant concentration of phthalates, well-known endocrine disruptors, disrupts the EV secretion pathway in HESC by inducing abnormal DNA methylation, which impairs the estrogenic promotion of HIF2α expression. Collectively, these findings highlight the essential role of the RUNX1-HIF2α-RAB27B pathway in mediating the regulation of EV secretion from endometrial stromal cells, emphasizing that disruptions caused by environmental insults or diminished expression of upstream factors or essential protein cargoes can impair EV secretion and hinder key processes vital for placental development and reproductive success."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Endometrial extracellular vesicles during pregnancy: their regulation by transcription factor RUNX1 and dysregulation by phthalate exposure"]}]}],"canonical_facts":{"dc:contributor":["Bagchi, Milan","Bagchi, Indrani","Raetzman, Lori","Flaws, Jodi","Nelson, Erik"],"dc:creator":["Beal, Jacob Reed"],"dc:date":["2025-07-17","2025-08"],"dc:description":["Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2027-08-01","The student, Jacob Beal, accepted the attached license on 2025-07-16 at 14:47.","The student, Jacob Beal, submitted this Dissertation for approval on 2025-07-16 at 14:54.","This Dissertation was approved for publication on 2025-07-17 at 16:33.","DSpace SAF Submission Ingestion Package generated from Vireo submission #22587 on 2025-10-25 at 15:54:09","During early pregnancy, endometrial stromal cells in the maternal uterus play a crucial role in coordinating significant events necessary for reproductive success by secreting paracrine factors, including extracellular vesicles (EVs) that contain diverse molecular cargo, facilitating critical processes such as embryo implantation, uterine neoangiogenesis, and trophoblast differentiation. The secretion of EVs from endometrial stromal cells is regulated by a conserved pathway involving hypoxia-inducible factor HIF2α, which controls the expression of RAB27B, a vesicular trafficking protein necessary for the release of EVs into the extracellular space. In human endometrial stromal cells (HESCs), runt-related transcription factor RUNX1 has been identified to act upstream of HIF2α to facilitate proper EV secretion and the inclusion of specific protein cargoes, including insulin-like growth factor IGF2. Consequently, EVs collected from HESCs with reduced RUNX1 or IGF2 expression were less effective in promoting angiogenesis or trophoblast differentiation. In a conditional knockout mouse model in which the gene encoding IGF2 was ablated in the maternal uterus, we observed a reduction in litter size and smaller offspring, attributed to defective placental development. Understanding the regulation of the EV signaling pathway and how it can be disrupted is critical, as impairment of cell-to-cell communication within the uterus during early pregnancy can significantly affect placental development and fetal growth. Our study demonstrated that exposure to an environmentally relevant concentration of phthalates, well-known endocrine disruptors, disrupts the EV secretion pathway in HESC by inducing abnormal DNA methylation, which impairs the estrogenic promotion of HIF2α expression. Collectively, these findings highlight the essential role of the RUNX1-HIF2α-RAB27B pathway in mediating the regulation of EV secretion from endometrial stromal cells, emphasizing that disruptions caused by environmental insults or diminished expression of upstream factors or essential protein cargoes can impair EV secretion and hinder key processes vital for placental development and reproductive success."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2142/130194"],"dc:language":["en","eng"],"dc:rights":["Copyright 2025 Jacob Beal"],"dc:subject":["Extracellular Vesicles","Phthalates","Pregnancy","Placentation"],"dc:title":["Endometrial extracellular vesicles during pregnancy: their regulation by transcription factor RUNX1 and dysregulation by phthalate exposure"],"dc:type":["text"],"thesis:degree_discipline":["Molecular & Integrative Physi"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois Urbana-Champaign"]},"updated_at":"2026-07-22T22:25:06Z"}