{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/129382"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/129382","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Toward a mechanistic understanding of poly- and perfluoroalkyl substances and testicular cancer","abstract":"Submission original under an indefinite embargo labeled 'Open Access'. The submission was exported from vireo on 2025-10-19 without embargo terms","abstract_html":"Submission original under an indefinite embargo labeled 'Open Access'. The submission was exported from vireo on 2025-10-19 without embargo terms","abstract_has_math":false,"creators":["Boyd, Raya Iman"],"institution":"University of Illinois Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"VMS - Comparative Biosciences","degree_department":null,"school":null,"contributors":["Spinella, Michael J","Flaws, Jodi A","Reddi, Prabhakara","Irudayaraj, Joseph"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-04-15","date_published":"2025-04-15","updated_at":"2026-07-22T22:25:05Z","subjects":["PFAS","Poly- and perfluoroalkyl substances","testicular cancer","lipid metabolism"],"languages":["en","eng"],"rights":["Copyright 2025 Raya Boyd"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2142/129382","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Spinella, Michael J","Flaws, Jodi A","Reddi, Prabhakara","Irudayaraj, Joseph"]},{"key":"dc:creator","label":"Author","values":["Boyd, Raya Iman"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2025-04-15","2025-05"]},{"key":"dc:type","label":"Dc Type","values":["text","Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["VMS - Comparative Biosciences"]},{"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":["PFAS","Poly- and perfluoroalkyl substances","testicular cancer","lipid metabolism"]}]},{"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 Raya Boyd"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2142/129382"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Submission original under an indefinite embargo labeled 'Open Access'. The submission was exported from vireo on 2025-10-19 without embargo terms","The student, Raya Boyd, accepted the attached license on 2025-04-14 at 13:12.","The student, Raya Boyd, submitted this Dissertation for approval on 2025-04-14 at 13:17.","This Dissertation was approved for publication on 2025-04-15 at 10:55.","DSpace SAF Submission Ingestion Package generated from Vireo submission #21711 on 2025-10-19 at 18:17:56","Poly- and perfluoroalkyl substances (PFAS) are ubiquitous chemicals used in daily life. These chemicals are used in water- and oil-repellants, food-wrapping paper, and industrial-based firefighting foams, to name a few. PFAS have strong carbon-fluorine bonds, which lead to their persistent and bioaccumulative nature in the environment and organisms. PFAS exposure is also linked with increased cancer risk in exposed populations, including testicular cancer. Testicular germ cell tumors (TGCTs) are a type of testicular cancer that affects men aged fifteen to forty-five. TGCTs are thought to arise from germ cells that have undergone improper differentiation to become germ cell neoplasia in situ cells. The uncontrolled proliferation of germ cell neoplasia in situ cells is thought to be triggered by a hormonal surge during puberty. While associations between TGCT incidence and PFAS have been made, there is a lack of mechanistic studies on the effects of PFAS on TGCT cells. This dissertation summarizes some of the first investigations of the effects of PFAS on TGCT cells. While exposure to perfluorooctanesulfonic acid (PFOS) and lithium bis(trifluoromethylsulfonyl)imide (HQ-115) did not increase the proliferation of parental and cisplatin-resistant TGCT cells in vitro, TGCT growth was increased in mouse models. Further, PFOS, HQ-115, and hexafluoropropylene oxide dimer acid (GenX) did not alter in vitro cell migration. PFOS and HQ-115 altered the metabolomic profile of lipid metabolism pathways of TGCT cells. In vivo exposure to PFOS and GenX showed alterations in pro-cancer phenotypes based on gene expression and lipid metabolism. The effects of PFAS on major regulators of lipid metabolism, peroxisome-proliferator activation receptors (PPARs), were also analyzed. PFOS did not alter the expression of PPAR target genes. HQ-115 increased PPAR target genes Plin2 and Fads2 in cisplatin-resistant cells. GenX exposures altered Plin2 expression in parental and cisplatin-resistant cells. PFOS and HQ-115 showed partial-agonist activity toward PPARα. PFOS and GenX showed antagonist activity toward PPARα and PPARγ. HQ-115 also showed antagonist activity toward PPARγ. Lastly, a spontaneous testicular cancer mouse model was established in the lab to study the effects of in utero PFAS exposures on testicular cancer development, as well as to study experimental testicular cancer therapies in an immune system intact animal model."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Toward a mechanistic understanding of poly- and perfluoroalkyl substances and testicular cancer"]}]}],"canonical_facts":{"dc:contributor":["Spinella, Michael J","Flaws, Jodi A","Reddi, Prabhakara","Irudayaraj, Joseph"],"dc:creator":["Boyd, Raya Iman"],"dc:date":["2025-04-15","2025-05"],"dc:description":["Submission original under an indefinite embargo labeled 'Open Access'. The submission was exported from vireo on 2025-10-19 without embargo terms","The student, Raya Boyd, accepted the attached license on 2025-04-14 at 13:12.","The student, Raya Boyd, submitted this Dissertation for approval on 2025-04-14 at 13:17.","This Dissertation was approved for publication on 2025-04-15 at 10:55.","DSpace SAF Submission Ingestion Package generated from Vireo submission #21711 on 2025-10-19 at 18:17:56","Poly- and perfluoroalkyl substances (PFAS) are ubiquitous chemicals used in daily life. These chemicals are used in water- and oil-repellants, food-wrapping paper, and industrial-based firefighting foams, to name a few. PFAS have strong carbon-fluorine bonds, which lead to their persistent and bioaccumulative nature in the environment and organisms. PFAS exposure is also linked with increased cancer risk in exposed populations, including testicular cancer. Testicular germ cell tumors (TGCTs) are a type of testicular cancer that affects men aged fifteen to forty-five. TGCTs are thought to arise from germ cells that have undergone improper differentiation to become germ cell neoplasia in situ cells. The uncontrolled proliferation of germ cell neoplasia in situ cells is thought to be triggered by a hormonal surge during puberty. While associations between TGCT incidence and PFAS have been made, there is a lack of mechanistic studies on the effects of PFAS on TGCT cells. This dissertation summarizes some of the first investigations of the effects of PFAS on TGCT cells. While exposure to perfluorooctanesulfonic acid (PFOS) and lithium bis(trifluoromethylsulfonyl)imide (HQ-115) did not increase the proliferation of parental and cisplatin-resistant TGCT cells in vitro, TGCT growth was increased in mouse models. Further, PFOS, HQ-115, and hexafluoropropylene oxide dimer acid (GenX) did not alter in vitro cell migration. PFOS and HQ-115 altered the metabolomic profile of lipid metabolism pathways of TGCT cells. In vivo exposure to PFOS and GenX showed alterations in pro-cancer phenotypes based on gene expression and lipid metabolism. The effects of PFAS on major regulators of lipid metabolism, peroxisome-proliferator activation receptors (PPARs), were also analyzed. PFOS did not alter the expression of PPAR target genes. HQ-115 increased PPAR target genes Plin2 and Fads2 in cisplatin-resistant cells. GenX exposures altered Plin2 expression in parental and cisplatin-resistant cells. PFOS and HQ-115 showed partial-agonist activity toward PPARα. PFOS and GenX showed antagonist activity toward PPARα and PPARγ. HQ-115 also showed antagonist activity toward PPARγ. Lastly, a spontaneous testicular cancer mouse model was established in the lab to study the effects of in utero PFAS exposures on testicular cancer development, as well as to study experimental testicular cancer therapies in an immune system intact animal model."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2142/129382"],"dc:language":["en","eng"],"dc:rights":["Copyright 2025 Raya Boyd"],"dc:subject":["PFAS","Poly- and perfluoroalkyl substances","testicular cancer","lipid metabolism"],"dc:title":["Toward a mechanistic understanding of poly- and perfluoroalkyl substances and testicular cancer"],"dc:type":["text","Thesis"],"thesis:degree_discipline":["VMS - Comparative Biosciences"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois Urbana-Champaign"]},"updated_at":"2026-07-22T22:25:05Z"}