{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/101356"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/101356","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"The effects of di (2-ethylhexyl) phthalate (dehp) on lesion development in a mouse model of endometriosis","abstract":"Endometriosis is a common gynecological disorder affecting 6%–10% of women of reproductive age and 35%–50% of women experiencing chronic pelvic pain and/or infertility. The most widely accepted mechanism of this disease is the entry of endometrial cell aggregates into the peritoneal cavity via the fallopian tubes in a process known as retrograde menstruation. These endometrial fragments attach and invade the peritoneal surfaces, eventually forming lesions. Primates are the only species that naturally develop endometriosis, however due to the expense and difficulty of working with these species, models based in laboratory species have been developed. Using a mouse transplantation model of endometriosis that mimics the progression of the disease in humans, we investigated the effects of di (2-ethylhexyl) phthalate, a known endocrine disruptor, on establishment of endometriotic lesions and neuroinflammation. To accomplish this, we validated the optimal estrogen dose for supplementation and monitored lesion progression over time following transplantation surgery. We then determined if mice with endometriotic lesions show signs of pain or discomfort using a behavioral assay. We also examined whether there is a genetic impact on the incidence and progression of endometriosis in our mouse model by comparing two different strains of mice. Finally, we determined the effects of di (2-ethylhexyl) phthalate (DEHP) on lesion development in our mouse model. Our main findings are that, 1) supplementing ovariectomized mice with 100 ng or 1 µg of 17β-estradiol every 4 days is not sufficient for the long term maintenance of endometriotic lesions. However supplementation with estradiol valerate resulted in a higher incidence of endometriotic lesions containing glands; 2) mice with endometriotic lesions show signs of discomfort or pain in association with induction of endometriosis; 3) the presence of endometriotic lesions resulted in increased numbers of activated microglia in the hippocampus of the brain; 4) C57BL/6 mice are a superior mouse strain for use in a mouse model of endometriosis; and 5) treatment of mice with 30 mg/kg/day or 60 mg/kg/day DEHP resulted in increased incidence and size of lesions and increased cell proliferation in endometriotic lesions. These results show that we have validated a mouse model for endometriosis that can be used to investigate how the presence of these lesions leads to increased neuroinflammation and visceral pain and how exposure to environmental factors such as phthalates may promote establishment and progression of this disease. The findings of these studies are highly relevant to understanding the mechanisms of endometriosis in women.","abstract_html":"Endometriosis is a common gynecological disorder affecting 6%–10% of women of reproductive age and 35%–50% of women experiencing chronic pelvic pain and/or infertility. The most widely accepted mechanism of this disease is the entry of endometrial cell aggregates into the peritoneal cavity via the fallopian tubes in a process known as retrograde menstruation. These endometrial fragments attach and invade the peritoneal surfaces, eventually forming lesions. Primates are the only species that naturally develop endometriosis, however due to the expense and difficulty of working with these species, models based in laboratory species have been developed. Using a mouse transplantation model of endometriosis that mimics the progression of the disease in humans, we investigated the effects of di (2-ethylhexyl) phthalate, a known endocrine disruptor, on establishment of endometriotic lesions and neuroinflammation. To accomplish this, we validated the optimal estrogen dose for supplementation and monitored lesion progression over time following transplantation surgery. We then determined if mice with endometriotic lesions show signs of pain or discomfort using a behavioral assay. We also examined whether there is a genetic impact on the incidence and progression of endometriosis in our mouse model by comparing two different strains of mice. Finally, we determined the effects of di (2-ethylhexyl) phthalate (DEHP) on lesion development in our mouse model. Our main findings are that, 1) supplementing ovariectomized mice with 100 ng or 1 µg of 17β-estradiol every 4 days is not sufficient for the long term maintenance of endometriotic lesions. However supplementation with estradiol valerate resulted in a higher incidence of endometriotic lesions containing glands; 2) mice with endometriotic lesions show signs of discomfort or pain in association with induction of endometriosis; 3) the presence of endometriotic lesions resulted in increased numbers of activated microglia in the hippocampus of the brain; 4) C57BL/6 mice are a superior mouse strain for use in a mouse model of endometriosis; and 5) treatment of mice with 30 mg/kg/day or 60 mg/kg/day DEHP resulted in increased incidence and size of lesions and increased cell proliferation in endometriotic lesions. These results show that we have validated a mouse model for endometriosis that can be used to investigate how the presence of these lesions leads to increased neuroinflammation and visceral pain and how exposure to environmental factors such as phthalates may promote establishment and progression of this disease. The findings of these studies are highly relevant to understanding the mechanisms of endometriosis in women.","abstract_has_math":false,"creators":["Lawrence, Catherine Reed"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"M.S.","degree_level":"Thesis","degree_discipline":"Animal Sciences","degree_department":null,"school":null,"contributors":["Nowak, Romana A.","Steelman, Andrew","Li, Quanxi"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2018,"date_issued":"2018-09-04T20:47:27Z","date_published":"2018-09-04T20:47:27Z","updated_at":"2026-07-22T22:24:38Z","subjects":["Endometriosis","DEHP","Phthalate","Mouse model","Brain","Microglia","Neuroinflammation"],"languages":["en"],"rights":["Copyright 2018 Catherine Lawrence"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/101356","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Nowak, Romana A.","Steelman, Andrew","Li, Quanxi"]},{"key":"dc:creator","label":"Author","values":["Lawrence, Catherine Reed"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2018-09-04T20:47:27Z","2020-09-05T09:15:23Z","2018-04-20","2018-05"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Animal Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["M.S."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Endometriosis","DEHP","Phthalate","Mouse model","Brain","Microglia","Neuroinflammation"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2018 Catherine Lawrence"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/101356"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Endometriosis is a common gynecological disorder affecting 6%–10% of women of reproductive age and 35%–50% of women experiencing chronic pelvic pain and/or infertility. The most widely accepted mechanism of this disease is the entry of endometrial cell aggregates into the peritoneal cavity via the fallopian tubes in a process known as retrograde menstruation. These endometrial fragments attach and invade the peritoneal surfaces, eventually forming lesions. Primates are the only species that naturally develop endometriosis, however due to the expense and difficulty of working with these species, models based in laboratory species have been developed. Using a mouse transplantation model of endometriosis that mimics the progression of the disease in humans, we investigated the effects of di (2-ethylhexyl) phthalate, a known endocrine disruptor, on establishment of endometriotic lesions and neuroinflammation. To accomplish this, we validated the optimal estrogen dose for supplementation and monitored lesion progression over time following transplantation surgery. We then determined if mice with endometriotic lesions show signs of pain or discomfort using a behavioral assay. We also examined whether there is a genetic impact on the incidence and progression of endometriosis in our mouse model by comparing two different strains of mice. Finally, we determined the effects of di (2-ethylhexyl) phthalate (DEHP) on lesion development in our mouse model. Our main findings are that, 1) supplementing ovariectomized mice with 100 ng or 1 µg of 17β-estradiol every 4 days is not sufficient for the long term maintenance of endometriotic lesions. However supplementation with estradiol valerate resulted in a higher incidence of endometriotic lesions containing glands; 2) mice with endometriotic lesions show signs of discomfort or pain in association with induction of endometriosis; 3) the presence of endometriotic lesions resulted in increased numbers of activated microglia in the hippocampus of the brain; 4) C57BL/6 mice are a superior mouse strain for use in a mouse model of endometriosis; and 5) treatment of mice with 30 mg/kg/day or 60 mg/kg/day DEHP resulted in increased incidence and size of lesions and increased cell proliferation in endometriotic lesions. These results show that we have validated a mouse model for endometriosis that can be used to investigate how the presence of these lesions leads to increased neuroinflammation and visceral pain and how exposure to environmental factors such as phthalates may promote establishment and progression of this disease. The findings of these studies are highly relevant to understanding the mechanisms of endometriosis in women.","Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2020-05-01","The student, Catherine Lawrence, accepted the attached license on 2018-04-19 at 10:54.","The student, Catherine Lawrence, submitted this Thesis for approval on 2018-04-19 at 10:55.","This Thesis was approved for publication on 2018-04-20 at 09:39.","DSpace SAF Submission Ingestion Package generated from Vireo submission #12374 on 2018-08-31 at 17:30:06","Made available in DSpace on 2018-09-04T20:47:27Z (GMT). No. of bitstreams: 2 LAWRENCE-THESIS-2018.pdf: 9398379 bytes, checksum: 10c08f70d72beac7f2187c9b1289294e (MD5) LICENSE.txt: 4215 bytes, checksum: 98925ab2f6ceafdfbe1e7eba2cc9efdc (MD5) Previous issue date: 2018-04-20","Embargo set by: Seth Robbins for item 107441 Lift date: 2020-09-04T20:47:38Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system","Embargo set by: Seth Robbins for item 107441 Lift date: 2020-09-04T20:50:11Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system","Limited Restriction Lifted for Item 107441 on 2020-09-05T09:15:23Z."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["The effects of di (2-ethylhexyl) phthalate (dehp) on lesion development in a mouse model of endometriosis"]}]}],"canonical_facts":{"dc:contributor":["Nowak, Romana A.","Steelman, Andrew","Li, Quanxi"],"dc:creator":["Lawrence, Catherine Reed"],"dc:date":["2018-09-04T20:47:27Z","2020-09-05T09:15:23Z","2018-04-20","2018-05"],"dc:description":["Endometriosis is a common gynecological disorder affecting 6%–10% of women of reproductive age and 35%–50% of women experiencing chronic pelvic pain and/or infertility. The most widely accepted mechanism of this disease is the entry of endometrial cell aggregates into the peritoneal cavity via the fallopian tubes in a process known as retrograde menstruation. These endometrial fragments attach and invade the peritoneal surfaces, eventually forming lesions. Primates are the only species that naturally develop endometriosis, however due to the expense and difficulty of working with these species, models based in laboratory species have been developed. Using a mouse transplantation model of endometriosis that mimics the progression of the disease in humans, we investigated the effects of di (2-ethylhexyl) phthalate, a known endocrine disruptor, on establishment of endometriotic lesions and neuroinflammation. To accomplish this, we validated the optimal estrogen dose for supplementation and monitored lesion progression over time following transplantation surgery. We then determined if mice with endometriotic lesions show signs of pain or discomfort using a behavioral assay. We also examined whether there is a genetic impact on the incidence and progression of endometriosis in our mouse model by comparing two different strains of mice. Finally, we determined the effects of di (2-ethylhexyl) phthalate (DEHP) on lesion development in our mouse model. Our main findings are that, 1) supplementing ovariectomized mice with 100 ng or 1 µg of 17β-estradiol every 4 days is not sufficient for the long term maintenance of endometriotic lesions. However supplementation with estradiol valerate resulted in a higher incidence of endometriotic lesions containing glands; 2) mice with endometriotic lesions show signs of discomfort or pain in association with induction of endometriosis; 3) the presence of endometriotic lesions resulted in increased numbers of activated microglia in the hippocampus of the brain; 4) C57BL/6 mice are a superior mouse strain for use in a mouse model of endometriosis; and 5) treatment of mice with 30 mg/kg/day or 60 mg/kg/day DEHP resulted in increased incidence and size of lesions and increased cell proliferation in endometriotic lesions. These results show that we have validated a mouse model for endometriosis that can be used to investigate how the presence of these lesions leads to increased neuroinflammation and visceral pain and how exposure to environmental factors such as phthalates may promote establishment and progression of this disease. The findings of these studies are highly relevant to understanding the mechanisms of endometriosis in women.","Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2020-05-01","The student, Catherine Lawrence, accepted the attached license on 2018-04-19 at 10:54.","The student, Catherine Lawrence, submitted this Thesis for approval on 2018-04-19 at 10:55.","This Thesis was approved for publication on 2018-04-20 at 09:39.","DSpace SAF Submission Ingestion Package generated from Vireo submission #12374 on 2018-08-31 at 17:30:06","Made available in DSpace on 2018-09-04T20:47:27Z (GMT). No. of bitstreams: 2 LAWRENCE-THESIS-2018.pdf: 9398379 bytes, checksum: 10c08f70d72beac7f2187c9b1289294e (MD5) LICENSE.txt: 4215 bytes, checksum: 98925ab2f6ceafdfbe1e7eba2cc9efdc (MD5) Previous issue date: 2018-04-20","Embargo set by: Seth Robbins for item 107441 Lift date: 2020-09-04T20:47:38Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system","Embargo set by: Seth Robbins for item 107441 Lift date: 2020-09-04T20:50:11Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system","Limited Restriction Lifted for Item 107441 on 2020-09-05T09:15:23Z."],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/2142/101356"],"dc:language":["en"],"dc:rights":["Copyright 2018 Catherine Lawrence"],"dc:subject":["Endometriosis","DEHP","Phthalate","Mouse model","Brain","Microglia","Neuroinflammation"],"dc:title":["The effects of di (2-ethylhexyl) phthalate (dehp) on lesion development in a mouse model of endometriosis"],"dc:type":["text"],"thesis:degree_discipline":["Animal Sciences"],"thesis:degree_level":["Thesis"],"thesis:degree_name":["M.S."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:24:38Z"}