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by claude@2026-07, 2026-07-16
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This study found that DEHP exposure increased the incidence, size, and cell proliferation of endometriotic lesions in a validated mouse model, which also exhibited signs of discomfort and neuroinflammation.
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by claude@2026-07, 2026-07-16
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This thesis used a mouse transplantation model that mimics endometriosis progression to test how di(2-ethylhexyl) phthalate (DEHP) and estrogen-supplementation strategies affect lesion establishment and neuroinflammation, with estradiol dose/vehicle optimization and longitudinal lesion monitoring after surgery. Across experiments, lesion induction was associated with behavioral evidence of discomfort or pain and with increased numbers of activated microglia in the hippocampus, and C57BL/6 mice were reported to be superior to another strain for this model; a stated limitation is that estradiol supplementation with 17β-estradiol at 100 ng or 1 µg every 4 days was not sufficient for long-term maintenance of lesions. The key DEHP findings were that treatment at 30 mg/kg/day or 60 mg/kg/day increased the incidence and size of endometriotic lesions and increased cell proliferation within lesions. This paper is centrally about endometriosis — it investigates how DEHP exposure and model parameters affect lesion development, neuroinflammation, and associated pain in an endometriosis mouse model.
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.
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The effects of di (2-ethylhexyl) phthalate (dehp) on lesion development in a mouse model of endometriosis
Lawrence, Catherine Reed
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https://hdl.handle.net/2142/101356
Description
- Title
- The effects of di (2-ethylhexyl) phthalate (dehp) on lesion development in a mouse model of endometriosis
- Author(s)
- Lawrence, Catherine Reed
- Issue Date
- 2018-04-20
- Director of Research (if dissertation) or Advisor (if thesis)
- Nowak, Romana A.
- Committee Member(s)
- Steelman, Andrew
- Li, Quanxi
- Department of Study
- Animal Sciences
- Discipline
- Animal Sciences
- Degree Granting Institution
- University of Illinois at Urbana-Champaign
- Degree Name
- M.S.
- Degree Level
- Thesis
- Date of Ingest
- 2018-09-04T20:47:27Z
- Keyword(s)
- Endometriosis
- DEHP
- Phthalate
- Mouse model
- Brain
- Microglia
- Neuroinflammation
- 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.
- Graduation Semester
- 2018-05
- Type of Resource
- text
- Permalink
- http://hdl.handle.net/2142/101356
- Copyright and License Information
- Copyright 2018 Catherine Lawrence
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Graduate Dissertations and Theses at Illinois PRIMARY
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